Culture

Scientists use public databases to leap over scourge of publication bias

image: Step 1. Evaluation and listing of upregulation and downregulation of hypoxia-inducible genes. Step 2. Confirmation of known hypoxic stimulation-related genes. Step 3. Discovery of novel genes related to hypoxic stimulus-response.

Image: 
Yoko Ono, Hiroshima University

Scientists have leapt over the emerging problem of publication bias within genetic research by performing a meta-analysis of publicly available databases of 'transcriptomes', or the full range of messenger RNA molecules produced by an organism. Researchers from Hiroshima University applied the technique to their own field--the study of the genes that are activated when an organism experiences low-oxygen conditions--but it should also be applicable in any other fields that make use of the transcriptome, providing a powerful weapon against the threat posed by publication bias.

The meta-analysis technique was published in a paper appearing in the journal Biomedicines in May 2021.

Scientists are often held up as the pinnacle of objective, disinterested observation and investigation. But in recent years, the danger of what is called publication bias, or sometimes the 'file-drawer problem' is being recognized right across the natural sciences. It describes the bias of researchers and of scientific journals toward the publication of results that support the hypotheses of researchers or otherwise show a significant finding. Both researchers and journals are frequently not very excited about experiments that do not support their hypotheses, and so the findings are left 'in the researcher's file drawer.' There may be no malevolent intention behind such exclusion, but the lack of publication of these 'boring' results does skew, or bias, what exists across the published scientific literature. Ironically, the more well studied the field, the greater the effect of such publication bias.

The Hiroshima University researchers had noticed that there were some 600,000 publications in scientific journals that described around 20,000 human genes that code for the building of a specific protein (as opposed to 'non-coding' genes that perform other functions but do not code for a protein). Across this enormous number of publications, there were a whopping 9,000 articles that discussed the p53 gene, but some 600 genes were not mentioned at all.

Within their own field, they found that this sort of publication bias had led to a great focus on genes that are already well known to be activated during conditions of hypoxia, or low-oxygen conditions.

Under hypoxic conditions, hypoxia-inducible transcription factors, or HIFs, are produced. Transcription factors are proteins that control the rate of transcription (copying a segment of DNA into RNA in order for the RNA to then be translated into a protein). When human cells are deprived of sufficient oxygen, there is a response system governed by the HIFs that attempts to ameliorate the effects of hypoxia by preventing cells from differentiating and by promoting the formation of blood vessels. And HIFs are known to be activated by certain genes.

"But are there other genes that are activated during hypoxia that all researchers have up till now somehow missed due to this publication bias?" asked lead author Hidemasa Bono, professor in the Graduate School of Integrated Sciences for Life at Hiroshima University.

As transcriptome researchers, Bono and his team knew that, unlike with scientific articles in journals, all transcriptome data have to be archived in public databases, not just the interesting transcriptome data.

"So we thought that if we performed a meta-analysis--or an analysis of analyses--on these transcriptome data, we might be able to identify novel hypoxia-inducible genes that had been buried by publication bias," Bono added.

They searched publicly available transcriptome databases to obtain hypoxia-related experimental data, retrieved the metadata, and then manually curated it. They then selected all the genes that are expressed during hypoxic stimulation, and evaluated their relevance in hypoxia by performing gene enrichment analyses. This latter method allows the statistical identification of groups of genes that are over-represented in a large set of genes, and so may be associated with a particular condition.

Alongside this, the researchers performed a bibliometric analysis, a statistical method of analyzing the occurrence of particular words or phrases commonly used in library and information science. The bibliometric analysis in this case was used on the gene2pubmed--a gene literature data source that describes which genes have been discussed where in the scientific literature--to identify genes that have not been well studied in relation to hypoxia. This is a new type of analysis that within biomedical research is called the 'bibliome'.

By combining the transcriptomic meta-analysis and the bibliome, the researchers were indeed able to find four genes that were not previously known to be associated with hypoxia.

The results have encouraged the researchers to keep going with their meta-analysis technique. They plan to keep using public databases to discover similar new findings, in particular to investigate gene activation (expression) of non-coding RNAs, or RNA molecules that are not translated into proteins, during hypoxic stress.

Credit: 
Hiroshima University

DNA methylation changes and characteristics in neurons of bipolar disorder patients

image: (Left) The number of hypermethylated DNA regions in both neuronal and non-neuronal cells is reduced in the bipolar patient group (BD) compared to the healthy group (CT).
(Right) Methylation status of the BDNF (brain-derived neurotrophic factor) receptor gene (NTRK2), which is important for mental and neurological functions. The upper panel shows the hypermethylated region in patients, and the lower panel shows the DNA methylation status in patients and healthy controls.

Image: 
Professor Kazuya Iwamoto

A research collaboration based in Kumamoto University, Japan has revealed the DNA methylation status of gene transcriptional regulatory regions in the frontal lobes of patients with bipolar disorder (BD). The regions with altered DNA methylation status were significantly enriched in genomic regions which were reported to be genetically related to BD. These findings are expected to advance the understanding of the pathogenesis of BD and the development of therapeutic drugs targeting epigenetic conditions.

BD is a mental disorder that affects about 1% of the population and requires long-term treatment. Epidemiological studies have suggested that the onset of the disease is related to a complex interaction of genetic and environmental factors. Epigenetic changes in the genome, particularly in the repression of gene expression through DNA methylation, are thought to be deeply involved in the pathogenesis of various diseases, including mental disorders.

