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Fertility Specialist in Hyderabad

Fertility Specialist Doctors in Pakistan

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M.B.B.S, MPhil (Anatomy), Certified in Interventional ultrasound
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MD, MSc (Embryology), FACOG, FACS
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bsc hons , mphill, dpharm
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B.Sc,MBBS,M-Phi,FCPS(UROL)i,MSPH,Ph.D Scholer,Member Sexual Society of North America

Fertility Specialist in Hospitals of Hyderabad

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Fertility Specialist in Hyderabad

The medical field is divided into different categories and Fertility Specialist have a significant place among them. Fertility Specialist in Hyderabad analyzes symptoms of a patient and prescribes them with the required medicine or treatment. They use surgical or medical procedures as per the condition and severity of disease or illness. On the other side, they also refer to other professional healthcare providers in case of a medical issue beyond their area of expertise.

You might also visit a Fertility Specialist in order to increase your knowledge about the risk factors involved in various diseases and find out what preventive measures you can take for maintaining healthy life. A lot of people prefer to consult with a Fertility Specialist of same gender. However, the information about both male and female Fertility Specialist is present on our website. The list of Fertility Specialist in Hyderabad includes all key details such as qualification, specialty, phone no, clinic timings. View information of Fertility Specialist from different areas of Hyderabad and book the appointment as per your ease or convenience. You can also view details about neurologist, physical therapist, dietitian, ENT specialist in Hyderabad on their respective pages.

Latest Comments
Aslam-o-Alikum sir meri wife ki age 33 aur meri age 32 hai 7 years ho gaye hai pregnancy consive nahi ho rahi hum ne Hameed Latif Hospital bhi checkup karwaya hai. 2 month before test karwaya hai sperm ka 55% the total. IVF ke kitne percent chance ho ge. Konse Doctor se checkup karwana chahye fertility wale se ya IVF wale doctor se plz hume mashwara de de
By: Muhammad kamran, Form: Islamabad, on Tuesday, March 22, 2022
Sir how to treat azoospermia in low cost test tube ivf etc for pregnancy.kindly provide me easy and cheapest treatment.
By: Waheed khan, Form: Peshawar, on Sunday, October 17, 2021
Salaam doctor i just wont to ask how much is for test tub baby if we wont to get done can you please reply soon we in uk i need doctor uour number so i can talk to you on the phone
By: Sobia , Form: Islamabad, on Wednesday, September 15, 2021
Salam sir mjy infertility ka treatment krwana h .
By: Uzair , Form: Karachi, on Monday, August 23, 2021
Assalamoalaekum Madam I am Muhammad Junaid from Astra Biotech I have a tesult oriented product of infertility by the name of Crystal F I want to meet you about that product my cell number 03152165768 this also my Watsup number
By: Muhammad Junaid, Form: Karachi, on Thursday, March 4, 2021
salam o alikom my active sperm is 15% how money price is the IVF
By: enyatullah, Form: Islamabad, on Monday, December 14, 2020
Procedure for appointment
By: Dr Saeed Ahmad , Form: Karachi, on Thursday, November 26, 2020
Dr shab mughe fabriod hy or harmouns disturb hyn olad nh hy mere shadi ko one year hojainge age mere 36 hy or mere husband ki age 55 hy koi gal batade olad K liyel
By: Amreen Sagheer , Form: Karachi, on Monday, November 23, 2020
Plz bataye k is mothod SE baby boy hoga
By: Sadaf, Form: Karachi, on Monday, May 4, 2020
Dr. Rizwan Malik se appointment leny k lye rabta karen. 0515147149/ 0331 556 5570 RAWALPINDI CENTER: 161, Next to Street No. 5, Main Racecourse Road, Rawalpindi
By: Arsalan Khan, Form: Islamabad, on Monday, March 9, 2020

Disclaimer: All material on this website is provided for your information only and may not be construed as medical advice or instruction. No action or inaction should be taken based solely on the contents of this information; instead, readers should consult appropriate health professionals on any matter relating to their health and well-being. The data information and opinions expressed here are believed to be accurate, which is gathered from different sources but might have some errors. Hamariweb.com is not responsible for errors or omissions. Doctors and Hospital officials are not necessarily required to respond or go through this page.


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Difference Between White and Red Stretch Marks

Stretch marks or striae are a form of scarring on the body, particularly women that occur due to tearing of dermis.

Stretch marks are often a result of rapid and excessive stretching of the skin that is associated with the growth in mass of the body, which is commonly seen during puberty or due to weight gain as seen during pregnancy.

The human skin is made up of three layers: the epidermis, the dermis, and subcutis.

Stretch marks that occur on the dermis layer, the resilient middle layer that helps the skin retain its shape.

The dermis layers sometimes tears and loses elasticity, resulting in discolored scarring of the skin, or a stretch mark.

The marks can appear anywhere on the body but can most commonly be observed on abdomen, thighs, buttocks, breast and upper arm, where a large number of fats is stored.

The glucocorticoid hormone is also responsible for the development of stretch marks by causing damage to the epidermis by preventing the fibroblasts from forming collagen and elastin fibers, which are important to keep the rapidly growing skin intact.

This condition creates a lack of supportive material, as the skin is stretched and leads to epidermal tearing.

Stretch marks can happen to both men and women.

Though usually, women are most afflicted by it due to pregnancy, men also often do suffer from this problem, in case of weight gain, weight loss, and growth spurts.

Read: Why we get Stretch Marks>

Many teenagers get stretch marks due to these factors.

Studies suggest that as many as, 70% of girls and 40% boys are affected by the stretch marks during their adolescence.

What are Red Stretch Marks?

Red stretch marks are marks which appear on the skin at initial stages when it is distressed. They are also sometimes called purple marks.

So, it becomes somewhat red or purplish in color. In due time, and depending on the skin type and color, these then fade to off-white or silvery color.

The stretch marks are early because they are red in color. These are typically less than a year old.

They are easier to treat because the skin is still in the process of trying to heal.

Red colored stretch marks are medicinally known as striae rubra.

The red stretch marks have a wrinkled and crinkled strip like appearance and are often raised.

Over the time, the red marks turn to brown dusky or purple color and finally turns to white stripes.

What are White Stretch Marks?

The stretch marks which lack pigments or hypo-pigmented appear to be as white or silver stretch marks. They are also known as matured stretch marks. These are medically known as striae distensae alba.

This stage when stretch marks mature and turn white indicates that collagen bundles mix with abnormally thin elastin fibers but are unable to fully realign themselves. Normal elastin fibers are still absent.

This transition from red to white marks is due to the eventual the contraction of the blood vessels, leaving only the fats under the skin visible which makes the red marks fade away to white color.

Difference between Red and White Stretch Marks

The key difference between the red and the white stretch marks is that red stretch marks are "young" or "immature" stretch marks while the red ones are "old" or "mature" stretch marks.

Here are some more differences explained -

  • Red stretch marks are medically known as, striae rubra whereas white stretch marks are medically known as striae distensae alba.
  • Red stretch marks indicate the immature or the initial form of stretch marks, whereas white marks indicate the matured form of stretch marks.
  • Red stretch marks occur normally during puberty and pregnancy, whereas the white marks occur due to collagen remodeling and inflammation, which leads to hypo-pigmentation.

Difference Between White and Red Stretch Marks

How treatment of Red and White Stretch Marks differ?

Most types of stretch marks usually fade with time, but there is no evidence that they can disappear entirely.

Pharmaceutical companies and the people in the medical field recommend various oils, creams to prevent the stretch marks from coming.

The observed treatment for the diminishing effect of stretch marks can also be seen with laser treatments or chemical peels.

These procedures fade away the visibility of stretch marks by making the skin supple, encouraging healthy cell turn over and stimulating the collagen growth so that the scar tissue eventually goes away.

The treatment for red stretch marks differs from that of white stretch marks in a way that, red stretch marks are not yet mature.

So they need a treatment, by which the damage to the dermis can be limited.

Whereas white stretch marks treatment includes medication by which their appearance can be improved.

Options for treating Red Stretch Marks

1. Mederma

This cream is preferably advised for red stretch marks and has to be applied 3 to 4 times a day, for six to twelve months.

This cream has shown good results for treating red, raised stretch marks. It is safe to use while pregnancy and nursing.

The cream has natural ingredients, it uses the onion-juice extract as the active ingredient.

Read More about Mederma here>

2. L- ascorbic acid

This is one of the active ingredients in creams such as cellex-C and skin ceuticals. Apply a 15-20% serum daily for six to twelve months.

L-ascorbic acid helps to stimulate fibroblasts to produce collagen and elastin fibers, which help in preventing stretch marks.

3. Retin-A or Tazorac cream ( 0.1% tretinoin)

This is to be applied at night for twelve months. This is the prescribed option, but a non-prescribed option is skin- ceuticals 1% retinol.

