Culture

Advancing the understanding of synovial sarcoma, a highly aggressive and rare cancer of young people, scientists at Dana-Farber Cancer Institute have discovered how an abnormal protein misdirects and disrupts the control of gene expression in cells, causing the aberrant activation of normally repressed genes that contribute to the malignant growth of sarcoma tumors.

The investigators, led by Cigall Kadoch, PhD, say the new insight could guide efforts to develop drugs to treat synovial sarcoma, which primarily affects muscle tissues in the extremities. The root cause of the sarcoma is a cellular accident -- the abnormal joining of two proteins, resulting in a "fusion protein" that sets in motion the malignant malfunctions.

"We have for the first time defined the molecular basis for the cancer-specific targeting properties of the culprit fusion protein, SS18-SSX, found in 100% of cases of synovial sarcoma." Kadoch said. "Importantly, this provides a powerful new therapeutic identification strategy for the drug discovery industry" to develop drugs to block the interaction between the abnormal fusion protein and nucleosomes - structures that package and organize DNA in cells, said Kadoch, senior author of the study published today in Nature Structural and Molecular Biology.

Nucleosomes, spool-like structures resembling beads on a string, make up chromatin, a term to describe DNA wrapped around proteins called histones. Chromatin is found throughout the genome, which in humans contains an estimated 20,000 genes and much other genetic information. Modifications in chromatin structure, carried out by protein complexes called chromatin remodelers, regulate the turning on and off of genes for cell- and tissue-specific purposes. Malfunctions of the chromatin remodeling system have been implicated in many cancers and neurodevelopmental disorders, a major focus of the Kadoch laboratory.

In synovial sarcoma, the SS18-SSX fusion oncoprotein replaces the normal SS18 subunit, or component, in BAF chromatin remodeling complexes. As a result, BAF chromatin remodeling complexes are "dragged around the genome to all the wrong sites" on chromatin "to aberrantly activate them and drive the gene expression and proliferation of synovial sarcoma," Kadoch and her team previously showed in a 2018 study. These "wrong" sites, she explained, are regions on chromatin marked by polycomb repressive complexes, which normally keep genes such as stem cell genes from being expressed when not needed. One might think of a complex traffic system in which millions of aircraft or ships normally proceed to specified destinations along specific routes - but in the case of some cancers, the targeting of these vessels is scrambled, with disastrous results.

However, this previous work had not revealed how the SS18-SSX fusion protein and BAF complexes were erroneously targeted to those repressed sites across the genome: "it was a mystery until now," Kadoch said.

In the experiments described in the new paper, Kadoch and her co-authors found that a minimal, small segment of the SS18-SSX fusion protein binds to the so-called "acidic patch" on nucleosomes. The acidic patch is a pocket of negatively charged molecules to which chromatin remodeling complexes, such as BAF complexes, can dock. The researchers found that the small segment of SSX - which they refer to as the "tail" of the fusion protein - is made up of only 34 amino acids, but binds extremely tightly to the acidic patch. Specifically, the SSX tail binds to the acidic patch on nucleosomes that are "decorated" with a histone modification known as ubiquitination of histone H2A (H2AK119Ub).

In fact, the tail of SSX binds so powerfully that it dislodges a BAF complex subunit known as SMARCB1 (BAF47) that normally engages the complexes on chromatin. "These complexes are really stuck, so once they get to the site, they stay there and strongly activate those cancer-related genes," noted Kadoch.

According to the researchers, the full-length SSX protein is normally only active in the testes, where it likely plays a role in sperm development. But when a part of the SSX protein is fused with the BAF complex SS18 subunit (via the characteristic t(X;18) chromosomal translocation in synovial sarcoma), it prompts an "unfortunate scenario" that leads to the remodeling or opening of chromatin over the regions where the SSX tail guides BAF complexes via the acidic patch, causing the activation of cancer-related genes

With these new insights into how the oncogenic fusion protein targets BAF chromatin remodeling complexes on the genome leading to activation of synovial sarcoma-related genes, said Kadoch, "these results suggest that inhibition of the interactions between SS18-SSX-bound BAF complexes and H2AK119Ub -marked nucleosomes using small molecules or peptides may prove a viable therapeutic strategy for synovial sarcoma."

ROCHESTER, Minn. -- As COVID-19 swept into the U.S., hospitals across the country have reported that their emergency departments are emptying out. In a new study published Monday, Aug. 3, in JAMA Internal Medicine, a team of researchers from multiple institutions provides insights into this phenomenon.

"We knew there were major changes in ED (emergency department) visit volume, but we didn't know how different communities were affected. It was especially important to know how much ED visits declined in areas that had a lot of COVID-19 cases, compared to those with fewer cases. Health care providers and our communities need real evidence for decision-making," says Molly Jeffery, Ph.D., scientific director of Emergency Medicine Research at Mayo Clinic. Dr. Jeffery is the study's lead author.

