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Why do some men not produce sperm?

KANSAS CITY, MO—October 20, 2023—Millions of couples worldwide experience infertility with half of the cases originating in men. For 10% of infertile…

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KANSAS CITY, MO—October 20, 2023—Millions of couples worldwide experience infertility with half of the cases originating in men. For 10% of infertile males, little or no sperm are produced. Now, new research from the Stowers Institute for Medical Research, in collaboration with the Wellcome Centre for Cell Biology at the University of Edinburgh, is shedding light on what may be going wrong in the process of sperm formation, leading to potential theories on possible treatments.  

Credit: Stowers Institute for Medical Research

KANSAS CITY, MO—October 20, 2023—Millions of couples worldwide experience infertility with half of the cases originating in men. For 10% of infertile males, little or no sperm are produced. Now, new research from the Stowers Institute for Medical Research, in collaboration with the Wellcome Centre for Cell Biology at the University of Edinburgh, is shedding light on what may be going wrong in the process of sperm formation, leading to potential theories on possible treatments.  

“A significant cause of infertility in males is that they just cannot make sperm,” said Stowers Investigator Scott Hawley, Ph.D. “If you know exactly what is wrong, there are technologies emerging right now that might give you a way to fix it.”  

The study published on October 20, 2023, in Science Advances from the Hawley Lab and Wellcome Centre Investigator Owen Davies, Ph.D., may help explain why some men do not make enough sperm to fertilize an egg. In most sexually reproducing species, including humans, a critical protein structure resembling a lattice-like bridge needs to be built properly to produce sperm and egg cells. The team led by former Postdoctoral Research Associate Katherine Billmyre, Ph.D., discovered that in mice, changing a single and very specific point in this bridge caused it to collapse, leading to infertility and thus providing insight into human infertility in males due to similar problems with meiosis. 

Meiosis, the cell division process giving rise to sperm and eggs, involves several steps, one of which is the formation of a large protein structure called the synaptonemal complex. Like a bridge, the complex holds chromosome pairs in place enabling necessary genetic exchanges to occur that are essential for the chromosomes to then correctly separate into sperm and eggs.  

“A significant contributor to infertility is defects in meiosis,” said Billmyre. “To understand how chromosomes separate into reproductive cells correctly, we are really interested in what happens right before that when the synaptonemal complex forms between them.”  

Previous studies have examined many proteins comprising the synaptonemal complex, how they interact with each other, and have identified various mutations linked to male infertility. The protein the researchers investigated in this study forms the lattices of the proverbial bridge, which has a section found in humans, mice, and most other vertebrates suggesting it is critical for assembly. Modeling different mutations in a potentially crucial region in the human protein enabled the team to predict which of these might disrupt protein function. 

The authors used a precise gene editing technique to make mutations in one key synaptonemal complex protein in mice, which allowed the researchers, for the first time, to test the function of key regions of the protein in live animals. Just a single mutation, predicted from the modeling experiments, was verified as the culprit of infertility in mice.   

“We’re talking about pinpoint surgery here,” said Hawley. “We focused on a tiny little region of one protein in this gigantic structure that we were pretty sure could be a significant cause of infertility.”  

Mice have long been used as models for human diseases. From the modeling experiments using human protein sequences, along with the high conservation of this protein structure across species, the precise molecule that caused infertility in mice likely functions the same way in humans.   

“What is really exciting to me is that our research can help us understand this really basic process that is necessary for life,” said Billmyre.  

For Hawley, this research is a true representation of the versatility of the Institute. Hawley’s lab typically conducts research in fruit flies, yet the protein discovered in this study was not present in fruit flies and demanded a different research organism to continue. Because of the resources and Technology Centers at the Institute, it was possible to quickly pivot and test the new infertility hypothesis in mice. 

“I can’t imagine another place where this could happen,” said Hawley. “I think it’s an amazing example of how the Stowers Institute’s dedication toward discovery can yield big results providing important leaps forward in understanding.”     