Previous studies analyzed DNA methylation using peripheral blood and saliva samples to identify genes with altered DNA methylation and use them as biomarkers. Since mental disorders are diseases of the nervous system, research using brain tissue is particularly important. However, in addition to the scarcity of samples, brain tissue is a mixture of various cell types, such as neurons and glial cells, and is affected by differences in the ratio of cell types contained in the tissue, making accurate analysis difficult.

The researchers used neuronal nuclear markers to fractionate frontal lobe samples from 34 BD patients and 35 healthy subjects into neuronal and non-neuronal cell nuclei. Genomic DNA extracted from each of these samples was then used to examine the DNA methylation status of the regulatory regions of gene transcription using an array method. They found that many genes in both neurons and non-neurons were hypomethylated in BD patients compared to healthy subjects. On the other hand, genes important for psychiatric and neurological functions were found to be hypermethylated in neurons.

To investigate the effects of mood stabilizers—drugs used to treat BD—the researchers cultured human neuroblastoma cells in the presence of mood stabilizers (lithium, valproate and carbamazepine) in effective blood concentration ranges and measured DNA methylation status. They found that about 30% of the regions with altered DNA methylation status in BD patients overlapped with mood stabilizers-induced DNA methylation changes. Most of the DNA methylation changes were in the opposite direction of those in the postmortem brain, which the researchers thought reflected the effects of the treatment. They also measured the expression levels of 10 genes associated with DNA methylation changes and found that the DNMT3B gene, a DNA methyltransferase, was elevated in BD patients, suggesting that it may be associated with neuron-specific DNA methylation changes.

Finally, the researchers compared the genomic regions associated with mental disorders as identified in genome-wide association studies (GWAS) with regions having an altered DNA methylation status. Significant accumulation was observed in the genomic regions reported in the GWAS for BD, while no accumulation was observed in the genomic regions reported for depression and schizophrenia.

"The clarification of neuron-specific DNA methylation changes and characteristics is expected to greatly advance our understanding of the pathogenesis of bipolar disorder," said Professor Kazuya Iwamoto, who led this study. "We also expect that this will help in the development of therapeutic drugs targeting epigenetic conditions."

This research was posted online in Molecular Psychiatry on 20 April 2021.

Credit: 
Kumamoto University

RUDN University chemist created coordination polymers with up to 99.99% antibacterial efficiency

image: RUDN University chemist with his colleagues from Portugal has developed two types of coating based on new coordination polymers with silver. Both compounds were successfully tested against four common pathogens.

Image: 
RUDN University

RUDN University chemist with his colleagues from Portugal has developed two types of coating based on new coordination polymers with silver. Both compounds were successfully tested against four common pathogens. The results are published in ACS Publications (ACS Appl. Mater. Interfaces).

Due to the rapid mutation, harmful microorganisms constantly adapt to new antibiotics and antiseptics. It is especially difficult to destroy bacteria when they form a biofilm. They stick together and create a community ready to fight antimicrobial agents back. Coordination polymers (scaffolds made of metal ions and organic ligands) can solve this problem. They prevent pathogens from forming biofilms and replicating on the surfaces. RUDN University chemists have created two coordination polymers with silver ions with almost 100% antibacterial activity.

"We developed a synthesis protocol and described the characteristics and structural features of two new silver-based bioactive coordination polymers. We immobilized these compounds acrylated epoxidized soybean oil and created a hybrid material for antimicrobial use", Alexander Kirillov, PhD, an associate of the Joint Institute for Chemical Studies at RUDN.

Coordination polymers consist of cyclic structures. Their central element is an atom or an ion. Scientists used silver nitrate and pyromellitic or trimesic acid to synthetise silver-based polymers. The polymers were obtained by self-assembly, it means that cyclic components themselves interacted to form a pattern which was then added to the substrate made of soybean oil. Chemists have created three types of films with different concentrations of the coordination polymer-0.05%, 0.1% and 0.5%.

RUDN chemists have tested whether the bacteria can form biofilms on surfaces that are coated with new polymers. For the experiment, they used four pathogens that can form biofilms in the human body and cause diseases. Staphylococcus epidermidis causes sepsis, endocarditis, conjunctivitis, Staphylococcus aureus causes purulent inflammatory processes in almost all organs and tissues, Pseudomonas aeruginosa is the agent of nosocomial infections in humans, and the mostly harmless Escherichia coli can sometimes cause severe food poisoning. The new polymers appeared to be active against all four bacteria. The effectiveness of protection depended on the concentration. One of the coatings proved to be more promising -- a film with 0.05% of the active polymer destroyed 99.99% of the bacteria of all four species.

"Our work opens up antibiofilm applications of CP-doped biopolymers, providing new perspectives and very promising results for the design of functional biomaterials", Alexander Kirillov, PhD, an associate of the Joint Institute for Chemical Studies at RUDN.

Credit: 
RUDN University

Food for thought: Eating soft foods may alter the brain's control of chewing

image: Low occlusal loading in malocclusion elicits neuroplastic changes in CMA and causes maladaptation of neuromuscular behavior in masticatory movements.
Inset: A typical example of electromyographic activity with jaw movement patterns elicited by electrical stimulation of the anterior part of the cortical masticatory area in an 11-week-old experimental animal.