The investigators collected information on emergency department visits and subsequent hospital admissions from Jan. 1 to April 30. Study data came from 24 emergency departments across five health care systems. Included in the study were four emergency departments in Colorado and five emergency departments in each of these states: Connecticut, Massachusetts, New York and North Carolina. These emergency departments spanned rural, urban and suburban settings, and included regions with a high COVID-19 caseload and regions with lower case counts. Annual baseline volume across these emergency departments ranged from 12,500 to 115,000 visits.

"We found a substantial decline in emergency department visits -- between 42% and 64% -- during the four-month period of our study, but most of that decline happened over just a few weeks in March," says Dr. Jeffery. "The largest declines were seen in the areas that had a lot of COVID-19 cases. If you think about that, it means that even more people with problems other than COVID-19 must have avoided the ED during this period."

These declining visit numbers corresponded to growing awareness of COVID-19 through increasing coverage in the national and local media, as well as the timing of a good portion of state-issued stay-at-home orders. Although the researchers were unable to determine specific numerical reductions from particular causes, they offered three likely explanations.

"Reductions in ED utilization could reflect: (1) failure to seek care by patients with serious or life-threatening conditions, including those unrelated to COVID-19; (2) avoidance of the ED for nonemergent conditions; or (3) displacement of ED care to other venues, such as telemedicine visits."

Conversely, the researchers noted that hospital admission rates from the emergency department remained relatively stable across the health systems until there was a local increase in COVID-19 cases, at which time there was an uptick.

"This increase in hospital admissions was dramatic," says Edward Melnick, M.D., an emergency medicine physician at Yale New Haven Health in Connecticut. Dr. Melnick is the study's senior author.

"Here at Yale New Haven, we saw a 36% increase, the median increase across the five systems," he says. "In New York, the epicenter of the largest outbreak of COVID in the U.S., the relative increase of hospital admissions at Mount Sinai Health was 149% -- so 2½ times the usual rate of emergency admissions."

The other systems also showed significant relative increases of emergency hospital admissions:

22%, UNC Health, North Carolina

29.4%, UCHealth, Colorado

51.7%, Baystate Health, Massachusetts

The increases in hospital admissions occurred despite the reductions in visits, allowing inferences that emergency hospitalizations for COVID-19 accounted for a substantial portion. However, the researchers note that they are unable to determine if people with serious symptoms, illnesses and injuries went untreated due to the COVID-19 pandemic.

Recently, the researchers examined May and June data from the states observed in their paper. They found that the lowest amount of visits to the emergency department occurred during the week of April 8, with increasing numbers since then -- but not a return to baseline.

Furthermore, although emergency hospital admissions initially increased in correspondence to rising rates of COVID in each state, they stabilized and began to trend downward around that same time. However, admissions have not returned to levels seen before COVID-19 either, even where the rate of new COVID-19 cases has sharply decreased.

"More widely available telehealth options may be keeping the emergency visits below historic norms," says Dr. Jeffery. "Many insurers, including Medicare, are paying for telehealth visits now that they previously did not cover. It will be important to understand how this shift from in-person to virtual visits affects both access to care and patient health outcomes."

As for emergency hospital admissions, Dr. Melnick thinks it's probably for similar reasons. "If a person stays home when sick and treats illnesses early, they may avoid increased severity and the need for emergency care."

"People should continue to seek medical assistance for serious illnesses, injuries and symptoms," says Dr. Melnick. "While nonemergencies make up a certain portion of usual visits, the steep drop in visits to the emergency department seems to indicate that many urgent health situations may have gone untreated. This could lead to worsening symptoms, disability or death. Emergency departments remain a safe place to receive care for non-COVID-related emergencies."

"Since the pandemic started, infection control measures have been increased," says Dr. Jeffery. "Appropriate measures should continue in both the emergency department and other clinical settings to reassure staff and ensure patients feel safe to pursue appropriate care."

Drs. Melnick and Jeffery echo what they and their colleagues said in the paper, "It is essential that public health authorities and health care systems provide guidance and resources to help patients determine the best place to receive care now (and) throughout the pandemic, and into the future."

What The Study Did: International professional societies developed recommendations for minimum clinical standards to determine brain death/death by neurologic criteria in adults and children to improve the consistency of these criteria within and among countries.

Authors: Gene Sung, M.D., M.P.H., of the University of Southern California in Los Angeles, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.11586)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Despite decades of positive messaging to encourage women and girls to pursue education tracks and careers in STEM, women continue to fall far below their male counterparts in these fields. A new study at Carnegie Mellon University examined 25 languages to explore the gender stereotypes in language that undermine efforts to support equality across STEM career paths. The results are available in the August 3rd issue of Nature Human Behavior.

Molly Lewis, special faculty at CMU and her research partner, Gary Lupyan, associate professor at University of Wisconsin-Madison, set out to examine the effect of language on career stereotypes by gender. They found that implicit gender associations are strongly predicted by the language we speak. Their work suggests that linguistic associations may be causally related to people's implicit judgement of what women can accomplish.

