Culture

PITTSBURGH--The science community has responded to the COVID-19 pandemic with such a flurry of research studies that it is hard for anyone to digest them all, underscoring a long-standing need to make scientific publication more accessible, transparent and accountable, two artificial intelligence experts assert in a data science journal.

The rush to publish results has resulted in missteps, say Ganesh Mani, an investor, technology entrepreneur and adjunct faculty member in Carnegie Mellon University's Institute for Software Research, and Tom Hope, a post-doctoral researcher at the Allen Institute for AI. In an opinion article in today's issue of the journal Patterns, they argue that new policies and technologies are needed to ensure relevant, reliable information is properly recognized.

Those potential solutions include ways to combine human expertise with AI as one way to keep pace with a knowledge base that is expanding geometrically. AI might be used to summarize and collect research on a topic, while humans serve to curate the findings, for instance.

"Given the ever-increasing research volume, it will be hard for humans alone to keep pace," they write.

In the case of COVID-19 and other new diseases, "you have a tendency to rush things because the clinicians are asking for guidance in treating their patients," Mani said. Scientists certainly have responded - by mid-August, more than 8,000 preprints of scientific papers related to the novel coronavirus had been posted in online medical, biology and chemistry archives. Even more papers had been posted on such topics as quarantine-induced depression and the impact on climate change from decreased transportation emissions.

At the same time, the average time to perform peer review and publish new articles has shrunk; in the case of virology, the average dropped from 117 to 60 days.

This surge of information is what the World Health Organization calls an "infodemic" - an overabundance of information, ranging from accurate to demonstrably false. Not surprisingly, problems such as the hydroxycholoroquine controversy have erupted as research has been rushed to publication and subsequently withdrawn.

"We're going to have that same conversation with vaccines," Mani predicted. "We're going to have a lot of debates."

Problems in scientific publication are nothing new, he said. As a grad student 30 years ago, he proposed an electronic archive for scientific literature that would better organize research and make it easier to find relevant information. Many ideas continue to circulate about how to improve scientific review and publication, but COVID-19 has exacerbated the situation.

Some of the speed bumps and guard rails that Mani and Hope propose are new policies. For instance, scientists usually emphasize experiments and therapies that work; highlighting negative results, on the other hand, is important for clinicians and discourages other scientists from going down the same blind alleys. Identifying the best reviewers, sharing review comments and linking papers to related papers, retraction sites or legal rulings are among other ideas they explore.

Greater use of AI to digest and consolidate research is a major focus. Previous attempts to use AI to do so have failed in part because of the often figurative and sometimes ambiguous language used by humans, Mani noted. It may be necessary to write two versions of research papers - one written in a way that draws the attention of people and another written in a boring, uniform style that is more understandable to machines.

Mani said he and Hope have no illusions that their paper will settle the debate about improving scientific literature, but hope that it will spur changes in time for the next global crisis.

"Putting such infrastructure in place will help society with the next strategic surprise or grand challenge, which is likely to be equally, if not more, knowledge intensive," they concluded.

What The Study Did: Psychological symptoms, nonsuicidal self-injury and suicidal ideation, plans, and attempts among children and adolescents were investigated in this observational study before the COVID-19 outbreak started (early November 2019) and two weeks after school reopening (mid-May 2020) in an area of China with low risk of COVID-19.

Authors: Ying Sun, M.D., of Anhui Medical University in the Anhui province of China, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.21482)

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

What The Study Did: This observational study investigated demographic and military service characteristics associated with suicide risk among U.S. veterans after the transition from active military service to civilian life.

Authors: Mark A. Reger, Ph.D., of the Veterans Affairs Puget Sound Health Care System in Seattle, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.16261)

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

What The Study Did: Researchers compared changes from 2000 to 2017 in premature deaths in the U.S. due to drug poisonings, suicide and alcohol-induced causes by geographic areas and demographic characteristics.

Authors: Meredith S. Shiels, Ph.D., of the National Cancer Institute in Rockville, Maryland, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.16217)

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

Clinical studies have found that bone mineral density in patients with anxiety or depression is lower than in ordinary people.

