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Scientists from Nanjing University and the University of Macau have devised a new approach to extend the survival of transplanted probiotics in vivo, enhancing the efficacy of cancer chemo-/immunotherapies in mice. The paper entitled "Smectite promotes probiotic biofilm formation in the gut for cancer immunotherapy" appears online today in Cell Reports.

The gut contains trillions of symbiotic bacteria. Disturbing the balance of intestinal flora may increase the occurrence of major diseases, including cancers. The gut microbiome plays an essential role in regulating the host immunity, which has inspired strategies to modulate intestinal microorganisms for augmenting cancer chemo-/immunotherapy. Studies have shown that probiotics such as Lactobacillus and Bifidobacterium in intestinal flora can activate host immunity and sensitise tumour immunotherapy. Nevertheless, the two major approaches to change the gut microbiome's composition have met with substantial challenges: oral administration of probiotics is often inefficient, and faecal microbiota transplantation (FMT) risks pathogen infection. Therefore, scientists are looking for new and safe strategies to enrich probiotics in the host intestine.

The study found that Smectite, a drug commonly used for treating gastrointestinal diseases such as diarrhoea, could selectively promote the formation of lactic acid bacteria (LAB) biofilms, which foster LAB colonisation in the intestinal tract. The increase of probiotics in the intestinal tract induces anti-tumour immune responses, thereby inhibiting tumour growth and improving immunotherapy efficacy.

The researchers found that Smectite treatment increased Lactobacillus and Bifidobacterium in mice guts. Meanwhile, electron microscopy showed that only Lactobacillus and Bifidobacterium could form biofilms on the surface of Smectite, thanks to the latter's ion-exchanging microstructure. The researchers then demonstrated that oral Smectite exerted anti-tumour effects by altering the intestinal flora of mice. Moreover, considering the low number of beneficial bacteria in the gut, the researchers constructed smectite-lactobacillus-biofilm microspheres (SLB) in vitro. They fed the melanoma model mice with these microspheres, and the SLB showed a more significant anti-tumour effect than using Smectite or Lactobacillus alone.

The team further discovered a possible mechanism that SLB could stimulate dendritic cells' maturation (DCs) through the toll-like receptor 2 (TLR2) signalling. Meanwhile, the proliferation of CD8+T cells was stimulated, and the expression of IFN-γ and IL12 increased. Intriguingly, SLB drove the mature DCs from the colon to the tumour tissue and play the anti-tumour effect. Finally, the researchers further used the SLB in combination with chemotherapy and immunotherapy. In a mouse model, the combination of SLB with doxorubicin or anti- PD-1 antibodies showed better anti-tumour efficacy compared with using SLB, doxorubicin, or anti-PD-1 antibody alone.

This study provides an effective and safe strategy to promote probiotic colonisation and expansion in gut microbiota, via the specific support of Smectite for probiotic biofilm formation. The smectite-aided probiotic treatment was effective in activating the anti-tumour immune responses of DCs and cytotoxic T cells. According to the lead author, Prof Lei Dong, because Smectite has been clinical used for half a century in many countries - albeit, for another application - its safety data may be readily found to accelerate its translation for immunotherapy purpose. This gut microbiome-based, DC-activating therapeutic approach may have immediate translational potential for cancer immunotherapy.

Tampa, FL (Feb. 10, 2021) - Percutaneous coronary intervention (PCI), commonly known as angioplasty with a stent, opens clogged arteries and saves lives. Despite its benefit in treating atherosclerosis that causes coronary artery disease, this common minimally-invasive procedure still poses severe complications for some patients.

Angioplasty involves inflating a balloon at the tip of a catheter to compress fatty deposits (plaques) against the artery wall, thereby restoring blood flow to the narrowed or blocked vessels. The image-guided procedure is often combined with the placement of either uncoated stents -- tiny expandable mesh devices- or stents coated with slowly-released antiproliferative drugs. The drug-eluting stents help avert the growth of scar tissue (smooth muscle cell proliferation) in the artery so that the vessel does not eventually close again, known as restenosis.

However, current antiproliferative drugs indiscriminately inhibit the growth of all nearby cells, including the layer of endothelial cells lining the blood vessels. These endothelial cells prevent blood clots (thrombosis) within the stent and the formation of more plaques (neoatherosclerosis), which can trigger a heart attack or sudden cardiac death.

Focused on tackling this treatment complication, University of South Florida Health (USF Health) Morsani College of Medicine researchers recently developed a next-generation nanotherapy. Their preclinical findings are detailed in a study published Feb. 2 in Molecular Therapy.

The nanotherapy comprised of a nontoxic peptide known as p5RHH and a synthetic messenger RNA (mRNA) that carries the genetic instructions, or code, needed by cells to make proteins. By simply mixing up the p5RHH with the mRNA, they spontaneously self assemble into compacted nanoparticles that specifically target the injured regions of the arteries in mouse models mimicking angioplasty. The nanoparticles contain an microRNA switch added to the mRNA.

"One of the main challenges of cardiovascular disease remains the delivery of targeted therapies specifically to the plaque regions and the cells that form plaques, including the smooth muscle cells and inflammatory cells -- without affecting the endothelial cells or the healthy regions," said the study's principal investigator Hana Totary-Jain, PhD, an associate professor of molecular pharmacology physiology at USF Health Morsani College of Medicine.