Retinoids have long been suspected of stimulating fibroblasts activity.. In addition, exfoliation will occur, helping create a more uniform surface.

This medication is advised to be avoided during pregnancy and nursing.

Options of Treatment for White Stretch Marks

1. Glycolic acid and Vitamin A creams

20% buffered Glycolic acid is one of the important ingredients in a cream called M. D. Forte is an ideal cream for white stretch marks, with a minimum amount of irritation.

Vitamin A cream should be applied in combination with it but at night, such that the face should be washed and the cream should be applied 30 minutes after, until the face is dry.

Both glycolic acid and vitamin creams can cause an increase in photosensitivity, so a sunscreen of SPF 30 should be used in combination with it.

For maximum results, glycolic acid cream should be applied in the morning, whereas the vitamin A cream should be applied at night.

2. Microdermabrasion

this is a helpful technique for stubborn, old white stretch marks.

In this procedure of microdermabrasion, the tiny particles are sandblasted against the skin, gradually removing scarred epithelial tissue.

Typically, this procedure is done in a series of six or more treatments.

Read more about microdermabrasion for stretch marks here.

3. Non-ablative lasers

one more treatment for the old white stretch marks is non- ablative lasers. Lasers of this type do not burn the skin, as in ablative lasers.

This procedure involves stimulating fibroblasts, which produce collagen fibres.

4. The XTRAC laser

This laser helps restore the skin color and pigmentation. For stretch marks of white color, re-pigmentation is possible with this laser technique.

Stretch marks or striae are the lines or stripes on the body, generally occurring at the regions where a large number of fats is stored.

The stretch marks initially begin as red marks on the body, which is crinkled but later mature to white stretch marks, which have a silvery outline.

The initial stretch marks, medically known as striae rubra, are raised and often give a scar-like appearance.

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noah es hearing aid programming

Noah ES officially released in the USA and Europe

COPENHAGEN, DENMARK — HIMSA has announced the official release of Noah ES. Released in late January 2022, Noah ES already has over 270 users in the USA and Europe.

Noah ES stands for Noah Extended Services and, as the logo implies, the project is to create a cloud-enabled version of Noah. With Noah ES, Noah Services will now reside and be maintained in the cloud, including database backup, maintenance, security monitoring and user authentication.

According to HIMSA, this means:

  • Always available – Access your Noah patient data 24×7, from anywhere there is Internet.
  • Simple and scalable – From small businesses to large chains, Noah ES provides customizable access, simple networking, and easy expandability.
  • Low maintenance – Noah ES handles all database maintenance and security in the cloud, so you can use more time on your business.
  • No training curve – The Noah System client performs in much the same way as always. This means no additional training.
  • Very Secure – Fully HIPAA and GDPR compliant. Your patient data is securely stored and protected in professionally maintained data centers.

Interested readers can visit the HIMSA website to learn more.

Source: HIMSA

About HHTM

HHTM's mission is to bridge the knowledge gaps in treating hearing loss by providing timely information and lively insights to anyone who cares about hearing loss. Our contributors and readers are drawn from many sectors of the hearing field, including practitioners, researchers, manufacturers, educators, and, importantly, consumers with hearing loss and those who love them.

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How to Get Your Hearing Clinic in Google’s Map Pack

When users search for businesses on Google, they are displayed on Google Maps and Search in different ways.

For example, if you use your phone or laptop to search for “teeth cleaning,” local results appear, providing a list of dentists in your local area. These results will point to Google My Business (GMB) listings of highly rated dentists in your neighborhood.

The Google Map Pack in Google’s local search results is the most popular and sought-after spot. It is often referred to as the “Google three pack,” a compilation of three highlighted Google-Maps-related results that feature the most highly ranked businesses. It appears at the top of the page, before the regular organic results (but after some sponsored Google ads).

The Google map pack is considered precious online real estate, as making it on this shortlist highlights you as a hearing health leader in your local area. This translates into more leads – The Google Maps Pack grabs as many as 44 percent of the overall clicks on search engine results sites, according to a recent study.

How to get your hearing practice to the top of the map pack

According to Moz, the first step in getting to the top of the map pack is through Google My business, which makes up the largest of the local pack ranking factors.

You will want to focus on three areas: Creating and optimizing your GMB listing, getting plenty of GMB reviews, and continuing other SEO efforts.

Step #1: Create and optimize your Google My Business Listing

The very first move is to create your business listing. This involves creating and filling in your business profile. Ensure that your business details suit your other online profiles to get the most out of your listing.

Here are some tips to optimize your listing once you have created your profile:

  • Ensure that all the information is correct, especially your address, as this is one way Google decides which companies to show in the local pack.
  • Add your business category.
  • Check that the information on your Google My Business page explicitly matches your website information and other local listings, precisely your name, address, and phone number. Accuracy is an important ranking factor for Google.

Step #2: Get more Google My Business reviews

It’s not easy to get reviews, but you’ll increase your chances by using the following steps:

Ask for them. If you’re trying to get a review, you must ask someone to leave a review. Here are some places you can do so:

  • After a hearing service is completed
  • Via email
  • When you are you’re sending the bill
  • After you end a phone call

Point them in the right direction. To leave the review, show your hearing aid customer that they have to log into Google, and go to your Google company listing. You can also send them a link to your listing on Google Maps, which prompts the review panel to open.

Remind them to review you.  It may take a week for them to get around to writing the review. Ensure that you follow up with them within two weeks and remind them to leave a review.

Keep paying attention to your other SEO efforts

Since the local Google pack is part of Google’s broader search results, keeping up with all aspects of your SEO is essential to improve your chances of ranking anywhere on Google’s results pages.

  • Confirm that your site is mobile-friendly. The mobile version of your website is indexed by Google, so your site must be mobile-optimized.
  • Check the meta tags of your website, especially on your homepage, and ensure that your position is included somehow.
  • You want visitors to quickly find what your company does by reading through your web content and making sure it is easy to understand for searchers and search engines.
  • Create a blog and populate it with hearing health-related information that answers your current and potential hearing aid customers’ questions.

Nick Fitzgerald is the President and Owner of AuDSEO. He also serves as the Chief Marketing Officer at Hearing Health & Technology Matters. With 13 years of digital marketing experience, Nick is a highly data-driven marketer, with expertise in search engine optimization, digital analytics and forensics, social media, digital advertising, and web development. He has been involved in the construction and optimization of nearly 1,000 web presences, including some of the largest Fortune 500 companies.

About HHTM

HHTM's mission is to bridge the knowledge gaps in treating hearing loss by providing timely information and lively insights to anyone who cares about hearing loss. Our contributors and readers are drawn from many sectors of the hearing field, including practitioners, researchers, manufacturers, educators, and, importantly, consumers with hearing loss and those who love them.

Leave a Reply

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You Have Been Prayed For… EPHESIANS 2:18

Hallelujah, praise the living God for another day to pray for you all and be used by Him. Today I offer these lines from Timothy Keller.

“The work of Son and Spirit should never be divorced, nor one made to obscure the other. The fullness of the Spirit is experienced as we meditate on the love of the Son. The gifts of the Son are enjoyed as we look to the Spirit to guide us.”

Ephesians 2:18
New American Standard Bible

18 for through Him we both have our access in one Spirit to the Father.

Heavenly Father, in the name of our Lord Jesus, Your servant praises and worships You.  Bless You, for sending Your Holy Spirit to reside in us, Your children. Thank You for uniting us to be one with You through Your Son, Jesus Christ. Praise the unifying power of Your love that opens the eyes of our hearts to the truth and allows us to walk with Your Spirit and in Christ for the glory of Your most precious name. Help us to never turn to the left or the right as we walk on Your path of righteousness for the sake of Your name. Father, we thank You that You have heard us. In Jesus’ name and in the power of the Holy Spirit, amen.

If this prayer blessed you or brought you peace, please share this with someone in need.

Published by HearUsJesus

Grateful Christian. Anything you enjoy here please give the glory and thanks to God, all writing is Spirit led.

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Shades of Gray

Lately, I have been fiddling with black & white photography in Lightroom. One thing that has surprised me is how varying shades of gray can greatly affect the contrast or hard edge between light and darkness.

Dunbar Beach – Indiana Dunes National Park

The more I learn about photography, the more I realize just how much I don’t know.

All photos are my own. ©Pepper Tron and Heaven’s Sunshine
No usage allowed in any form without my written consent.

13 responses to “Shades of Gray”

  1. 👌👌👌📷💝 perfectly 👏👏👏

    1. Thank you. You have inspired me to work on my photography a bit more.

  2. I love this one Irene. Thanks for joining in 🙂 🙂

    1. Thanks,Brian. So glad you enjoyed image. 😊

  3. Very nice! 🙂 I liked what kagould17 said!!

    1. Thank you, Donna. 😊

  4. Winter monochromes can be so dramatic. Photography is about learning with every photo. Cheers. Allan

    1. Thanks, Allan. 😊

  5. You have an eye for it — never forget you have two of them! That’s a lovely photo.

    1. Thanks, Rob. 😉

  6. Terrific lines for this week. So simple, but yet a strong photo 😀

    1. Thanks, Cee. 😊

Words can brighten the grayest of days.

error: All photos are copyrighted by Irene Tron/HeavensSunshine. All rights reserved. Unauthorized use prohibited.
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Harrisville State Park Cabin Fever Weekend – October, 2019 (Literally)!