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Department of Orthodontic Science,TMDU

Tokyo, Japan - Incoming sensory information can affect the brain's structure, which may in turn affect the body's motor output. However, the specifics of this process are not always well understood. In a recent study published in Scientific Reports, researchers from Tokyo Medical and Dental University (TMDU) found that when young rats were fed a diet of either soft or regular food, these different sensory inputs led to differences in muscle control and electrical activity of the jaw when a specific chewing-related brain region was stimulated.

Chewing is mainly controlled by the brainstem, a brain region that controls many automatic activities such as breathing and swallowing. For chewing, the brainstem is also influenced by signaling that comes from higher brain regions, including the cortical masticatory area (CMA), which can be split into the front (anterior) and back (posterior) parts. When the anterior CMA is stimulated, signals travel through the brainstem and reach the jaw muscles, causing chewing to occur. However, it remains unknown whether incoming sensory information affects chewing under the control of the anterior CMA, something researchers at Tokyo Medical and Dental University (TMDU) decided to address.

"In the developing brain, changes in sensory information can greatly affect the brain's structure," says senior author of the study Takashi Ono. "We fed 2-week-old rats either a soft diet or a regular diet, and then investigated a range of different neuromuscular outcomes in response to stimulation of the anterior CMA."

After rats had been fed the soft or regular diet for 3 to 9 weeks, electrodes were used to stimulate the anterior CMA while the rats' jaw movements were measured, along with the electrical activity of the jaw muscles. In response to anterior CMA stimulation, rats in the soft diet group had altered movement and electrical activity in the jaw muscles compared with the regular diet group.

"Our findings suggest that the anterior CMA strongly influences the regulation of chewing, and is affected by sensory inputs during development. As such, reduced chewing function during growth should be corrected as soon as possible to avoid any potential adverse effects on jaw muscle development and chewing ability," says Ono.

Given the importance of chewing for obtaining nutrients, the results of this study could be vital for monitoring and improving chewing ability in young children with chewing difficulties, as well as in adults after trauma or disease. The results of this study suggest that the brain's control of chewing may be influenced by simply increasing chewing difficulty.

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Tokyo Medical and Dental University

Māori connections to Antarctica may go as far back as 7th century, new study shows

image: The view of Te Kaiwhakatere o te Raki looking outward across the Ross Ice Shelf.

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© A short scan of M&#257;ori journeys to Antarctica / <em>Journal of the Royal Society of New Zealand</em>

Indigenous Māori people may have set eyes on Antarctic waters and perhaps the continent as early as the 7th century, new research published in the peer-reviewed Journal of the Royal Society of New Zealand shows.

Over the last 200 years, narratives about the Antarctic have been of those carried out by predominantly European male explorers.

However, this new study uncovers the story of the deep-rooted connections of Māori (and Polynesian) people with Antarctica dating back as far as the seventh century and continuing into the present day.

"We found connections to Antarctica and its waters have been occurring since the earliest traditional voyaging, and later through participation in European-led voyaging and exploration, contemporary scientific research, fishing, and more for centuries," explains lead author Dr Priscilla Wehi, from Manaaki Whenua Landcare Research the organisation which led the project, alongside researchers from Te R?nanga o Ngāi Tahu.

"Our exploration begins to construct a richer and more inclusive picture of Antarctica's relationship with humanity and builds a platform on which much wider conversations about New Zealand relationships with Antarctica can be furthered."

The study was compiled by a team of researchers who scanned literature and integrated this with oral histories. The outcome is a compiled record of Māori presence in, and perspectives of, Antarctic narratives and exploration, which - the team states - "plays an important role" to fill knowledge gaps about both Māori and Antarctic exploration.

And these stories start as far back as 1,320 years ago.

"We find Polynesian narratives of voyaging between the islands include voyaging into Antarctic waters by Hui Te Rangiora (also known as ?i Te Rangiora) and his crew on the vessel Te Ivi o Atea, likely in the early seventh century," Wehi says.

"These navigational accomplishments are widely acknowledged; and Māori navigators are described as traversing the Pacific much as Western explorers might a lake.

"In some narratives, Hui Te Rangiora and his crew continued south. A long way south. In so doing, they likely set eyes on Antarctic waters and perhaps the continent."

Other evidence gathered includes Māori carvings, which depict both voyagers and navigational and astronomical knowledge.

"As well," Wehi says, "a 'pou whakairo' (translating as carved post), represents Tamarereti as protector of the southern oceans stands on the southernmost tip of the South Island of New Zealand at Bluff. Ngāi Tahu, the largest tribal group in the South Island, and other tribal groups or iwi also cherish other oral repositories of knowledge in relation to these early explorers and voyagers."

These Māori narratives of connections with Antarctic were not limited to these early voyages either. Rather, voyaging and expedition was shown to continue to the present day; "but is rarely acknowledged or highlighted," Wehi says.

And this research, she hopes, will begin more on the path to ensure inclusion of Māori in future relationships with Antarctica.

"Taking account of responsibilities to under-represented groups, and particularly Māori as Treaty partners, is important for both contemporary and future programmes of Antarctic research, as well as for future exploration of New Zealand's obligations within the Antarctic Treaty System."