To do this, the researchers used mRNA that encodes for p27 protein, which blocks cell growth. They added to the mRNA an endothelial cell-specific microRNA to generate a microRNA switch. The design of this microRNA switch allowed the researchers to turn on the mRNA in smooth muscle cells to inhibit their growth and the formation of restenosis. It also enabled them to turn off the mRNA in endothelial cells so these cells could grow uninhibited and quickly heal the damaged blood vessel.

"If we can come up with an antiproliferative therapy that specifically targets the cardiovascular smooth muscles cells and the infiltrating inflammatory cells but spares the endothelial cells - which we've done with the design of our microRNA switches - then we should be able to achieve the therapeutic effects of drug-eluting stents without the downside of thrombosis and neoatherosclerosis," said the paper's lead author John Lockhart, PhD, who worked on the study as a doctoral student at USF Health Molecular Pharmacology and Physiology. Dr. Lockhart is continuing his postdoctoral training at Moffitt Cancer Center.

The latest study builds upon previous research by Dr. Totary-Jain, indicating that a microRNA-based therapy worked better than drug-eluting stents in a rat model of angioplasty. That work used an adenovirus vector to carry the cell-selective therapy to injured arteries. In this study the viral vector was replaced with a nanoparticle alternative - a change needed to avoid safety concerns and advance the therapy toward use in patients.

The investigational nanoparticles were injected into mice with arteries mimicking post-angioplasty vessel injury every three days for two weeks (5 doses total). Mice treated with the nanoparticles containing the miRNA switch had significantly reduced restenosis and completely restored endothelial cell growth in the injured artery, compared to animals treated with nanoparticles containing mRNA without the miRNA switch, the researchers report.

In addition, the nanoparticles efficiently delivered its mRNA cargo, without degradation, solely to regions of the artery where endothelial cells were damaged. The particles did not toxically accumulate either in the cells of healthy organs (the liver, spleen. lungs or kidneys), or in uninjured arteries adjacent to those requiring treatment. The researchers observed no adverse reactions or outcomes in mice treated with the nanoparticles.

Overall, the findings suggest that the miRNA-switch nanoparticles could be applied clinically to selectively prevent restenosis after PCI by specifically targeting areas of endothelial cell damage to allow quicker cell regrowth and repair of injured arteries.

The USF Health researchers next plan to investigate the potential of the microRNA-switch nanoparticles to directly treat atherosclerotic plaques, thereby eliminating the need for PCI.

"Cardiovascular disease is still the number one cause of death," said Dr. Totary-Jain, a member of the USF Health Heart Institute. "This research offers promise for the development of novel biomolecular therapies to advance the fight against coronary artery disease and peripheral artery disease,"

One person dies of cardiovascular disease every 36 seconds in the U.S., according to the Centers for Disease Control and Prevention.

Black carbon (BC) is the product of incomplete combustion of fossil fuels, biofuel, and biomass. By strongly absorbing solar radiation, BC can heat the atmosphere, affect its stability, and further deteriorate air quality.

The climatic and environmental effects of BC are determined by its loading in the atmosphere. Scientists find that microphysical characteristics of BC, such as particle size and mixing state, can also influence these effects.

The team pointed out that the reduction of the thickly coated BC would further lead to a decline of solar radiation absorption by atmospheric aerosols, besides the decline resulting from the BC loading itself.

Using a single-particle soot photometer (SP2), Dr. Yunfei Wu from the Institute of Atmospheric Physics (IAP) of the Chinese Academy of Science and his collaborators conducted long-term observations of BC loading and microphysical properties in urban Beijing.

In a study published in Environmental Pollution, the researchers reported temporal variations of BC loading and microphysical properties.

"We observed evident decreases of BC loading in the atmosphere of urban Beijing since the implementation of China's Action Plan of Prevention and Control of Air Pollution in 2013," said Dr. Wu. Apparently, strict emission controls contributed to the decrease.

The team also found that emission control measures had impacts on BC size and mixing state. The BC aerosols became "slim", with smaller core sizes and less coatings.

This phenomenon was more pronounced after the comprehensive implementation of the "coal to electricity" measures in Beijing and surrounding areas from 2016. "Coal combustion and biomass burning likely emitted more BC aerosols with larger core sizes and thicker coatings than vehicle exhaust," said Dr. Wu.

Tungsten hexanitride with armchairlike hexazine N6 ring has been synthesized by a group of scientists led by Dr. Jin Liu and his former postdoc Nilesh Salke at HPSTAR (Center for High Pressure Science & Technology Advanced Research). WN6 is a promising high-energy-density and superhard material. Their findings are published in the recent issue of Physical Review Letters.

Diatomic nitrogen is the most abundant molecule in Earth's atmosphere accounting for almost 78% volume. The strong triple bond in nitrogen makes it very stable and unreactive at near ambient conditions. However, in the intense-pressure and high-temperature conditions, nitrogen will behave entirely differently, it can form double- or even single-bonded structure or react with other elements to form novel nitrides. Single-bonded polymeric nitrogen or nitrides possessing single-bonded nitrogen are of great scientific interest as a high-energy-density material. And transition metal nitrides are the very promising candidates that might contain the planar nitrogen hexazine (N6) ring which are predicted to be impossible to stabilize experimentally due to the lone pair repulsion.