Let’s pretend I’m an overly important person standing at a lectern on a stage addressing a room full of about…500 people And I ask:

“Let’s see a show of hands – how many of you have seen the movie The Shining?”

Jack Nicholson as Jack Torrance in The Shining. Laying the groundwork for playing The Joker in Batman (1989)? #fantheory

I’m guessing about maybe half the folks in the room will raise their hands. It is kind of a popular movie, and it was released almost 40 years ago.

Then I’ll say, “The concept of ‘cabin fever,’ or people going nuts when shut in together is kind of the premise of The Shining. How many of you have ever been in this situation?”

Maybe I’ll get 10 honest folks or so raising their hands for this question…

Then I’ll ask:

“How many of you have ever had an actual fever – in a cabin?”

And for this question? I might be the only one to raise my hand!

My husband and I visited Harrisville State Park in Harrisville, MI last weekend and rented the cabin that is called “Number 300.” Here are some views of the cabin we rented, (interior and exterior):

2019-10-20 17.35.44.jpg

Exterior views of “Cabin 300” ⇑
And some interior shots (there was a note on the door indicating the cabin was undergoing renovation when we visited): ⇓

I think I’ve set the scene pretty well, haven’t I? I had the unfortunate luck to start coming down with what I *thought* was just a common cold on our trip up here, so I bought the supplies I thought I’d need – tissues, a generic version of Claritin (I was sneezing like one of those Looney Tunes characters inhaling black pepper) and later – some nasal spray, throat lozenges and cough syrup.

2019-10-20 16.43.08.jpg

Saturday night, I had quite the rough time getting to sleep because of both indigestion and a hacking cough. Out of desperation, I wound up finding some old generic Benadryl capsules in my toiletry bag and took three of those. More than the recommended dose, but I needed to be knocked out! To speed things along, I cracked one of the capsules open and dumped the powder into a bit of ginger beer, then just swallowed the other two whole. For a time, this seemed to irritate my cough even more (probably that raw medicine going down my gullet chased by a bit of soda), but after a time, I was…out.

My poor husband, who had earlier retreated to the car because of my unceasing cough, came in to check on me, saw that I was out cold, and felt my forehead. He said it felt “mildly warm.” I had noticed earlier in the evening that it felt kind of hotter than usual, and I got into a chilly/hot battle on the futon with my sleeping bag. I didn’t know whether to keep it zipped up – or open. Sometime during the night, I broke into quite an epic sweat, and after that happened, my forehead felt normal again (my fever must’ve broken).

What WASN’T normal was how frequently I had to pee! It was about every hour…to an hour and a half by my estimations. And the “real” bathroom was about 200 feet away! It seemed if I took a sip of water, water needed to come out of me at that EXACT moment… Of course this kind of thing couldn’t possibly happen in my own home where I have four bathrooms (yes our condo is quite strange).  I never knew having a fever caused increased urination, but…

I think I might’ve come up with a mild dose of the flu. Even now – four days later – my cold symptoms are virtually gone (just a little lingering cough), but I still feel…wiped out.

Despite all of what you just read, I did have a great time on the trip! It was nice getting away, watching the waves of Lake Huron do their best imitation of Lake Superior – here are some scenes from Alpena, MI (which is about 40 minutes north of Harrisville) ⇓:

Did I mention that I had a great time on the trip despite the “cabin fever?” Well, pictures or it didn’t happen!

Yes, it really was that cold by the water in Alpena! Those winds felt like 40-plus mile per hour winds. Just a bit further south in Harrisville, it was much milder (which you can tell by my lack of winter coat in the next two photos):

2019-10-19 17.44.25.jpg

Now How About Some Dog Pictures?

Our dear friend Janet came to visit us for a few hours on Sunday, and she brought along her two dogs – Lulu, an English setter – and Fefe, a Jack Russell terrier. Since EVERYONE loves animal photos, what kind of blogger would I be if I didn’t close out this blog with some dog photos?

Don’t let that cute face fool you even for a second! Fefe is a feisty girl…

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Browsing by Subject "TRANSCRIPTOME"

Sort by: Order: Results:

Now showing items 1-20 of 32
  • Rahikkala, Elisa; Urpa, Lea; Ghimire, Bishwa; Topa, Hande; Kurki, Mitja; Koskela, Maryna; Airavaara, Mikko; Hämäläinen, Eija; Pylkäs, Katri; Körkkö, Jarmo; Savolainen, Helena; Suoranta, Anu; Bertoli-Avella, Aida; Rolfs, Arndt; Mattila, Pirkko; Daly, Mark; Palotie, Aarno; Pietiläinen, Olli; Moilanen, Jukka; Kuismin, Outi (2022)
    Biallelic loss-of-function variants in the SMG9 gene, encoding a regulatory subunit of the mRNA nonsense-mediated decay (NMD) machinery, are reported to cause heart and brain malformation syndrome. Here we report five patients from three unrelated families with intellectual disability (ID) and a novel pathogenic SMG9 c.551 T > C p.(Val184Ala) homozygous missense variant, identified using exome sequencing. Sanger sequencing confirmed recessive segregation in each family. SMG9 c.551T > C p.(Val184Ala) is most likely an autozygous variant identical by descent. Characteristic clinical findings in patients were mild to moderate ID, intention tremor, pyramidal signs, dyspraxia, and ocular manifestations. We used RNA sequencing of patients and age- and sex-matched healthy controls to assess the effect of the variant. RNA sequencing revealed that the SMG9 c.551T > C variant did not affect the splicing or expression level of SMG9 gene products, and allele-specific expression analysis did not provide evidence that the nonsense mRNA-induced NMD was affected. Differential gene expression analysis identified prevalent upregulation of genes in patients, including the genes SMOX, OSBP2, GPX3, and ZNF155. These findings suggest that normal SMG9 function may be involved in transcriptional regulation without affecting nonsense mRNA-induced NMD. In conclusion, we demonstrate that the SMG9 c.551T > C missense variant causes a neurodevelopmental disorder and impacts gene expression. NMD components have roles beyond aberrant mRNA degradation that are crucial for neurocognitive development.
  • PanScan PanC4 consortia; Walsh, Naomi; Zhang, Han; Männistö, Satu; Weiderpass, Elisabete (2019)
    Background Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P Conclusion Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
  • Nikparvar, Bahareh; Andreevskaya, Margarita; Duru, Ilhan C.; Bucur, Florentina I.; Grigore-Gurgu, Leontina; Borda, Daniela; Nicolau, Anca I.; Riedel, Christian U.; Auvinen, Petri; Bar, Nadav (2021)
    Background The pathogen Listeria (L.) monocytogenes is known to survive heat, cold, high pressure, and other extreme conditions. Although the response of this pathogen to pH, osmotic, temperature, and oxidative stress has been studied extensively, its reaction to the stress produced by high pressure processing HPP (which is a preservation method in the food industry), and the activated gene regulatory network (GRN) in response to this stress is still largely unknown. Results We used RNA sequencing transcriptome data of L. monocytogenes (ScottA) treated at 400 MPa and 8(circle)C, for 8 min and combined it with current information in the literature to create a transcriptional regulation database, depicting the relationship between transcription factors (TFs) and their target genes (TGs) in L. monocytogenes. We then applied network component analysis (NCA), a matrix decomposition method, to reconstruct the activities of the TFs over time. According to our findings, L. monocytogenes responded to the stress applied during HPP by three statistically different gene regulation modes: survival mode during the first 10 min post-treatment, repair mode during 1 h post-treatment, and re-growth mode beyond 6 h after HPP. We identified the TFs and their TGs that were responsible for each of the modes. We developed a plausible model that could explain the regulatory mechanism that L. monocytogenes activated through the well-studied CIRCE operon via the regulator HrcA during the survival mode. Conclusions Our findings suggest that the timely activation of TFs associated with an immediate stress response, followed by the expression of genes for repair purposes, and then re-growth and metabolism, could be a strategy of L. monocytogenes to survive and recover extreme HPP conditions. We believe that our results give a better understanding of L. monocytogenes behavior after exposure to high pressure that may lead to the design of a specific knock-out process to target the genes or mechanisms. The results can help the food industry select appropriate HPP conditions to prevent L. monocytogenes recovery during food storage.
  • Zhang, Sidi; Samocha, Kaitlin E.; Rivas, Manuel A.; Karczewski, Konrad J.; Daly, Emma; Schmandt, Ben; Neale, Benjamin M.; MacArthur, Daniel G.; Daly, Mark J. (2018)
    Variation in RNA splicing (i.e., alternative splicing) plays an important role in many diseases. Variants near 5' and 3' splice sites often affect splicing, but the effects of these variants on splicing and disease have not been fully characterized beyond the two "essential" splice nucleotides flanking each exon. Here we provide quantitative measurements of tolerance to mutational disruptions by position and reference allele-alternative allele combinations. We show that certain reference alleles are particularly sensitive to mutations, regardless of the alternative alleles into which they are mutated. Using public RNA-seq data, we demonstrate that individuals carrying such variants have significantly lower levels of the correctly spliced transcript, compared to individuals without them, and confirm that these specific substitutions are highly enriched for known Mendelian mutations. Our results propose a more refined definition of the "splice region" and offer a new way to prioritize and provide functional interpretation of variants identified in diagnostic sequencing and association studies.
  • Wisgrill, Lukas; Fyhrquist, Nanna; Ndika, Joseph; Paalanen, Laura; Berger, Angelika; Laatikainen, Tiina; Karisola, Piia; Haahtela, Tari; Alenius, Harri (2022)
    Background In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized. Objective To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen. Methods The peripheral blood mononuclear cells of birch-allergic (n = 24) and non-allergic (n = 47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations. Results Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1 stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1. Conclusions and clinical relevance In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.
  • Madissoon, Elo; Jouhilahti, Eeva-Mari; Vesterlund, Liselotte; Tohonen, Virpi; Krjutskov, Kaarel; Petropoulos, Sophie; Einarsdottir, Elisabet; Linnarssons, Sten; Lanner, Fredrik; Mansson, Robert; Hovatta, Outi; Burglin, Thomas R.; Katayama, Shintaro; Kere, Juha (2016)
    PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.
  • Byers, Kelsey J. R. P.; Darragh, Kathy; Fernanda Garza, Sylvia; Abondano Almeida, Diana; Warren, Ian A.; Rastas, Pasi M. A.; Merrill, Richard M.; Schulz, Stefan; McMillan, W. Owen; Jiggins, Chris D. (2021)
    The degree to which loci promoting reproductive isolation cluster in the genome-that is, the genetic architecture of reproductive isolation-can influence the tempo and mode of speciation. Tight linkage between these loci can facilitate speciation in the face of gene flow. Pheromones play a role in reproductive isolation in many Lepidoptera species, and the role of endogenously produced compounds as secondary metabolites decreases the likelihood of pleiotropy associated with many barrier loci. Heliconius butterflies use male sex pheromones to both court females (aphrodisiac wing pheromones) and ward off male courtship (male-transferred antiaphrodisiac genital pheromones), and it is likely that these compounds play a role in reproductive isolation between Heliconius species. Using a set of backcross hybrids between H. melpomene and H. cydno, we investigated the genetic architecture of putative male pheromone compound production. We found a set of 40 significant quantitative trait loci (QTL) representing 33 potential pheromone compounds. QTL clustered significantly on two chromosomes, chromosome 8 for genital compounds and chromosome 20 for wing compounds, and chromosome 20 was enriched for potential pheromone biosynthesis genes. There was minimal overlap between pheromone QTL and known QTL for mate choice and color pattern. Nonetheless, we did detect linkage between a QTL for wing androconial area and optix, a color pattern locus known to play a role in reproductive isolation in these species. This tight clustering of putative pheromone loci might contribute to coincident reproductive isolating barriers, facilitating speciation despite ongoing gene flow.
  • Kautt, Andreas F.; Kratochwil, Claudius F.; Nater, Alexander; Machado-Schiaffino, Gonzalo; Olave, Melisa; Henning, Frederico; Torres-Dowdall, Julian; Härer, Andreas; Hulsey, C. Darrin; Franchini, Paolo; Pippel, Martin; Myers, Eugene W.; Meyer, Axel (2020)
    Population genomic analyses of Midas cichlid fishes in young Nicaraguan crater lakes suggest that sympatric speciation is promoted by polygenic architectures. The transition from 'well-marked varieties' of a single species into 'well-defined species'-especially in the absence of geographic barriers to gene flow (sympatric speciation)-has puzzled evolutionary biologists ever since Darwin(1,2). Gene flow counteracts the buildup of genome-wide differentiation, which is a hallmark of speciation and increases the likelihood of the evolution of irreversible reproductive barriers (incompatibilities) that complete the speciation process(3). Theory predicts that the genetic architecture of divergently selected traits can influence whether sympatric speciation occurs(4), but empirical tests of this theory are scant because comprehensive data are difficult to collect and synthesize across species, owing to their unique biologies and evolutionary histories(5). Here, within a young species complex of neotropical cichlid fishes (Amphilophus spp.), we analysed genomic divergence among populations and species. By generating a new genome assembly and re-sequencing 453 genomes, we uncovered the genetic architecture of traits that have been suggested to be important for divergence. Species that differ in monogenic or oligogenic traits that affect ecological performance and/or mate choice show remarkably localized genomic differentiation. By contrast, differentiation among species that have diverged in polygenic traits is genomically widespread and much higher overall, consistent with the evolution of effective and stable genome-wide barriers to gene flow. Thus, we conclude that simple trait architectures are not always as conducive to speciation with gene flow as previously suggested, whereas polygenic architectures can promote rapid and stable speciation in sympatry.
  • Berta, Davide G.; Kuisma, Heli; Välimäki, Niko; Räisänen, Maritta; Jäntti, Maija; Pasanen, Annukka; Karhu, Auli; Kaukomaa, Jaana; Taira, Aurora; Cajuso, Tatiana; Nieminen, Sanna; Penttinen, Rosa-Maria; Ahonen, Saija; Lehtonen, Rainer; Mehine, Miika; Vahteristo, Pia; Jalkanen, Jyrki; Sahu, Biswajyoti; Ravantti, Janne; Mäkinen, Netta; Rajamäki, Kristiina; Palin, Kimmo; Taipale, Jussi; Heikinheimo, Oskari; Bützow, Ralf; Kaasinen, Eevi; Aaltonen, Lauri A. (2021)