Additional authors include Emily A. Kesler, Dai Tsuchiya, Ph.D., Timothy J. Corbin, Kyle Weaver, Andrea Moran, Zulin Yu, Ph.D., Lane Adams, Kym Delventhal, Michael Durnin, Ph.D., and Owen Richard Davies, Ph.D. 

This work was funded by the Wellcome Centre for Cell Biology (award: 203149), the Wellcome Senior Research Fellowship (award: 219413/Z/19/Z), and by institutional support from the Stowers Institute for Medical Research.  

About the Stowers Institute for Medical Research 

Founded in 1994 through the generosity of Jim Stowers, founder of American Century Investments, and his wife, Virginia, the Stowers Institute for Medical Research is a non-profit, biomedical research organization with a focus on foundational research. Its mission is to expand our understanding of the secrets of life and improve life’s quality through innovative approaches to the causes, treatment, and prevention of diseases. 

The Institute consists of 20 independent research programs. Of the approximately 500 members, over 370 are scientific staff that include principal investigators, technology center directors, postdoctoral scientists, graduate students, and technical support staff. Learn more about the Institute at www.stowers.org and about its graduate program at www.stowers.org/gradschool. 

Media Contact: 

Joe Chiodo, Head of Media Relations 
724.462.8529 
press@stowers.org 


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Apparel Retailer Express Moving Toward Bankruptcy

Apparel Retailer Express Moving Toward Bankruptcy

During the company’s last earnings call in November, recently appointed CEO Stewart Glendinning…

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Apparel Retailer Express Moving Toward Bankruptcy

During the company’s last earnings call in November, recently appointed CEO Stewart Glendinning acknowledged the company made some missteps: Among other factors, there was a misalignment between its assortment and customer demand, Retail Dive's Nate Delesline reports.

An Express storefront at King of Prussia mall in Pennsylvania. The retailer said this week that it plans to initiate an international brand expansion starting next year

Express took a hit during the pandemic as its core offering — business casual — fell out of favor as work-from-home surged.

“Unfortunately, my previous assessment of Express’ fragile financial situation leading to a possible bankruptcy due to declining revenue, gross margin profits and ballooning debt of $280 million is a foregone conclusion,” Shawn Grain Carter, a retail industry consultant and professor at the Fashion Institute of Technology at the State University, said in an email to Retail Dive. “With high-interest rates, the retail company must decide between the ‘lesser of two evils.’ Moreover, until they fix the waning consumer demand for their merchandise and elevate the brand and product mix, financial wizardry will not resolve their retail woes.”

Over the past several years, the company has undergone a number of changes as it works to improve its performance. Last January, WHP Global closed on a strategic partnership with Express. The two entities formed an intellectual property joint venture under which WHP contributed $235 million for a 60% stake, while Express retained the remaining 40%. The two entities in November announced plans to expand Express internationally, including in Indonesia and Paraguay, and grow its presence in Central America and Mexico. 

And after the New York Stock Exchange warned of a potential delisting in late March, Express executed a 1-for-20 reverse stock split, which decreased outstanding shares to 3.7 million from 74.9 million. That stock split enabled Express to regain listing compliance with the New York Stock Exchange. Around the same time, Express said it planned to cut 150 jobs by the end of the third quarter.

The company also expanded its portfolio last year through a deal with WHP to acquire Bonobos from Walmart for $75 million. That acquisition helped guide the retailer to a 5% year-over-year uptick in Q3 net sales to $454.1 million from $434.1 million a year earlier. However, comparable sales for Express stores and e-commerce fell 4% and net loss grew to $36.8 million from $34.4 million in the year-ago period. Inventory was also up 14% for the quarter, rising to nearly $481 million from $422.7 million a year earlier. 

“Express has the right building blocks in place with a strong portfolio of brands, a high-potential partnership with WHP and a premier omnichannel platform,” Glendinning said in the earnings announcement. “Our efforts to unlock our full potential and improve our performance are already underway.”

The apparel retailer in late November lowered its full-year 2023 guidance, now expecting net sales to be between $1.84 billion and $1.87 billion, with Bonobos driving $150 million in net sales. 