The brain, commander of the body, receives and processes external signals, and then sends instructions to peripheral bones. But how does anxiety induce a decline in bone mineral density?

Researchers from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences and their collaborators now have an answer. They found that a central neural circuit from the forebrain to the hypothalamus mediates chronic stress-induced bone loss via the peripheral sympathetic nervous system.

Their study was published in the Journal of Clinical Investigation on September 10.

The researchers found that isolation can significantly increase anxiety levels, thus inducing bone loss in human subjects.

Biochemical analysis showed that prolonged isolation increases the concentration of norepinephrine and decreases osteogenic markers in serum. These changes were consistent with the observation of elevated anxiety and reduced bone formation in subjects.

In order to identify the neural mechanism underlying chronic stress-induced bone loss, the research team used a mouse model where mice were subjected to unpredictable chronic mild stress.

They found that after four to eight weeks of chronic stress, the mice displayed significant anxiety behaviors. The bone mineral density of the mice in the stress group was significantly lower than in the control group.

These results confirmed the correlation between stress-induced anxiety and bone loss in experimental animals, and provided a good animal model for follow-up neural mechanism analysis.

Through extensive experiments, researchers identified a population of inhibitory neurons expressing somatostatin in the brain nucleus that are known as the bed nucleus of the stria terminalis (BNST) in the forebrain. These neurons were activated when animals showed anxiety behaviors and transmitted "anxiety" information to the neurons in the ventromedial hypothalamus (VMH).

"Activating the BNST-VMH neural circuit can simultaneously induce anxiety-like behaviors and generate bone loss in the mice, whereas inhibition of this circuit can prevent stress-induced anxiety and bone loss at the same time," said Prof. YANG Fan from SIAT, the co-first and co-corresponding author of the study.

Furthermore, the researchers discovered that glutamatergic neurons in nucleus tractus solitaries (NTS) and the sympathetic system were employed to regulate stress-induced bone loss.

"This study provides a new perspective for the systematic study of the regulatory mechanism of brain homeostasis on metabolism and endocrine function of the body in special environments," said Prof. WANG Liping, Director of the Brain Cognition and Brain Disease Institute of SIAT.

Researchers working on the Seeds of Discovery (SeeD) initiative, which aims to facilitate the effective use of genetic diversity of maize and wheat, have genetically characterized 79,191 samples of wheat from the germplasm banks of the International Maize and Wheat Improvement Center (CIMMYT) and the International Center for Agricultural Research in the Dry Areas (ICARDA).

The findings of the study published today in Nature Communications are described as "a massive-scale genotyping and diversity analysis" of the two types of wheat grown globally -- bread and pasta wheat -- and of 27 known wild species.

Wheat is the most widely grown crop globally, with an annual production exceeding 600 million tons. Approximately 95% of the grain produced corresponds to bread wheat and the remaining 5% to durum or pasta wheat.

The main objective of the study was to characterize the genetic diversity of CIMMYT and ICARDA's internationally available collections, which are considered the largest in the world. The researchers aimed to understand this diversity by mapping genetic variants to identify useful genes for wheat breeding.

From germplasm bank to breadbasket

The results show distinct biological groupings within bread wheats and suggest that a large proportion of the genetic diversity present in landraces has not been used to develop new high-yielding, resilient and nutritious varieties.

"The analysis of the bread wheat accessions reveals that relatively little of the diversity available in the landraces has been used in modern breeding, and this offers an opportunity to find untapped valuable variation for the development of new varieties from these landraces", said Carolina Sansaloni, high-throughput genotyping and sequencing specialist at CIMMYT, who led the research team.

The study also found that the genetic diversity of pasta wheat is better represented in the modern varieties, with the exception of a subgroup of samples from Ethiopia.

The researchers mapped the genomic data obtained from the genotyping of the wheat samples to pinpoint the physical and genetic positions of molecular markers associated with characteristics that are present in both types of wheat and in the crop's wild relatives.

According to Sansaloni, on average, 72% of the markers obtained are uniquely placed on three molecular reference maps and around half of these are in interesting regions with genes that control specific characteristics of value to breeders, farmers and consumers, such as heat and drought tolerance, yield potential and protein content.