    One in four women suffers from uterine leiomyomas (ULs)-benign tumours of the uterine wall, also known as uterine fibroids-at some point in premenopausal life. ULs can cause excessive bleeding, pain and infertility(1), and are a common cause of hysterectomy(2). They emerge through at least three distinct genetic drivers: mutations in MED12 or FH, or genomic rearrangement of HMGA2(3). Here we created genome-wide datasets, using DNA, RNA, assay for transposase-accessible chromatin (ATAC), chromatin immunoprecipitation (ChIP) and HiC chromatin immunoprecipitation (HiChIP) sequencing of primary tissues to profoundly understand the genesis of UL. We identified somatic mutations in genes encoding six members of the SRCAP histone-loading complex(4), and found that germline mutations in the SRCAP members YEATS4 and ZNHIT1 predispose women to UL. Tumours bearing these mutations showed defective deposition of the histone variant H2A.Z. In ULs, H2A.Z occupancy correlated positively with chromatin accessibility and gene expression, and negatively with DNA methylation, but these correlations were weak in tumours bearing SRCAP complex mutations. In these tumours, open chromatin emerged at transcription start sites where H2A.Z was lost, which was associated with upregulation of genes. Furthermore, YEATS4 defects were associated with abnormal upregulation of bivalent embryonic stem cell genes, as previously shown in mice(5). Our work describes a potential mechanism of tumorigenesis-epigenetic instability caused by deficient H2A.Z deposition-and suggests that ULs arise through an aberrant differentiation program driven by deranged chromatin, emanating from a small number of mutually exclusive driver mutations.
  • Dias, Fernando H.C.; Williams, Lucia; Mumey, Brendan; Tomescu, Alexandru I. (2022)
    Minimum flow decomposition (MFD) is an NP-hard problem asking to decompose a network flow into a minimum set of paths (together with associated weights). Variants of it are powerful models in multiassembly problems in Bioinformatics, such as RNA assembly. Owing to its hardness, practical multiassembly tools either use heuristics or solve simpler, polynomial time-solvable versions of the problem, which may yield solutions that are not minimal or do not perfectly decompose the flow. Here, we provide the first fast and exact solver for MFD on acyclic flow networks, based on Integer Linear Programming (ILP). Key to our approach is an encoding of all the exponentially many solution paths using only a quadratic number of variables. We also extend our ILP formulation to many practical variants, such as incorporating longer or paired-end reads, or minimizing flow errors. On both simulated and real-flow splicing graphs, our approach solves any instance in
  • Alonso Serra, Juan Antonio; Shi, Xueping; Peaucelle, Alexis; Rastas, Pasi; Bourdon, Matthieu; Immanen, Juha; Takahashi, Junko; Koivula, Hanna; Eswaran, Gugan; Muranen, Sampo Johannes; Help-Rinta-Rahko, Hanna; Smolander, Olli-Pekka; Su, Chang; Safronov, Omid; Gerber, Lorenz; Salojärvi, Jarkko; Hagqvist, Risto; Mähönen, Ari Pekka; Helariutta, Yrjö; Nieminen, Kaisa (2020)
    Tree architecture has evolved to support a top-heavy above-ground biomass, but this integral feature poses a weight-induced challenge to trunk stability. Maintaining an upright stem is expected to require vertical proprioception through feedback between sensing stem weight and responding with radial growth. Despite its apparent importance, the principle by which plant stems respond to vertical loading forces remains largely unknown. Here, by manipulating the stem weight of downy birch (Betula pubescens) trees, we show that cambial development is modulated systemically along the stem. We carried out a genetic study on the underlying regulation by combining an accelerated birch flowering program with a recessive mutation at the ELIMAKI locus (EKI), which causes a mechanically defective response to weight stimulus resulting in stem collapse after just 3 months. We observed delayed wood morphogenesis in eki compared with WT, along with a more mechanically elastic cambial zone and radial compression of xylem cell size, indicating that rapid tissue differentiation is critical for cambial growth under mechanical stress. Furthermore, the touch-induced mechanosensory pathway was transcriptionally misregulated in eki, indicating that the ELIMAKI locus is required to integrate the weight-growth feedback regulation. By studying this birch mutant, we were able to dissect vertical proprioception from the gravitropic response associated with reaction wood formation. Our study provides evidence for both local and systemic responses to mechanical stimuli during secondary plant development.
  • Sablok, Gaurav; Powell, Jonathan J.; Kazan, Kemal (2017)
    Plants use a wide range of mechanisms to adapt to different environmental stresses. One of the earliest responses displayed under stress is rapid alterations in stress responsive gene expression that has been extensively analyzed through expression profiling such as microarrays and RNA-sequencing. Recently, expression profiling has been complemented with proteome analyses to establish a link between transcriptional and the corresponding translational changes. However, proteome profiling approaches have their own technical limitations. More recently, ribosome-associated mRNA profiling has emerged as an alternative and a robust way of identifying translating mRNAs, which are a set of mRNAs associated with ribosomes and more likely to contribute to proteome abundance. In this article, we briefly review recent studies that examined the processes affecting the abundance of translating mRNAs, their regulation during plant development and tolerance to stress conditions and plant factors affecting the selection of translating mRNA pools. This review also highlights recent findings revealing differential roles of alternatively spliced mRNAs and their translational control during stress adaptation. Overall, better understanding of processes involved in the regulation of translating mRNAs has obvious implications for improvement of stress tolerance in plants.
  • Kuosmanen, Anna; Norri, Tuukka; Mäkinen, Veli (2018)
    Transcript prediction can be modeled as a graph problem where exons are modeled as nodes and reads spanning two or more exons are modeled as exon chains. Pacific Biosciences third-generation sequencing technology produces significantly longer reads than earlier second-generation sequencing technologies, which gives valuable information about longer exon chains in a graph. However, with the high error rates of third-generation sequencing, aligning long reads correctly around the splice sites is a challenging task. Incorrect alignments lead to spurious nodes and arcs in the graph, which in turn lead to incorrect transcript predictions. We survey several approaches to find the exon chains corresponding to long reads in a splicing graph, and experimentally study the performance of these methods using simulated data to allow for sensitivity/precision analysis. Our experiments show that short reads from second-generation sequencing can be used to significantly improve exon chain correctness either by error-correcting the long reads before splicing graph creation, or by using them to create a splicing graph on which the long-read alignments are then projected. We also study the memory and time consumption of various modules, and show that accurate exon chains lead to significantly increased transcript prediction accuracy. Availability: The simulated data and in-house scripts used for this article are available at
  • Eising, Else; Huisman, Sjoerd M. H.; Mahfouz, Ahmed; Vijfhuizen, Lisanne S.; Anttila, Verneri; Winsvold, Bendik S.; Kurth, Tobias; Ikram, M. Arfan; Freilinger, Tobias; Kaprio, Jaakko; Boomsma, Dorret I.; van Duijn, Cornelia M.; Jarvelin, Marjo-Riitta R.; Zwart, John-Anker; Quaye, Lydia; Strachan, David P.; Kubisch, Christian; Dichgans, Martin; Smith, George Davey; Stefansson, Kari; Palotie, Aarno; Chasman, Daniel I.; Ferrari, Michel D.; Terwindt, Gisela M.; de Vries, Boukje; Nyholt, Dale R.; Lelieveldt, Boudewijn P. F.; van den Maagdenberg, Arn M. J. M.; Reinders, Marcel J. T. (2016)
    Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.
  • Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H. Annika; Nuutila, Kristo; Tervaniemi, Mari H.; Vuola, Jyrki; Johnsson, Anna; Lonnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha (2015)
    Background: Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. Results: We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. Conclusions: The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.
  • Int Headache Genetics Consortium; HUNT All-in Headache; Danish Blood Donor Study Genomic C (2022)
    Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants. Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
  • Psychiat Genomics Consortium; 23andMe Res Team; Psychosis Endopheno-types Int Cons; Wellcome Trust Case Control Consor; Lee, Phil H.; Anttila, Verneri; Won, Hyejung; Kaprio, Jaakko; Keski-Rahkonen, Anna; Churchhouse, Claire; Rehnström, Karola; Raevuori, Anu; Palotie, Aarno; Daly, Mark J.; Neale, Benjamin M. (2019)
    Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
  • Sood, Sanjana; Szkop, Krzysztof J.; Nakhuda, Asif; Gallagher, Iain J.; Murie, Carl; Brogan, Robert J.; Kaprio, Jaakko; Kainulainen, Heikki; Atherton, Philip J.; Kujala, Urho M.; Gustafsson, Thomas; Larsson, Ola; Timmons, James A. (2016)
    DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (similar to 90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS identified a variety of AEU events, including 3'UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identification of AEU while the variety of exon usage between human tissues is 5-10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.
  • Eising, Else; de Leeuw, Christiaan; Min, Josine L.; Anttila, Verneri; Verheijen, Mark H. G.; Terwindt, Gisela M.; Dichgans, Martin; Freilinger, Tobias; Kubisch, Christian; Ferrari, Michel D.; Smit, August B.; de Vries, Boukje; Palotie, Aarno; van den Maagdenberg, Arn M. J. M.; Posthuma, Danielle; Int Headache Genetics Consortium (2016)
    Background Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura. Methods To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated. Discussion Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background.
  • Hakonen, Elina; Chandra, Vikash; Fogarty, Christopher L.; Yu, Nancy Yiu-Lin; Ustinov, Jarkko; Katayama, Shintaro; Galli, Emilia; Danilova, Tatiana; Lindholm, Paivi; Vartiainen, Aki; Einarsdottir, Elisabet; Krjutskov, Kaarel; Kere, Juha; Saarma, Mart; Lindahl, Maria; Otonkoski, Timo (2018)
    There is a great need to identify factors that could protect pancreatic beta cells against apoptosis or stimulate their replication and thus prevent or reverse the development of diabetes. One potential candidate is mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum (ER) stress inducible protein. Manf knockout mice used as a model of diabetes develop the condition because of increased apoptosis and reduced proliferation of beta cells, apparently related to ER stress. Given this novel association between MANF and beta cell death, we studied the potential of MANF to protect human beta cells against experimentally induced ER stress. Primary human islets were challenged with proinflammatory cytokines, with or without MANF. Cell viability was analysed and global transcriptomic analysis performed. Results were further validated using the human beta cell line EndoC-beta H1. There was increased expression and secretion of MANF in human beta cells in response to cytokines. Addition of recombinant human MANF reduced cytokine-induced cell death by 38% in human islets (p <0.05). MANF knockdown in EndoC-beta H1 cells led to increased ER stress after cytokine challenge. Mechanistic studies showed that the protective effect of MANF was associated with repression of the NF-kappa B signalling pathway and amelioration of ER stress. MANF also increased the proliferation of primary human beta cells twofold when TGF-beta signalling was inhibited (p <0.01). Our studies show that exogenous MANF protein can provide protection to human beta cells against death induced by inflammatory stress. The antiapoptotic and mitogenic properties of MANF make it a potential therapeutic agent for beta cell protection.


