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Diseases and Conditions

Unraveling the Mysteries of Cohesin: A Protein That Forms Loops in the Human Genome

Cohesin is a protein that forms a ring-shaped complex which wraps and alters the DNA molecule shape. It moves through the DNA and creates specific loops in the genetic material which determine the architecture of the genome and gene expression. Some mutations in the genes of the cohesion complex are responsible for rare diseases (cohesinopathies), such as the Cornelia de Lange syndrome (SCdL) or Roberts syndrome, which affect several organs and cause malformations during development.

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Cohesin, a protein complex that forms loops in the human genome, plays a crucial role in determining the architecture of our genetic material and regulating gene expression. However, its function and behavior have remained somewhat mysterious until now.

Researcher Professor Eva Estébanez-Perpiñá from the University of Barcelona, along with her team and international collaborators, has made significant strides in understanding how cohesin works. Their study, published in Nucleic Acids Research, sheds light on the protein’s interaction with chromatin structure and its role in altering gene expression.

Cohesin consists of four subunits: SMC1, SMC3, SCC1/RAD21, and STAG (also known as SA or SCC2). Previous studies had identified 25 proteins that regulate these subunits and their biological function. Estébanez-Perpiñá’s team has now discovered how the NIPBL protein interacts with both MAU2 and the glucocorticoid receptor (GR), a transcription factor essential for cellular functions.

This ternary complex, comprising NIPBL, MAU2, and GR, modulates transcription by facilitating the interaction of GR with these two proteins. When GR interacts with NIPBL and MAU2, it alters chromatin structure and affects gene expression. This discovery has significant implications for understanding Cornelia de Lange syndrome, a rare disease caused by mutations in genes involved in cohesin formation.

The researchers used advanced microscopic techniques to visualize real-time molecular complexes binding to chromatin, as well as biochemical and biophysical methods to analyze the complex from different structural and cellular perspectives.

Their findings not only improve our comprehension of cohesin’s role but also highlight its potential involvement in other diseases, such as asthma and autoimmune pathologies. As research continues, scientists will likely uncover more about this enigmatic protein and its intricate relationships with chromatin structure and gene expression.

Allergy

Nature’s Longevity Hack: How Human Eggs Stay Fresh for 50 Years

Human eggs stay dormant for decades by slowing down their waste disposal systems, according to new research involving over 100 freshly donated eggs. This clever energy-saving strategy appears to help protect the eggs from damage over time, allowing them to remain viable for years.

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In a groundbreaking study published in The EMBO Journal, researchers have uncovered the remarkable secret behind human eggs’ ability to remain viable for up to 50 years. By examining over 100 freshly donated eggs from 21 healthy donors aged 19-34, scientists have discovered that these cells deliberately slow down their internal waste disposal systems as they mature.

This “longevity hack” allows the eggs to maintain a low metabolic rate and minimize damage caused by reactive oxygen species (ROS), harmful molecules that can damage DNA and membranes. The study’s corresponding author, Dr. Elvan Böke, explains that this strategy is likely an evolutionary design that keeps the cells pristine for many years.

The research highlights the importance of protein recycling in maintaining cellular health. Lysosomes and proteasomes are the cell’s main waste disposal units, but every time they degrade proteins, they consume energy, which can lead to ROS production. By tapping the brakes on recycling, the egg keeps ROS production to a minimum while still doing enough housekeeping to survive.

This study builds upon previous research by Dr. Böke’s group, published in 2022, which showed that human oocytes deliberately skip a fundamental metabolic reaction to curb ROS production. Together, these studies suggest that human eggs power down in different ways to keep potential damage as low as possible for as long as possible.

The researchers’ findings have significant implications for fertility treatments and IVF success rates. By understanding how human eggs maintain their quality over time, scientists can develop new strategies to improve the chances of pregnancy. Dr. Böke notes that current advice for fertility patients often involves taking random supplements to improve egg metabolism, but evidence for any benefit is patchy.

In contrast, this study suggests that maintaining the egg’s naturally quiet metabolism could be a better approach for preserving quality. The researchers now plan to examine eggs from older donors and failed IVF cycles to see whether throttling the activity of cellular waste disposal units falters with age or disease.

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Anger Management

The Hidden Depression Crisis in Early Menopause: Uncovering the Unexpected Risks

Premature menopause isn t just a hormonal issue it s a deeply emotional one for many women. A new study reveals that almost 30% experience depression, and it s not just about hormone loss but also grief, identity, and support systems.

