Culture

FGFR2 and gastric cancer

Fibroblast growth factor receptor 2 is a protein that aids in the growth of new cells. So, for example, FGFR2 helps repair injuries by aiding in the growth of new tissue cells in the affected area. What FGFR2 does not do however, is tell cells to stop growing. FGFR2 is like a mindless robot that does the same job over and over again, even if that job is no longer needed. This means sometimes FGFR2 continues churning out new cells beyond their need, i.e. even after the injured area has been repaired, at which point these cells form tumors and turn into cancer. When the tumor saps all the resources from its surroundings, FGFR2 is activated and new cancer cells are sent down the bloodstream to areas with untapped resources. An "overexpression" of FGFR2 may mean this protein has been activated to make cells to cancerous levels, evidenced in FGFR2 overexpression having a reported 3-10% association with gastric cancers.

Why "in the blood" matters

Cancer has "heterogeneity" in that it may differ in nature between the primary site and the site of recurrence and metastasis. This makes tracking cancer a game of cat and mouse with a blindfold on. Unless you have access to the molecular structure of the cells passing through the bloodstream, you cannot see where the cancer has spread until its fledgling cells have settled into a new area and grown into an obtrusive tumor.

"If circulating cancer cells in the blood can be detected, it will be possible to investigate the characteristics of cancer metastases that are rarely removed, and it will be a useful diagnostic method for selecting molecular-targeted therapeutic agents suitable for the characteristics of each patient's unique form of cancer", says lead researcher Masakazu Yashiro, Department of Molecular Oncology and Therapeutics, Graduate School of Medicine, Osaka City University. With his team, they measured the FGFR2 expression level of circulating tumor cells with a FACScan on a 2ml sample of blood periphery to a tumor they had previously assessed the FGFR2 expression level via immunohistochemistry. They found that FGFR2 overexpression in the blood samples was significantly correlated to the FGFR2 expression level of the tumor.

"The significantly poorer relapse-free survival of patients with these higher correlations suggests that with this new method of finding FGFR2-positive cancer cells in the bloodstream, scientists can target an existing tumor quicker and with more accurate therapeutic agents", adds Masakazu. "Inhibitors targeting FGFR2 abnormalities are under development. By successfully identifying FGFR2-expressing cancer cells with a small amount of blood, we expect this tool to contribute to appropriate decision-making on the use of anticancer drugs, such as determining when to start FGFR inhibitors."

In school bullying, there are people who are chronic victims. The acts of aggression that they experience are not limited to a particular moment or period of time, but rather part of a sustained process over a long period of time. These aggressions have much more serious consequences: chronic victims show higher levels of stress and personality issues that do not appear in students who have no connection to school bullying or those who have experienced it for shorter periods of time.

Studies on bullying tend to analyze the variables that influence the victimization of certain people but usually overlook the variable of time, which is an important factor in order to understand the processes that a person who is constantly a victim of intimidation and aggression undergoes. A University of Cordoba research team wanted to study how levels of popularity, acceptance and friendship vary over time depending on if the victims are sporadic, chronic or experience varying degrees of bullying.

"There were several questions we came up with. Does being a victim for a prolonged period of time lead to deteriorated peer relationships? Does improving social status and friendship with schoolmates help to break free from victimization?" explains Eva Romera, researcher on the study along with researchers Rosario Ortega, Ana Bravo and Carmen Jiménez. This research study is part of the project "Social and moral competence and peer group ecology in violence among schoolchildren: a longitudinal and transactional study", coordinated by Eva Romera. This project aims to analyze how the dynamics between social, motivational and moral factors develop in peer groups in relation to bullying and cyberbullying.

The study is particularly relevant in preteen and teenage years, stages when the relationships between friendship, acceptance and visibility within the group acquire greater prominence and when there is greater vulnerability in terms of bullying. Questionnaires were given out at three different moments: the first in October 2017, the second in May 2018 and the third in October 2018. In total, 1346 students participated who, when data was first gathered, were in fifth grade (primary school), seventh grade (secondary school) and ninth grade (secondary school) at 22 different schools in the province of Cordoba. Among the students who took part in the study, 38.80% had been victims of school bullying by their schoolmates at some time. Of those, 64.4% were categorized as sporadic victims, 26.8% as victims of varying degrees and 8.8% as chronic victims.

The results verified that, in each class, people take on roles and positions in a social hierarchy that tend to remain fixed for some time, making it difficult for victims to break free from this destructive pattern of domination and submission. This could explain why bullying can be prolonged over time and create chronic victims. These results support the idea that a key intervention tactic in these situations could be trying to break down those social structures that become toxic in the classroom.

As far as sporadic victims and victims of varying degrees, these had stable levels of acceptance, popularity and friendship over time. However, in the case of chronic victims, these levels decreased, meaning that as victimization becomes chronic, people are viewed as less popular by the others and they lose friendships with them. This situation of rejection and isolation that victims undergo is exacerbated and makes it difficult for the victim to find opportunities to break free from the bullying by themselves. This demonstrates that maintaining quality friendships could act as a protective factor against bullying.

