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Researchers at the University of Gothenburg now suggest a possible cure for children with hard-to-treat forms of neuroblastoma using a new combination of drugs. In a new study in the journal Cancer Research, they describe how a two small molecule-based drug combination likely inhibit the tumor's growth.

Neuroblastoma is the most common form of childhood cancer, derived from the peripheral nervous system, i.e., the part of the nervous system that is not the brain or spinal cord. The disease can occur in the chest, neck, abdomen and adrenal glands and can also spread to the spine. Symptoms include general aches, anemia and skeletal pain.

The average age of children at diagnosis is 17 months, and it is rarely diagnosed over the age of five. The milder form of neuroblastoma can, in some cases, self-heal, while the more aggressive form is the deadliest form of childhood cancer. Treatment is successful in less than half of these cases.

Central molecule in the study is the p53 gene. The p53 gene is often mutated in other cancer forms but rarely in neuroblastoma. When it is not mutated, p53 codes for a protein that inhibit the growth of cancer. This study shows that how the expression levels of a long non-coding RNA molecule influences the function of p53 protein. "Interestingly, this long non-coding RNA increases p53 function in the nucleus to make tumor cells more susceptible to cytostatic treatment," says Chandrasekhar Kanduri, professor of medical genetics specialized in RNA epigenetics at the University of Gothenburg.

The RNA molecule NBAT1 changes the function of the protein CRM1, which transports p53 from nucleus to cytoplasm. NBAT1 also helps in keeping the p53 protein in the nucleus to increase p53 controlled gene expression. Based on these findings, the research group tested a new treatment that combines the drugs Selinexor and Nutlin-3a. Both drugs are currently undergoing clinical trials for cancer treatments but not for neuroblastoma. Selinexor restores p53's ability to inhibit cancer growth and Nutlin-3a inhibits the breakdown of p53.

"The combination treatment blocks the protein export function of CRM1, which leads to p53 accumulation in the cell nucleus. This treatment increases p53 dependent functions, such as DNA damage and cell death. We think that combining these two drugs with current treatment strategies may allow us to cure hard-to-treat neuroblastomas."

The results are promising, but they are based on preclinical studies of cancer cell lines and mouse models (xenografts) and more research is needed before the findings can be translated into treatment. These laboratory results have been partly validated with the neuroblastoma patient data, obtained in collaboration with the researchers at Karolinska Institutet. Thus, this study has clearly opened the way for a potential new treatment strategy for high-risk neuroblastoma patients.

Our reluctance to think, talk or communicate about death is even more pronounced when we deal with others' loss compared to our own, new research finds, but either way we tend to frame attitudes and emotions in a sad and negative way.

Teaching new more positive ways to address these difficult conversations is the focus of a new paper in PLOS ONE journal by palliative care specialists across Australia.
Led by Flinders University's Research Centre for Palliative Care, Death and Dying (RePaDD) and Palliative and Supportive Services, researchers from Flinders, CQUniversity Australia, NT Palliative Care Central Australia and University of Technology Sydney, surveyed 1,491 people about the use of language to express their feelings and insights into death and dying.

Those surveyed were enrolled in Dying2Learn, a six-week MOOC (massive open online course) course developed at Flinders University to encourage open conversation about death and dying.

Analysis of the emotional content of the words used by the group showed that by the end of the course participants were able to use "more pleasant, calmer and dominating (in-control) words to express their feelings about death", researchers conclude in PLOS ONE.

"In an ageing population, when our elders and terminally ill are often cared for by health professionals in residential care rather than in the home, we can go through life without really discussing or witnessing the end of life," says lead author Dr Lauren Miller-Lewis, Flinders University research associate and CQUniversity positive psychology lecturer.

"Tackling and changing these perspectives will help the community to plan for and manage future needs and expectations of care at end-of-life, improve patient and family care - including greater preparedness for death - and also help develop future health services.

"Words aren't neutral, so understanding the emotional connotations tied to words we use could help guide palliative care conversations," Dr Miller-Lewis says.

Dying2Learn was an innovative online course developed as part of the CareSearch project, with funding from the Australian Government. The course ran four times in 2016, 2017, 2018 and 2020.

A new interactive online resource will be released on the CareSearch website in mid-2021 using insights, feedback and suggestions from the Dying2Learn program to "help all of us be able to start and respond to conversations about death and dying with our family, our neighbours, and work colleagues" (see the webpage here).

Flinders Professor Jennifer Tieman, RePaDD Centre Director and Dying2Learn lead investigator, says the new web content will further assist community to help them feel more comfortable thinking about - and talking about - death and dying as a part of life.

Professor Tieman says further studies using sentiment analysis could provide valuable insights into the way people feel about this issue, and other topics including palliative care, advance care planning, voluntary assisted dying and COVID-19.

Co-author Flinders University Computer Scientist Dr Trent Lewis says automated sentiment or emotional analysis of the words used showed a greater benefit for younger participants of the course who showed a bigger increase in pleasantness (valence) and dominance (power or control) by the end of the course, showing the benefit of gaining insights into becoming more emotionally accepting of death.