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The URJ Heller High Experience

For the Reform Jewish teen looking for the ultimate in Jewish living and learning, URJ Heller High (formerly NFTY-EIE)  is an unparalleled experience.

Since 1961, thousands of exceptional young Reform Jews have had a profound experience on our program, spending an unforgettable semester living and learning in Israel.

Spend four months immersing yourself in the richness of the land, culture, people, and history of Israel. Celebrate Reform Judaism and progressive Jewish life, and take part in extensive tours of the country.

Discover a new passion for Judaism, and find out what it means to be a young leader as you gain critical knowledge and form lifelong friendships!

What awaits you at Heller High?

Exciting and engaging hands-on learning, stimulating discussions, and the chance to literally dig through thousands of years of Jewish history. Immerse yourself directly in the material you study through small classes, extensive touring, and field trips every week. Discover new things every day about your Jewish history and your personal future as a leader of the Jewish people.

Much of the learning at Heller High is done in the field. Students spend upwards of three days a week on field trips and cultural excursions, visiting the very historical sites they are learning about in their classes.

From participating in active archaeological digs in the desert, to engaging with modern Israeli culture in Tel Aviv, students become intimately acquainted with the land, people and culture of Israel.

Spend three unforgettable days and nights of hiking and exploring the Negev Desert! Ride camels across the desert, jump off sand dunes, and sip fresh tea in a Bedouin tent.

Then, travel from the Negev to Eilat to snorkel the waters of the Red Sea and dive to coral reefs from the beaches of Eilat.

Take part in a challenging and rewarding hike from the Kinneret (Sea of Galilee) to the Mediterranean Sea.

Camp out under the stars, swim in natural streams and waterways, and bike the terrain, all while intimately getting to know the land of Israel. Gain experience and skills in climbing, orienteering, mountain biking, and wilderness camping.

Students spend 4 days working side-by-side with Israeli soldiers, learn about their lives and backgrounds, and make a meaningful contribution to the military base. They get a deeper knowledge of the role the IDF plays in the defense of Israel and in the social fabric of the country. At the end of the semester, hours worked at Sar-El are counted as community service and confirmation will be provided to the student and their home high school.


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ORE ID - Getting Started Guide

Here we'll run you through the steps to setup your integration and start using ORE ID!

1. Pre-requisites

Before we jump into setting up your app, these are the few things you'll need in-order to use our support libraries for ORE ID.

  1. First make sure your node version is at least node v10.3
  2. Also make sure you have npm installed: https://www.npmjs.com/get-npm

2. Running the Sample App

Pulling down and running the sample app is a great way to see how all the moving pieces fall into place with ORE ID. The hosted version of the sample app is here,

The following walkthrough videos will guide you on how to setup and run the Sample App and how to Sign Transactions.

  1. Running the Sample App
  2. Signing Transactions

3. Creating your Test App

When you're ready to start working on your own app, you can register your app at: https://oreid.io/developer/new-app

For a walkthrough on registering your app and running it you can watch the video here:

Creating your Test App.

4. Setting up Create Bridge

After you've created your Test App, you will probably need to setup your Create Bridge account.

For a quick overview of what Create Bridge is you can watch the following video:

Understanding Create Bridge

The Create Bridge reference can be found here:

Setting up Create Bridge

If you still have any questions or want further assistance with your integration feel free to reach out to us in our Developer Telegram channel, or your Developer Point of Contact if we have already setup a support channel.


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How to Clear a Browser's Cache, Cookies, and History

  • Updated

When visiting a website, a copy is stored in your browser's cache to help load future visits faster. Sometimes, changes made to a website won't display because of the cache that is stored.

It's can be useful to clear your cache, cookies, and history when your browser isn't performing as expected.

Before You Begin

Clearing your web browser's cache, cookies, and history may remove data such as the following:

  • Saved passwords

  • Address bar predictions

  • Shopping cart contents, etc.

Note: You may wish to record some of your saved information first. If you are unable to do so, see Troubleshooting Alternatives below.

Troubleshooting Alternatives

If you need to clear your cache, cookies, and history for troubleshooting purposes, but aren't yet prepared to lose the content listed above, you may wish to consider using a private browsing window in your preferred browser as a temporary solution:

Quick tip before getting started: For desktop browsers, quickly open the menu used to clear your cache, cookies, and history, by pressing Ctrl-Shift-Delete (Windows)  or Command-Shift-Delete (Mac)

  1. In the browser's URL bar, enter: chrome://settings/clearBrowserData

  2. At the top of the "Clear browsing data" window, click Advanced

  3. Select from the following:
    Browsing history
    Cookies and other site data
    Cached images and files

  4. From the "Time range" drop-down menu, choose the period of time for which you want to clear cached information. To clear your entire cache, select All time

  5. Click CLEAR DATA and either close the browser and reopen, or refresh the page in each of your open browser tabs

  1. From the History  menu, select Clear Recent History

  2. From the Time range to clear: drop-down menu, select the desired range. To clear your entire cache, select Everything

  3. Next to "Details", click the down arrow to choose which elements of the history to clear. To clear your entire cache, select all items

  4. Click Clear Now

  5. Close all open browser windows and reopen

Microsoft Edge

  1. Select Settings and more ...   > Settings   > Privacy and services

  2. Under Clear browsing data , select Choose what to clear

  3. Choose a time range from the Time range  drop-down menu

  4. Select Clear now

Note: The above instructions are for the newer version of Microsoft edge. Get help for the legacy version of Microsoft Edge.

Safari 8 and later

  1. From the Safari menu, select Clear History...  or Clear History and Website Data...

  2. Select the desired time range, and then click Clear History

  3. Go to Safari > Quit Safari  or press Command-Q  to exit the browser completely

  • If the instructions don't exactly match what you see, you may need to update your web browser to the latest version.

  • If you don't see instructions for your specific version or browser, search your browser's Help menu for "clear cache". If you're unsure what browser version you're using, from the Help menu or your browser's menu, select About [browser name].

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To make you payment via bank wire transfer, simply select “Wire transfer” as the payment method when ordering. You will be provided with detailed instructions, including your order reference number and the bank details for your payment.

If you would like more information, don't hesitate to contact us.

If you would like to buy an Aid4Mail license, visit the Aid4Mail website.

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Internet radio synchronization with the DJ?

As you know there is a bunch icecast + ices. While ices is autodega. If necessary, connect DJ mixxx.

But the library server does not synchronize with the mix. Boot the server separately

Are there ways to make friends with the DJ and the server so he could upload audio to the server
July 9th 19 at 13:53

Find more questions by tags Icecast


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Harmony Project on Internationalization announces Digital Storytelling Competition for Integrated Master’s Students at UoH

Theme: Youth, Intercultural Awareness and Cultural Diversity (IACD)

What do you need to do: Creatively showcase a multimedia product (using a mixture of mediums such as audio, video, and photographs) of not more than 4 minutes as a digital story on the theme above. The idea is to challenge long-standing beliefs and how individuals view themselves and the world around them. Your digital story could be based on lived experience or scripted from imagination, but reflecting contemporary realities. No advanced cameras or other equipment are required to produce your digital story. You are encouraged to use your smartphones for the purpose.

Who is eligible: Individuals (Indian and foreign nationals) who are currently enrolled in an Integrated Master’s programme (I.M.A./I.M.Sc./I.M.Tech) at University of Hyderabad. To be eligible, they should be students continuing their education at University of Hyderabad in 2023-2024.

How and where to submit: The final product must be submitted in MP4 format at the Department of Communication, University of Hyderabad

Deadline: December 24, 2022

The Prize: Three winners will be able to attend a two-week boot camp on intercultural awareness and cultural diversity (IACD) to be organised by Varna University of Management (VUM), Varna, Bulgaria in June/July 2023. All expenses towards travel, visa processing, and stay will be borne by the project. The winners must have a valid passport by January 15, 2023.

To help you prepare:

one-day, free workshop on digital storytelling will be conducted by the Department of Communication, University of Hyderabad on October 31, 2022 from 2 pm-5.30 pm.

You will learn to:

  • Use your mobile phone to shoot excellent video.
  • Use mobile apps to complete your story using video, audio, images, and insert titles.

Register online here for the workshop latest by October 27, 2022.

Shortlisted contestants will be given additional training/technical support to finish their digital stories.


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Is Omegle Safe? The Way To Protect Children On Omegle In 2022

The helpful useful resource are established and saved updated with useful materials. I’ve used this unimaginable web site for numerous seasons presently, and don’t stress about your secrecy and safety. Its content has loads of wonderful customers to talk with and meeting finally. I adore flirting, and that internet web site produces myself together with services for this sort of a pleasure. The web site does not follow any hard registration guidelines.

What mother and father need to learn about Omegle?

Omegle just isn’t an app that kids should use, because of the excessive risks to security, privateness, and well-being. Sexual predators can benefit from the anonymity and interact in conversations with minors, exposing them to inappropriate content and groom them.

I would counsel this software program due to its comfort. No pressure degree together with attainable alternative to maneuver into hookups or look for soulmates is essential for starters anything like me. The buttons are in their right places as on many different websites folks usually visit on the Web. Very, this is an excellent service with plenty of intriguing content material material and useful traits. I’m capable of really say that I’m now a tremendously delighted manhood. Numerous individuals turn out to be on-line everyday to talk and plenty of responsive dad and mom to hold up.