"The results of this study suggest that the stabilization of the victimization of a person at school has highly negative social repercussions and requires prevention and intervention measures in order to remedy not only the effects associated with this process, but also the conditioning factors that reinforce the act of subjecting certain children to being isolated from and rejected by their schoolmates", explains Romera.

The aim of this study is to raise awareness among the educational community, especially among educators, on the crucial role that they must perform to prevent behaviors of rejection suffered by victims as well as pointing out their role as a guide in the management of group relations. The results emphasize that fostering a friendly atmosphere among children in the classroom, as well as promoting the development of social, moral and emotional competences, are key to preventing school bullying. All this can be done using resources that favor dialog, conflict resolution, cooperation and free expression of opinions as a positive way to manage social relations.

(Vienna, 21 October 2020) A recent study conducted by a research team led by Florian Kiefer from MedUni Vienna's Division of Endocrinology and Metabolism shows that cold ambient temperatures increase vitamin A levels in humans and mice. This helps convert "bad" white adipose tissue into "good" brown adipose tissue which stimulates fat burning and heat generation. This "fat transformation" is usually accompanied by enhanced energy consumption and is therefore considered a promising approach for the development of novel obesity therapeutics. The study has now been published in the leading journal Molecular Metabolism.

In humans and mammals, at least two types of fatty depots can be discerned, white and brown adipose tissue. During obesity development, excess calories are mainly stored in white fat. In contrast, brown fat burns energy and thereby generates heat. More than 90% of the body fat depots in humans are white which are typically located at the abdomen, bottom, and upper thighs. Converting white into brown fat could be a new therapeutic option to combat weight gain and obesity.

A research group led by Florian Kiefer from the Division of Endocrinology and Metabolism, Department of Medicine III at MedUni Vienna demonstrated now that moderate application of cold increases the levels of vitamin A and its blood transporter, retinol-binding protein, in humans and mice. Most of the vitamin A reserves are stored in the liver and cold exposure seems to stimulate the redistribution of vitamin A towards the adipose tissue. The cold-induced increase in vitamin A led to a conversion of white fat into brown fat ("browning"), with a higher rate of fat burning.

When Kiefer and his team blocked the vitamin A transporter "retinol-binding protein" in mice by genetic manipulation, both the cold-mediated rise in vitamin A and the "browning" of the white fat were blunted: "As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold," explains Kiefer. In contrast, the addition of vitamin A to human white fat cells led to the expression of brown fat cell characteristics, with increased metabolic activity and energy consumption.

"Our results show that vitamin A plays an important role in the function of adipose tissue and affects global energy metabolism. However, this is not an argument for consuming large amounts of vitamin A supplements if not prescribed, because it is critical that vitamin A is transported to the right cells at the right time," explains the MedUni Vienna researcher. "We have discovered a new mechanism by which vitamin A regulates lipid combustion and heat generation in cold conditions. This could help us to develop new therapeutic interventions that exploit this specific mechanism."

Volunteers from the Catholic Church in Brazil helped to mitigate the impact of COVID-19 among the elderly, a new study shows.

Peter Kevern, Professor Values in Health and Social Care at Staffordshire University, partnered with The Pontifical Catholic University of São Paulo to carry out the study which looked at the contribution of the Pastoral da Pessoa Idosa (PPI) programme in Brazil.

And Professor Kevern suggests that the study findings may well assist the UK whose social care system has been severely tested during the pandemic.

PPI is a volunteer movement that uses the organisational structure of the Catholic Church of Brazil to provide a range of support to isolated elderly people right across the country. Anyone can be a volunteer in their community or in their building to support older people through the scheme.

Last year, approximately 25,000 'Pastoral Agents', provided home visits, personalised practical help and support to 164,000 older people. Pastoral Agents are also trained to measure and report indicators of wellbeing such as fragility, fluid intake, annual flu vaccination, and to refer people to government agencies.

Professor Kevern explained: "Brazil has a fragile social infrastructure so there are many unmet social needs to be addressed. The aim of this research was to estimate the contribution of the PPI programme to the health and social support of older people. Almost 4,000 volunteers were interviewed over a one-week period using a 21-item telephone questionnaire to evaluate the impact of its activities during 'normal' times, and how they changed to address the challenge of COVID-19."

The arrival of COVID-19 led to a temporary stop in visits following recommendations by the World Health Organization but efforts to provide material and immaterial support and remote monitoring by phone calls were encouraged through a campaign.

Professor Kevern added: "The striking thing about PPI was how quickly and flexibly the movement responded to the pandemic. Innumerable initiatives were undertaken by volunteers such as making masks, collecting food and other donations in order to make the lives of the elderly people monitored by the PPI better throughout Brazil. This was especially important for those who live in places far from urban centres, or in peripheries of large cities where access to social and health services is limited."

"I think we have some lessons to learn from PPI. In the UK, our social care system is also very fragile, and the experience of the early days of the lockdown, where older people were sent into care homes from hospital untested and many died from Covid-19, shows that the present system can't cope. Voluntary movements like PPI, supported and trained by the government, may be indispensable at times of population-level stress like a pandemic. There are some challenges coming down the line - possible future pandemics, Brexit, climate change - when again we might need to adjust to an unstable and rapidly-changing situation. Organisations like PPI might be part of the answer."