The team created WN6 in a laser-heated diamond anvil cell by elemental reaction between tungsten and nitrogen above pressure of about 1.3 Mbar and temperature of ~3500 K. In-situ synchrotron x-ray diffraction (XRD) allowed them to identify the tungsten hexanitride phase, crystallizing with novel armchair-like N6 rings, and the high-pressure Raman spectroscopy measurement confirmed the presence of N-N single bonds in N6 rings. Further theoretical calculations also support their experimental observations.

"The armchair-like hexazine nitrogen sublattice in the WN6 is remarkable and comparable to that in the polymeric nitrogen phases, making it a promising high-energy-density material candidate," remarked Dr. Nilesh Salke, now a postdoctoral researcher at the University of Illinois at Chicago.

Additionally, WN6 shows a Vickers hardness of up to?57 GPa, the highest hardness among all transition metal nitrides along with good toughness. They credited the ultra-stiffness of WN6 to balance between the attractive interaction of N6 rings with W atoms and the repulsive interaction of N6 rings with each other based on theoretical calculations.

"To our knowledge, this is the first experimental report on the single-bonded transition metal nitride," said Dr. Jin Liu, "We believe that this work will stimulate further experimental efforts to synthesize other nitrides with novel structural, chemical, and physical properties."

"Our experimental demonstration of stabilizing armchairlike hexazine N6 ring in WN6 paves the way for future efforts to stabilize planar hexazine ring," added Dr. Liu.

Researchers report that large-scale commercial farms on deforested land in the southern Amazon result in higher temperature increases and less rainfall than small-scale farms.

Deforestation has converted swaths of land in the southern Amazon region from rainforest to farmland. The uses of the deforested land are diverse, and activities can range from small-scale farming in rural settlements to large-scale commodity agriculture. Commercial farms in the Southern Amazon can reach hundreds of thousands of hectares in area, exporting millions of tons in grains and beef every year.

Eduardo Maeda from the University of Helsinki and colleagues used satellite data to compare areas dominated by different land uses and farm sizes to evaluate their impacts on the regional climate. Although small rural settlements experienced no clear changes in rainfall during recent decades, areas dominated by commodity farms have become significantly drier. Areas of commodity farming also experienced a much higher increase in temperature, in comparison with small-scale rural settlements, largely due to intense management of commercial crops leading to reduced vegetation cover throughout the year and decreased plant transpiration. According to the authors, mitigating climate change in the Amazon basin will require alternatives to current commodity farming practices.

"Our results show that deforestation caused by big commodity farms can cause a local temperature increase up to 3x higher than what is observed in deforestation caused by small rural settlements", says Maeda.

Tropical forests are natural air conditioners

Tropical forests act as a water pump, getting water from the land surface and throwing it back into the atmosphere. Because this process requires energy, it causes a reduction in the surface temperature. The water that returns to the atmosphere, often falls back into the forest in the form of rain. The trees then becomes a critical component of a complex water recycling machine, which guarantee that the forest is kept always moist. When the forest is removed, the water returning to the atmosphere is reduced, and the unused energy contributes to increase local temperatures.

The research by Maeda and colleagues demonstrate that this process is further aggravated by large commodity farms. The production of commodity crops in the Amazon forest is often associated with a very intensive management of the land. Because of the favorable climatic conditions, farmers often have two harvesting/seeding seasons per year. These activities completely remove vegetation from the land surface, leading to a warmer and drier local climate.

Although areas dominated by small rural settlements also experience temperature increase, the magnitude of the changes are substantially smaller than those observed in big commodity farms. The authors of the study argue that the main reason is because these small rural settlements are often less managed, leaving a denser and more continuous vegetation cover than in the large monoculture farms.

Alternative agricultural practices needed to help saving the Amazon rainforest

The results of this research provide compelling evidence that alternative agricultural practices will be critical for a sustainable future in the Amazon rainforest.

"This means that stopping deforestation is no longer enough. To protect the remaining forests, farmers in the Amazon region will have to incorporate more sustainable practices".

According to the research, this means that agricultural activities need to be better integrated with the natural Amazon ecosystem.

Agroforestry is for example an interesting alternative, as it seeks to manage forest services and agriculture at the same time, improving soil fertility, increasing water availability, while preserving vegetation cover and microclimate. Reforestation of abandoned pastures and areas of illegal deforestation are also important pathways to mitigate environmental changes.

The authors of the study warn that such changes will not come easily. The production of commodity crops in the Southern Amazon can be a very profitable business. Hence, local and international policies, in combination with actions led by the food industry and civil society organizations, will play a critical role in changing the current mentality. Finally, increasing international awareness and consumers' preference for more sustainable products, will be essential to create real pressure in the supply-chain, hopefully giving some hope for the future of the Amazon rainforest.

Research groups at University of Helsinki and Institut Jacques Monod, Paris, discovered a new molecular mechanism that promotes cell migration. The discovery sheds light on the mechanisms that drive uncontrolled movement of cancer cells, and also revises the 'text book view' of cell migration.

The ability of cells to move within our bodies is critical in wound healing, as well as for immune cells to patrol in our tissues to hunt bacterial and viral pathogens. On the flip-side, uncontrolled movement of cells is a hallmark of cancer invasion and metastasis.