Real Life Evaluation

I’ve already chatted a variety of everyone on the net and located some. Next, I turned more demanding and fulfilled a nice person for courting. We however don’t know whether it’s the right selection I think, but I feel favorable thoughts and opinions. I resolve to night benefit from my very own time, in addition to subsequently I’ll think about lasting love. When you end up on the site, the system will automatically join you to a random interlocutor. You can change the chat to a different room if you don’t just like the one you see on the display screen.

Which nation use Omegle most?

  • USA. 29.89%5.97%
  • India. 9.95%2.02%
  • Philippines. 5.12%13.25%
  • UK. 4.52%7.83%
  • Germany. three.48%3.57%

You can use this Omegle different not only to fulfill new individuals but additionally to make use of FaceFlow to chat with family and pals. All you should do is to seek out pals within the «search function» and send them a request to add to friends. After that, you can chat on the webcam free of charge and even organize a video convention with a quantity of pals. FaceFlow is more than just chatting with casual users. It is a complete social platform for video chat and video conferencing.

Why Cannot I Entry Omegle?

So, the platform’s performance set off no grievances. Some haters yell about phony users, but that’s definitely not an issue. Officially, the web page is secure for your family, your laptop computer or pc, or a cell hardware. Majority relies on exactly how efficient and welcoming that you are in the society.

Does Omegle save chat history?

Each chat log is saved in Omegle's server after a person exits a conversation, Bhuyan mentioned in an e-mail. "After a consumer disconnects his chat, Omegle saves the complete chat log of their server completely," Bhuyan mentioned. Omegle's privacy policy states that "Chat messages are screened by an automatic system for spam.

The sending message on Omegle is completely free. All you should do is join through the browser or on the app. There is no way for you to conduct a personal search. The matching and looking system on Omegle is automated.

How Does Omegle Work?

First of all, your web site is pleasant to the attention and its convenient to make use of. When you start shopping, pressing, and scrolling, you acknowledge at a time tips on how to discover the required selection. Subsequently, I’m able to effortlessly poised your profile after omegle comm which make lots of changes. Lots of analysis screens include onboard, and are truly helpful. I organized the bing search as mentioned in your likes and launched getting picture of really beautiful customers .

And if they do come throughout something uncomfortable, you can talk about with them what they’ve seen. In some cases, reviewers of the app have even reported being uncovered to youngster pornography, violence, suicide, and bestiality. She provides folks the instruments they require to deal with their emotions, enhance their communication, and reflect on their value. Many interlocutors offer you to hitch a web-based chat of 18+ subjects. Unlimited communication in a textual content area and live cam chat. I earned preparations to fulfill customers for a espresso and an event. The facet doesn’t have a special version free of charge and paid members.

Is Omegle Costly Or Cheap?

Besides, I take pleasure in that software program is really helpful to make the most of, whether it’s about routing or price. Rates attempt common, and that I normally grudge cash to them since I have get one of the best significance for costs they might require. I’ve already satisfied some decent persons to get very hot dates. Besides, we message with a number of individuals to speak, snort, and reveal totally different content, like intercourse.

Is Omegle untraceable?

But, are your chats really Anonymous? No, all of your chats are recorded and saved by the service. So, when you have shared your private particulars such as your name, telephone quantity, or e mail handle, with anyone over the service, you’re no extra nameless.

I use many sites, but this platform was my personal favourite. Needless to say, it is not at all different from the sleep, implies it’s necessary to watch out with whom most of us choose to big date. Close resources, specifications, and approaches to make use of dating online. Great web site for web dating, regardless of needs and plans.

There is definitely numerous very hot fish found in this lake. On Omegle, there is the monitored chat and unmonitored chat. There is not any restriction on entering the unmonitored chat. Even though the unmonitored web site requires that you simply affirm you’re up to 18 years, there is no safeguard restriction in reality. You merely choose the video chat on the Omegle homepage, and you enable adobe flash on your browser. These two processes will permit you to use the camera seamlessly on Omegle.

Who runs Omegle?

Leif K-Brooks, who at the younger age of 18 based Omegle, a chat platform utilized by tens of millions, joins previous Under 30 inductees who occur to be his Octane AI cofounders, Ben Parr and Matt Schlicht.

It helped myself restore management over my favorite romantic life and stand out once more on the a relationship stage. We do not think so, since will rely upon a personality. Online courting websites might be simple and attention-grabbing to me. Omegle aims to build friendships among strangers without any prejudices whatsoever. The platform is a great initiative for folks to have the power to get related to others whom they would maybe by no means meet ever.

Omegle Complaints 845

For real-life goes, a lot of them normally are greater than folks, but get even had a fairly distressing experiences when. Anyhow, I’m utterly pleased with this service. Omegle was launched on 25th March 2009 as a textual content chat platform to fulfill and chat with strangers. In 2010, the Omegle web site began the video chat, which increased the user-based. While you would possibly have had these conversations together with your youngster hundreds of times, it’s crucial to reiterate the importance of preserving personal information private. Remind your youngster that they should never share private details such as their name, age, or where they reside or attend faculty.

  • Its well-designed and incredibly user-friendly and uncomplicated.
  • I’ve previously satisfied my very own beloved, so we’re delighted.
  • The stranger can do no matter they need with these items, similar to share them with others, publish them on-line, or use them as blackmail.
  • There isn’t any signup course of at Omegle, and it is certainly one of the strengths of this relationship web site.

I consider that I am inside my league from the realm is actually useful. Consumers do not decide a person, since it can be when you have obtained anyone in a bar. As they are saying, i personally use this specific service in taste function. Without a doubt, because of this used to do not positioned your desires into follow and performedn’t come across mate. That’s why I want to reveal some techie information with different individuals. 1st, I’d declare that the internet web site may be very efficient. And that’s actually crucial to me, as a end result of I’m receiving mad as soon as a website starts reducing, freezing, or have glitches.

Is Omegle com a secure site?

Is Omegle safe? Omegle doesn’t seem to have strong moderation neither is there a registration or age verification making them a potential goal for online predators. Its web site states “predators have been identified to use Omegle, so please watch out.”

The operators are ensuring that these spammers are much less through several measures. This is finished through lots of moderation, and an actual consumer can get kicked out of Omegle relying on their actions. There is a excessive level of obscenity within website, however it’s heavily moderated. If customers wish to access the unmoderated section, they’ll accomplish that utilizing this function. This opens up the choice of chatting obscene and adult topics with a stranger without any threat of a ban. A member can choose to turn out to be a ‘spy’ and throw up inquiries to strangers. The spy is not going to be entering into an precise dialog.

Does Omegle monitor video?

After January 2013, Omegle carried out a "monitored" video chat, to monitor misbehavior and defend individuals under the age of 18 from doubtlessly harmful content material, together with nudity or sexual content material. However, the monitoring isn’t very efficient, and customers can often skirt around bans.


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spreading love whilst chasing perfection in the streets

Government Negotiates 23.5% Salary Increment For Lecturers

Adamu Adamu, the minister of education, stated on Tuesday that the government could only afford to boost lecturers’ pay by 23.5%, while professors will receive a 35% raise. The minister also mentioned that Major General Muhammadu Buhari, the President, had issued a warning against entering into commitments that the government would not be able to fulfill. During the discussion with vice chancellors and other university system stakeholders, Adamu made this disclosure.

He said,”The Federal Government can only afford a 23.5% salary increase for all category of the workforce in Federal Universities, except for the professorial cadre which will enjoy a 35% upward review.

“Henceforth, allowances that pertain to ad-hoc duties of the academic and non-academic staff shall be paid as at when due by the Governing Councils of Universities to which such services are rendered and to the staff who perform

“That a sum of 150 billion Naira shall be provided for in the 2023 Budget as
funds for the revitalization of Federal Universities, to be disbursed to the
Institutions in the First Quarter of the year, and that a sum of 50 billion Naira shall be provided for in the 2023 Budget for the payment of outstanding areas of earned academic allowances, to be paid
in the First Quarter of the year”.


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Exoplanet Axis Study Boosts Hopes of Complex Life, Just Not Next Door

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Summary Sentence:

An exoplanet study on axis tilts raises hopes that advanced life may exist elsewhere in the universe.

Full Summary:

There's new hope that advanced beings may exist on exoplanets. A new study on the dynamics of axis tilts of exoplanets in Goldilocks zones says about 87% of planets like Earth in two-star, or binary, systems should have axes conducive to the evolution of complex life. But in the star system nearest us, Alpha Centauri AB, the study pours some water on those hopes.

  • Alpha Centauri AB Alpha Centauri AB
  • Astrophysicist Billy Quarles at the telescope atop Georgia Tech's observatory Astrophysicist Billy Quarles at the telescope atop Georgia Tech's observatory
  • Earth frigid around Alpha Centauri B Earth frigid around Alpha Centauri B

“They’re out there,” goes a saying about extraterrestrials. It would seem more likely to be true in light of a new study on planetary axis tilts.