A new study led by scientists at IUPUI and Indiana University Bloomington is the first to describe a biochemical mechanism that increases the activity of a molecule whose presence is observed in many types of cancer.

The molecule, an enzyme called Pif1helicase, plays a role in many important cellular processes in the body. Tightly regulating this protein is vital to genome stability because too little -- or too much -- activity can influence aging and age-related diseases, primarily cancer. A common cancer therapy, HDAC inhibitors, can also impact the mechanism that regulates this enzyme.

"We're currently giving people drugs that change the acetylation status of the cell without knowing how it affects many proteins that play a role in genome stability," said Lata Balakrishnan, an associate professor of biology in the School of Science at IUPUI, who is co-lead author on the study.

"HDAC inhibitors upregulate certain tumor-suppression genes, and therefore are used in combination therapies to treat specific cancers, but when it comes to their impact on other parts of the cell, we're basically operating in the dark."

The study's other lead author is Matthew Bochman, an associate professor in the IU Bloomington College of Arts and Sciences' Department of Molecular and Cellular Biochemistry. Other co-authors are Christopher Sausen and Onyekachi E. Ononye, Ph.D. students in Bochman's and Balakrishnan's labs, respectively, at the time of the study.

The effect of lysine acetylation on Pif1 is the mechanism described in the study. Lysine acetylation occurs when a small molecule called an acetyl group binds to lysine, an amino acid used to build common proteins in the body. This action transforms lysine from a positively charged molecule to a neutrally charged molecule. This neutralization can impact protein function, protein stability and protein-protein interaction in cells, among other things.

Helicases are known as the genetic "zippers" of cells because they pull apart DNA for the purpose of genetic replication and repair. They also help maintain telomeres, the structure at the end of chromosomes that shorten as people age.

In the new study, the researchers identified lysine acetylation on Pif1 helicase and showed the addition of the acetyl group increases the protein's activity -- as well as its "unzipping" function. They also found that lysine acetylation changes the shape -- or "conformation" -- of the Pif1 protein. They believe that this shape change increases the amount of Pif1 helicase.

"The dynamic interplay of the addition and removal of the acetyl group on lysine regulates a wide variety of proteins within the cell," Balakrishnan said. "Perturbations to this process can play a role in cancer, aging, inflammatory responses and even addiction-related behaviors."

"As a class, helicases are involved in a lot of processes necessary for genome integrity," Bochman added. "Any significant failure in these processes is generally carcinogenic."

The precise details of lysine acetylation in Pif1, its effect of the enzyme's shape and the resulting impact on helicase activity took nearly five years to observe and report. The study, carried out in parallel on two IU campuses, was made possible by the lead scientists' complementary expertise. As a biochemist who has previously studied lysine acetylation in other proteins, Balakrishnan was able to isolate Pif1 in vitro to observe its response to chemical reactions in a test tube. In contrast, as a geneticist working in yeast as a model organism to study Pif1, Bochman was able to modify cells in vivo to watch reactions play out in a living organism.

"The ability to observe these reactions in a living cell is often more relevant, but it's also a lot messier," Balakrishnan said. "Our experiments were constantly informing each other as to where to go next."

Looking to the future, Bochman said intricate knowledge of cellular processes -- such as lysine acetylation -- will increasingly play a role in personalized therapy.

"If you sequence a patient's tumor, you can fine-tune drugs to target very specific enzymes," he said. "Instead of a drug that broadly affects the whole cell, it will be possible to take a targeted approach that reduces potential side effects. This level of personalization is really the future of cancer biology and cancer medicine."

The newly published thesis research of University of Guam Master of Environmental Science graduate Benjamin Deloso now adds to the body of knowledge about asexual propagation of the most endangered plant group in the world, cycads. His work was part of a set of UOG studies, all focused on improving the asexual propagation of cycads, published in the September 2020 issue of HortScience, one of the oldest horticultural journals in the United States.

With the assistance of his professors, Deloso designed a set of experiments to examine the speed of adventitious rooting in "pups," external stems produced from parent plants. He used two species of Zamia, a group of cycads native to the New World. These model species were chosen for two replicated rooting studies utilizing indole-3-butyric acid (IBA), the most common rooting hormone used in asexual propagation protocols.

Cycad horticulturists typically employ the use of IBA in asexual propagation, and previous research utilizing IBA on angiosperms, or flowering plants, suggests that an ideal concentration of IBA exists for cycads. However, the efficacy of IBA on cycads was unknown. "Do cycads actually benefit from IBA?" wondered Deloso, lead author of the study.

"That was one of our objectives," he said. "So we included a range of IBA that was 10 times higher than the dose that is most commonly used in commercial horticultural operations to see if there would be a negative response."

In contrast to all expectations, the cycad stem cuttings did not appear to benefit from any of the IBA doses used as the control groups performed just as well as the other treatment groups.

"The results were surprising. Our research illuminates how much is still unknown about cycad biology and highlights how different they are from other groups of plants," Deloso said.