"Young children have strong gender stereotypes as do older adults, and the question is where do these biases come from," said Lewis, first author on the study. No one has looked at implicit language - simple language that co-occurs over a large body of text - that could give information about stereotypical norms in our culture across different languages."

In general, the team examined how words co-occur with women compared to men. For example, how often is 'woman' associated with 'home,' 'children' and 'family,' where as 'man' was associated with 'work,' 'career' and 'business.'

"What's not obvious is that a lot of information that is contained in language, including information about cultural stereotypes, [occurs not as] direct statements but in large-scale statistical relationships between words," said Lupyan, senior author on the study. "Even without encountering direct statements, it is possible to learn that there is stereotype embedded in the language of women being better at some things and men at others."

They found that languages with a stronger embedded gender association are more clearly associated with career stereotypes. They also found that a positive relationship between gender-marked occupation terms and the strength of these gender stereotypes.

Previous work has shown that children begin to ingrain gender stereotypes in their culture by the age of two. The team examined statistics regarding gender associations embedded in 25 languages and related the results to an international dataset of gender bias (Implicit Association Test).

Surprisingly, they found that the median age of the country influences the study results. Countries with a larger older population have a stronger bias in career-gender associations.

"The consequences of these results are pretty profound," said Lewis. "The results suggest that if you speak a language that is really biased then you are more likely to have a gender stereotype that associates men with career and women with family."

She suggests children's books be written and designed to not have gender-biased statistics. These results also have implications for algorithmic fairness research aimed at eliminating gender bias in computer algorithms.

"Our study shows that language statistics predict people's implicit biases -- languages with greater gender biases tend to have speakers with greater gender biases," Lupyan said. "The results are correlational, but that the relationship persists under various controls [and] does suggest a causal influence."

Lewis notes that the Implicit Association Test used in this study has been criticized for low reliability and limited external validity. She stresses that additional work using longitudinal analyses and experimental designs is necessary to explore language statistics and implicit associations with gender stereotypes.

A team of researchers from Japan has demonstrated a light-based reaction that yields high numbers of the base chemical component required to produce bioactive compounds used in common industry products.

They published their results on June 11 in Organic Letters.

"We developed a redox potential-controlled and cost-effective method to synthesize multisubstituted cyclobutanes, which are present in the core structure of various products and bioactive components," said paper author Yujiro Hoshino, a research associate at Yokohama National University.

Cycloaddition reactions allow to prepare carbocyclic and heterocyclic organic compounds with atom-efficiency. For a long time, researchers carried out photocycloadditions of olefins such as styrenes, a chemical used in the production of plastics and rubber, by treating them with high-energy ultraviolet light or transition metal catalysts, which are known to be toxic and expensive chemical reagents. The reaction mainly provides homo-dimer, not hetero-dimer. In addition, the powerful light damages the bonds holding the chemical together, allowing it to break apart and reform in a new configuration, known as a cyclobutene ring.

Redox potential refers to how easily a chemical loses or gains electrons. Hoshino and co-workers take advantage of this characteristic and applied a green, visible light to styrenes situated in a two-by-two arrangement, allowing the chemical components and bonds to selectively reorganize as the light freed electrons from the styrenes. The newly organized chemical components were multisubstituted cyclobutanes.

"By focusing on the different redox potential between various styrenes and optimizing our light catalysts, we developed a mild and clean method to synthesize multisubstituted cyclobutanes," Kenta Tanaka, paper first author and an assistant professor at Tokyo University of Science, said.

"Emphasis will be placed on the strategy which shows the potential to synthesize multisubstituted cyclobutanes via radical cation species without any transition metal catalysts," said another corresponding author Kiyoshi Honda, a professor at Yokohama National University.

Next, the researchers plan to expand the use of various visible-light catalysis methods.

"We hope our reaction system provides an efficient and new method for green-light-driven organic chemical reactions, and that we continue to contribute to the field," Hoshino said.

Researchers have demonstrated the use of a ground-breaking circuit design that could transform manufacturing processes for wearable technology.

Silicon-based electronics have aggressively become smaller and more efficient over a short period of time, leading to major advances in devices such as mobile phones. However, large-area electronics, such as display screens, have not seen similar advances because they rely on a device, thin-film transistor (TFT), which has serious limitations.

In a study published by IEEE Sensors Journal, researchers from the University of Surrey, University of Cambridge and the National Research Institute in Rome have demonstrated the use of a pioneering circuit design that uses an alternative type of device, the source-gated transistor (SGT), to create compact circuit blocks.

In the study, the researchers showed that they are able to achieve the same functionality from two SGTs as would normally be the case from today's devices that use roughly 12 TFTs - improving performance, reducing waste and making the new process far more cost effective.