Concluding, she says: "Growing more Māori Antarctic scientists and incorporating Māori perspectives will add depth to New Zealand's research programmes and ultimately the protection and management of Antarctica."

Further evidence of Māori exploration is likely to enter the public domain in future as tribal researchers partner with iwi to share these narratives, and Māori leadership in Antarctic research grows more visible, including that of the Kāhui Māori in the Antarctic Science Platform.

Credit: 
Taylor & Francis Group

RUDN professor clarified benefits of Mg supplementation in pregnancy and hormonal disorders

image: RUDN University professor and her colleagues from France proved that higher intake of magnesium and vitamin B6 helps to cope with the consequences of magnesium deficiency during pregnancy and in hormone-related conditions in women. Within four weeks, the painful symptoms become less severe, the quality of life improves, and the risks of miscarriage are reduced.

Image: 
RUDN Unviersity

RUDN University professor and her colleagues from France proved that higher intake of magnesium and vitamin B6 helps to cope with the consequences of magnesium deficiency during pregnancy and in hormone-related conditions in women. Within four weeks, the painful symptoms become less severe, the quality of life improves, and the risks of miscarriage are reduced. The results of the study are published in Scientific Reports.

Magnesium is involved in important processes in the human body -- from protein synthesis to respiration. The most common causes of magnesium imbalance are a lack of this element in the diet, diabetes, and hypertension. The problem of magnesium deficiency is more acute for woman, because magnesium is in higher demand during pregnancy. The lack of magnesium also leads to conditions associated with hormonal disorders -- endometriosis or polycystic ovary syndrome.

"Our study was aimed to assess the effectiveness of magnesium-vitamin B6 intake in achieving normalization of total serum Mg for patients with different starting levels of deficiency. It was also important to determine at what Mg level the painful symptoms are eliminated, and the patients notice changes and quality of life", said Svetlana Orlova, Doctor of Medicine, Head of the Laboratory of Molecular Nutrition of RUDN University.

The study involved 869 pregnant women, with a median age of 28, and 957 women with hormone-related conditions. The median age in this group was higher -- 44 years. The participants were residents of varying size cities in Russia. Laboratory tests showed that they had a lower level of magnesium in the serum (less than the 0.8 mmol per liter). Pregnant women have experienced symptoms associated with the risk of miscarriage, such as high blood pressure and excessive activity of the uterine muscles. Patients in the group with hormone-related conditions, along with the main symptoms were concerned about osteoporosis, premenstrual and menopausal syndromes.

Participants received magnesium and vitamin B6 supplementation in the standard dosage for their gender, age, and weight for four weeks. During this time, for most women (73.8% in the group of pregnant women and 58.9% in the group with hormone-related conditions) Mg level increased to 0.8 mmol / L and higher. In most of the others, it was in the between 0.66 to 0.8 mmol / L, which is considered as a moderate magnesium deficiency. At the same time, the total number of complaints about painful symptoms both during pregnancy and in the group of women with hormone-related conditions decreased by an average of 1.

"Along with the physiological state, we monitored the quality of life of the patients. World Health Organization quality of life questionnaire assessed such aspects as physical health, psychological health, social relationships, and environment. During the study, the scores increased, and the most noticeable effect was among the group of women who reached normal Mg level starting from a moderate deficiency. Thus, we have shown that the consequences of a minor magnesium deficiency can be eliminated by receiving supplementation. For more ssevere deficiency below 0.5 mmol / L, treatment must target the cause of the Mg deficiency", said Svetlana Orlova, Doctor of Medicine, Head of the Laboratory of Molecular Nutrition of RUDN University.

Credit: 
RUDN University

Researchers realize unconventional coherent control of solid-state spin qubits

The research team led by Prof. GUO Guangcan from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS), together with Prof. Adam Gali from Wigner Research Centre for Physics, realized robust coherent control of solid-state spin qubits using anti-Strokes (AS) excitation, broadening the boundary of quantum information processing and quantum sensing. This study was published in Nature Communications.

Solid-state color center spin qubits play an important role in quantum computing, quantum networks and high-sensitivity quantum sensing. Considered as the basis of quantum technology application, optically detected magnetic resonance (ODMR) technology offers a readout approach to detect the spin state. Conventional ODMR detection of solid-state spin states is almost all under Strokes excitation, which requires that the excitation laser has higher energy than emitted photons.

To extend the scope of solid-state quantum technologies, the researchers first realized the AS excited ODMR detection of silicon vacancy defect spin in silicon carbide (SiC), where the energy of exciting laser is lower than that of the emission photons.

By investigating the dependence of laser power and temperature on AS excited ODMR signals, the researchers proved that the AS photoluminescence (PL) was induced by phonon-assisted single photon absorption process, and was applicable to all-optical high-temperature temperature sensing.

On the basis of this, they found that AS and Strokes excited ODMR followed similar behavior facing the change of laser power, microwave (MW) power and temperature, while the AS ODMR contrast remained approximately three times larger than the Strokes one.

Furthermore, the researchers realized the coherent manipulation of solid-state spin states in SiC under AS excitation. The results showed that the AS excitation method increased the signal contrast by around three times, enabling the potential applications of AS excited ODMR approach to quantum information processing and quantum sensing.

This study improves any ODMR-based measurement. This AS demonstration can be used in yet unforeseen development.