This knowledge could benefit cycad conservation in countries where commercial IBA products are difficult to obtain.

Previous asexual propagation studies utilizing cycad stem cuttings did not involve the use of a range of IBA nor did they include a control group.

"After reviewing the scientific literature, it was clear that previous studies did not employ typical horticultural protocols," said Frank Camacho, UOG associate professor of biology and one of the authors of the study.

This makes Deloso's study the first of its kind in the cycad horticulture literature.

While IBA may not influence successful propagation of Zamia cycads, Deloso's study notes that additional studies are needed to determine its effectiveness on the other 300- plus cycad species, in particular those that are threatened, such as the endemic Cycas micronesica of Guam, Rota, Yap, and Palau. He also noted other factors found in his previous research that have proven to assist the propagation process.

"Our previous research has highlighted the relative ease of asexually propagating cycad plants. High survivability is achieved when hygienic conditions are adhered to, cuttings are obtained from healthy plants, the cut surfaces are covered with a sealant to prevent desiccation, the growing medium exhibits adequate aeration and drainage capacity, and underwatering during the propagation phase is followed," Deloso said.

Anders Lindström of the Nong Nooch Tropical Botanical Garden, another author of the study, said he is encouraged by the results of the study, saying, "Continued improvements in cycad horticulture are of great importance to the conservation of this unique plant group. We ... look forward to collaborating more with the University of Guam in the future."

We employ our cognitive skills daily to assimilate and process information. A new empirical study shows that we do better at this task than those born a century ago. But cognitive capacity still begins to stagnate at around the age of 35.

Every day our brains are continuously called upon to meet high-level cognitive challenges. When we write, play games or watch films on our computers, drive a car or carry on a telephone conversation, neurons are constantly transmitting and evaluating the electrical impulses that enable us to filter the incoming sensory information, process it, and decide on and execute the appropriate response. It is now accepted that the ability to perform cognitively demanding tasks and adapt to rapidly changing demands is becoming increasingly important - especially in the workplace.

Perhaps surprisingly, relatively little is known about how an individual's cognitive performance changes over the course of a lifetime. Most research on this topic has been done by psychologists, who have mainly been interested in probing concepts such as the relative contributions of innate and acquired intelligence. But the test procedures employed in this work suffer from two serious shortcomings. First, the tests themselves are usually based on abstract tasks, which have little to do with everyday situations and are therefore unfamiliar to those being tested. Secondly, such experiments provide only a snapshot of each subject's performance level, and therefore have little to say about how a person's cognitive performance changes with age.

Chess as a data source

The authors of the new study - Anthony Strittmatter (University of St. Gallen), Uwe Sunde (Ludwig-Maximilians-Universitaet (LMU) in Munich) and Dainis Zegners (Rotterdam School of Management) - have chosen a very different approach to assess the long-term pattern of change in cognitive capacity with age. "In our empirical model, we have used data derived from chess games played in professional tournaments, since chess is a paradigmatic example of a cognitively complex task," Sunde explains. In fact, the choice of chess as a data source has a number of significant advantages. Detailed data are available that record all the moves made by current and former world champions (and their opponents) over the past 125 years. This makes it possible to gauge the cognitive skills of each player by comparing his actual moves with those suggested by a modern chess computer, which can calculate the optimal move in each configuration that arises during a game. With the aid of mathematical analyses, the resulting data can be converted into a continuous record of each player's level of performance over the course of his entire career. Moreover, because the data cover a period of 125 years, one can also ask whether and how the cognitive abilities of professional chess-players have changed over the course of more than a century.

The empirical model employed by Sunde and his colleagues draws on data for over 24,000 chess games played in professional tournaments between the years 1890 and 2014, which record more than 1.6 million individual moves. When these data are analyzed for 'age cohorts' - groups defined by the birthdates of the players - the following conclusions can be drawn:

Cognitive performance follows an age-dependent trajectory. It increases steadily at first, before reaching a plateau at around the middle of the fourth decade.

The form of this profile has changed over the past 125 years. On average, those born later during this time-span exhibit a higher level of cognitive ability than their predecessors at the same age, as indicated by the relative increase in the choice of optimal moves during a game.

However, as Sunde explains, one must take one feature of the data into account when interpreting these results. "The problem arises from the fact that professional chess-players stop participating in tournaments at some stage, because they are no longer good enough to be competitive. This factor opens up the possibility that what are called 'selection effects' might distort the quantitative analysis of the data, which would reduce confidence in the interpretation of the model. This effect is expected to set in from the age of 50 or so. "If players continued to play regularly in public tournaments throughout their lives, the impact of the selection effect would be lower, and the trajectory of the curve for overall cognitive performance would probably fall off at a somewhat faster rate." For this reason, Sunde explains, the performance curve may not apply to the general population, but rather represents an upper bound.

Professor Sunde and his co-authors also provide a possible rationale for their finding the mean cognitive capacity of today's 30-year-olds is higher than that of the corresponding age group 100 years ago. "Our results suggest that the conditions under which people grow up these days - which of course include the rapid growth of digital technology -­ have a decisive impact on the development of their cognitive abilities," he says. However, he adds, the model has nothing to say about whether this trend is likely to continue.