The machinery that drives cell migration is a complex network of dynamic filaments composed of a protein actin. Actin exists in monomeric form, but like Lego bricks, different types of filamentous structures can be built from actin monomers in cells. Actin filaments are organized in cells in a way that their rapidly elongating plus-ends face the plasma membrane, whereas their minus-ends are oriented away from the plasma membrane. Elongation of actin filaments at their plus-ends against the plasma membrane generates the force to push the leading edge of cell forward during cell migration. To maintain a sufficient supply of monomeric actin subunits for filament elongation, actin filaments must be rapidly disassembled in cells, and this is believed to occur at their minus-ends. An important factor that limits actin filament disassembly to their minus-ends is Capping Protein, which binds very tightly to filament plus-ends to block filament elongation and shortening (see related figure).

A new study published in Nature Cell Biology reveals that this 'text book view' of cell migration needs to be revised. The research, led by Academy Professor Pekka Lappalainen from HiLIFE Institute of Biotechnology, University of Helsinki, revealed that a conserved actin-binding protein, Twinfilin, efficiently removes Capping Protein from the filament plus-ends ends. This leads to filament depolymerization also from their 'aged' plus-ends, which no longer push the leading edge of cell forward. In the absence of Twinfilin, actin filament recycling is diminished, filaments push the cell edge forward less efficiently, and cell migration is slower.

"Our results suggest that Twinfilin and Capping Protein make together a 'molecular clock', which ensures that the 'productive' actin filaments pushing the plasma membrane have a sufficient supply of actin monomers, whereas the 'aged' actin filaments that no longer push the plasma membrane are disassembled," says Lappalainen.

"This study highlights the need of several proteins with different functions to act in synergistic manner to maintain the normal morphology and functions of actin networks in cells," continues Dr. Markku Hakala who is the main author of this study.

Despite extensive studies, the precise mechanisms by which actin monomers are recycled in cells has remained elusive. The new study adds an important piece in this puzzle by reveling how Capping Protein is removed from actin filament plus-ends to enable their rapid disassembly. These findings also create a basis for further studies to understand how irregularities in actin disassembly machinery cause severe diseases and developmental disorders.

"Uncontrolled expression of Twinfilin is linked to many diseases, such as breast cancer invasion and lymphoma progression. Our work, therefore, also sheds light on the molecular mechanisms that drive uncontrolled movement of cancer cells," concludes Lappalainen.

Science always strives to replace complex natural objects and phenomena with simpler models. Scientists of Samara Center for Theoretical Materials Science (SCTMS) of Samara Polytech have developed methods to simplify the crystal structure of a substance to obtain chemically important knowledge. The main approaches are described in the article published in the Structural Chemistry journal IF 2.081 (doi:10.1007/s11224-020-01724-4).

"The main goal of simplifying any crystal structure is to understand the features of its structure and properties, and the simplification can be considered justified if it helps to achieve this goal," professor Vladislav Blatov, the SCTMS director, explains. "Another important requirement is that the simplification must follow a strict algorithm in order to avoid human subjectivity, and be applicable to thebig crystallographic data".

The crystallographic model of the crystal structure contains information only about the positions of atoms in space and requires special methods to restore the bond between atoms. All these methods use interatomic distances as the main criterion for the type of bond, but the best results were obtained with additional criteria such as bond strength or parameters of atomic Voronoi polyhedra. As a result, the crystallographic model is transformed into a crystallochemical one, where interatomic contacts of different types are represented by a grid. If all types of interatomic contacts are included in the grid, then it contains comprehensive information about the topology (connectivity) of the substance structure, and, consequently, about its properties associated with the structure. If some nodes (atoms) and / or links (bonds between atoms) are removed from this complete grid, a simplified model is obtained. In general, the simplification procedure can include the following basic operations: removing some atoms, removing some bonds, and combining some atoms together with the bonds between them into structural groups (units).

All these operations are easy to perform in the automated complex of computer programs and electronic databases ToposPro, developed by Vladislav Blatov's team. By analyzing simplified structures, one can find patterns in their structure, hidden in the original complete structures.

Causal reasoning is ubiquitous - from physics to medicine, economics and social sciences, as well as in everyday life. Whenever we press the button, the bell rings, and we think that the pressing of the button causes the bell to ring. Normally, causal influence is assumed to only go one way - from cause to effect - and never back from the effect to the cause: the ringing of the bell does not cause the pressing of the button that triggered it. Now researchers from the University of Oxford and the Université libre de Bruxelles have developed a theory of causality in quantum theory, according to which cause-effect relations can sometimes form cycles. This theory offers a novel understanding of exotic processes in which events do not have a definite causal order. The study has been published in Nature Communications.

One of the ways in which quantum theory defies classical intuitions is by challenging our ideas of causality. Quantum entanglement can be used to produce correlations between distant experiments that are known to evade satisfactory causal explanations within the framework of classical causal models. Furthermore, a unification of quantum theory and gravity is expected to allow situations in which the causal structure of spacetime is subject to quantum indefiniteness, suggesting that events need not be causally ordered at all. Recently, a team of researchers from Oxford and Brussels has developed a theory of causality in quantum theory, in which causal concepts are defined in intrinsically quantum terms rather than pertaining to an emergent classical level of measurement outcomes. This has offered, in particular, a causal understanding of the correlations produced by entangled states. Now, they have generalized the theory to allow causal influence to go in cycles, providing a causal understanding of processes with events in indefinite causal order.