Credit: 
University of Science and Technology of China

Identifying the main culprit of the COVID-19 disaster

image: The evolution of the COVID-19 pandemic. (a) The global daily new cases, with deep (light) blue denoting the cases in the Northern (Southern) Hemisphere. (b) The weekly, seasonal and trend components decomposed by the EEMD method. (c)~(f) show the scenario simulations in Russia (c), US (d), Brazil (e) and India (f). The thin dashed black lines in (c)~(f) denote the reported daily new cases in each country, while the thick solid and dashed lines denote the simulation in two different scenarios.

Image: 
©Science China Press

A research team led by Professor Jianping Huang from Lanzhou University has launched a Global Prediction System for COVID-19 pandemic. Their recent work explored the periodicity and mutability in the evolutionary history of the COVID-19 pandemic and investigated the principle mechanisms behind them. They attributed the periodic oscillations of COVID-19 daily cases to seasonal modulations and reporting bias, and identified the unrestricted mass gatherings as the main culprit of the COVID-19 disaster.

Their findings, entitled "The oscillation-outbreaks characteristic of the COVID-19 pandemic", were published in National Science Review.

In this study, the influence of human interventions and environmental influence were isolated based on statistical analysis and model simulations. They have decomposed the time series of COVID-19 daily cases into the oscillations over weekly and seasonal timescales. Weekly oscillations are mainly attributable to reporting bias, while seasonal oscillations are likely caused by variations in the meteorological and environmental factors due to seasonality. The seasonal components indicate higher infectivity and mortality in colder climates for both hemispheres. "Though accurate quantification of the environmental influence on the COVID-19 dynamic remains a challenge, what is certain is that the seasonal oscillations with limited amplitude are not able to reverse the long-term growing trend of the cases," said Prof. Huang. The authors concluded that beneficial climate conditions (e.g. onset of higher temperatures during the warm seasons) should not be used as a criterion to decide on relaxing control measures.

The evolution of COVID-19 cases is also strongly regulated by some rapid growth periods. Model simulations indicate that these abrupt shifts are mainly attributable to changes in the governmental response and public adherence, as well as the unexpected natural and socio-economic crisis. The government response, public adherence, and the unexpected natural and socio-economic crisis would ultimately influence the frequency and size of gathering activities. Higher risk of mass gathering would then give rise to multiple super-spreading events and the subsequent COVID-19 disaster. Prof. Huang further pointed out, "We identify mass gatherings as the main culprit of the COVID-19 disaster. Environmental factors do influence the transmission, but their limited impact is not able to reverse the growth of cases."

Additionally, this work highlights the decisive role of Non-pharmacological interventions (NPIs). "Though vaccination has streamed into the community, we still can't let down our guard." Prof. Huang said, "Before high levels of vaccine-mediated protection can be achieved across the world, NPIs remain the most effective measure to control the epidemic in the foreseeable future."

Credit: 
Science China Press

Meiosis: Mind the gap

image: Scientists have now discovered that cells sometimes liberate DNA fragments at sites of paired, or double, DSBs.

Image: 
© Franz Klein, Chromosomenbiologie, Universität Wien

Scientists from the lab of Franz Klein from the Department of Chromosome Biology at the Max Perutz Labs, a joint venture of the University of Vienna and the Medical University of Vienna, have now discovered that cells sometimes liberate DNA fragments at sites of paired, or double, DSBs. Whilst this presents an obvious risk of germline mutations as a consequence of erroneous repair or of integration of fragments from elsewhere at break sites, it may also be a source of evolutionary diversity. The study is published as a research article in Nature.

Genetic information in humans is encoded in 23 chromosome pairs, where one pair consists of two slightly different copies or homologs. One is inherited from the father and one from the mother. Human gametes, however, are haploid - they start out with only half the number of chromosomes. When gametes fuse during sexual reproduction they create an organism with the full set of chromosomes. The random assortment of parental chromosomes together with the exchange of genetic material between homologous chromosomes during early meiosis, account for genetic diversity in the offspring.

Meiosis begins with controlled self-harm

Each human gamete contains one of billions of possible combinations of the genetic information they inherit from their parental cells. Sexually reproducing organisms take a high risk to achieve this diversity. To initiate meiotic recombination, cells introduce hundreds of dangerous DNA DSBs in chromosomes with an enzyme called Spo11-complex. By using the homologous copy as a template, the breaks are repaired and genetic information is exchanged between chromosomes. "Cells have been observed to keep double strand breaks far apart from one another", explains group leader Franz Klein. "However, rather surprisingly, we have now discovered that approximately 20% of breaks correspond to closely positioned pairs of DSBs, that punch out entire pieces of the chromosome. These gaps can also initiate recombination, something that has not been considered before."

Spo11 recognizes physical strain of DNA

The team led by molecular biologist Dr. Silvia Prieler and bioinformatician Dr. Doris Chen mapped the liberated fragments across the entire yeast genome with single nucleotide precision, better than DSBs had ever been mapped before. This precision led to several new observations, for instance that DNA may have to be bent during the cleavage reaction. They also found that sites where DNA is frequently under high topological stress are cleaved more efficiently. During transcription, the two DNA strands are separated to allow RNA production. This causes the DNA-strands on both sides of the transcription-bubble to be over- or underwound and generates considerable physical strain. This kind of topological strain is resolved by so-called topoisomerases, to which the Spo11-complex is closely related. A key question, therefore, is why a topoisomerase-relative initiates meiotic recombination, given that the cell has dedicated nucleases that could cleave the DNA. "The goal in meiosis is to provide chances for novel genetic combination on as many sites as possible, to combine even closely spaced parental alleles", says Franz Klein. "Our study provides a hint as to why Spo11 may be so suitable to initiate meiotic recombination: instead of recognizing specific DNA sequences, which would recombine chromosomes always at predetermined positions, it recognizes stressed DNA, something that can occur at any sequence that is frequently used."