At all events, those of us who have already passed the 35-year threshold need no longer worry about its looming approach. - And if one continues to exercise one's gray matter regularly, there's a good chance that the brain will return the favor by remaining sprightly for longer.

TAMPA, Fla. -- Prostate cancer is the most common type of cancer among American men after skin cancer, but the disease does not affect all races equally. African American men are nearly two times more likely to develop prostate cancer, and more often have an aggressive form of the disease that grows and spreads quickly. They are also two times more likely to die from prostate cancer compared to white men. While the health care community is aware of this disparity, little is known about why prostate cancer affects African American men differently. It has become increasingly evident that both socio-economic and biological factors may contribute to the disparity.

Moffitt Cancer Center researchers are taking a closer look at the genomic features of prostate cancer tumors among men of different races in hopes of better understanding why African Americans are more susceptible to the disease. In a new article published in Clinical Cancer Research, the research team describes the immune-oncologic differences in prostate cancer tumors of African American men and how those variations may be exploited to develop more personalized treatment approaches for this population.

"Previous studies have looked at the immune landscape of prostate cancer in white or European American men but have lacked validation among their African American counterparts," said Kosj Yamoah, M.D., Ph.D., lead study author and assistant member of the Radiation Oncology and Cancer Epidemiology Programs at Moffitt. "Our genomic analysis, the largest of its kind, revealed there are major immune pathways that are significantly elevated in African American men, which can correlate with risk of cancer recurrence and poor outcomes."

The Moffitt researchers analyzed whole transcriptome data from nearly 1,200 proctectomy samples in the Decipher Genomic Resource Information Database registry. Transcriptomic data provides a complete look at all the RNA sequences within a cell, which in turn can show when and where each gene is turned on or off. The team focused on 1,260 immune specific genes to determine differences between prostate cancer tumor cells in African American and European American men.

They discovered striking differences between the two races. Major immune pathways, including cytokine, interferon and interleukin signaling, are elevated in African American prostate tumors. These pathways can contribute to and escalate the growth and spread of cancer cells. The immune biologic signatures suggest prostate cancer tumors in African American men may be more sensitive to radiotherapy and could have a better response to immunotherapy.

"Currently there are only two immunotherapy options for prostate cancer patients: the sipuleucel-T cell vaccine and pembrolizumab. However, not everyone responds to those therapies," said Yamoah. "Our study shows that African American men have higher overall immune content within their tumor microenvironment and higher expression of T lymphocytes. We can use that information to select a therapy that better targets their tumor and therefore improve their outcome."

The team also discovered six genes that expression levels were consistently different between African American and European American men. One gene, IFITM3, is often an indicator that a patient has a significantly higher risk of biochemical recurrence, meaning their prostate antigen score continues to rise despite surgery or radiation. In addition to cancer progression, this gene also plays an important role in metastasis.

The researchers say further study will be needed to determine if their findings can have positive implications on the treatment and management of prostate cancer in African American men.

BUFFALO, N.Y. -- Chemicals that haven't been manufactured in the U.S. for years or even decades are still turning up in the bodies of migratory terns in the Great Lakes region, a new study finds.

The research focused on three types of compounds: polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and the breakdown products, called metabolites, of dichlorodiphenyltrichloroethane (DDT).

Scientists discovered all three kinds of chemicals in the organs of over two dozen common terns in breeding grounds along the Niagara River and the shore of Lake Erie. The pollutants were found at various life stages, in chicks, in juveniles and in adults.

Researchers also detected the compounds in emerald shiners, a small fish that is the terns' primary food source in the area.

The research was published online on Sept. 3 in Environment International, and will appear in the journal's November issue. Authors included University at Buffalo chemists Diana Aga and Steven Travis, and SUNY Buffalo State biologist Alicia Pérez-Fuentetaja.

Sales of PBDEs, a class of flame retardants used in car seats, carpet padding, mattresses and many other household products, were phased out in the U.S. in 2013. Production of PCBs, once widely used as a coolant or insulating fluid in electrical transformers and capacitators, ended in the country in 1979. And use of DDT, an insecticide, has been prohibited in the U.S. for almost half a century, since 1972. The metabolite of DDT that the team found in the birds and fish is called dichlorodiphenyldichloroethylene (DDE).

"These chemicals are still there. They don't just go away. With PCBs, for example, they haven't been produced in the U.S. for a long time now, but you can still find them in the environment, in sediments and in water. They don't degrade for many years. The fish eat organisms that accumulate them, and then the birds eat the fish," says Aga, PhD, Henry M. Woodburn Professor of Chemistry in the University at Buffalo College of Arts and Sciences.

"The common tern is a threatened species in New York State, and their numbers have not increased much despite state efforts to provide nesting sites and surveillance. This study shows how wildlife is affected by human pollution of aquatic systems and how the chemicals we produce can have a multigenerational effect, being passed from mothers to chicks," says Pérez-Fuentetaja, PhD, Professor of Biology at SUNY Buffalo State and Research Scientist at the Great Lakes Center at SUNY Buffalo State.