Open access

The data, analysis and visualization tools of the study are freely available to the scientific community for advancing wheat research and breeding worldwide.

"These resources should be useful in gene discovery, cloning, marker development, genomic prediction or selection, marker-assisted selection, genome wide association studies and other applications," Sansaloni said.

In a new study in Cell Discovery, Liang Li and Chen-Yu Zhang group at Nanjing University and two other groups report that SIDT1 polymorphism remarkably decreases HD-MIR2911 absorption in human. Exosome isolated from volunteers that carry SIDT1 polymorphism has lower level of HD-MIR2911 and fails to inhibit of SARS-CoV-2 replication.

Previously, Chen-Yu Zhang's group have identified SID1 transmembrane family member 1 (SIDT1) as a critical membrane protein mediating dietary miRNAs absorption, which is abolished in SIDT1 deficient mice. In the present study, they demonstrate a significant frequency of human population (16%) that carry a SIDT1 polymorphism with amino acid replacement (Val78Met). Functional analysis reveals that such polymorphism (SIDT1poly) undermines its low pH-dependent uptake of exogenous miRNAs in vitro compared to wildtype SIDT1 protein. Additionally, people with SIDT1poly have lower serum levels of exogenous miRNAs (~10%) compared to SIDT1wt group. Dynamic absorption of MIR2911 after oral administration of honeysuckle decoction also significantly declines in SIDT1poly population. These findings suggest the critical role of SIDT1 in dietary miRNAs uptake in human. Furthermore, people with SIDT1poly have lower level of MIR2911 both in serum and isolated exosomes. The exosome from those polymorphic subjects show no effects on S-protein expression or virus replication. Notably, one out of six SARS-CoV-2 patients we observed who takes significantly longer time (17 days versus average 3.8 days) to become SARS-CoV-2 PCR-negative after MIR2911 antiviral therapy carries the exact polymorphism (SIDT1-Val78Met). Although it needs larger number of human subjects to strengthen the conclusions, it clearly shows that MIR2911 is indispensable to the antiviral effect of honeysuckle decoction.

1. This study provides evidence that SIDT1 medias dietary miRNAs uptake in human, which further confirm its critical role in exogenous miRNAs absorption.

2. Combined with their previous finding, it is clearly showed that MIR2911 is both necessary and sufficient to the antiviral effects of honeysuckle decoction against SARS-CoV-2.

"We have demonstrated that absorbed MIR2911 in honeysuckle decoction necessarily and sufficiently inhibits SARS-CoV-2 replication in vitro and in human subjects". Liang Li said. "Therefore, we wish that people could discard prejudice to traditional medicine and perform clinic trail to help controlling COVID-19 pandemic. Basically, you reject MIR2911 in honeysuckle decoction, you reject life". Liang Li added.

For anisotropic crystals, it has been known for many years that the birefringence effect rising from anisotropic refractive index should be considered for angle-resolved polarized Raman (ARPR) intensity. For opaque anisotropic crystals (OAC), not only the birefringence effect but also the dichroism effect from anisotropic absorption is responsible for ARPR intensity. With boomed emergence of in-plane anisotropic layered materials (ALMs), e.g., black phosphorus (BP), the investigations of their ARPR intensity have received great attention, which are commonly fitted by its Raman tensor and polarization of incident laser and scattered signal outside the crystals with a fitted complex Raman tensor due to dichroism or a fitted birefringence-induced phase delay. However, these approaches cannot be applicable to the case of ARPR intensity at oblique laser incidence because of the complex depth-dependent polarization and intensity of incident laser and scattered signal inside ALMs, and additional angle-dependent reflection and refraction at the interface between ALM lakes and air. Fundamentally, only real Raman tensor is generally involved if no magnetic perturbation occurs. Thus, this leaves an open question whether it is possible to reproduce ARPR intensity of OAC by only the real Raman tensor, especially for emergent ALMs.