"It shows how the general public can gain an acceptance of death as a natural part of life by learning how to openly discuss and address these feelings and attitudes," he says.

The study also found differences between how course participants described the feelings towards death and dying of other people in the community compared to their own - with 'sad', 'fear', 'scary' and 'loss' more common than their own preference for less emotionally negative words such as 'inevitable', 'peace' and 'natural'.

"The assumption was that others feel more negatively about death then they do themselves," Dr Lewis says.

"This could impact on our willingness to start conversations about death with others," adds Dr Miller-Lewis. "Do we avoid it because we think others will get upset if we bring it up, and does this then leave important things unsaid?" she asks.

Writing, driving a screw or throwing darts are only some of the activities that demand a high level of skill. How the brain masters such exquisite movements has now been described in the journal "Nature" by a team of researchers at the University of Basel and the Friedrich Miescher Institute for Biomedical Research. A map of brainstem circuits reveals which neurons control the fine motor skills of the arm and hand.

Picking up a pen and writing our name or reaching for a fork to eat spaghetti with tomato sauce are things we take for granted. However, holding a pen properly or bringing spaghetti to the mouth without making a mess requires precise arm movements and a high level of skill.

Underlying all our motor behavior is a perfect interplay between neurons in the brain, the spinal cord, and the muscles. But which neuronal circuits control the fine motor skills of the arms, hands and fingers? Prof. Silvia Arber's team has been addressing this question in recent work. The neurobiologists who work at both the Biozentrum of the University of Basel and at the Friedrich Miescher Institute for Biomedical Research (FMI) have been investigating how the nervous system controls motor behavior for many years.

Neurons in the brainstem control fine motor skills

Using a mouse model, the researchers have been able to demonstrate that a specific region of the brainstem is responsible for various fine motor activities of the forelimbs. For their investigations they applied so-called optogenetic and viral methods in order to mark neurons and observe their activity. This enabled the team to localize four neuronal subpopulations in this region and correlate with specific functions. For example, one group of neurons was able to elicit forelimb reaching, while another group controls handling of the food.

In terms of evolution, the brainstem is the oldest part of the brain and is the direct extension of the spinal cord. The brainstem is an important switchboard between higher order movement planning centers in the brain and the executive circuits in the spinal cord. In the spinal cord, information streams about movement ultimately reach motor neurons that are directly connected to muscles cells. These in turn control movement through contraction. It has only recently been discovered that the brainstem consists of many areas containing functionally specialized neuronal populations, engaged with the control of diverse forms of body movements.

Map of brainstem circuits for fine motor skills

In their study, Arber's team has defined the organization of the neurons in one of those brainstem regions called the "lateral rostral medulla» (latRM) and traced their communication pathways. This enabled the researchers to associate different behavioral activities with specific groups of latRM neurons. "Relatively simple forelimb actions such as reaching for food are accomplished by latRM neurons with direct projections to the spinal cord," explains the first author Ludwig Ruder.

Executing more complex forelimb movements, which also involve the fingers, i.e. grasping or bringing a piece of food to the mouth, are controlled by latRM neurons with connections to neurons in other brainstem regions. "The connections and circuits within the brainstem are indispensable for more complex motor skills," says Arber. "The neuronal populations we identified in the latRM very specifically control motor skills of the forelimbs. Notably, the generation of complex and precise forelimb movements such as throwing, grasping or writing require the communication between different brainstem regions."

Control of motor actions is similar in man and animals

The division of neuronal populations according to different forms of movements based on spatial organization and connectivity provides insights into the function of the brainstem and the control of motor behavior, in this case fine motor skills of the arm and hand. Many neuronal circuits of the brainstem are similar in humans and animals. It is therefore possible to hypothesize which neuronal populations control which movements or how diseases or injury may impair fine motor skills or other behaviors in humans.

The distribution and concentration of dissolved oxygen and water temperature in the oceans and freshwaters are usually far more influential in shaping the growth and reproduction of fish than the distribution of their prey.

In a new paper in Science Advances, Daniel Pauly, principal investigator of the Sea Around Us initiative at UBC's Institute for the Oceans and Fisheries, argues that scientists need to avoid attaching human attributes to fish and start looking at their unique biology and constraints through a different lens.

This lens is Pauly's own Gill Oxygen Limitation Theory (GOLT), which explains many features of fish biology and whose core principle is that as fish grow, the surface area of their gills - their respiratory organs - can't keep up with the oxygen requirement of their bodies.

The GOLT emphasizes that gills are surfaces through which water must flow - a bit like the wind through blinds. Gill surface area grows in two dimensions, that is, in length and width, but they cannot keep up with bodies that grow in three dimensions, length, width and depth. Thus, as fish get bigger, they have less gill surface area and their gills provide less oxygen per unit volume or weight.

"The problem is that many colleagues fail to understand the basic geometry of gills, and argue that, as fish grow bigger and, thus, require more oxygen, they can just grow larger gills," Pauly said. "But they can't pack their heads full of gills because, if that were to happen, water wouldn't be able to flow through."