The levels of PCBs and PBDEs in the birds were high enough to potentially harm the birds' health and affect population recovery, the authors write in their paper.

Pollutants impact terns in every stage of life

The findings illustrate how household and industrial chemicals have become ubiquitous in the environment, where they can endure for many years, posing risks to wildlife.

In the case of terns, the threat begins from the earliest moments of their lives, even before they hatch, says Travis, the paper's first author, who successfully defended his PhD thesis at UB this fall.

He notes that the smallest chicks the team studied harbored higher concentrations of the chemicals than older birds and adults, indicating that the compounds are being passed from parent to progeny. To test this hypothesis, Travis has begun work on a study examining the levels of pollutants in the eggs of common terns and other wild aquatic birds.

"We see these really high concentrations in the smaller chicks, which indicates that there is maternal transfer of contaminants into the eggs," he says.

"These substances interfere with the reproductive system and are endocrine disruptors," Pérez-Fuentetaja says. "They tax the terns' livers as they have to try and get rid of these pollutants, but the bioaccumulative nature of PCBs, PBDEs and DDEs means that the birds will not be able to fully detoxify themselves, and that they will pass part of their body-load to the next generation. These substances can alter development and neurological processes and could cause deformities, cancers and impaired behavior."

The research highlights the risks associated with legacy contaminants, as well as the urgency of protecting the environment as new issues surrounding other classes of persistent chemicals, such as per- and polyfluoroalkyl substances (PFAS), emerge. Aga says that once persistent pollutants become pervasive in water and soil, it's very difficult to get rid of them.

The new study shows how long-banned chemicals continue to jeopardize the health of Great Lakes ecosystems.

"We can't say that all the chemicals we're seeing in the birds are coming from the Great Lakes, as the birds migrate and could be accumulating these compounds in other places along their migration route, too," Travis says. "But the specific types of PCBs and PBDEs we're seeing in the emerald shiners is similar to what we're seeing in the birds. This pattern of chemical concentrations suggests that pollution in the Great Lakes region is the source of at least some of this contamination."

He adds, however, that, "One positive outcome of the study is that we only see the metabolite of DDT, called 'DDE,' in the fish. This likely indicates that there aren't new sources of DDT being introduced to Lake Erie and the Niagara River, and that the DDT that was there is breaking down."

During cell division specific target proteins have to be turned over in a precisely regulated manner. To this end specialized enzymes label the target proteins with signaling molecules. However, the enzymes involved in this process can also label themselves, thus initiating their own degradation. In a multidisciplinary approach, the researchers identified a mechanism of how enzymes can protect themselves from such self-destruction and maintain sufficient concentrations in the cell. These results have been published in the latest issue of Science Signaling.

Vital functions of the multicellular organisms, such as growth, development, and tissue regeneration, depend on the precisely controlled division of cells. A failure in the underlying control mechanisms can lead to cancer. A team of researchers led by Dr. Sonja Lorenz from the Rudolf Virchow Center - Center for Integrative and Translational Bioimaging at the University of Würzburg and by Dr. Jörg Mansfeld from the Biotechnology Center (BIOTEC) at the Technical University of Dresden discovered a new mechanism that modulates cell division.

Ubiquitination - a central regulatory element

A critical step in cell division is the distribution of the genetic information evenly between the daughter cells. This process is controlled by a large protein complex, the anaphase-promoting complex/cyclosome (APC/C), which labels proteins with a signaling molecule known as "ubiquitin". The ubiquitin label functions essentially as a molecular postal code, targeting labeled proteins to the cellular protein degradation machinery. To allow for the efficient and precise labeling of target proteins, the APC/C works together with an ubiquitin-conjugating enzyme, UBE2S. However, UBE2S also has the ability to modify itself with ubiquitin, thus initiating its own degradation. This ability applies to ubiquitination enzymes in general. "This raises the fundamental question of how ubiquitination enzymes find the right balance between labeling their targets and labeling themselves to ensure that sufficient quantities of the enzymes are available in the cell," says Sonja Lorenz.

Switching between active and inactive states

The new study provides an answer to this question by showing that UBE2S can adopt an inactive state in which it is unable to label itself with ubiquitin. "When UBE2S forms a dimer, i.e., two molecules pair with each other, they become inactive and protected from self-destruction," says Jörg Mansfeld. The scientists suggest that this mechanism ensures that a stable cellular pool of UBE2S is preserved and re-activated when required. The cell can thus control the ratio of active and inactive UBE2S to fine tune cell division. These findings provide a structural framework for the development of new cancer-therapeutic strategies and drug discovery.

Ubiquitin research in the Lorenz and Mansfeld groups

The current study presents the second successful, published collaboration of the Lorenz and Mansfeld groups on the regulation of UBE2S. Notably, both research articles were featured in dedicated commentary pieces.