Recently, a research team led by Prof. Ping-Heng Tan from Institute of Semiconductors, Chinese Academy of Sciences proposed a so-called birefringence-linear-dichroism (BLD) model to quantitively understand the ARPR intensity at both normal and oblique laser incidences on in-plane ALMs, by taking the bulk black phosphorus (BP) as an example. The depth-dependent polarization and intensity of incident laser and scattered signal induced by birefringence and linear dichroism are considered by complex refractive indexes along three principle axes, which is experimentally determined by the incident-angle resolved reflectivity. The experimental ARPR intensity can be well reproduced by the same set of real Raman tensors for a certain laser excitation, which are obtained from the relative Raman intensity along its principle axes. No fitting parameter is needed.

Fig.1 shows the setup for ARPR measurements at laser normal incidence and the corresponding ARPR intensity excited by 488 nm and 532 nm lasers. The good agreement between the calculated results (solid lines) experimental data (open circles) indicates that the ARPR intensity in ALMs can be quantitatively understand by the real Raman tensor once the birefringence and linear dichroism effects are considered based on the BLD model. In Fig.2, the ARPR intensity at oblique laser incidence can also be well reproduced by the same set of Raman tensors without any fitting parameters, which implies that the BLD model is possible to quantitatively reproduce the ARPR intensity of all ALMs for a given excitation wavelength under any scattering and polarization configurations.

The results suggest that the previously reported ARPR intensity of ultrathin ALM flakes deposited on a multilayered substrate at normal laser incidence can be also understood based on the BLD model by considering the depth-dependent polarization and intensity of incident laser and scattered Raman signal induced by both birefringence and linear dichroism effects within ALM flakes and the interference effects in the multilayered structures, which are dependent on the excitation wavelength, thickness of ALM flakes and dielectric layers of the substrate. This work can be generally applicable to any OAC, offering a promising route to predict and manipulate the polarized behaviors of related phonons.

Luxembourg, 10 September 2020 - In a seven-year research effort, an international team of scientists has clarified the cause for certain genetic forms of Parkinson's disease, and has identified potential pharmacological treatments. The interdisciplinary research team, led by Prof. Rejko Krüger, of the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg, experimented on patient-based cell cultures in the laboratory. The new combination of active substances they identified will have to undergo clinical trials before they can be used to treat patients. The research team published its results today in the prestigious scientific journal Science Translational Medicine.

Lack of protein DJ-1 makes you sick

A protein called DJ-1 plays a crucial role in keeping nerve cells functioning. If the body is unable to produce ample amounts of DJ-1, important nerve cells die. The result is the onset of neuro-degenerative diseases such as Parkinson's. The production of important proteins like DJ-1 can be disrupted or halted permanently if the genetic blueprints or the production processes they encode are defective.

Now, Prof. Rejko Krüger's research team in Luxembourg has succeeded in identifying for the first time the importance of an error in the production process known as 'splicing' in the development of a certain form of Parkinson's disease. "In the patients, an essential tool for the assembly of the protein DJ-1 fails to dock properly," Krüger explains. "In scientific terms, we call that exon skipping. As a result of this defect, the protein doesn't get built at all." The research result offers an entirely new point of attack for treating this malfunction of protein synthesis with drugs. "This insight fundamentally changes our view of the causes of the disease and presents entirely new possibilities for treatment," says Dr Ibrahim Boussaad, LCSB scientist and first author of the scientific paper. "We could only gain this new understanding thanks to the skin cells from the patients," Boussaad emphasises.

Cell donation enables progress

The Luxembourg Parkinson's Study, initiated in 2015 (see also http://www.parkinson.lu), includes a group of 800 Parkinson's patients and 800 healthy control subjects. Thanks to the donation of skin cells taken by small biopsies, the researchers in Luxembourg were able to reprogram these cells to grow into nerve cells in vitro. These nerve cells are very similar to the neurons in affected regions of the donor's brain and can be used for analyses and tests in the laboratory. Because it is not possible to take neurons directly from the brain of patients, for health and ethical reasons, reprogramming is the only way to examine the clinical features of the patient's neurons in vitro. In scientific jargon, this is called a patient-based in vitro model, and is an important step in personalised medicine. Using this method, Prof. Krüger's team was able to explain the cause of the genetic form of Parkinson's disease in which the PARK7 gene is mutated. Prof. Thomas Gasser, a medical director at the Tübingen University Hospital and co-author of the paper, adds, "We are proud to have been able to contribute our expertise in the reprogramming of patient cells to this stem cell work of our colleagues in Luxembourg." Institutions from Germany, Italy and the USA collaborated in the research project.