Pauly's research indicates that the gill issue is a constraint, not something fish can evolve out of. This means that once their gills reach a point where the oxygen they supply cannot support a bigger body, they stop growing.

"This is particularly important in the context of climate change because warm waters contain less oxygen. This means that gills have less oxygen to supply to bodies that require more oxygen at higher temperatures", Pauly said, "This double whammy occurs because fish cannot maintain their body temperature constant, and higher water temperatures accelerate their metabolisms."

Higher temperatures force fish to stop growing at a smaller size, given the little oxygen available to them. This has important implications for fisheries and aquaculture.

Despite having many applications, the GOLT has been the subject of criticisms. In this new paper, Pauly responds to these challenges point by point.

"In contrast to regular scientific papers, the 'data' here are published arguments against the GOLT and their counterarguments, presented in table form. These arguments are not serious; they are more like barnacles on the hulls of a boat, which slow it down but do not sink it", Pauly said. "They are based on a lack of understanding of key geometrical and biological concepts. Thus, it was important to clear them out so that the GOLT can start to be seriously studied, and its real problems addressed."

The fact that the Gill Oxygen Limitation Theory is mainly qualitative and makes few quantitative predictions, is one of the real problems that Pauly himself has noticed and would like his colleagues to address, as well as the fact that it doesn't deal with bioenergetics and the role food plays in the life of fish.

"Food is necessary for life and the GOLT is structured around the notion that there is enough food but what if there isn't enough food? The relationships between food and oxygen will have to be studied, too," he said.

Chinese scientists from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences (CAS) have found a gene that plays an important role in helping rice adapt to low soil nitrogen.

Nitrogen fertilizer application is a strategic challenge for sustainable agriculture: On the one hand, it plays an indispensable role in increasing crop yields, thus ensuring global food security. On the other hand, it creates a severe threat to ecosystems. For this reason, breeding new crop varieties with high nitrogen use efficiency (NUE) is a high priority for both agricultural production and environmental protection.

Using a diversified rice population derived from different ecogeographical regions, the scientists carefully evaluated how various agronomic traits responded to nitrogen in fields with different nitrogen supply conditions. They further performed a genome-wide association study (GWAS). Surprisingly, only one very significant GWAS signal was identified. The detail mechanisms how OsTCP19 works in regulating rice tillering were also characterized.

More interestingly, by analyzing global soil nitrogen content data, the researchers found a strong correlation between the allelic variation of OsTCP19 and global soil nitrogen-content distribution. OsTCP19-H, the high NUE allele, was highly preserved in rice types grown in nitrogen-poor regions, but has been lost in rice types grown in nitrogen-rich regions.

Notably, OsTCP19-H is also highly prevalent in wild rice--the ancestor of modern cultivated rice--which was grown in natural soil without artificial fertilizer input. As modern rice cultivars are mainly grown with a bountiful nitrogen supply, OsTCP19-H has thus largely been lost. Therefore, breeding high-yield crops with decreased nitrogen input can be realized by bringing OsTCP19-H back to modern cultivars.

Indeed, OsTCP19-H introgression into modern cultivars can improve nitrogen use efficiency 20-30% under conditions of decreased nitrogen supply. For this reason, modern cultivated rice may be greatly improved by bringing the lost allele back through the use of poor-soil landraces that largely preserve the valuable genes of wild rice.

"This is truly groundbreaking. It will have implications not only for the basic understanding of how plants/rice works, but also has enormous implications for reducing fertilizer use," said Prof. Dale Sanders, director of the John Innes Centre in the UK.

The findings represent an important breakthrough in plant nutrition research and high NUE breeding and will greatly benefit sustainable agriculture. The work not only offers novel insights about the genetic basis for the geographic adaption of cultivated rice to soil fertility, but also gives a hint about efficiently dissecting other complex traits.

Engineers at the University of Maryland (UMD) have created a new shape-changing or "morphing" 3D printing nozzle that was featured as a Frontispiece in the January 5th issue of the journal Advanced Materials Technologies.

The team's morphing nozzle offers researchers new means for 3D printing "fiber-filled composites" - materials made up of short fibers that boost special properties over traditional 3D-printed parts, such as enhancing part strength or electrical conductivity. The challenge is that these properties are based on the directions or "orientations" of the short fibers, which has been difficult to control during the 3D printing process, until now.

"When 3D printing with the morphing nozzle, the power lies on their side actuators, which can be inflated like a balloon to change the shape of the nozzle, and in turn, the orientations of the fibers," said Ryan Sochol, an assistant professor in mechanical engineering and director of the Bioinspired Advanced Manufacturing (BAM) Laboratory at UMD's A. James Clark School of Engineering.

To demonstrate their new approach, the researchers set their sights on emerging "4D printing" applications. "4D printing refers to the relatively new concept of 3D printing objects that can reshape or transform depending on their environment," said UMD mechanical engineering professor David Bigio, a co-author of the study. "In our work, we looked at how printed parts swelled when submerged in water, and specifically, if we could alter that swelling behavior using our morphing nozzle."