"The key idea behind our proposal is that causal relations in quantum theory correspond to influence through so-called unitary transformations - these are the types of transformations that describe the evolutions of isolated quantum systems. This is closely analogous to an approach to classical causal models that assumes underlying determinism and situates causal relations in functional dependences between variables," says Jonathan Barrett from the University of Oxford.

The main idea of the new study is to apply the same principle to processes in which the order of operations can be dynamical or even indefinite, seeing as a large class of these processes can be understood as arising from unitary transformations, too, just not ones that unfold in an ordinary sequence.

"Previously, processes with indefinite causal order were typically regarded as simply incompatible with any causal account. Our work shows that a major class of them - those that can be understood as arising from unitary processes and which are believed to be the ones that could have a physical realisation in nature - could in fact be seen as having a definite causal structure, albeit one involving cycles," says Robin Lorenz, a corresponding author of the study.

"The idea of cyclic causal structures may seem counterintuitive, but the quantum process framework within which it is formulated guarantees that it is free of logical paradoxes, such as the possibility of going back in time and killing your younger self," explains Ognyan Oreshkov from the Université libre de Bruxelles. "Exotic as they appear, some of these scenarios are actually known to have experimental realisations in which the variables of interest are delocalized in time."

Does this mean that spacetime does not have the acyclic causal structure it is normally assumed to have? Not exactly, since in the mentioned experiments the events that are causally related in a cyclic fashion are not local in spacetime. However, the researchers believe that the causal structure of spacetime itself could become cyclic in this quantum way at the intersection of quantum theory and general relativity, where analogous processes to those realizable in the lab are expected, but with the events being local in their respective spacetime reference frames.

Low-income mothers feminize their children in the womb by adjusting their hormones, whereas high-income mothers masculinize their children, a major study based on finger length, led by a Swansea University expert, has found.

The phenomenon is an unconscious evolutionary response aimed at boosting their offspring's chances of successful reproduction.

It helps, in part, explain associations between low income, low levels of testosterone before birth, and major causes of mortality such as cardiovascular disease.

The study was based on the relationship between the length of a person's index and ring fingers, known as the 2D:4D ratio. A longer ring finger is a marker of higher levels of testosterone, whereas a longer index finger is a marker of higher levels of oestrogen. Generally, men have longer ring fingers, whereas women have longer index fingers.

The 2D:4D ratio is a widely-debated measure that has been the subject of over 1000 studies, but what is significant about the new report is that the team examined the ratio in relation to parental income.

Led by Professor John Manning of Swansea University, with colleagues in Austria and Jamaica, the team tested a hypothesis about evolutionary influences on the mother and her children. This suggests that for higher-income mothers, sons have higher reproductive success compared to daughters. For lower-income mothers, in contrast, daughters will be more reproductively successful. Known as the Trivers-Willard hypothesis, its senior author, Professor Robert Trivers, was also involved in this new study.

The team used data from over 250,000 people from around 200 countries, who were taking part in an online BBC survey. Participants were asked to measure their index and ring fingers and given instructions on how to do this accurately. They were also asked to indicate their parents' income level.

The results showed:

Children of parents of above-average income had a low 2D:4D ratio, with longer ring fingers, which indicates high testosterone and low oestrogen before birth, hallmarks of a more masculinized foetus

Conversely, the children of parents of below-average income had a high 2D:4D ratio with longer index fingers, which indicates lower testosterone and higher oestrogen before birth, markers of a more feminized foetus

These effects were present for both men and women

Professor John Manning of Swansea University's A-STEM research team in sport science, lead researcher on the study, said:

"Our results show that mothers with high income may secrete high levels of testosterone relative to oestrogen early in pregnancy, thereby masculinizing their male and female children. In contrast, women with low income may secrete low levels of testosterone, which will feminize their male and female children.

This is an evolutionary response, which mothers will not be aware of, let alone able to control. It is geared towards giving their offspring the best chance of reproductive success.

For high-income mothers, the advantages of high testosterone for their sons are likely to outweigh its disadvantages for their daughters. For low-income mothers, the fitness gain from feminized daughters is likely to outweigh the fitness loss for feminized sons.

This pattern is consistent with the Trivers-Willard hypothesis."

Professor Manning explained how the findings could shed light on susceptibility to disease:

"These patterns suggest important effects on public health which are linked to poverty.

Low testosterone and high oestrogen in male foetuses may predispose those men, as adults, to diseases linked to poverty such as heart attacks, strokes, and high blood pressure.

It is well known that poverty is closely associated with poorer health. What our research indicates is that this link can be replicated across generations".

Anaphylaxis is a systemic allergic reaction that can affect the skin, the gastrointestinal tract, the respiratory system and the cardiovascular system. The most severe form of anaphylaxis is anaphylactic shock, which features hypotension and can cause death. This reaction can have several causes, such as allergic reactions to food, medicines or insect venom.

The molecular mechanisms that cause the severity of these kinds of reactions is still unknown. In a study led by researchers of the University of Barcelona and IDIBAPS, researchers analyzed the mutation of a gen detected in a patient who suffered from recurrent anaphylactic shocks caused by the allergy to paper wasp venom (Polistes dominula). The results, published in the Journal of Allergy and Clinical Immunology, revealed a new molecular mechanism that can control the degree of severity in an anaphylactic reaction.