Luxembourg's interdisciplinarity is a key to this success

Precise bioinformatics algorithms developed at the LCSB allowed the research team to immediately carry out an automated search for potential active substances for drug treatment. This yielded a hit in the form of the active compounds phenylbutyric acid and RECTAS (RECTifier of Aberrant Splicing). Administered in combination, these two active substances allow the cells in the test tube to effectively reactivate the production of the important protein DJ-1. "Only by combining numerous disciplines - from medical practice, to laboratory research, to computer science - could we understand the cause and at the same time identify active substances for a potential treatment," Prof. Rejko Krüger explains. He adds, "This kind of scientific progress 'Made in Luxembourg' is possible because all the necessary disciplines have been unified in Luxembourg for several years now." This work represents the high point to date of the PEARL program of the Luxembourg National Research Fund (FNR), through which the research of Prof. Krüger and his team is funded. The team of scientists especially expresses its gratitude to the people who are participating in the Luxembourg Parkinson's Study and who have made this research possible in the first place.

Since every process in lateral root development, including initiation, emergence and elongation is governed by auxin, the question arises of how auxin responds to the local presence of ammonium which is a major nitrogen source in natural and agricultural soils. "Our work shows that ammonium uptake by roots provokes pH changes that bring the plant hormone auxin into a protonated form allowing auxin to diffuse into outer root cells where it triggers the emergence of lateral roots", says Prof. von Wirén. These research results have now been published in the scientific journal Nature Plants.

Monitoring pH and auxin reporters indicate that ammonium uptake acidifies the root apoplast, i.e. the cell wall space, which increases import of protonated auxin into cortical and epidermal cells overlaying lateral root primordia, and subsequently promotes their emergence from the parental root. Although nitrogen-deficient plants also accumulate auxin in the root vasculature, like ammonium-supplied roots do, they have a more alkaline apoplast around the vasculature, which retains auxin in these tissues and prevents lateral root emergence. In simple words, local exposure of roots to ammonium makes roots losing control over the transport of this growth-promoting hormone.

Auxin import into cortical and epidermal cells enhances expression of genes involved in cell wall loosening, decreasing the mechanical resistance required for lateral root emergence. "Our study reveals that pH-dependent auxin diffusion can be recruited as a regulatory mechanism to coordinate the plasticity of root system architecture with fluctuating nutrient availabilities", says Prof. von Wirén. "To what extent this enhanced lateral root density promotes acquisition also of other nutrients remains to be shown."

In soils, ammonium-triggered lateral root emergence is not only relevant for shaping root system architecture under patchy nitrogen availability in natural environments, e.g. when roots touch organic matter-rich soil releasing ammonium through mineralisation, but also in agricultural plant production. "The increasing demand to reduce nitrogen fertilizer input is progressively met by banding sparingly soluble ammonium phosphate-based fertilizer strips in the soil", says Prof. von Wirén. Such local ammonium depots have been shown to enhance lateral root formation of field-grown crops as well as the mobilization and uptake of co-supplied phosphate. "Since local phosphate typically stimulates lateral root elongation while ammonium triggers lateral root emergence, it is tempting to speculate that knowledge on nutrient-dependent lateral root development can be further exploited to optimize the adaptation of crop root architecture to agricultural nutrient management practices."

Insect pollination is as important to Arctic plants as it is to plants further south. When flowers abound, the plants have to compete for pollinators. Researchers at the University of Helsinki reveal that higher temperatures cause the flowering periods of different plant species to pile up in time. As a consequence, climate change may affect the competitive relationships of plants.

The most attractive plant species steal the majority of pollinators, making other plants flowering at the same time suffer from poorer pollination.