Recent advances in 4D printing rely on materials capable of both "anisotropic" expansion, swelling more in one direction than another, as well as "isotropic" expansion, swelling identically in all directions. Unfortunately, switching between these conditions has typically required researchers to print with multiple, different materials.

"What was exciting was discovering that we could cause a single printed material to transition between anisotropic and isotropic swelling just by changing the nozzle's shape during the 3D printing process," said Connor Armstrong, lead author of the study. Armstrong developed the approach as part of his MS thesis research at UMD.

"Importantly, the nozzle's ability to morph and to even up the score in terms of swelling properties is not limited to 4D printing," said study co-author and recently graduated mechanical engineering undergraduate student Noah Todd. "Our approach could be applied for 3D printing many other composite materials to customize their elastic, thermal, magnetic or electrical properties for example."

Interestingly, to build the morphing nozzle itself, the team actually turned to a different 3D printing technology called "PolyJet Printing." This multi-material inkjet-based approach offered by UMD's Terrapin Works 3D Printing Hub allowed the researchers to 3D print their nozzle with flexible materials for the inflatable side actuators and the shape-changing central channel, but then rigid materials for the outer casing and the access ports.

"The use of multi-material PolyJet 3D printing enabled us to design the nozzle with an operating power range or set of pressure magnitudes that can be reproduced in essentially any research laboratory," said study co-author and mechanical engineering PhD candidate Abdullah Alsharhan.

In one application of this new approach, the team is exploring the use of their strategy to realize biomedical applications in which bulk printed objects could reshape in the presence of particular stimuli from the body. The team is also in discussions with several DoD laboratories to use the morphing nozzle to support the production of weapons for defense and other military systems.

"By providing researchers with an accessible way to 3D print fiber-filled composite materials with on-demand control of their fiber orientations, and thus, their ultimate performance," Sochol said, "this work opens the door for new applications of 3D printing that harness these unique material properties and the distinctive capabilities they enable."

A microbe found in the colon and commonly associated with the development of colitis and colon cancer also may play a role in the development of some breast cancers, according to new research from investigators with the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy. Breast tissue cells exposed to this toxin retain a long-term memory, increasing the risk for disease.

In a series of laboratory experiments, researchers discovered that when enterotoxigenic Bacteroides fragilis (ETBF) was introduced to the guts or breast ducts of mice, it always induced growth and metastatic progression of tumor cells. A description of the work is published in the January 6 issue of the journal Cancer Discovery.

While microbes are known to be present in body sites such as the gastrointestinal tract, nasal passages and skin, breast tissue was considered sterile until recently, says senior study author Dipali Sharma, Ph.D., a professor of oncology at Johns Hopkins Medicine.

The study is a first step to show the involvement of ETBF in breast cancer development, Sharma says. Additional studies are needed to clarify how ETBF moves throughout the body, whether ETBF can be a sole driver to directly trigger the transformation of breast cells in humans, and/or if other microbiota also have cancer-causing activity for breast tissue.

"Despite multiple established risk factors for breast cancer, such as age, genetic changes, radiation therapy and family history, a large number of breast cancers arise in women harboring none of these, indicating the need to look beyond," Sharma says. "Our study suggests another risk factor, which is the microbiome. If your microbiome is perturbed, or if you harbor toxigenic microbes with oncogenic function, that could be considered an additional risk factor for breast cancer."

Sharma and colleagues performed several experiments to study the role of ETBF. First, they performed a meta-analysis of clinical data looking at published studies comparing microbial composition among benign and malignant breast tumors and nipple aspirate fluids of breast cancer survivors and healthy volunteers. B. fragilis was consistently detected in all breast tissue samples as well as the nipple fluids of cancer survivors.

In the lab, the team gave the ETBF bacteria by mouth to a group of mice. First, it colonized the gut. Then, within three weeks, the mouse mammary tissue had observable changes usually present in ductal hyperplasia, a precancerous condition. In additional tests, investigators found that hyperplasia-like symptoms also appeared within two to three weeks of injecting ETBF bacteria directly to the teats of mice, and that cells exposed to the toxin always exhibited more rapid tumor progression and developed more aggressive tumors than cells not exposed to the toxin. Breast cells exposed to the toxin for 72 hours retained a memory of the toxin and were able to start cancer development and form metastatic lesions in different mouse models. Investigators also found the Notch1 and beta-catenin cell signaling pathways to be involved in promoting EBFT's role in breast tissue.

In clinical studies, the investigators have started looking for microbiome changes among breast cancer patients to see how this impacts tumor progression and response to therapy. Meanwhile, Sharma says, "we definitely should try to maintain a healthy microbiome, including eating a healthy diet and exercising, and maintaining the correct body mass index."

Down the road, screening for microbiome changes could be as simple as stool sample tests, said lead author Sheetal Parida, a postdoctoral fellow at Johns Hopkins Medicine. "This is just one indicator, and we think there will be multiple," she said. "If we find additional bacteria responsible for cancer development, we can easily look at the stool and check for those. Women at high risk of developing breast cancer might have a high population of some of these."

Post-traumatic stress disorder, or PTSD, affects many people who are exposed to extreme situations, such as torture. Recent research suggests that chronic pain may make it more difficult to treat trauma.