The study is led by UB and IDIBAPS researchers Margarita Martín and Rosa Muñoz-Cano. Both are members of the Asthma, Allergic and Adverse Reactions Network (ARADyAL) of the Carlos III Institute.

Researchers carried out the biochemical, functional and structural characterization of mutations in the KARS gen, detected in the patient. "The study combines clinical data from the patient with severe anaphylaxis and carrier of a mutation in the KARS gen, with biochemical, functional and structural data that show an anomalous function of the LysRS protein, coded by this gen", notes Margarita Martín.

The LysRS protein is an enzyme with a dual function. It plays a key role in the protein synthesis, and it is regulated by the phosphorylation in the highaffinity receptor for immunoglobulin E (IgE) and activates the MITF transcription factor, which takes part in the transcription of proinflammatory mediators in the mast cell, a type of cells in the immune system that act as inflammatory processes caused by allergic reactions.

From the biochemical perspective, results show that the replacement of a proline for an arginine in the LysRS protein aminoacid 542 causes structural changes. These changes affect the protein, which moves towards the nucleus and stops its function in the protein synthesis, activating the MITF transcription factor when there is a lack of stimuli. "This cause sthe increase in the synthesis of proinflammatory mediators and an activation of the mast cell in presence of the allergen, which drives to an anaphylactic shock. The new mechanism identified in this study involves the signalling base IgE-LysRWS-MITF, which would control the degree of severity in an anaphylactic reaction", says Margarita Martín.

"This discovery will enable us to identify those patients at risk of having severe anaphylaxis, probably beyond those caused by the paper wasp, and set the proper prophylactic measures", concludes Rosa Muñoz-Cano, also doctor in the Allergology Department of Hospital Clínic.

Moreover, the analysis of the structure and dynamics of LysRS carried out by the group led by researcher Modesto Orozco (UB-IRB Barcelona), who took part in the study as well, identifies for the first time the change mechanism f LysRS from translation to transcription at a molecular level.

A team of researchers from the Laboratory of Biophysics at NUST MISIS, Lomonosov Moscow State University and D. Mendeleev University of Chemical Technology of Russia has summarized metal-containing diagnostic agents for positron emission tomography (PET), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) imaging of Alzheimer's disease (AD). According to the researchers, metal-containing radiopharmaceuticals are not only highly effective for detecting early markers of Alzheimer's disease, but also synchrotron-independent and long-lived. Thus, their use could improve access to diagnostic imaging of AD among the risk groups. The review was published in the International Journal of Molecular Sciences.

Alzheimer's disease is the most common form of dementia. It is a progressive neurological disease that leads to a decline in memory and other cognitive abilities. AD is associated with the deposition of so-called amyloid protein plaques in the brain that disrupt communication among neurons, resulting in loss of function and cell death. Amyloid plaques are a hallmark of AD, occurring 7-15 years before the onset of cognitive symptoms of the pathology. They allow doctors to diagnose Alzheimer's earlier -- even before any symptoms appear.

Timely diagnostic imaging plays an important role in managing AD. Identifying it at an early stage and initiating therapy can delay the progression of the disease. Amyloid deposits in the brain can be PET-traced using special radioactive markers that bind to different amyloids. However, using these drugs requires an expensive laborious synthesis with confirmation of radio purity at each stage. The short half-lives of the currently used radionuclides carbon-11 (11C) and fluorodeoxyglucose (18F) -- 20 and 109 minutes respectively -- may also limit the widespread use of these imaging agents, since they can only be transported a short distance before use and have to be used immediately upon arrival.

The solution could lie in metal-containing diagnostical agents. Copper, zinc and iron cations have been proven to bind to amyloids, highlighting amyloid plaques, which raises the possibility of designing copper-, zinc and iron-based metal complexes for the diagnosis and theranostics of AD. AD diagnostic agents radiolabeled with the copper isotope 64Cu are attractive not only due to the simple and fast introduction of radionuclide at the last stage of non-radioactive synthesis, but also due to its 12-hour half-life, perfect for PET imaging.

Another promising PET radionuclide is gallium-68 (68Ga). Its parent nuclide, 68Ge, has a half-life of 271 days, and the existing generators can provide sufficient quantities of 68Ga for up to one year, resulting in a relatively inexpensive and reliable source of a positron-emitting radionuclide. In addition to PET imaging of amyloids, metal-containing agents could be used for AD visualization by the means of single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI).

However, the development of AD imaging agents is restricted by the presence of the blood-brain barrier (BBB) which limits the substance from reaching the cerebral target. The BBB is a highly selective mechanism that controls the passage of substances from the blood into the cerebrospinal fluid and thus into the brain, and serves as the clearance path for waste metabolites of the brain. Thus, the BBB makes it difficult to develop new treatments of brain diseases, or new radiopharmaceuticals for neuroimaging of the brain.

A few metal-based agents have demonstrated the ability to cross the BBB and bind with amyloid in the brain: 64Cu, 68Ga and 99mTc (technetium-99 m). These isotopes are significantly easier to produce than 11C and 11F, with a longer life-span. Among the variety of compounds considered in the review, the most promising results were shown by copper-based coordination compounds for PET imaging, gallium-based coordination compounds for MRI, and technetium -based coordination compounds for SPECT imaging.