"Most flowering plants are dependent on the pollination services provided by insects. Thus, plants need to time their flowering to periods of maximal pollinator abundances. On the other hand, plant species compete with each other for pollination. Thus, plant species flowering at the same time can affect each other's pollination success. Temperature is one of the most important environmental determinants of the onset of flowering. As the climate warms, plant species change their flowering periods, thereby changing their competition for pollinators," explains Mikko Tiusanen, researcher at the Faculty of Agriculture and Forestry, University of Helsinki, and lead scientist behind the study.

Avens is popular with pollinators - and competition is fierce

"We have been studying the relationship between plants and pollinators in North East Greenland, where the climate is warming twice as fast as the global average. The most common flowering plant in this region is Avens, a widespread and abundant flowering species. The shape of an Avens' flower is an open, white cup of nectar, irresistibly attractive to any pollinators around. In our comparisons, Avens was found to attract many more visitors than other plant species. When in bloom, it thus monopolizes insect pollination services at the expense of other plants in flower," says Tiusanen.

By studying the timing of flowering of different plant species under different environmental conditions, the researchers found that higher temperatures caused the flowering periods of different plant species to contract. In particular, the flowering of the Moss Campion advanced relative to the flowering of Avens. This affects the competition between the two species, since the flowering of Avens is directly reflected in how many insects carry Campion pollen: with more Avens in bloom, fewer insects carried the pollen of the Campion.

Global warming may thus affect competition between plant species for pollination services, thereby changing interactions between species. For example, overlap in flowering between a plant species and a more attractive competitor reduces pollination and may impair the species' chances of survival in the long run. This is likely to be a particular threat to rare plant species, as well as to flower species less attractive to insects, scientists speculate.

"To me, the Arctic represents a planetary research laboratory for studies of climate change," says Tomas Roslin, director of the research group spanning the University of Helsinki and the Swedish University of Agricultural Sciences (SLU). "The climate of this region is now changing twice as fast as the global average. What this means is that what happens in the Arctic today may later occur in the rest of the world. At the same time, relatively low species richness in the Arctic allows us to resolve their interactions in great detail. But scientific reasons are only half the arctic appeal. Northeast Greenland is one of the most beautiful areas in the world, and at the same time one of the largest uninhabited areas in the world. When studying insects here, you may even run into a polar bear. Such a combination keeps the researchers alert and awake."

Worldwide, cancer is the second leading cause of death - in 2018 alone, it claimed approximately 9.6 million lives, or one in six deaths. The development of cancer is incredibly complex and is controlled by an interplay of various factors - only recently, it became clear that the majority of human cancers such as cervical, gastrointestinal and breast among others, originate from adult stem cells becoming deregulated. These adult stem cells are present in many of our organs, where they provide a constant supply of cells to replace old and dead cells. Identifying the mechanisms of how these developmentally tightly regulated stem cells break free from their regulations is an important topic within the scientific community, including the Knoblich lab at IMBA.

One key step in tumorigenesis are the mechanics driving tumor cell initiation, which trigger their fate in becoming tumorigenic. They have, thus far, mainly been studied at gene regulation levels, by researching tumor suppressor genes MYC, p53 or KRAS. Metabolic changes within tumor cells are a well-known characteristic, but whether these are a consequence or the cause of tumor cell immortalization is still not known, and thus the focus of the most recent publication from Knoblich's team.

The researchers chose the fruit fly Drosophila melanogaster as tumor model - this established yet somewhat unconventional model organism boasts a long history in tumor studies, with discoveries in mutations of tumor suppressor genes dating back to the 1970s. Learnings from this simple model organism can then be used as a powerful tool as basis for further studies on human genes. In Drosophila, the scientists visualized the exact timepoint when tumor initiating cells became immortal and manipulated the process genetically - a feat which is not readily accomplished in mammalian tumors, due to their high complexity.

"We used a Drosophila neural stem cell (NSCs) tumor model, which is induced by the depletion of the well-known tumor suppressor called Brat. By using this model, we investigated whether the metabolism plays an active role in Brat tumor cell immortalization. Our findings in Drosophila will then be used as a basis for subsequent studies in human cells and lay the basis for mechanistic studies of human cancers," explains Jürgen Knoblich, IMBA group leader and Scientific Director.