High risk - high potential

Why cells undergo the risk to punch out chromosome pieces is still unclear. The gaps and their corresponding fragments pose an enhanced risk for mutations, caused by deletions or by the insertion of fragments in irregular positions. The scientists show that although these pairs of double strand breaks are spread across the genome, they often correspond with promoter regions that are especially prone to topological stress. Promoters are genetic elements that regulate the level of transcription. "Evolutionarily, it would be great to be able to exchange functional regulatory elements between different sites in the genome. This raises the intriguing possibility that meiotic gaps at double DSBs could stimulate the evolution of control elements in the genome", concludes Franz Klein. A risky business for a single cell, no doubt, but perhaps worth the risk for the species.

Credit: 
University of Vienna

Language extinction triggers loss of unique medicinal knowledge

image: A Yucuna man overlooking Indigenous Lands in the Amazonian rainforest, where many languages are predicted to go extinct by the end of the 21st century.

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(Image: UZH / Rodrigo Cámara-Leret)

Language is one of our species' most important skills, as it has enabled us to occupy nearly every corner of the planet. Among other things, language allows indigenous societies to use the biodiversity that surrounds them as a "living pharmacy" and to describe the medicinal properties of plants. Linguists estimate that there are nearly 7,400 languages in the world today.

Most of these languages, however, are not recorded in writing, and many languages are not being passed on to the next generation. This has led linguists to estimate that 30 percent of all languages will disappear by the end of the 21st century. For indigenous cultures who mostly transmit knowledge orally, this high risk of language extinction also threatens their knowledge of medicinal plants.

Threatened languages support most of unique knowledge

Researchers from the University of Zurich have now assessed the degree to which indigenous knowledge of medicinal plants is linked to individual languages. Senior researcher Rodrigo Cámara-Leret and Jordi Bascompte, professor of ecology, analyzed 3,597 medicinal species and 12,495 medicinal applications associated with 236 indigenous languages in North America, northwest Amazonia and New Guinea. "We found that more than 75 percent of all medicinal plant services are linguistically-unique and therefore only known to one language," Cámara-Leret points out.

To quantify how much of this linguistically-unique knowledge may vanish as languages or plants go extinct, the researchers turned to the Glottolog catalogue of the world's languages and the IUCN Red List of Threatened Species to gain information on the threat to languages and medicinal plant species, respectively. They found that threatened languages support over 86 percent of all unique knowledge in North America and Amazonia, and 31 percent of all unique knowledge in New Guinea. By contrast, less than 5 percent of medicinal plant species were threatened.

International Decade of Indigenous Languages

The findings of this study indicate that each indigenous language provides unique insights into the medicinal applications associated with biodiversity. Unfortunately, the study suggests that language loss will be even more critical to the extinction of medicinal knowledge than biodiversity loss. The study coincides with the United Nations proclaiming the next 10 years as the International Decade of Indigenous Languages to raise global awareness of the critical situation of many indigenous languages. "The next steps, in line with the vision of the UN, will require mobilizing resources for the preservation, revitalization and promotion of these threatened languages," Bascompte says. Additionally, launching large-scale community-based participatory efforts will be crucial to document endangered medicinal knowledge before it vanishes.

Credit: 
University of Zurich

Innovation projects can reinvent the UN

Researchers at the University of Geneva (UNIGE) demonstrate that innovative projects spearheaded by United Nations (UN) country offices are remodeling the institution and expanding its role. Digital initiatives, particularly those scaled through headquarters, were shown to have the strongest impact, changing ways of working, embedding new skills, and restructuring teams across the UN. These findings, published in the Journal of Management Studies, highlight that fostering even single innovative projects could lead to fundamental transformations in the UN.

How do International Organizations build innovation capabilities through intrapreneurship and entrepreneurial behavior? To answer this question, researchers Tina Ambos and Katherine Tatarinov of the Geneva School of Economics and Management (GSEM) at the UNIGE looked at how innovative projects, particularly those born in country offices, are changing the institutional system in a sustainable way.

The role of digital technology

In one of the case studies conducted for this research, a refugee cash transfer initiative using blockchain widened the responsible UN body's role from 'ending poverty and hunger' to that more closely resembling a fintech company or development bank. By providing a platform for aid delivery, the organization is now helping its partners bypass unstable third-parties and save on transaction costs. "Such new activities often stretch the original mission of the organization", explains Tina Ambos, professor of international management at GSEM and director of the i2i Hub for Innovation and Cross-Sector Partnerships. "The use of blockchain could spread across the entire UN system, changing the ways of working and increasing transparency."

Sensitive data on vulnerable groups held by the UN often means that digital innovation cannot be outsourced. This results in the organization upgrading its institutional knowledge and creating new teams to manage digital projects, which were found to have the biggest impact on how the UN operates overall. "Other skills have also been internalized, such as technical skills and human-centered design approaches", says co-author and PhD student Katherine Tatarinov. "After learning in one context, the UN was able to test different technologies in its sites of operation according to local needs without depending on external experts."