Finally, on Friday, Bloomberg reported that at least one lender to Express has approached the retailer to put aside a pool of money for expenses tied to a potential future bankruptcy filing.

A demand to set aside so-called cash reserves, if enforced, could push Express into Chapter 11 as it would eat into limited liquidity available for necessary payments to vendors, landlords and other parties.

Creditors have been growing increasingly antsy and considering whether to push the company to file for bankruptcy, Bloomberg previously reported.

Express, which is burning through a short supply of cash as it attempts to fix troubled operations, is looking to avoid any move to fund reserves for as long as possible, other people familiar with the matter said. The retailer lost over $150 million in three quarters through late October as it faced an escalating competitive threat from fast-fashion rivals.

Tyler Durden Fri, 02/23/2024 - 18:00

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Apparel Retailer Express Moving Toward Bankruptcy

Apparel Retailer Express Moving Toward Bankruptcy

During the company’s last earnings call in November, recently appointed CEO Stewart Glendinning…

Published

on

Apparel Retailer Express Moving Toward Bankruptcy

During the company’s last earnings call in November, recently appointed CEO Stewart Glendinning acknowledged the company made some missteps: Among other factors, there was a misalignment between its assortment and customer demand, Retail Dive's Nate Delesline reports.

An Express storefront at King of Prussia mall in Pennsylvania. The retailer said this week that it plans to initiate an international brand expansion starting next year

Express took a hit during the pandemic as its core offering — business casual — fell out of favor as work-from-home surged.

“Unfortunately, my previous assessment of Express’ fragile financial situation leading to a possible bankruptcy due to declining revenue, gross margin profits and ballooning debt of $280 million is a foregone conclusion,” Shawn Grain Carter, a retail industry consultant and professor at the Fashion Institute of Technology at the State University, said in an email to Retail Dive. “With high-interest rates, the retail company must decide between the ‘lesser of two evils.’ Moreover, until they fix the waning consumer demand for their merchandise and elevate the brand and product mix, financial wizardry will not resolve their retail woes.”

Over the past several years, the company has undergone a number of changes as it works to improve its performance. Last January, WHP Global closed on a strategic partnership with Express. The two entities formed an intellectual property joint venture under which WHP contributed $235 million for a 60% stake, while Express retained the remaining 40%. The two entities in November announced plans to expand Express internationally, including in Indonesia and Paraguay, and grow its presence in Central America and Mexico. 

And after the New York Stock Exchange warned of a potential delisting in late March, Express executed a 1-for-20 reverse stock split, which decreased outstanding shares to 3.7 million from 74.9 million. That stock split enabled Express to regain listing compliance with the New York Stock Exchange. Around the same time, Express said it planned to cut 150 jobs by the end of the third quarter.

The company also expanded its portfolio last year through a deal with WHP to acquire Bonobos from Walmart for $75 million. That acquisition helped guide the retailer to a 5% year-over-year uptick in Q3 net sales to $454.1 million from $434.1 million a year earlier. However, comparable sales for Express stores and e-commerce fell 4% and net loss grew to $36.8 million from $34.4 million in the year-ago period. Inventory was also up 14% for the quarter, rising to nearly $481 million from $422.7 million a year earlier. 

“Express has the right building blocks in place with a strong portfolio of brands, a high-potential partnership with WHP and a premier omnichannel platform,” Glendinning said in the earnings announcement. “Our efforts to unlock our full potential and improve our performance are already underway.”

The apparel retailer in late November lowered its full-year 2023 guidance, now expecting net sales to be between $1.84 billion and $1.87 billion, with Bonobos driving $150 million in net sales. 

Finally, on Friday, Bloomberg reported that at least one lender to Express has approached the retailer to put aside a pool of money for expenses tied to a potential future bankruptcy filing.

A demand to set aside so-called cash reserves, if enforced, could push Express into Chapter 11 as it would eat into limited liquidity available for necessary payments to vendors, landlords and other parties.