Ithaca, NY--Love them or hate them, there's no doubt the European Starling is a wildly successful bird. A new study from the Cornell Lab of Ornithology examines this non-native species from the inside out. What exactly happened at the genetic level as the starling population exploded from just 80 birds released in New York City's Central Park in 1890, peaking at an estimated 200 million breeding adults spread all across North America? The study appears in the journal Molecular Ecology.

"The amazing thing about the evolutionary changes among starling populations since they were introduced in North America is that the changes happened in a span of just 130 years in parallel with a huge expansion in the bird's range and population size," says lead author Natalie Hofmeister, a doctoral candidate at the Cornell Lab. "For a long time we didn't think that was possible--that it took millions of years for genetic mutations to change a genome."

The genetic differences found among North American starlings are very subtle. In fact, after researchers sequenced the genomes of birds from widely distributed locations around the United States, the genomes were all remarkably alike--any starling could undoubtedly mate successfully with another, no matter where they're originally from. But the researchers did find the genetic signatures of change in areas of the genome that control how starlings adapt to variations in temperature and rainfall. Study authors concluded the birds had undergone "rapid local adaptation," adjusting to conditions not found in their native European range.

Another key factor is movement. The study points out that there's a lot of movement among starlings. All that movement means starlings kept establishing new populations as they spread westward, and each population had to adapt to new environments. The adaptation may not have resulted from a new mutation but from an existing genetic variation in the founding population.

"A genetic variation that might not have been useful in one environment could turn out to be very beneficial in another," Hofmeister explains. "So, a variation related to temperature and rainfall that enhanced survival became more common in a new environment." The massive size of the total starling population across North America meant these gene variants could be passed along across the generations.

European Starlings in North America are unusual in another way. Species with a highly restricted gene pool--a genetic bottleneck--are more likely to become extinct because of fertility issues associated with in-breeding, a problem that endangered animals also face. The introduction of just 80 birds in Central Park (released in an attempt to introduce all the birds mentioned in Shakespeare's plays to North America) was one of many attempted introductions in other parts of the country. It's possible the resulting gene flow among these populations prevented the species from dying out. It's an area of speculation ripe for further study.

"What I think is really cool is that the starlings in North America appear to have adapted to different conditions across the range," Hofmeister says. "So, it wasn't just that they reproduced really quickly, and then just kept reproducing. It's that they specialized once they arrived in new areas."

Despite their success and large numbers, the European Starling is now in steep decline, like so many other species in North America. The current population is half the size it was 50 years ago--down from an estimated 166.2 million breeding birds in 1970 to 85.1 million (Rosenberg et. al. Science 2019) . The species is also declining in Europe.

Though starlings are reviled for some of their less admirable habits and their impact on native species, Hofmeister says they're fascinating birds and really quite beautiful. And they're allowing scientists to follow one of the many threads that influence avian evolution.

LAWRENCE -- Traditional burial in a graveyard has environmental costs. Graves can take up valuable land, leak embalming chemicals and involve nonbiodegradable materials like concrete, as well as the plastic and steel that make up many caskets. But the other mainstream option -- cremation -- releases dangerous chemicals and greenhouse gasses into the environment.

So, what's an environmentalist to do when making plans for the end of life?

A new study from the University of Kansas in the journal Mortality details how older environmentalists consider death care and how likely they are to choose "green" burials and other eco-friendly options.

"This article is specifically asking if older adult environmentalists consider how their bodies are going to be disposed as part of their environmental activism," said lead author Paul Stock, associate professor of sociology and environmental studies at the University of Kansas.

In addition to a literature review on the ecological costs of various disposal methods, Stock and co-author Mary Kate Dennis of the University of Manitoba interviewed 20 people in the Kansas. Participants were 60 years and older, engaged in environmental activities and possessed spiritual values that guided their environmentalism.

"We were really surprised to see both answers -- that yes, they're planning on green burial, and no, it's not even on their radar," Stock said. "We were often the ones introducing these people that are so knowledgeable in so many areas of the environment and activism to green burial. We would ask them, 'Do you want your body to be buried in a green burial?' And many would say, 'I don't know what that is, can you tell me about it?'"

The researchers said awareness of green burials -- where a body is placed into the soil to facilitate decomposition without durable caskets or concrete chambers -- is growing for some older people. But the practice of green burial remains clouded by a funeral industry looking to make profits, and it can be influenced by considerations of family, religious and cultural traditions, as well as the practices of institutions like the military that carry out funerals.

"The business of burial has shaped all of our ideas about how we can be buried," Dennis said. "A lot of participants said they weren't aware of green burial. We're sort of presented with two choices -- you're going to be put in the cemetery or cremated. Then, we start expanding to other options, but that's only been in recent times. You see some of their desires, like, 'I want to be put out on the land.' Or you see in some of our green-burial narratives where people took it into their own hands. But you have to have be empowered to go against the grain, so I think for a lot of us we didn't even know a green burial was possible, and pushback from society, capitalism and the funeral industry has created a situation where we don't even know the possibilities -- some of the environmentalists in our study didn't know there were laws that say they can be buried on their own land."

The researchers found more than half of their environmentally minded participants planned on eventual cremation.