The research team believe that the new fabrication process could result in a generation of ultralightweight, flexible electronics for wearables and sensors.

Dr Radu Sporea, lead author of the study and Lecturer in Semiconductor Devices at the University of Surrey, said: "We are entering what may be another golden age of electronics, with the arrival of 5G and IoT enabled devices. However, the way we have manufactured many of our electronics has increasingly become overcomplicated and has hindered the performance of many devices.

"Our design offers a much simpler build process than regular thin-film transistors. Source-gated transistor circuits may also be cheaper to manufacture on a large scale because their simplicity means there is less waste in the form of rejected components. This elegant design of large area electronics could result in future phones, fitness tracker or smart sensors that are energy efficient, thinner and far more flexible than the ones we are able to produce today."

African-Americans have up to three times the risk of dying from strokes as people of European descent, yet there has been little investigation of if and how genetic variants contribute to their elevated stroke risk. Until now.

A large international team of scientists has completed the largest analysis of stroke-risk genes ever undertaken in individuals of African descent. The new study examined the genomes of more than 22,000 people of African ancestry, identifying important genetic contributors to stroke risk. These findings will help doctors better understand stroke risk, identify those at high risk and prevent the debilitating condition.

"Given the undue burden that people of African ancestry endure from stroke and other cerebrovascular disease, the lack of investigation of risk factors in this group has been a substantial gap," said researcher Bradford B. Worrall, MD, a neurologist at UVA Health. "Our work is an important step toward filling that gap, albeit with much more work to be done. These findings will provide greater insight into ethnic-specific and global risk factors to reduce the second leading cause of death worldwide."

Understanding Stroke Risk

Stroke is the leading cause of adult disability in the United States. But strokes strike African-Americans more often and at younger ages than people of European descent. In addition, African-Americans who survive strokes often face greater disability.

Family history is a major risk factor for stroke, suggesting our genes play a significant role in our stroke risk. But most genetic stroke studies, until now, have primarily focused on people of European descent. And the results have not always held true in African-Americans.

The new meta-analysis comes from the Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS). The researchers revisited previous studies to identify genetic risk factors specific to people of African descent. In total, they examined the genomes of 3,734 people who had suffered strokes and more than 18,000 who had not.

The researchers discovered that a common variation near the HNF1A gene was strongly associated with increased stroke risk in those of African ancestry. The gene previously has been associated to both stroke and cardiovascular disease.

While that variant had the strongest link to stroke risk, the researchers identified 29 other variants that also appear likely to influence stroke risk.

The variants occur at 24 different locations on our chromosomes. Sixteen of the "loci," as the locations are known, appeared also to influence stroke risk in other populations, the researchers report.

"Studies of this nature are critical given the paucity of genetic studies focused on people of African descent and other minority populations and the substantial health disparities related to stroke in these groups," said Keith Keene, PhD, a former UVA researcher and frequent collaborator of Worrall's who now leads the Center for Health Disparities at East Carolina University's Brody School of Medicine. "Furthermore, we increasingly recognize the power of looking at genetic risk factors across different race ethnic groups, known as transethnic analyses, for unlocking the underlying biology of diseases like stroke. If we understand the biology, we can develop new treatment and prevention strategies."

In a paper outlining their findings, the researchers note the importance of such studies in understanding stroke risk among minorities. These studies have "huge potential to provide insight into the mechanisms underlying stroke disparities," the researchers write. "Our study identified novel associations for stroke that might not otherwise be detected in primarily European cohort studies. Collectively, this highlights the critical nature and importance of genetic studies in a more diverse population with a high stroke burden."

In this age of racial reckoning, new research findings indicate that racial discrimination is so painful that it is linked to the ability to die by suicide, a presumed prerequisite for being able to take one's own life. However, the ability to emotionally and psychologically reframe a transgression can mitigate its harmful effects.

Over the last decade, suicide rates in the United States have increased dramatically among racial and ethnic minorities, and Black Americans in particular. For Black young adults ages 15-24 years, suicide is the third leading cause of death with approximately 3,000 Black Americans dying by suicide each year.

Two studies conducted independently tell a compelling story.

"Our findings demonstrate that for Black adults, perceived discrimination serves as a sufficiently painful experience that is directly associated with higher capability to overcome one's inherent fear of death and achieve an increased capacity for self-harm," reports Rheeda Walker, professor of psychology and director of the University of Houston's Culture, Risk and Resilience Lab. As author of the newly released "The Unapologetic Guide to Black Mental Health," Walker is one of the leading researchers in the U.S. specializing in culture, race, mental health and suicide.

The studies were led by Jasmin Brooks, a doctoral student in the research lab, and published in the journals Suicide and Life-Threatening Behavior and Cultural Diversity and Ethnic Minority Psychology, premier journals in suicide science and cultural psychology, respectively.