Innovation units were found to be key in helping the UN scale initiatives by driving forward dynamic solutions. Such units nurture initiatives through boot camps, cross-sectoral connections, helping teams overcome internal barriers, and broadcasting new learnings to the entire organization. The UN also involves local people to ensure sustainability and maximize social impact. End-users, such as refugees, are often active members of development teams, helping ensure that projects 'do no harm.'

The power of bottom-up innovation

Innovations often start life in UN country offices, where staff need to respond quickly to unfolding crises. To circumvent slow central procedures, in-country innovators may decide not to involve the headquarters. Good ideas then spread from country to country, such as an anonymous SMS polling tool designed to gauge opinions on taboo topics in remote communities. "The idea grew organically, as other country offices could see the value of access to data on taboo topics", says Tina Ambos. Such country-level innovations can achieve scale and have been shown to change the organization's culture when digital technology is involved.

Innovation champions at the country level are willing to employ workarounds to avoid head office bureaucracy, because they are motivated to solve an urgent problem - rather than by internal rewards or recognition. They are therefore able to access funds and forge partnerships which may have been disregarded by the large, centralized machinery of the UN, but which nevertheless align with broader organizational values.

"Strict hierarchies, risk-averse donors, and lengthy sign-off processes can stifle ideas, yet international organizations need to innovate to stay relevant", says co-author Katherine Tatarinov. "Greater public scrutiny, funding challenges, and the push towards digital means that bodies like the UN need to reinvent themselves - their culture, identity, and management styles. By becoming more responsive and fostering innovative ideas, they can better achieve their missions and our shared global goals." The study findings show that the seed from one good idea can grow throughout a complex organization like the UN, changing it from the inside, and creating new space for enterprising ideas to flourish.

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Université de Genève

Solving mystery of the four-headed echidna penis

image: The echidna penis has four heads, or glans.

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Picture: Jane Fenelon

Scientists from the University of Melbourne and University of Queensland have revealed the mystery behind the unique reproductive parts of the much-loved echidna.

In the paper, "The Unique Penile Morphology of the Short-Beaked Echidna, Tachyglossus aculeatus", the team detail how the male monotreme's testes never descend, have no scrotum, and when not in use, their penis is stored internally.

They also detail how the echidna penis has four heads, which are actually rosette-like glans at the end. Just two of the four glans ever become functional during erection and which glans are functional appears to alternate between subsequent erections.

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University of Melbourne

A study analyzes the risk of karst groundwater contamination to human consumption

image: Fluorescent innocuous organic substances used as testing techniques to simulate the trajectory followed by a pollutant.

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University of Malaga

Led by Professor Andreas Hartmann, from the University of Freiburg (Germany), the researchers analyzed the presence of several pollutants in water from many karst aquifers of Europe, North Africa, and the Middle East, relating fast infiltration processes to an increased concentration of these substances. The findings of this research are published in the scientific journal Proceedings of the National Academy of Sciences (PNAS).

This way, they warn that during rainfall events -when aquifers recharge, especially during autumn rainfall- the concentration of pollutants and pathogenic microorganisms can significantly exceed the safe levels, causing serious consequences for human consumption.

"About one quarter of the world's population obtains water from karst aquifers, which are especially vulnerable to contamination due to their functioning. Groundwater usually flows fast in this type of environment, which favors the infiltration of pollutants", explains the Professor of External Geodynamics from the UMA Bartolomé Andreo, Director of CEHIUMA.

The risks of fertilizers

The researchers considered the degradable pesticide named glyphosate, a widely used agricultural herbicide, as an example to demonstrate their findings. The simulations performed show that rapid transport of glyphosate to the groundwater may cause this pesticide to exceed by 19 times the maximum values permitted by law. "The highest risk of groundwater contamination occurs in regions where agriculture depends on degradable fertilizers and pesticides", they assure.

In this regard, the researcher from the UMA Matías Mudarra, another author of this study, stresses that the risk from degradable pollutants like pesticides, pharmacological products or pathogens must be considered in the studies, as it is significantly higher than expected and has a direct impact on the water quality, "a critical aspect for its potential use for water supply", he says.

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University of Malaga

A study shows the unexpected effect of black holes beyond their own galaxies

image: Artistic composition of a supermassive black hole regulating the evolution of its environment.

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Gabriel P&eacute;rez D&iacute;az, SMM (IAC) and Dylan Nelson (Illustris-TNG).

At the heart of almost every sufficiently massive galaxy there is a black hole whose gravitational field, although very intense, affects only a small region around the centre of the galaxy. Even though these objects are thousands of millions of times smaller than their host galaxies our current view is that the Universe can be understood only if the evolution of galaxies is regulated by the activity of these black holes, because without them the observed properties of the galaxies cannot be explained.

Theoretical predictions suggest that as these black holes grow they generate sufficient energy to heat up and drive out the gas within galaxies to great distances. Observing and describing the mechanism by which this energy interacts with galaxies and modifies their evolution is therefore a basic question in present day Astrophysics.