"Trauma-focused therapy is effective for many patients with PTSD, enabling them to talk through the trauma they experienced", according to Iselin Solerød Dibaj, a psychologist at Oslo University Hospital.

However, not everyone benefits equally from this form of therapy.

"Torture victims who struggle with both chronic pain and PTSD unfortunately often reap less benefit from ordinary treatment," says Dibaj.

The Red Cross estimates that between 10 000 and 35 000 people with a refugee background who have come to Norway have experienced torture, reflecting the great need for effective treatment in this country as well.

"Torture is one of the most extreme abuses a person can experience. Physical and mental pain is inflicted with the intention of breaking a person down or obtaining information," says Håkon Stenmark, a specialist in clinical psychology at RVTS Midt, a regional resource centre for violence, traumatic stress and suicide prevention in central Norway.

"Mental health therapists find it difficult to provide effective help to victims of torture. They are pushing to increase their knowledge and find more effective methods," says Stenmark.

Now Dibaj and Stenmark, along with Professor Leif Edward Ottesen Kennair and Joar Øveraas Halvorsen, a specialist in clinical psychology and PhD  at the Regional Unit for Trauma Treatment at St. Olavs Hospital, have published an article in the journal Torture about treating this patient group.

Professor Kennair, from the Norwegian University of Science and Technology, has been a supervisor and the driving force behind the research project that might lead to better treatment of torture victims.

"Exposure therapy" involves delving into patients' memories and trying to talk through the trauma.

"But trauma-focused treatment for torture victims has been criticized in several clinical and academic settings for being too concerned with the traumas and not taking context into account, such as social, political and historical factors," says Dibaj.

Dibaj says they understand this criticism, at the same time as they do not want to write off a trauma treatment for this group that has documented effectiveness in other patient groups.

Other trauma-exposed groups in recent years have shown evidence that chronic pain and PTSD mutually contribute to reinforcing the other condition. One disorder can trigger the other, ensuring that neither disappears.

"So people with both disorders have worse treatment results with both the trauma condition and the chronic pain than if they only had one disorder," says Kennair.

Having both disorders also brings with it a number of additional challenges that therapists do not address specifically and purposefully in either trauma treatment or pain treatment.

"So we're questioning whether these factors are partly to blame for the trauma treatment being less effective for victims of torture," Kennair says.

Effective trauma treatment is largely about experiencing mastery and learning new ways to deal with painful memories.

"But if the patient experiences unmanageable pain, without the tools to deal with it, he or she risks not having this experience. The patient might then drop out or not be willing to delve into the memories," says Dibaj.

In the same way, pain treatment with the physiotherapist rarely works directly with trauma memories. Thus, this therapy can fall into the same trap - that the patient doesn't dare to do the rehabilitative exercises for fear of re-experiencing the trauma.

"We're criticizing the current 'gold standard trauma therapies' for not working purposefully and specifically enough with important maintenance mechanisms for patients who have both pain and PTSD," says Dibaj.

But these patients might actually achieve better outcomes if the therapists worked with the pain and trauma simultaneously.

"In other words, psychologists and physiotherapists should collaborate more in treating these patients," Dibaj says.

"We also have to remember that torture is such an extreme and unique experience that we can't just conclude that the pain problems in these patients are the same as we see in other patients with the same problem," says Dibaj.

Norway has ratified the UN Convention against Torture. It states that people who have been subjected to torture have the right to rehabilitation. In a report from earlier this year, the Red Cross found the services offered to torture victims in Norway to be fragmented and highly person-dependent.

"At the same time, those of us working in the health care services are obliged to offer evidence-based treatment and equal health services," says Halvorsen.

This means that patients with PTSD need to be offered the form of treatment that currently seems to have the best documented effect. This guideline applies regardless of background. The treatment has to be adapted to each individual patient.

"International guidelines for the rehabilitation of torture victims recommend interdisciplinary, specialized follow-up of these patients. However, studies show that even patients who receive such multi-faceted treatment experience only modest effects. We simply need to gain more knowledge about how we can help this group," says Dibaj.

"We've been pointing out that Norway lacks specialized rehabilitation services for victims of torture for a long time. But since we still have limited knowledge of what characterizes effective rehabilitation for this group, funding and implementing clinical studies need to become an integral part of a specialized rehabilitation programme," Halvorsen says.

But why do some people suffer from PTSD?

"From an evolutionary perspective, we can understand the function of both pain and anxiety. These are alarm systems that signal us that something could potentially pose a danger to us. These signals cause us to avoid that situation. This can be adaptive in the short term, so that we steer clear of potential harm," says Dibaj.

With PTSD and/or chronic pain, our alarm system is overactive and fires a series of false alarms about danger.

Avoidance normally decreases when the acute danger is over, but with PTSD and/or chronic pain, our alarm system is overactive and fires a series of false alarms about danger.

"If we respond to these alarms as a real danger and avoid what's triggering the alarm, we risk making the alarm system more sensitive," Dibaj says.