The research group of Sonja Lorenz investigates the structural basis of the ubiquitin system, which controls almost all cellular processes. She is particularly interested in revealing the factors that account for the enormous specificity of ubiquitin as a molecular signal. Her group combines high-resolution structural techniques that yield atomic-resolution views with biochemical, biophysical, and cell-based methods. The Lorenz laboratory is funded by the Emmy Noether program of the German Research Foundation (DFG) and an ubiquitin-focused Research Training Group (GRK2243; DFG), which Sonja Lorenz represents as a co-speaker. Sonja Lorenz is also a founding member of the Mildred Scheel Early Career Center (German Cancer Aid) in Würzburg and has been engaged with transregional ubiquitin initiatives. In 2018 Dr. Lorenz was accepted into the highly selective EMBO Young Investigator Program. A member of the Lorenz laboratory, Anna Liess was part of the Würzburg Graduate School of Life Sciences and the GRK2243 and successfully defended her PhD thesis in 2020.

Jörg Mansfeld and his research group focus on ubiquitination and other protein modifications. The Mansfeld group uses cell biology and biochemical methods to investigate the role of these modifications in the decision whether a cell continues to divide or stops, in order to fulfill a specialized function. The Mansfeld group is funded by the ERC under the European Union's Horizon 2020 research and Innovation Program as well as Emmy Noether and project grants of the DFG. Alena Kučerová is a PhD student of the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB) and was supported by a DIGS-BB Fellowship.

According to the Mayo Clinic, about 15% of couples are infertile, and male infertility plays a role in over one-third of these cases. Often, problems with sperm development are to blame. Now, researchers reporting in ACS Nano have found a way to deliver a protein important for sperm cell production directly to mouse testicles, where it restored normal sperm development and allowed previously infertile mice to father pups.

Male infertility often happens because of a lack of sperm in the semen, which can result from damage to the blood-testis barrier (BTB). This barrier protects reproductive cells from harmful toxicants and drugs, and a protein called PIN1 is important for its function. Mice genetically engineered to lack PIN1 are infertile, with small testes, depleted sperm stem cells and a low sperm count. Although scientists have considered gene therapies to treat male infertility, these procedures are risky because they could cause unwanted genetic changes in reproductive cells that might be passed onto offspring. Hyun-Mo Ryoo and colleagues wanted to develop a system to deliver proteins (such as PIN1) instead of genes to the testes, but first they had to find a way to get proteins through the complex tubes of the testicles and into cells.

The researchers developed a delivery system called Fibroplex, which consisted of spherical nanoparticles made of silk fibroin and a coating of lipids. They loaded PIN1 into Fibroplex, and showed that the particles appeared safe and didn't show signs of toxicity or testicular damage in mice. When the team injected the PIN1-loaded Fibroplex into the testes of young mice with PIN1 deletions, the treatment restored nearly normal PIN1 levels and sperm stem cell numbers and repaired the BTB. Treated mice had normal testicular weight and size and about 50% of the sperm count of wild-type mice. Until about 5 months after treatment, when the protein degraded, the PIN1-Fibroplex-treated mice fathered a similar number of pups as wild-type mice, whereas untreated mice with PIN1 deletions remained infertile. This is the first demonstration of direct delivery of proteins into the testis to treat male infertility, the researchers say.

Wrong-site surgery, medication errors, and fires in operating rooms can be devastating for patients, providers, hospitals, and insurance companies alike. In risk management, these are referred to as sentinel adverse events. Determining the true causes of these events can help hospitals improve their processes, leading to large impacts on costs and outcomes of care. Typically, hospital risk managers and improvement teams do this through either Root Cause or Failure Mode analysis—both methods that can only point to possible causes and that do not look at patterns over time or across sites.

In an editorial in the Quality Management in Healthcare journal, Dr. Farrokh Alemi calls for moving past these methods, as they are unsupported by data. Dr. Alemi is a professor of health informatics in the George Mason University’s College of Health and Human Services. He is a national thought leader on statistical methods relevant for quality improvement.

“Relying on clinicians’ insights for understanding root causes has not worked well. It has perpetuated the system that produces these events. What is needed is objective data that can provide fresh insights into causes of these events,” adds Alemi. “Risk managers need to rethink their case-by-case reasoning about adverse events and examine patterns across these events. Only then they can understand true underlying causes of adverse events.”

While individual events should still continue to be reviewed, it’s important that risk managers look at patterns of data across cases. The editorial has called for use of modern causal analysis to produce new insights into why sentinel adverse events keep reoccurring.

To help risk managers orient themselves to modern causal analysis, several articles in the special issue demonstrate different methods of relying on objective data. In the special issue, Alemi also authored a causal network tutorial. The tutorial shows how improvement teams and risk managers can create data-based causal networks through repeated use of regression analysis. This method can more reliably identify the root cause of adverse events rather than just possible causes.

“Unlike in some other industries, we continue to see adverse events happening at a high rate in health care,” explains Alemi. “We actually have an opportunity to prevent them, and that is promising. This tutorial shows how risk managers can use tried-and-true statistical methods to see which factors are actually causing these adverse events so they can prioritize addressing the factors that will reduce these events.”

In his tutorial, Alemi gives step-by-step instructions for conducting a type of multivariate regression analysis—a least absolute shrinkage and selection operator (LASSO) regression to create a causal network. Once the LASSO regression is completed, the findings must be tested and then the parameters of the network are determined through analysis of objective data. The method objectively identifies causes of adverse events.