With this aim in mind, a study led by Ignacio Martín Navarro, a researcher at the Instituto de Astrofísica de Canarias (IAC), has gone a step further and has tried to see whether the matter and energy emitted from around these black holes can alter the evolution, not only of the host galaxy, but also of the satellite galaxies around it, at even greater distances. To do this, the team has used the Sloan Digital Sky Survey, which allowed them to analyse the properties of the galaxies in thousands of groups and clusters. The conclusions of this study, started during Ignacio's stay at the Max Planck Institute for Astrophysics, are published today in Nature magazine.

"Surprisingly we found that the satellite galaxies formed more or fewer stars depending on their orientation with respect to the central galaxy", explains Annalisa Pillepich, researcher at the Max Planck Institute for Astronomy (MPIA, Germany) and co-author of the article. To try to explain this geometrical effect on the properties of the satellite galaxies the researchers used a cosmological simulation of the Universe called Illustris-TNG whose code contains a specific way of handling the interaction between central black holes and their host galaxies. "Just as with the observations, the Illustris-TNG simulation shows a clear modulation of the star formation rate in satellite galaxies depending on their position with respect to the central galaxy", she adds.

This result is doubly important because it gives observational support for the idea that central black holes play an important role in regulating the evolution of galaxies, which is a basic feature of our current understanding of the Universe. Nevertheless, this hypothesis is continually questioned, given the difficulty of measuring the possible effect of the black holes in real galaxies, rather than considering only theoretical implications.

These results suggest, then, that there is a particular coupling between the black holes and their galaxies, by which they can expel matter to great distances from the galactic centres, and can even affect the evolution of other nearby galaxies. "So not only can we observe the effects of central black holes on the evolution of galaxies, but our analysis opens the way to understand the details of the interaction", explains Ignacio Martín Navarro, who is the first author of the article.

"This work has been possible due to collaboration between two communities: the observers and the theorists which, in the field of extragalactic Astrophysics, are finding that cosmological simulations are a useful tool to understand how the Universe behaves", he concludes.

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Instituto de Astrofísica de Canarias (IAC)

Study of hyperhomocysteinemia in rats elucidates tracks to treating migraine

image: Parameters of CSD at different cortical depths in rats from the control and hHCY groups. The average CSD amplitude (A), CSD half-duration (SD-T1/2,B), rise time (C) and CSD depolarization rate (D) in different cortical layers in the control (white circles) and hHCY (black circles) groups. Data are expressed as mean ± SEM. ?p

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Kazan Federal University

Homocysteine (HCY) is a sulfur-containing aminoacid, which attract more and more attention as the increase of homocysteine level associates with a number of pathological conditions. Hyperhomocysteinemia (hHCY) is an elevation of HCY level in plasma and develops due to genetic mutations of enzymes involved in regulation of HCY metabolism, nutritional deficiencies of vitamins B12, B6 and folate; chronic renal failure; alcoholism, smoking, excess coffee consumption, hypothyroidism; taking a number of medications like antiepileptic drugs and LDOPA; and aging. hHcy is a well-known independent risk factor for cardio-vascular diseases, neurodegenerative disorders, and associated with common pregnancy complications such as preeclampsia, and adverse pregnancy outcomes. High level of oxidative stress was shown in brain tissues of rodents in the model of hHCY.

Population studies suggested a link between migraine and HCY level, especially migraine with aura; however, there is no evidence of this link in animal studies. Migraine is a disabling neurovascular disorder, characterized mainly by unilateral pulsating headache and several neurological symptoms, including hypersensitivity to light known as photophobia, which is one of the leading symptoms of migraine. Moreover, migraine sufferers often acquire various autonomic, cognitive and emotional dysfunctions, including depression and anxiety. About a third of migraine patients complain of transient aura symptoms starting from minutes to hours before the headache or during the headache phase. Cortical spreading depression is a slowly propagating wave of transient neuronal and glial depolarization - an electrical phenomenon of the brain underlies the migraine with aura. In this study, the team used the model of prenatal hHCY to evaluate the sensitivity of rats to cortical spreading depression and behavioral features of migraine. Electrophysiological data indicated that rats with an elevated plasma level of HCY have a higher susceptibility to the development of the cortical spreading depression. Moreover, in the behavioral tests, the authors revealed typical migraine related symptoms in rats with hHCY, such as mechanical allodynia, photophobia and higher anxiety. Taken together, the findings support a link between HCY and migraine with aura; this suggests that timely correction of the elevated HCY level in persons from higher risk groups may be beneficial for treatment.

The study is part of a project related to the investigation of the etiology of migraine. Using experimental animal models, one can reveal mechanisms underlying the excitability of the brain cortex and peripheral afferents innervating the meninges, which triggers migraine attacks. Moreover, the search for endogenous factors provoking migraines will help to develop strategies for the correction of pathological conditions.

The researchers plan to analyze sensitivity of rats with hHCY in nitroglycerine-induced hyperalgesia, photophobia and anxiety, which is widely used to imitate migraine symptoms in rodents. To reveal the molecular mechanisms underlying the higher susceptibility of rats with hHCY to migraine-like symptoms, they will assess the excitability of the peripheral part of the trigeminal system, including recordings of the electrical activity of trigeminal nerve and the membrane properties of isolated trigeminal neurons. Finally, the authors will develop and test strategies for correcting high homocysteine levels, such as administrating vitamins of the B group or antioxidants.

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Kazan Federal University