Indeed, the researchers found Brat tumors to be highly oxidative, with higher oxygen consumption rates compared to normal brains. This proved to be quite the surprising discovery, as tumors are widely considered to be glycolytic.

In an additional exciting finding, the scientists from Knoblich's team found that the oxidative metabolism, which is a mitochondrial oxygen-dependent bioenergetic pathway, plays a key role in tumor cell immortalization. "We noticed that during tumor initiation, the mitochondrial membranes are fused. This drastic change in mitochondrial morphology leads to an increase in efficiency in oxidative phosphorylation, which explains why we found increased levels of NAD+ and NADH, two key molecules involved in bioenergetics," explains François Bonnay, postdoc in the Knoblich lab and first author of the study.

With additional experiments, the scientists showed that in the Drosophila brain, it is indeed the increased oxidative phosphorylation and NADH/NAD+ metabolism mediated by mitochondrial fusion which is absolutely necessary for tumor initiating cells to become immortal.

"Our findings overturn previous concepts about the biology of these tumors and open up an array of exciting follow up questions, including whether the mechanisms we just discovered in the fruit fly are also applicable to mammalian tumors. Questions we will also strive to answer are, how exactly does the NADH/NAD+ metabolism favour tumor cell immortalization, and does it achieve this via signalling, or through epigenetic changes? We are thrilled to advance our work in this field", says Knoblich.

A group of researchers from Charité - Universitätsmedizin Berlin have been able to show that maternal psychological wellbeing during pregnancy has a positive effect on newborn infants. Increased telomere length suggests a reduced rate of cell aging, which could have an effect on children's future health. Results from this study have been published in the American Journal of Psychiatry*.

A variety of pregnancy-related factors can have an impact on child development. Until now, researchers had primarily focused on the negative effects of stress, excess weight and poor nutrition - and how these might affect, say, placental function, premature birth and children's general health. At the cellular level, various pregnancy-related factors can have a direct impact on 'telomeres', cellular structures which protect the ends of chromosomes during cell division and can be lengthened by the enzyme telomerase. Telomere length is a molecular biology marker of cell aging which is linked to life expectancy and a range of age-related disorders. Although the effects of maternal stress have been widely studied, data on protective maternal factors and their positive effects on child development remain limited.

A group of researchers led by Prof. Dr. Sonja Entringer of Charité's Institute of Medical Psychology have been able to show that the mother's ability to cope with stress during pregnancy - her 'psychological resilience' - is linked to telomere length. The more positive a mother's attitude during pregnancy, the longer the children's telomeres. "Positive maternal psychological characteristics are biologically embedded and have a protective effect on the fetus," says Prof. Entringer.  

In an earlier study, the researchers examined the way in which maternal stress during pregnancy affects telomere length in their offspring. The current study, which saw Prof. Entringer's team work with a team of researchers led by Nobel Laureate Elizabeth Blackburn of the University of California and colleagues in Finland, had access to a large study population comprising 650 mother and child pairs. Telomere length was determined at birth, using cells from cord blood. Positive attitude in the face of stress was determined using a 'resilience index', which also took into account the pregnant women's psychological wellbeing and perceived social support.

"This study underlines the importance of maternal psychological wellbeing during pregnancy in terms of the developmental programming of lifelong health and disease, and the significance of improved psychosocial support measures during pregnancy," explains Prof. Entringer, who is also an Associate Professor at the University of California. Prof. Entringer was awarded a European Research Council 'Starting Grant' in 2016, which enabled her to set up and develop her own research group. The researchers are currently conducting more detailed investigations into the molecular mechanisms underlying the biological embedding of psychosocial effects in the cells of unborn children. As a next step, they are planning to conduct an interventional study on stress reduction in the day-to-day lives of pregnant women.

ITHACA, N.Y. - Cornell food scientists show in animal studies that a mother's high-fat diet may lead to more sweet-taste receptors and a greater attraction to unhealthy food in their offspring - resulting in poor feeding behavior, obesity in adulthood.

The researchers' findings were published July 31 in Scientific Reports.