Creditors have been growing increasingly antsy and considering whether to push the company to file for bankruptcy, Bloomberg previously reported.

Express, which is burning through a short supply of cash as it attempts to fix troubled operations, is looking to avoid any move to fund reserves for as long as possible, other people familiar with the matter said. The retailer lost over $150 million in three quarters through late October as it faced an escalating competitive threat from fast-fashion rivals.

Tyler Durden Fri, 02/23/2024 - 18:00

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Apparel Retailer Express Moving Toward Bankruptcy

Apparel Retailer Express Moving Toward Bankruptcy

During the company’s last earnings call in November, recently appointed CEO Stewart Glendinning…

Published

on

Apparel Retailer Express Moving Toward Bankruptcy

During the company’s last earnings call in November, recently appointed CEO Stewart Glendinning acknowledged the company made some missteps: Among other factors, there was a misalignment between its assortment and customer demand, Retail Dive's Nate Delesline reports.

An Express storefront at King of Prussia mall in Pennsylvania. The retailer said this week that it plans to initiate an international brand expansion starting next year

Express took a hit during the pandemic as its core offering — business casual — fell out of favor as work-from-home surged.

“Unfortunately, my previous assessment of Express’ fragile financial situation leading to a possible bankruptcy due to declining revenue, gross margin profits and ballooning debt of $280 million is a foregone conclusion,” Shawn Grain Carter, a retail industry consultant and professor at the Fashion Institute of Technology at the State University, said in an email to Retail Dive. “With high-interest rates, the retail company must decide between the ‘lesser of two evils.’ Moreover, until they fix the waning consumer demand for their merchandise and elevate the brand and product mix, financial wizardry will not resolve their retail woes.”

Over the past several years, the company has undergone a number of changes as it works to improve its performance. Last January, WHP Global closed on a strategic partnership with Express. The two entities formed an intellectual property joint venture under which WHP contributed $235 million for a 60% stake, while Express retained the remaining 40%. The two entities in November announced plans to expand Express internationally, including in Indonesia and Paraguay, and grow its presence in Central America and Mexico. 

And after the New York Stock Exchange warned of a potential delisting in late March, Express executed a 1-for-20 reverse stock split, which decreased outstanding shares to 3.7 million from 74.9 million. That stock split enabled Express to regain listing compliance with the New York Stock Exchange. Around the same time, Express said it planned to cut 150 jobs by the end of the third quarter.

The company also expanded its portfolio last year through a deal with WHP to acquire Bonobos from Walmart for $75 million. That acquisition helped guide the retailer to a 5% year-over-year uptick in Q3 net sales to $454.1 million from $434.1 million a year earlier. However, comparable sales for Express stores and e-commerce fell 4% and net loss grew to $36.8 million from $34.4 million in the year-ago period. Inventory was also up 14% for the quarter, rising to nearly $481 million from $422.7 million a year earlier. 

“Express has the right building blocks in place with a strong portfolio of brands, a high-potential partnership with WHP and a premier omnichannel platform,” Glendinning said in the earnings announcement. “Our efforts to unlock our full potential and improve our performance are already underway.”

The apparel retailer in late November lowered its full-year 2023 guidance, now expecting net sales to be between $1.84 billion and $1.87 billion, with Bonobos driving $150 million in net sales. 

Finally, on Friday, Bloomberg reported that at least one lender to Express has approached the retailer to put aside a pool of money for expenses tied to a potential future bankruptcy filing.

A demand to set aside so-called cash reserves, if enforced, could push Express into Chapter 11 as it would eat into limited liquidity available for necessary payments to vendors, landlords and other parties.

Creditors have been growing increasingly antsy and considering whether to push the company to file for bankruptcy, Bloomberg previously reported.

Express, which is burning through a short supply of cash as it attempts to fix troubled operations, is looking to avoid any move to fund reserves for as long as possible, other people familiar with the matter said. The retailer lost over $150 million in three quarters through late October as it faced an escalating competitive threat from fast-fashion rivals.

Tyler Durden Fri, 02/23/2024 - 18:00

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