Capability for suicide: Discrimination as a painful and provocative event

In this study, the research team measured the relationship between a person's experiences of discrimination and their level of capability for suicide. The study included 173 Black and 272 white college students, who responded to questionnaires about their experiences.

The findings suggest that while perceived discrimination creates emotional disturbance for white adults, it is a uniquely painful event for Black adults.

"For Black adults, perceived discrimination accounted for statistically significant variance above and beyond both feelings of depression and non-discriminatory stressors in predicting suicide capability. For white adults, perceived discrimination was not uniquely associated with capability for suicide," reports Walker.

In a separate, but timely study, Walker and her team examined how some of the effects of racism could be mitigated.

The moderating effect of dispositional forgiveness on perceived racial discrimination and depression for African American adults

While perceived racial discrimination is associated with depression for African American adults, insight into protective measures for racism and depression in African Americans is limited. In this study, 101 African American college students reported their personal experiences and feelings, and Walker's team investigated whether dispositional forgiveness is associated with less depression. Dispositional forgiveness, the ability to reframe an incident, is not the same as excusing, encouraging reconciliation, or freeing an offender from the consequences of their actions.

"Using internal coping strategies is vital for marginalized populations that experience racial discrimination daily. The results of this study suggest that dispositional forgiveness, a robust internal coping mechanism, can serve as a helpful coping strategy associated with fewer depressive symptoms for African American adults who have experienced racial discrimination," reports Walker.

Walker said the findings could have important clinical implications in that dispositional forgiveness, and specifically the ability to engage in cognitive restructuring and reframing, prevents prolonged rumination.

"In a better, more inclusive world, racism would not exist. Until that happens, psychological tools are critical for mitigating acute and long-term emotional consequences of racial discrimination in African American individuals," said Walker.

Philadelphia, August 3, 2020--Whether children have ongoing sleep problems from birth through childhood or do not develop sleep problems until they begin school, a new study by researchers at Children's Hospital of Philadelphia (CHOP) has found that sleep disturbances at any age are associated with diminished well-being by the time the children are 10 or 11 years old. The findings, which were published in the Journal of Child Psychology and Psychiatry, suggest health care providers should screen children for sleep problems at every age and intervene early when a sleep problem is identified.

"Our study shows that although those with persistent sleep problems have the greatest impairments when it comes to broad child well-being, even those with mild sleep problems over time experience some psychosocial impairments," said Ariel A. Williamson, PhD, a psychologist in the Sleep Center and faculty member at PolicyLab and the Center for Pediatric Clinical Effectiveness at CHOP. "The range of impairments across academic and psychosocial domains in middle childhood indicate that it is important to screen for sleep problems consistently over the course of a child's development, especially to target children who experience persistent sleep problems over time."

The researchers examined data from an Australian birth cohort involving more than 5,000 patients. Caregivers reported on whether their children had sleep problems at multiple points in time, from birth through 10 or 11 years of age. To assess child well-being, which included psychosocial measures like self-control and emotional/behavioral health and academic performance measures, the researchers used a combination of reports from caregivers and teachers as well as child-completed assessments.

In analyzing caregiver-reported sleep behaviors, the researchers found five distinct sleep problem trajectories, or patterns that characterized child sleep problems over time: persistent sleep problems through middle childhood (7.7%), limited infant/ preschool sleep problems (9.0%), increased middle childhood sleep problems (17.0%), mild sleep problems over time (14.4%) and no sleep problems (51.9%).

Using those with no sleep problems as a benchmark, the researchers found that children with persistent sleep problems had the greatest impairments across all outcomes except in their perceptual reasoning skills. Children with increased middle childhood sleep problems also experienced greater psychosocial problems and worse quality of life, but did not score lower on academic achievement. Children with limited infant/preschool sleep problems or mild increases in sleep problems over time also demonstrated psychosocial impairments and had worse caregiver-reported quality of life, but the effects were smaller than the other sleep trajectories.

While the researchers found impairments related to all of the sleep problem trajectories, they note the possibility that for certain trajectories, the relationship could be bidirectional - that is, psychosocial issues like anxiety could lead to sleep issues, and vice versa, particularly in children who develop sleep problems later in childhood.

"Although this study cannot answer whether minor, early or persistent sleep problems represent a marker for the onset of behavioral health or neurodevelopmental conditions, our findings support consistently integrating questions about sleep into routine developmental screenings in school and primary care contexts," Williamson said.

Chlamydia are bacteria that cause venereal diseases. In humans, they can only survive if they enter the cells. This is the only place where they find the necessary metabolites for their reproduction. And this happens in a relatively simple way: the bacteria create a small bubble in the cell and divide in it over several generations.

What is the decisive step that initiates the reproduction of the bacteria? It has not been known so far. Researchers from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, have now discovered it. This is important because the first step in the reproduction of the pathogens is likely to be a good target for drugs.