Maternal exposure to a high-fat diet during the perinatal period - before the animal gets pregnant - appears to induce physical, detectable changes in the taste buds for offspring, said senior author Robin Dando, associate professor of food science in the College of Agriculture and Life Sciences.

"We see this is something actually happening in the taste buds themselves," Dando said. "Adult progeny, fed such a diet, have more sweet-taste receptors inside their taste buds than in the control group, whose mothers ate a steady, healthy diet."

Five weeks before mating, female mice were fed high-caloric, high-fat meals; other mice were also fed the high-fat diet from their pregnancy through lactation.

The progeny, weaned after the lactation period, ate healthy, high-quality laboratory chow. When the offspring became adults, the mice received their first taste of the high-fat diet.

"Up until then, the animals showed no difference between themselves and the control group," Dando said. "But as soon as the offspring of the moms who consumed the unhealthy diet had access to it, they loved it and they over-consumed it."

The offspring only encountered a high-fat diet by way of the maternal environment.

"If a mother has an unhealthy diet where she consumes a lot of calories through high-fat and sugary products," Dando said, "the offspring are going to have a predisposition for liking the unhealthy diet. The origin of this is not only the changes the brain, but there are other physical changes happening within the taste buds."

As Dando stressed, these results are in mice, but obesity in humans combined with an environmental component, the heritability is between 40% to 70%. "Obesity in the offspring is strongly predicted by the metabolic state of the parents," he said.

While the specific mechanism remains unclear, Dando said, the results introduce the concept of "taste" to the list of metabolic alterations arising from fetal programming.

"Our research adds to the evidence that the taste bud plays a role in the etiology of obesity," he said. "From a public health standpoint, improving our knowledge of prenatal and early postnatal factors that program obesity in offspring may provide insight into therapeutic targets to combat the obesity epidemic - a disease easier to prevent than to cure."

If you open up a pea pod, you will find that all of the peas inside are the same size and the same distance apart. The same is true of princess beans, runner beans and soybeans as well as various other peas and beans, and it also applies to non-pulses. This is surprising because both the seed size and number and the pod size differ substantially from one variety to the next.

A team of researchers based in Germany, Australia, Japan, the USA and Italy under the supervision of Prof. Dr. Rüdiger Simon from HHU's Institute of Developmental Genetics has analysed the genetic mechanisms behind this phenomenon. The team used different wild varieties of thale cress to examine the genetic processes taking place behind the initiation of ovules - the primordia from which seeds emerge after fertilisation - and the growth of the pod. These wild varieties are sourced from different locations. Thale cress or Arabidopsis thaliana is a model plant used in biology. Prof. Simon commented: "The individual seeds compete with each other for nutrients. To ensure that each seed gets an equal supply and can develop well, it is important that the seeds are spread as evenly as possible at equal distances in the pod."

There is considerable variation in fruit size and seed number even amongst the different wild varieties of Arabidopsis thaliana. However, the researchers also discovered a uniform genetic mechanism that controls seed position in the pod regardless of environmental factors such as temperature.

The team established that seed formation is controlled by several signalling pathways at precisely defined positions. These signalling pathways are activated by small secreted proteins from the EPFL family. These peptides are detected on the cell surface by receptors from the ERECTA family. One of the peptides, EPFL2, is formed between the developing ovules, where it adjusts the spacing between the seeds. Where this peptide is not present, the researchers found irregular spacing - meaning that adjacent seeds compete more for nutrients - or even ovule twinning, which generally results in neither ovule developing fully. EPFL2 and a very closely related peptide, EPFL9, also control fruit development. As a result, seed formation is closely linked to pod growth.

Dr. Nozomi Kawamoto, the first author of the study, highlighted another aspect: "The same signalling substances and receptors that we have identified as being responsible for relative pod size and seed spacing are also in charge of the spacing of leaf stomata and the microstructure of serrated leaves." A plant uses the stomata to regulate the exchange of gases with its environment. Dr. Kawamoto is carrying out post-doctoral research at Prof. Simon's Institute as part of the Cluster of Excellence on Plant Sciences CEPLAS in Düsseldorf.