The journal’s special section also includes articles by a number of authors analyzing adverse events in operating rooms, blood administration, and treatments that diminish the risk of blot clots. A review article shows the history of development of causal networks and how these methods may be relevant to risk managers.

About George Mason University

George Mason University is Virginia's largest and most diverse public research university. Located near Washington, D.C., Mason enrolls 39,000 students from 130 countries and all 50 states. Mason has grown rapidly over the past half-century and is recognized for its innovation and entrepreneurship, remarkable diversity and commitment to accessibility. For more information, visit https://www2.gmu.edu/.

About the College of Health and Human Services

George Mason University's College of Health and Human Services prepares students to become leaders and shape the public's health through academic excellence, research of consequence, community outreach, and interprofessional clinical practice. George Mason is the fastest-growing Research I institution in the country. The College enrolls 1,918 undergraduate and 1,371 graduate students in its nationally-recognized offerings, including: 5 undergraduate degrees, 13 graduate degrees, and 7 certificate programs. The college is transitioning to a college public health in the near future. For more information, visit https://chhs.gmu.edu/.

PROVIDENCE, R.I. [Brown University] -- As researchers and medical professionals work to develop new treatments for cancer, they face a variety of challenges. One is intratumor heterogeneity -- the presence of multiple kinds of cancer cells within the same tumor. Often, these "mosaic" tumors include cells, such as polyploidal giant cancer cells, that have evolved to become aggressive and resistant to chemotherapy and radiation.

In the past, polyploidal giant cancer cells (PGCCs) have been largely ignored because studies had found that they do not undergo mitosis, which is the mechanism that is typically required for cell division. However, recent studies have found that PGCCs undergo amitotic budding -- cell division that does not occur through mitosis -- and that their cell structure enables them to spread rapidly.

A new study, published this month by a team of Brown University scientists in Proceedings of the National Academy of Sciences, sheds more light and identifies a potential target for treating these aggressive cancer cells.

Specifically, PGCCs rely on cell filaments called vimentin in order to migrate. Vimentin is found in cells throughout the body, but PGCCs were found to have a greater amount of vimentin compared to non-PGCC control cells, and their vimentin was much more evenly distributed throughout the cell.

"These cells appear to play an active role in invasion and metastasis, so targeting their migratory persistence could limit their effects on cancer progression," said study author Michelle Dawson, an assistant professor of molecular pharmacology, physiology and biotechnology at Brown University.

As cells replicate within a tumor, they become increasingly crowded, and neighboring cells press tightly against them. Eventually, the cells become jammed together in a solid-like mass. Vimentin provides PGCCs with a more flexible, elastic structure, which helps protect them from damage in this situation and allows them to squeeze past their neighboring cells to escape to new, less crowded areas.

Thus, when the researchers disrupted vimentin, they dramatically reduced the cells' ability to move. In addition, vimentin appears to play an important role in rearranging the nucleus of a dividing cell, so vimentin disruption could also help prevent PGCCs from forming daughter cells.

As a next step, Dawson and her colleagues hope to find a biomarker for PGCCs so that they can study these cells in human tumors.

"This study shows vimentin is overexpressed in PGCCs and is likely responsible for several of their abnormal behaviors," Dawson said. "Vimentin is a ubiquitous protein, so targeting vimentin directly may not be an answer, but drugs that target vimentin interactions may be effective in limiting the effects of these cells."

Results from a new study published in Alzheimer's & Dementia support emerging evidence suggesting that noise may influence individuals' risk of developing dementia later in life.

Researchers studied 5,227 participants of the Chicago Health and Aging Project who were aged 65 years or older, of whom 30% had mild cognitive impairment and 11% had Alzheimer's disease. They found that persons living with 10 decibels more noise near their residences during the daytime had a 36% higher odds of having mild cognitive impairment and a 30% higher odds of having Alzheimer's disease.

"These findings suggest that within typical urban communities in the United States, higher levels of noise may impact the brains of older adults and make it harder for them to function without assistance. This is an important finding since millions of Americans are currently impacted by high levels of noise in their communities," said senior author Sara D. Adar, ScD, of the University of Michigan School of Public Health, Ann Arbor. Professor Adar added that "although noise has not received a great deal of attention in the United States to date, there is a public health opportunity here as there are interventions that can reduce exposures both at the individual and population level."

The study was supported by grants from the Alzheimer's Association and the National Institute on Aging.

Numerous studies have examined interventions aimed at preventing violence against children. A recent analysis reveals various gaps not adequately addressed by these studies.

The analysis, published in Campbell Systematic Reviews, points to the need for more quantitative and qualitative research to assess the effectiveness of interventions to combat violence against children, with attention to expand studies to different regions of the world and to analyze interventions targeting specific forms of violence.

"Sharing and discussing these findings with policy makers and other key actors is necessary for a coordinated approach to filling knowledge gaps and ensuring research has a real impact. Regular updating of such maps will help to maintain a global overview of gaps and tell us how well the violence prevention field is doing to strengthen evidence-informed strategies," said corresponding author Ramya Subrahmanian, PhD, of UNICEF-Innocenti.