Glutamine import into the host cell increases

In the case of Chlamydia, the first step is to reprogram the metabolism of their human host cells. The cells then increasingly import the amino acid glutamine from their environment. If this does not work, for example because the glutamine import system is out of order, the bacterial pathogens are no longer able to proliferate. This was reported by a JMU team led by Dr. Karthika Rajeeve, who has meanwhile been awarded a professorship at the Aarhus University in Denmark, and Professor Thomas Rudel in the journal Nature Microbiology.

"Chlamydiae need a lot of glutamine to synthesize the ring-shaped molecule peptidoglycan," explains Professor Rudel, who heads the Chair of Microbiology at the JMU Biocenter. In bacteria, this ring molecule is generally a building material of the cell wall. Chlamydiae use it for the construction of a new wall that is drawn into the bacterial cell during division.

Next, the JMU team hopes to clarify the importance of the glutamine metabolism in chronic chlamydiae infections. This might provide information that might help to better understand the development of severe diseases as a result of the infection.

Facts about Chlamydia

Chlamydiae cause most venereal diseases in Germany. The bacteria are sexually transmitted and can cause inflammation in the urethra, vagina or anal area. If an infection is detected in time, it can be treated well with antibiotics.

Around 130 million people worldwide are infected with Chlamydia. The biggest problem is that the infection usually proceeds without noticeable symptoms. This makes it easier for the pathogen to spread, this leads to severe or chronic diseases such as cervical and ovarian cancer.

Considered the "guardian of the genome," TP53 is the most commonly mutated gene in cancer. TP53's normal function is to detect DNA damage and prevent cells from passing this damage on to daughter cells. When TP53 is mutated, the protein made from this gene, called p53, can no longer perform this protective function, and the result can be cancer. Across many cancer types, mutations in TP53are associated with worse outcomes, like disease recurrence and shorter survival.

As with all our genes, TP53 exists in duplicate in our cells. One copy we get from our mothers, the other we get from our fathers. Up until now, it has not been clear whether a mutation was needed in one or both copies of TP53 to affect cancer outcomes. A new study led by researchers at Memorial Sloan Kettering definitively answers this question for a blood cancer called myelodysplastic syndrome (MDS), a precursor to acute myeloid leukemia.

"Our study is the first to assess the impact of having one versus two dysfunctional copies of TP53 on cancer outcomes," says molecular geneticist Elli Papaemmanuil, a member of MSK's Epidemiology and Biostatistics Department and the lead scientist on the study, published August 3 in the journal Nature Medicine. "From our results, it's clear that you need to lose function of both copies to see evidence of genome instability and a high-risk clinical phenotype in MDS."

The consequences for cancer diagnosis and treatment are immediate and profound, she says.

A Large, Definitive Study

The study analyzed genetic and clinical data from 4,444 patients with MDS who were being treated at hospitals all over the world. Researchers from 25 centers in 12 countries were involved in the study, which was conducted under the aegis of the International Working Group for the Prognosis of MDS whose goal is to develop new international guidelines for the treatment of this disease. The findings were independently validated using data from the Japanese MDS working group led by Seishi Ogawa's team in Kyoto University.

"Currently, the existing MDS guidelines do not consider genomic data such as TP53 and other acquired mutations when assessing a person's prognosis or determining appropriate treatment for this disease," says Peter Greenberg, Director of Stanford University's MDS Center, Chair of the National Comprehensive Cancer Network Practice Guidelines Panel for MDS, and a co-author on the study. "That needs to change."

Using new computational methods, the investigators found that about one-third of MDS patients had only one mutated copy of TP53. These patients had similar outcomes as patients who did not have a TP53 mutation -- a good response to treatment, low rates of disease progression, and better survival rates. On the other hand, the two-thirds of patients who had two mutated copies of TP53 had much worse outcomes, including treatment-resistant disease, rapid disease progression, and low overall survival. In fact, the researchers found that TP53 mutation status -- zero, one, or two mutated copies of the gene -- was the most important variable when predicting outcomes.

"Our findings are of immediate clinical relevance to MDS patients," Dr. Papaemmanuil says. "Going forward, all MDS patients should have their TP53 status assessed at diagnosis."

As for why it takes two "hits" to TP53 to see an effect on cancer outcomes, the study's first author Elsa Bernard, a postdoctoral scientist in the Papaemmanuil lab, speculates that one normal copy is enough to provide adequate protection against DNA damage. This would explain why having only one mutated copy was not associated with genome instability or any worse survival rates than having two normal copies.

Given the frequency of TP53 mutations in cancer, these results make a case for examining the impact of one versus two mutations on other cancers as well. They also reveal the need for clinical trials designed specifically with these molecular differences in mind.

"With the increasing adoption of molecular profiling at the time of cancer diagnosis, we need large, evidence-based studies to inform how to translate these molecular findings into optimal treatment strategies," Dr. Papaemmanuil says.

AMES, Iowa -- New research suggests that demolishing abandoned houses may lead nearby property owners to better maintain their homes.