"Research indicates that post-traumatic cognitions or thoughts - that is, thoughts that come up after experiencing a trauma - play an important role in developing and prolonging post-traumatic distress. Examples of this kind of post-traumatic cognition might be, 'The world is a dangerous place' or 'I'm a broken person,'" says Halvorsen.

Both PTSD and chronic pain are characterized by numerous such false alarms. The affected person might have flashbacks, for example, where something dangerous from the past is perceived as dangerous now. Victims can also experience pain signals without connecting them to something actually being wrong in their body.

"Torture is designed to create this form of distress and, especially in recent times, to create pain that doesn't result in visible scars," says Dibaj.

Many victims of torture experience that completely normal movements trigger their alarm system. This naturally leads to less physical activity and also makes a lot of people afraid to move. This condition is called kinesiophobia, when normal activities can lead to severe pain and re-experiencing the trauma.

"When patients develop a fear of completely normal movements, it's difficult to do physiotherapy or other things that could help them get better - and that's why we think that kinesiophobia contributes to reinforcing the ailments. But this is something we rarely focus on in ordinary trauma treatment. Therapists therefore need to broaden their understanding of these connections," says Stenmark.

Starting as a single cell, organisms undergo millions of generations of divisions to ultimately generate the bones, heart, brain and other components that make up a living being. The mainspring within this intricate process is the transfer of DNA through each subsequent cell split within discrete packets called chromosomes.

It's critical that all chromosomes are duplicated and precisely distributed through every generation of cell division. If the inherited chromosome components are altered, even slightly, birth defects and certain cancers can result.

A new study published in the journal Science by postdoctoral scholar Pablo Lara-Gonzalez, Division of Biological Sciences Professor Arshad Desai and their colleagues addresses the mystery of how chromosomes are inherited correctly every time a cell divides. Using a novel probe that monitors a key aspect of this process, Lara-Gonzalez and Desai have detailed the mechanics behind a "wait" signal that ensures that cell division isn't prematurely set in motion.

The researchers concentrated their investigations on a pathway in the cell called the "spindle checkpoint," which is a type of quality control mechanism that ensures accurate chromosome inheritance during cell division. The spindle checkpoint pathway is activated at a site on the chromosome called the kinetochore, a mechanical interface where protein fibers are coupled to pull chromosomes apart.

"When kinetochores are not attached to these protein fibers, they send out a 'wait' signal that halts the cell in mitosis (cell division), thereby giving time for attachments to be formed," said Desai, a professor in the Section of Cell and Developmental Biology (Biological Sciences) and the Department of Cellular and Molecular Medicine (School of Medicine). "In this way, the cell makes sure all chromosomes are attached properly and ready to be pulled apart before the cell divides, thereby leaving no chromosome behind."

In the Science paper, the researchers describe how the wait checkpoint signal is specifically generated at kinetochores of unattached chromosomes. Serendipitously, they developed a fluorescent probe that enabled them to watch for the first time the key molecular event in wait signal generation at kinetochores in living cells.

"This work identified a key 'matchmaker' molecule that brings together two constituents of the wait signal that do not like to associate with each other on their own," said Lara-Gonzalez. "These findings help explain why the 'wait' checkpoint signal is selectively generated at kinetochores and not elsewhere in the cell."

The findings offer a framework for ways in which the accuracy of chromosome inheritance can be lowered in certain states of disease, such as cancer, the researchers said.

The pandemic has exacerbated isolation and fears for one very vulnerable group of Americans: the 4.3 million older adults with cognitive impairment who live alone.

As the coronavirus continues to claim more lives and upend others, researchers led by UC San Francisco are calling for tailored services and support for older adults living alone with memory issues, who are experiencing extreme isolation, and are exposed to misinformation about the virus and barriers to accessing medical care.

In their qualitative study, researchers interviewed 24 San Francisco Bay Area residents whose average age was 82. Of these, 17 were women, and 13 were either monolingual Spanish-speakers or Cantonese speakers; 18 were widowed or divorced; 10 depended only on the in-person care of their family, eight only on in-person home care aides and six on both family and aides. Findings appear in The Gerontologist on Jan. 6, 2021.

Among the most extreme emotions expressed was a desire by a few participants for the coronavirus to take their own lives "so that they could finally end their struggles." One participant said they were "fed up with the life that I have been given" and a second, who was struggling with an Alzheimer's disease diagnosis, said that they would welcome the virus as "an escape plan."

"One-third of those with cognitive impairment live alone. This is a demographic at high risk for loneliness and distress, as well as negative health outcomes, even before the pandemic," said first author Elena Portacolone, PhD, MBA, MPH, of the UCSF Institute for Health & Aging. "Public health recommendations that mitigate the spread of COVID-19, including shelter-in-place and physical distancing, reduce access to those amenities that had offered support to isolated older adults."

Some of the study participants lived in cramped or inhospitable accommodation and reported that they felt "trapped in their own homes." Most participants were no longer able to seek companionship at church services, senior centers, restaurants or to interact with neighbors.

"I was most concerned by participants' extreme isolation," said Portacolone. "Some participants were particularly distressed, two of them had had suicidal ideation before the pandemic, yet they received little or no support for their mental health."