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The diagnosis of premature menopause can be life-altering, with profound physical, psychological, and social consequences. Women affected by this condition not only experience the effects of estrogen deficiency but also face the unanticipated loss of reproductive function. However, some women are more adversely impacted by these changes than others. A new study has shed light on the reasons behind these differences, revealing a hidden depression crisis in early menopause.

Premature menopause, medically known as premature or primary ovarian insufficiency (POI), is a condition where the ovaries cease to function normally before the age of 40. This condition has been linked to an elevated lifetime risk for depression and anxiety. A recent meta-analysis revealed that women with POI are three times more likely to experience depression and nearly five times more likely to suffer from anxiety compared to those without the condition.

The increased risk is understandable, given the combined experience of infertility and the additional burdens resulting from estrogen deficiency, such as hot flashes, vaginal dryness, reduced bone mineral density, and an increased risk of cardiovascular disease. For some women, infertility means altered life goals, loss of sense of control, social stigma, and disrupted social roles.

However, not all women experience depression or the same level of depression when presented with the same diagnosis. In this new study, researchers gathered data from nearly 350 women with POI to identify specific variables that contribute to the likelihood of depressive symptoms. Their findings revealed a high prevalence of depression among participants, with nearly one-third (29.9%) of the women suffering from depressive symptoms.

The researchers also found that a younger age at POI diagnosis, severe menopause symptoms, fertility-related grief, and lack of emotional support were risk factors for depressive symptoms. Interestingly, a genetic cause for POI was associated with lower depressive symptoms. Another unexpected result was that hot flashes (specifically night sweats) were not independently associated with depressive symptoms.

This is the first large-scale study to investigate specific variables associated with depressive symptoms in women with POI. The researchers believe their results highlight the importance of comprehensive care addressing both physical and psychological aspects of menopause at an early age.

The high prevalence of depressive symptoms in those with POI highlights the importance of routine screening in this vulnerable population. Although hormone therapy is recognized as the standard of care for managing some menopause-related symptoms and preventive care, it is not a first-line treatment for mood disorders. Addressing behavioral-health concerns with evidence-based interventions should be part of any comprehensive POI care plan.

As Dr. Monica Christmas, associate medical director for The Menopause Society, notes, “The hidden depression crisis in early menopause requires attention from healthcare providers and policymakers to ensure that women receive the necessary support and care to manage their mental health and overall well-being.”

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Disability

The Silent Threat: How Hearing Loss and Loneliness Fuel Memory Decline

A massive European study has uncovered a powerful connection between hearing loss, loneliness, and memory decline. Researchers at the University of Geneva found that older adults with hearing impairments who also feel lonely—regardless of actual social isolation—experience faster cognitive decline.

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The silent threat of hearing loss and loneliness is fueling memory decline, particularly among older adults. Researchers at the University of Geneva have analyzed data from 33,000 people across Europe and identified three distinct profiles related to social isolation and perceived loneliness. The findings show that hearing loss accelerates cognitive decline, especially among individuals who feel lonely, regardless of whether they are socially isolated.

The World Health Organization (WHO) predicts that nearly 2.5 billion people will experience hearing loss or impairment by 2050. More than 25% of people over the age of 60 experience disabling hearing impairment, which is linked to a significantly increased risk of cognitive decline in later life. This risk may be two to three times higher for those affected.

The study used data from the SHARE survey (Survey of Health, Ageing and Retirement in Europe), which examines the health and aging of Europeans aged 50 and over. The researchers identified three distinct profiles related to social isolation and perceived loneliness:

1. Isolation: This profile refers to individuals who are socially isolated, meaning they have few or no social connections.
2. Loneliness: This profile refers to individuals who feel lonely, but may not be socially isolated. They may have social connections, but still feel disconnected from others.
3. Deafness and isolation: This profile refers to individuals who experience both hearing loss and social isolation.

The study found that people in the “deafness and isolation” profile had the most accelerated cognitive decline, while those in the “loneliness” profile also experienced significant declines. However, it’s essential to note that the “loneliness” profile was not necessarily linked to social isolation, but rather a subjective feeling of being disconnected from others.

The researchers emphasize the importance of addressing both hearing loss and the social and emotional dimensions of individuals in efforts to prevent cognitive decline. This is particularly crucial for people who are not socially isolated but still feel lonely, as simple hearing interventions may be enough to help them engage more fully in social life and protect their cognitive health.

In conclusion, the silent threat of hearing loss and loneliness is fueling memory decline, especially among older adults. It’s essential to address both aspects to prevent cognitive decline and ensure a healthy and happy aging process.

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