This study, by Daniel Kuhlmann, assistant professor of community and regional planning at Iowa State University, was published recently in the peer-reviewed Journal of Planning Education and Research. He examined whether the demolition of dilapidated and abandoned housing affects the maintenance decisions of nearby homeowners.

In the wake of the 2008 recession, many cities experienced an increase in the number of vacant and abandoned houses. Some cities, such as Cleveland and Detroit, received federal funding to acquire vacant properties through land bank programs. While land banks were able to remodel and sell some of these properties, for the most distressed houses, demolition was the only option.

Kuhlmann wondered how effective those policies and demolitions had been.

"Demolition programs have two goals. The first is to get nuisance properties out of neighborhoods because they can be dangerous," he said. "The second goal is to help stabilize declining neighborhoods."

Past research showed that demolitions have little effect on neighboring property values. But what about the physical condition of nearby homes?

Kuhlmann looked at changes to houses over time, including the presence of boarded or broken windows, dumping or yard debris, and damages to roofs, paint, siding, gutters and porches.

Using the results of two property condition surveys and administrative records on demolitions in some of the most distressed neighborhoods in Cleveland, Kuhlmann found properties near demolitions were more likely to show signs of improvement between the two surveys and less likely to deteriorate themselves.

Kuhlmann recognizes the longstanding disinvestment in some of these neighborhoods, many of which are doubly affected by racial inequities. This fact makes studies like Kuhlmann's "challenging because even if distressed housing contributes to decline, it is certainly also a symptom of it." He suggests that future research should look at demolitions' long-term effects on a neighborhood.

"Community-wide, residents tend to see demolitions as a good idea in specific instances, but they would like larger investments," he said. "It can't end with demolitions."

These findings are useful for planners, policymakers and academics concerned about damages caused by abandoned and deteriorating housing, Kuhlmann says.

"My research in general focuses on the extremes of decline, but I do think these types of properties exist in more cities than we might expect," he said.

LAWRENCE -- A new paper in the journal NeuroImage: Clinical from researchers at the University of Kansas reveals a possible early indicator of Fragile X-associated tremor/ataxia syndrome, or FXTAS. The disease afflicts some older people who carry a "premutation" of the gene known as FMR1, which can lead to impairments in movement and cognition -- while other people who carry the premutation are unaffected.

Among people with the FMR1 premutation, scientists have struggled to find biomarkers to indicate who might develop FXTAS.

The new study of 16 people with the FMR1 premutation and 18 healthy controls recorded participants' brain activity with functional magnetic resonance imaging while they performed a test of sensorimotor control. Participants were asked to manipulate images on a screen using a grip-force controller while the fMRI machine recorded the small changes in blood flow that occur when different parts of the brain become more active.

"It's one of the first studies we know about to use fMRI to look at brain system function during motor behavior in a patient population at risk for developing motor deterioration and motor degeneration where they show a loss of balance, increased shaking or tremor as they reach their 50s, 60s or 70s," said Matthew Mosconi, KU associate professor of clinical child psychology and associate scientist at KU's Life Span Institute, who oversaw the investigation in his BRAIN Lab. "But we know very little about which premutation carriers will develop FXTAS. We know males are at greater risk than females. Otherwise, we don't know a whole lot about which premutation carriers are going to get it. And we don't know a whole lot about what's going on in the brain functionally."

The investigators were able to identify brain processes specifically linked to sensorimotor issues in aging people with the FMR1 premutation.

"We found the functional connectivity of cerebellum - a brain region that controls our movement accuracy and timing -- and the extrastriate cortex, a brain area critically involved in processing visual information, is reduced in aging FMR1 premutation carriers," said Walker McKinney, lead author of the new paper and a KU doctoral student in clinical child psychology. "In some people, these longer connections -- like highways between the different parts of the brain -- aren't communicating as efficiently. Each part may be firing, but they're not firing together."

Significantly, the researchers found very little overlap in terms of functional connectivity of this pathway between premutation carriers and healthy controls in the study, suggesting connectivity levels between the cerebellum and extrastriate cortex could serve as an early emerging indicator of FXTAS, or predict who among FMR1 carriers will develop the characteristic symptoms of FXTAS before they develop.

"When studies get reported, oftentimes we're talking about a 'mean difference' between groups -- there's always overlap with healthy people and there's variability there," Mosconi said. "With our study, the fact that there's minimal overlap between premutation carriers and controls suggests that this may be what we would call a biomarker. What we need to do now is follow this measure and these people over time to determine who gets FXTAS and who doesn't. In other words, this seems like a clear target for understanding brain degeneration in FXTAS and identifying it early in its course."

ITHACA, N.Y. - When it comes to the future of solar energy cells, say farewell to silicon and hello to calcium titanium oxide - the compound mineral better known as perovskite.