Astrophysicists at the Georgia Institute of Technology modeled a theoretical twin of Earth into other star systems called binary systems because they have two stars. They concluded that 87% of exo-Earths one might find in binary systems should have axis tilts similarly steady to Earth’s, an important ingredient for climate stability that favors the evolution of complex life.

“Multiple-star systems are common, and about 50% of stars have binary companion stars. So, this study can be applied to a large number of solar systems,” said Gongjie Li, the study’s co-investigator an assistant professor at Georgia Tech’s School of Physics.

Single-star solar systems like our own with multiple planets appear to be rarer.

Alpha Centauri B? Wretched

The researchers started out contrasting how the Earth’s axis tilt, also called obliquity, varies over time with the variation of Mars’ axis tilt. Whereas our planet’s mild obliquity variations have been great for a livable climate and for evolution, the wilder variations of Mars' axis tilt may have helped wreck its atmosphere, as explained in the section below.

Then the researchers modeled Earth into habitable, or Goldilocks, zones in Alpha Centauri AB – our solar system’s nearest neighbor, a binary system with one star called “A” and the other “B.” After that, they expanded the model to a more universal scope.

“We simulated what it would be like around other binaries with multiple variations of the stars’ masses, orbital qualities, and so on,” said Billy Quarles, the study’s principal investigator and a research scientist in Li’s lab. “The overall message was positive but not for our nearest neighbor.”

Alpha Centauri A actually didn’t look bad, but the outlook for mild axis dynamics on an exo-Earth modeled around star B was wretched. This may douse some hopes because Alpha Centauri AB is four lightyears away, and a mission named Starshot with big-name backers plans to launch a space probe to examine the system, including for signs of advanced life.

The researchers published their study, which was co-led by Jack Lissauer from NASA Ames Research Center, in Astrophysical Journal on November 19, 2019, under the title: Obliquity Evolution of Circumstellar Planets in Sun-like Stellar Binaries. The research was funded by the NASA Exobiology Program.

No exoplanets have been confirmed around A or B; an exoplanet has been confirmed around the nearby red dwarf star Proxima Centauri, but that planet is likely to be uninhabitable.

[Ready for graduate school? Here's how to apply to Georgia Tech.

Earth? Just right

Even with its ice ages and hot phases, Earth’s climatological framework has been calm for hundreds of millions of years - in part because of its mild orbital and axis-tilt dynamics - allowing evolution to take big strides. Sharply varying dynamics, and thus climate, like on Mars could stand to regularly kill off advanced life, stunting evolution.

Earth’s orbit around the sun is on a slight incline that seesaws gently and very slowly through a slight precession, a kind of oscillation. As Earth revolves, it shifts position relative to the sun, circling it a little like a spirograph drawing. The orbit also precesses in shape between slightly more and slightly less oblong over 100,000-year periods.

Earth’s axis tilt precesses between 22.1 and 24.5 degrees over the course of 41,000 years. Our large moon stabilizes our tilt through its gravitational relationship with Earth, otherwise, bouncy gravitational interconnections with Mercury, Venus, Mars, and Jupiter would jolt our tilt with resonances.

“If we didn’t have the moon, Earth’s tilt could vary by about 60 degrees,” Quarles said. “We’d look maybe like Mars, and the precession of its axis appears to have contributed to a loss of atmosphere.”

Mars’ axis precesses between 10 degrees and 60 degrees every 2 million years. At the 10-degree tilt, the atmosphere condenses at the poles, creating caps that lock up a lot of the atmosphere in ice. At 60 degrees, Mars could grow an ice belt around its equator.

Universe? Hopeful

In Alpha Centauri AB, star B, about the size of our sun, and the larger star, A, orbit one another at about the distance between Uranus and our sun, which is very close for two stars in a binary system. The study modeled variations of an exo-Earth orbiting either star but concentrated on a modeled Earth orbiting in the habitable zone centered around B, with A being the orbiting star.

A’s orbit is very elliptical, passing close by and then moving very far away from B and slinging powerful gravity, which, in the model, overpowered exo-Earth’s own dynamics. Its tilt and orbit varied widely; adding our moon to the model didn’t help.

“Around Alpha Centauri B, if you don’t have a moon, you have a more stable axis than if you do have a moon. If you have a moon, it’s pretty much bad news,” Quarles said.

Even without a moon and with mild axis variability, complex, Earthlike evolution would seem to have a hard time on the modeled exo-Earth around B.

“The biggest effect you would see is differences in the climate cycles related to how elongated the orbit is. Instead of having ice ages every 100,000 years like on Earth, they may come every 1 million years, be worse, and last much longer,” Quarles said.

But a sliver of hope for Earthlike conditions turned up in the model: “Planetary orbit and spin need to precess just right relative to the binary orbit. There is this tiny sweet spot,” Quarles said.

When the researchers expanded the model to binary systems in the broader universe, the probability of gentle obliquity variations ballooned.

“In general, the separation between the stars is larger in binary systems, and then the second star has less of an effect on the model of Earth. The planet’s own motion dynamics dominate other influences, and obliquity usually has a smaller variation,” Li said. “So, this is quite optimistic.”

Also READ: Observing a “Cosmic Symphony” Using Gravitational Wave Astronomy

The research was funded by the NASA Exobiology Program (grant NNX14AK31G). Any findings, conclusions, or recommendations are those of the authors and not necessarily of the NASA Exobiology Program.

Writer & Media Representative: Ben Brumfield (404-272-2780)

Email: ben.brumfield@comm.gatech.edu

Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia  30332-0181  USA

Additional Information

College of Sciences, News Room, Research Horizons

Research, Environment, Life Sciences and Biology, Physics and Physical Sciences
Related Core Research Areas
Bioengineering and Bioscience
Newsroom Topics
Earth and Environment, Science and Technology
exoplanet, Alpha Centauri, Proxima Centauri, Proxima Centauri b, obliquity, axis, axis tilt, axis tilt variation, obliquity variation, Alpha centauri AB, binary system, binary star, Binary Star System, habitable exoplanets, habitable planets, Habitable Worlds Across Time and Space, habitable zone, goldilocks zone, Starshot, Ames Research Center, precession, ice age
  • Created By: Ben Brumfield
  • Workflow Status: Published
  • Created On: Nov 20, 2019 - 10:06am
  • Last Updated: Dec 9, 2019 - 2:24pm


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Developing a family business transition plan is a complex process, and although saving tax is an important consideration, it is not the only one. When you have spent much of your life establishing and successfully running a family business, of course it’s natural that you want to pass it on to the next generation, and to do so as tax efficiently as possible.  You haven’t done all that work just to hand a big chunk of the wealth you created over in taxes!

At Henry H. Jones, CPA, we’re passionate about helping family businesses get things right at the planning stages, including tax, of course.  But overemphasizing the role of tax planning in your family business transition plan is likely to lead to one that is not the one you really want. The main focus of your plan should be on what your business truly needs, and how you can help your family in the way that benefits them most.

Of course, every family business is unique.  Ours has its own characteristics, and so does yours. We all have issues that will continue when it is handed over to the next generation; or if it is not to be passed on, then how it is to be sold or wound down. Thus every transition plan is unique too, but there are also a number of key issues that must be addressed.

Family Business Transition Plan Preparation

  • You need to think about whether your children will still have enough cash to continue running the business after estate taxes have been paid. You also need to ensure that you have valued the business correctly and that you have done everything possible to reduce the tax liability.
  • Ask yourself, “Do my children really want to run the business and are they capable of doing so?” Remember that only one in three businesses pass successfully to the next generation (read more here).
  • How will you equitably deal with your children who wish to stay in the business and those who want to do their own thing? Have you made any family promises that you must stick too? (read our post on the generation gap here)
  • What are the issues regarding other stakeholders? For instance you might have a divorced ex-spouse who still holds stock and voting rights but has no other involvement in the business. Make sure these issues are considered.
  • Will the business still be able to function if there are probate delays following your death? Probate can take a considerable time.  Possibly the best solution is to set up a trust which can give the trustees permission to transfer wealth prior to probate.
  • Will the business still be able to provide you with a retirement income and will doing so conflict with the interests of the new owners?
  • What is the actual value of the business and how do you measure it?
  • Are there likely to be any disputes regarding ownership and management?
  • Is succession the best solution or would it be better to sell the business?

Addressing tax issues is part of the package but only part. You want to ensure that the family business transitions in the way that you wish, but you have to also factor in all these other issues.

Family Business Transition Plan: Moving Gradually

Naturally it is important to ensure that you maximize the value of the business and you will need to make plans to do this which will include the various taxes and how to reduce them. There’s much to be said for transitioning your family business gradually. You keep control while gradually passing over power to its future owners. This can have a big impact on your tax position too as long as you keep below the annual gift tax liability levels.

But it all depends on your unique circumstances so your first step is to talk with an an expert on business transitioning – and fortunately, we’re right here! Your family business transition plan can begin anytime. No one case suits all, but it is certainly not all about saving tax.