Among those planning burials, there was "unequal knowledge about green burial as an option" even though Lawrence is at the vanguard of green burial in its municipal regulations and even boasts a green-burial section in the local cemetery, Oak Hill, where "metal, concrete, plastic, other synthetic materials and/or stone may not be used for interment."

"We heard different stories and different requests or thoughts of what they're going to ask their loved ones to do with their bodies," Stock said. "The introduction of green burials is very much -- like a lot of their thoughts on where or how they wanted to be disposed of -- about a sense of place. What struck us and what was so interesting was that Lawrence had, at least at the time, the only municipal-owned cemetery in the country that allowed green burials."

Perhaps the varying answers given by participants is a result of a lack of conclusive evidence that no one form of handling human remains is decidedly more eco-friendly than another, as the issue has been little-studied.

"There's not a clear line," Stock said. "What really struck us was there's not actually too much science done on comparing what's more environmental. There are really just one or two papers out there using common environmental measurements -- whether it's a carbon footprint or some other kind of way -- to even give us technical measurements to compare. We essentially don't have too much information to guide us as scientists, much less for older adults as to what is the greenest way of taking care of ones remains."

The investigators predicted that as green burials gain in popularity, more options for green disposal of bodies will become commonly available, even ones that today seem eccentric.

"The mushroom suit -- when we talk about that with our undergrads they're usually sort of puzzled and intrigued," Dennis said. "People wonder, 'How does that work?" But it's an interesting one. Basically, you're wrapped in material and then mushrooms grow out of you, and it cleans the toxins. There's going to be more new and awesome ways to be buried that we haven't even heard of yet."

UCLA RESEARCH ALERT

FINDINGS

In a study of mice, researchers at the UCLA Jonsson Comprehensive Cancer Center have identified a new approach that combines an anti-psychotic drug, a statin used to lower high cholesterol levels, and radiation to improve the overall survival in mice with glioblastoma. Glioblastoma is one of the deadliest and most difficult-to-treat brain tumors. Researchers found the triple combination extended the median survival 4-fold compared to radiation alone.

BACKGROUND

Radiation therapy is part of the standard-of-care treatment regimen for glioblastoma, often helping prolong the survival of patients. However, survival times have not improved significantly over the past two decades and attempts to improve the efficacy of radiotherapy through the use of pharmaceuticals have been hampered by the normal tissue toxicity of the drugs and the inability to penetrate the blood-brain barrier.

UCLA researchers previously reported that the first-generation dopamine receptor antagonist trifluoperazine in combination with radiation prolonged survival in mouse models of glioblastoma, but ultimately, the mice become resistant to the therapy. To help overcome this resistance, the team used quetiapine, a second-generation dopamine receptor antagonist, which not only enhanced the efficacy of radiotherapy in glioblastoma but also generated a metabolic vulnerability in the lipid homeostasis. The discovery that the combination induced the cholesterol biosynthesis pathway allowed the team to target this process with statins.

METHOD

The team tested the approach using patient-derived glioblastoma lines provided by the Biospecimen and Pathology Core of the UCLA SPORE in Brain Cancer. Quetiapine was identified in a screen of dopamine receptor antagonists for their ability to prevent phenotype conversion of non-tumorigenic glioblastoma cells into radiation-induced glioma initiating cells. Atorvastatin (Lipitor) was selected because of its known ability to cross the blood-brain-barrier.

IMPACT

While radiation alone prolongs survival of glioblastoma to some extent, attempts to enhance the treatment have not been successful. The results of the study provide evidence that using a dopamine receptor antagonist in combination with Atorvastatin and radiation may help extend the survival for people with glioblastoma. The combination therapy also includes FDA-approved drugs that can rapidly be translated into a clinical trial.

The construction of a major railway through Kenya will have long-term environmental impacts on the area, suggesting more work needs to be done to limit the damage on future infrastructure projects, a major study reveals.

The biggest impact of the Standard Gauge Railway (SGR), which runs from Mombasa to Nairobi, was pollution and contamination of soil, water and air, as well as disruption of natural processes.

The research, led by the University of York and part of the Development Corridors Partnership project, also showed environmental issues as a result of breaking up large areas of habitat into smaller, more isolated patches, that may not be able to support long-term natural processes.

The SGR project was given the go-ahead following the completion of two Environmental and Social Impact Assessments, but scientists question how effectively recommendations were implemented in the development, given the evidence of widespread environmental degradation that can be seen in the area.

Professor Robert Marchant, from the University of York's Department of Environment and Geography, said: "African nations are looking forward to large-scale infrastructure investment as a catalyst for economic growth, but our research shows that before this can happen more work is needed to quantify ecological impacts on the land.

"Not only this, but should issues arises once the projects are complete, there must be a ready-to-go mitigation strategy that can be applied to reduce further damage quickly."

The researchers recommend that environmental impacts are integrated into the planning of largescale infrastructure projects at every stage, and call for a particular focus on engaging and consulting key stakeholders in the design and implementation phases of the project.

Dr Tobias Nyumba, Post-Doctoral Researcher at the Development Corridors Partnership, said: "These steps are essential, if a 'transportation corridor' is to become a true 'development corridor', bringing sustainable development and social wellbeing to a country such as Kenya, while minimizing or eliminating environmental damage."