Cornell University engineers have found that photovoltaic wafers in solar panels with all-perovskite structures outperform photovoltaic cells made from state-of-the-art crystalline silicon, as well as perovskite-silicon tandem cells, which are stacked pancake-style cells that absorb light better.

In addition to offering a faster return on the initial energy investment than silicon-based solar panels, all-perovskite solar cells mitigate climate change because they consume less energy in the manufacturing process, according to Cornell research published in Science Advances.

"Layered tandem cells for solar panels offer more efficiency, so this is a promising route to widespread deployment of photovoltaics," said Fengqi You, Professor in Energy Systems Engineering at Cornell.

The paper, "Life Cycle Energy Use and Environmental Implications of High-Performance Perovskite Tandem Solar Cells," compares energy and life-cycle environmental impacts of modern tandem solar cells made of silicon and perovskites.

Perovskite needs less processing, and much less of the heat or pressure, during the fabrication of solar panels, You said.

Silicon photovoltaics require an expensive initial energy outlay, and the best ones take about 18 months to get a return on that investment. A solar cell wafer with an all-perovskite tandem configuration, according to the researchers, offers an energy payback on the investment in just four months. "That's a reduction by a factor of 4.5, and that's very substantial," You said.

But solar panels don't last forever. After decades of service, silicon solar panels become less efficient and must be retired. And as in the manufacturing phase, breaking down silicon panels for recycling is energy intensive. Perovskite cells can be recycled more easily.

"When silicon-based solar panels have reached the end of their efficiency lifecycle, the panels must be replaced," You said. "For silicon, it's like replacing the entire automobile at the end of its useful life," while replacing perovskite solar panels is akin to installing a new battery.

Adopting materials and processing steps to make perovskite solar cell manufacturing scalable is also critical to developing sustainable tandem solar cells, You said.

"Perovskite cells are promising, with a great potential to become cheaper, more energy-efficient, scalable and longer lasting," You said. "Solar energy's future needs to be sustainable."

Children who suffer trauma from abuse or violence early in life show biological signs of aging faster than children who have never experienced adversity, according to research published by the American Psychological Association. The study examined three different signs of biological aging--early puberty, cellular aging and changes in brain structure--and found that trauma exposure was associated with all three.

"Exposure to adversity in childhood is a powerful predictor of health outcomes later in life--not only mental health outcomes like depression and anxiety, but also physical health outcomes like cardiovascular disease, diabetes and cancer," said Katie McLaughlin, PhD, an associate professor of psychology at Harvard University and senior author of the study published in the journal Psychological Bulletin. "Our study suggests that experiencing violence can make the body age more quickly at a biological level, which may help to explain that connection."

Previous research found mixed evidence on whether childhood adversity is always linked to accelerated aging. However, those studies looked at many different types of adversity--abuse, neglect, poverty and more--and at several different measures of biological aging. To disentangle the results, McLaughlin and her colleagues decided to look separately at two categories of adversity: threat-related adversity, such as abuse and violence, and deprivation-related adversity, such as physical or emotional neglect or poverty.

The researchers performed a meta-analysis of almost 80 studies, with more than 116,000 total participants. They found that children who suffered threat-related trauma such as violence or abuse were more likely to enter puberty early and also showed signs of accelerated aging on a cellular level-including shortened telomeres, the protective caps at the ends of our strands of DNA that wear down as we age. However, children who experienced poverty or neglect did not show either of those signs of early aging.

In a second analysis, McLaughlin and her colleagues systematically reviewed 25 studies with more than 3,253 participants that examined how early-life adversity affects brain development. They found that adversity was associated with reduced cortical thickness - a sign of aging because the cortex thins as people age. However, different types of adversity were associated with cortical thinning in different parts of the brain. Trauma and violence were associated with thinning in the ventromedial prefrontal cortex, which is involved in social and emotional processing, while deprivation was more often associated with thinning in the frontoparietal, default mode and visual networks, which are involved in sensory and cognitive processing.

These types of accelerated aging might originally have descended from useful evolutionary adaptations, according to McLaughlin. In a violent and threat-filled environment, for example, reaching puberty earlier could make people more likely to be able to reproduce before they die. And faster development of brain regions that play a role in emotion processing could help children identify and respond to threats, keeping them safer in dangerous environments. But these once-useful adaptations may have grave health and mental health consequences in adulthood.

The new research underscores the need for early interventions to help avoid those consequences. All of the studies looked at accelerated aging in children and adolescents under age 18. "The fact that we see such consistent evidence for faster aging at such a young age suggests that the biological mechanisms that contribute to health disparities are set in motion very early in life. This means that efforts to prevent these health disparities must also begin during childhood," McLaughlin said.

There are numerous evidence-based treatments that can improve mental health in children who have experienced trauma, McLaughlin said. "A critical next step is determining whether these psychosocial interventions might also be able to slow down this pattern of accelerated biological aging. If this is possible, we may be able to prevent many of the long-term health consequences of early-life adversity," she says.