For Some, Long Lines Trigger Memories of War, Famine

Because the participants lived alone, they faced their fears alone. Some were afraid of dying of the virus, despite limited contact with the outside world, and some shared that long lines outside grocery stores reminded them of past experiences of war or famine. Others worried about racial attacks and rioting that had followed the death of George Floyd.

Misinformation about the virus was apparent in many interviews. One participant learned from WhatsApp, the messaging app, that gargling with salt water would treat the virus; another said that a doctor on TV had dissuaded them from getting the vaccine. Other participants claimed that going out without a face covering would result in a $400 fine or jail time.

Many participants struggled with gaining access to their medical provider. Some were concerned that entering a clinic would put them at risk for COVID-19, while one participant with diabetes expressed frustration with the phone appointment that was offered, since "I don't even answer my phone ... (and) I have a poor mind." Another participant said that it had taken them three or four months to make an appointment with their eye doctor after they were told that services were not available.

While the participants who had family support reported less distress, home care aides were recognized as providing companionship, as well as assistance with meal preparation and chores. But unlike other Western countries, the United States only covers the cost of home care aides for those with medical needs on very low incomes, Portacolone noted.

"Well-trained and state-subsidized home care aides are the life blood in the support system for older adults with cognitive impairment living alone. The regular presence of someone reliable to ask questions, receive nudges and instrumental support, as well as company, is invaluable."

The home care aides should be integral to a "therapeutic alliance" that offers tailored services and support from social workers, case managers and mental health services if required, she said.

"These services are critical for maintaining the health and wellbeing of older adults living alone with cognitive impairment," said senior author Julene K. Johnson, PhD, of the UCSF Institute for Health & Aging and the Center for Aging in Diverse Communities. "More robust financial support of home care aides is needed."

A recent study published in Acta Obstetricia et Gynecologica Scandinavica found that sons born to mothers who fell within the overweight range were more likely to be diagnosed with infertility during adulthood than sons of mothers with normal-range weight. No association between maternal weight and infertility was seen in daughters.

In the Danish study of 9,232 adult sons and daughters, 9.4% of participants were infertile. The authors adjusted for several potential confounding factors and found that sons whose mothers had a body mass index over 25 kg/m2 before pregnancy had 1.4-times higher odds of infertility than sons whose mothers had a body mass index of 18.5 to 24.9 kg/m2.

Approximately 12.5% of couples are affected by infertility, which is often defined as unsuccessfully attempting to conceive for a year or longer. Overall, one-third of couples' infertility cases are caused by male reproductive issues, one-third by female reproductive issues, and one-third is either a combination or due to unknown factors.

"Infertility is a global public health issue, and it is important that research focus on addressing risk factors," said lead author Linn Arendt, MD, PhD, a postdoc at Aarhus University and Aarhus University Hospital. "We know that children born to mothers in the overweight or obesity weight range face higher risks of several adverse outcomes, both in the short and long term. These findings add to evidence that weight during pregnancy may also affect male future reproductive health; however, the findings need to be corroborated in future studies."

Separating infants and their mothers after a Caesarean section delivery is common. A new study published in Acta Paediatrica has found that providing skin-to-skin contact with the father may provide benefits to a newborn.

In the study, 95 newborns were randomized to cot, father's arms, or skin-to-skin contact with the father after Caesarean section delivery. Heart rates were higher and showed more stability over time in the skin-to-skin than cot or fathers' arms groups. Wakefulness was also initially higher in the skin-to-skin group.

"The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation," the authors wrote.

Tsukuba, Japan - Does losing weight while you sleep sound too good to be true? According to a study by the University of Tsukuba, it seems that drinking oolong tea might help you do just that.

While all tea comes from the same plant, Camellia sinensis, the degree of oxidation, a chemical reaction that turns tea leaves black, defines its specific type. For example, green tea is unoxidized and mild in flavor, while the distinctive color of black tea comes from complete oxidation. Oolong tea, being only partially oxidized, lies somewhere in between and displays characteristics of both green and black tea. But while green tea is lauded for its health benefits, oolong tea remains more of an unknown.

"Like all teas, oolong contains caffeine, which impacts energy metabolism by increasing our heart rate. However, studies suggest that tea consumption may also increase the breakdown of fat, independent of the effects of caffeine," explains senior author of the study Professor Kumpei Tokuyama. "We therefore wanted to examine the effects of oolong consumption versus caffeine alone on energy and fat metabolism among a group of healthy volunteers."

Publishing their results in a recent issue of the journal Nutrients, the researchers found that both oolong tea and pure caffeine increased fat breakdown by about 20% in the healthy volunteers compared with the placebo, and that oolong tea continued to have an effect while the participants were asleep. Interestingly, neither treatment caused an increase in energy expenditure, indicating that the volunteers developed a tolerance to the stimulatory effects of caffeine over the 2-week study period.

Because a lack of sleep can impact energy metabolism, and because caffeine is known to inhibit sleep, the researchers also studied the sleep patterns of the volunteers. Significantly, there was no noticeable difference in sleep patterns or the time it took participants to fall asleep between the treatment and placebo groups, indicating that drinking oolong tea is unlikely to prevent you from getting a good night's rest.

So should we all be downing copious cups of oolong tea to counteract the indulgences of the festive season?

According to Professor Tokuyama, the answer is maybe.

"The stimulatory effects of oolong tea on fat breakdown during sleep could have real clinical relevance for controlling body weight. However, we need to determine whether the effects we observed in the 2-week study translate into actual body fat loss over a prolonged period. In addition, we want to trial a decaffeinated oolong tea to better distinguish the effects of caffeine from other components of tea, which will help us understand exactly how oolong helps with fat breakdown."

El Niño events have long been perceived as a driver for low rainfall in the winter and spring in Hawai'i, creating a six-month wet-season drought. However, a recent study by researchers in the University of Hawai'i at Mānoa School of Ocean and Earth Science and Technology (SOEST) revealed the connection between Hawai'i winter rainfall and El Niño is not as straightforward as previously thought.

Studies in the past decade suggested that there are at least two types of El Niño: the Eastern Pacific and Central Pacific, when the warmest pool of water is located in the eastern or central portions of the ocean basin, respectively. El Niño events usually begin in summer and last for about one year.

The UH Mānoa team of atmospheric scientists analyzed data on the large-scale circulation patterns over the eastern and central Pacific to find that Hawai'i drought is only associated with the Eastern Pacific El Niño. For the central Pacific El Niño events, deficient rainfall in Hawaii occurred only 60% of the time. Therefore, a winter drought is not guaranteed following a Central Pacific El Niño.

The differences in how the Eastern and Central Pacific El Niño affect rainfall can be critical for proper planning and water resource management.

"This new result is a boon for many agencies in Hawai'i, for example, the Board of Water Supply, Hawai'i Department of Land and Natural Resources, and Hawai'i Department of Agriculture," said Pao-Shin Chu, SOEST professor, Hawai'i State Climatologist and co-author of the study. "Beyond these agencies, ranchers, flower growers, and other stakeholders that are concerned with the relationship between El Niño and water supply in Hawai'i may also benefit from the new findings."

Given that El Niño is a recurring phenomenon, knowing the type of El Niño that occurs will allow researchers and resource managers to more easily evaluate and prepare for Hawaiian regional climate in winter.

The team continues their research to explore other large-scale climate factors dominating the Hawaiian regional climate and affecting trade winds and rainfall patterns.

This study was also co-authored by SOEST atmospheric scientists Bo-Yi Lu, doctoral candidate and lead author; postdoctoral researcher Sung-Hun Kim; and associate professor Christina Karamperidou.

Most forms of life -- species of mammals, birds, plants, reptiles, amphibians, etc. -- are most diverse at Earth's equator and least diverse at the poles. This distribution is called the latitudinal gradient of biodiversity.

A group of Santa Fe Institute collaborators was intrigued by the fact that human cultural diversity shows exactly the same distribution with latitude: human cultures are more diverse near the equator and least at the poles. Their big question was: why? Life is more diverse within richer environments, but it's not clear why human cultural diversity would show this pattern too.

To find answers, the group conducted a biogeographic and macroecological study of the distribution of mammal species diversity and human ethnolinguistic diversity around the world.

In Scientific Reports, they share their study and a novel sampling method developed to explore biodiversity.

One of the authors, Marcus Hamilton, an associate professor of data analytics in the Department of Anthropology at the University of Texas at San Antonio and a former SFI postdoc, is interested in human cultural diversity and its distribution around the planet. He's particularly curious about the ways humans and their cultures are both similar and different to other forms of biodiversity.

"Some aspects of human systems are very predictable for a mammal and others are seemingly novel," Hamilton says.

So the group decided to explore the link between mammals and languages. "The most interesting finding here is that both mammal diversity and human linguistic diversity increase faster than you would expect with environmental richness in exactly the same way," says Hamilton.

In other words, parts of the planet that are diverse biologically and culturally are even more diverse than you'd expect. This led to the title of their article: "Diversity begets diversity."

The group developed a theory to show that this is because not only can richer environments hold more species but richer environments are also more interactive, so there are more niches available, more competition, cooperation, mutualisms, etc. Because richer environments are also more complex environments, you tend to find more species and languages.

"One of the things I find most interesting in our study is that diversity cannot simply be explained from the total amount of living matter that an ecosystem supports," says SFI Professor Chris Kempes, a co-author of the article. "When we control for the amount of biomass within an environment we still see that diversity depends on 'kinetics,' the rate of interaction. This tells us that part of the diversity story emerges from the interaction amongst things and how often they interact, and generalizes distinct examples of species diversity and human cultures."

It also provides insight into the relationship between complexity and diversity, which is central to complex systems.

"Our study is important to understanding why some parts of the planet are more culturally diverse than others," says Hamilton. "It could also be very important for understanding links between the rapid loss of biodiversity and cultural diversity."

Both biological species and human languages are going extinct at an alarming rate, and this study suggests there's a fundamental link between the two.