Culture

Cellular powerplant recycles waste gases

image: CODH/ACS crystals obtained without oxygen. The brown color is coming from the natural metals harboured by the proteins (depicted as orange and green balls in the Figure 2).

Image: 
Max Planck Institute for Marine Microbiology/T. Wagner

Waste gases of many branches of industry contain mainly carbon monoxide and carbon dioxide. Nowadays, these gases are simply blown into our atmosphere, but this may soon change. The idea is to use the power of bacteria to turn toxic waste gases into valuable compounds such as acetate or ethanol. These can be used afterwards as biofuels or basic compounds for synthetic materials. The first real-size test plants are already under evaluation, using this conversion at an industrial scale, and the stars of these process are bacteria that devour carbon monoxide, carbon dioxide and dihydrogen, among which Clostridium autoethanogenum is by far the favorite.

"In this microbe, the main lines of the metabolism used to operate the gas conversion have been characterized," says Tristan Wagner, leader of the group Microbial Metabolism at the Max Planck Institute for Marine Microbiology. "But there are still a lot of question marks at the molecular level". The one in focus of the scientists from Bremen: How is the toxic carbon monoxide processed by enzymes at such stunning efficiency?

Big surprise in a crystal

The molecular-level knowledge of the carbon monoxide conversion is derived from studies performed in the species Moorella thermoacetica. This is a convenient and well-studied marine model organism but exhibits a poor ability to detoxify waste gases, unlike Clostridium autoethanogenum. Both bacteria use the same enzyme to convert carbon monoxide: the CO-dehydrogenase/Acetyl-CoA synthase, shortened as CODH/ACS. It is a very common enzyme which existed already in primeval times of the earth. "Since both species use the same enzyme to convert carbon monoxide, we were expecting to see exactly the same structure with eventually minor differences," says Wagner.

For their research, Wagner and his colleague Olivier N. Lemaire are studying the bacterium Clostridium autoethanogenum to understand how it can thrive at the thermodynamics of Life, using a metabolism similar to that of the first living forms. Olivier N. Lemaire grew the bacteria and purified its CODH/ACS in absence of oxygen, which is detrimental to the enzyme. The two scientists used the crystallization method to obtain crystals of the enzyme CODH/ACS and determine the protein 3D-structure by X-ray crystallography. "When we saw the results, we couldn't believe our eyes," says Wagner. "The CODH-ACS interface from Clostridium autoethanogenum drastically differs from the model of Moorella thermoacetica, even though it was the same enzyme and similar bacteria".

Same ingredients, different architecture

Afterwards, the two researchers carried out further experiments to prove that the first structure was not an artifact but the biological reality. Following experiments confirmed the initial model. Thus, the discovery clearly proves wrong the previous assumption that the enzyme CODH/ACS always has the same overall structure. "The enzyme of Moorella thermoacetica has a linear shape," explains Olivier N. Lemaire, first author of the study, which was recently published in the scientific journal BBA Bioenergetics. "In Moorella thermoacetica, the enzyme produces carbon monoxide in the CODH and uses in the ACS. Between them, it is trapped and funneled through a sealed gas-channel. ACS will ultimately synthesize acetyl-CoA, a building block further processed into acetate and ethanol. The rest of the cell do not see any carbon monoxide".

But Clostridium autoethanogenum absorbs carbon monoxide directly. "In Clostridium autoethanogenum the enzyme CODH/ACS has not only one opening, but several. In this way it can collect as much carbon monoxide as possible and conduct it into a whole system of tunnels, operating in both directions", says Lemaire. "These results show a reshuffling of internal gas-tunnels during evolution of these bacteria, putatively leading to a bidirectional complex that ensures a high flux of carbon monoxide conversion toward energy conservation and assimilation of carbon monoxide, acting as the main cellular powerplant". At the end of the process also acetate and ethanol are generated, which can be used to produce fuels.

"We now have a picture of what this very efficient and robust enzyme looks like", says Tristan Wagner. "But our discovery is only one step further. Among other things, it is still an open question how the bacterium can survive and use carbon monoxide to feed their whole cellular energy needs. We have some hypotheses, but we are still at the beginning. To understand the whole chemical process of converting carbon monoxide to acetate and ethanol, further proteins need to be studied".

Credit: 
Max Planck Institute for Marine Microbiology

Liver condition identified in patients using urine samples: new research

Fifty protein fragments known as peptides associated with liver fibrosis were found in the urine of patients, according to collaborative study between University of Warwick, Mosaiques Diagnostics, Hannover Medical School and University Hospitals Coventry and Warwickshire

The identified peptides could be potentially used in a test to spot people with the condition if further validated

Liver fibrosis is often symptomless in early stages and can progress to cirrhosis and liver cancer

Fifty fragments of proteins, termed peptides, have been identified in the urine of liver fibrosis patients in a new study that could pave the way for a potential diagnostic urine test for the condition if further validated.

The research was led by scientists from the University of Warwick, University Hospitals Coventry and Warwickshire (UHCW), Mosaiques Diagnostics and Hannover Medical School, who have published their analysis in the journal EBioMedicine.

Liver fibrosis can be a 'silent killer' as sufferers usually do not experience any symptoms until very late stage, when they start to lose the liver function. Patients then typically experience jaundice, ascites (build-up of fluid in the abdomen), variceal gastrointestinal bleeding, and in some cases can result in cancerous formation in the liver.

Previous research on biopsies from fibrotic livers has shown evidence of changes of proteins in liver tissue cells. As part of his PhD at the University of Warwick, Dr Ayman Bannaga, a clinical research fellow at UHCW, investigated whether these protein changes could also be present in a patient's urine, and whether they could act as a biomarker of the condition.

The research team used a total of 393 urine samples divided into discovery and test sets, representing individuals with various liver diseases and those with no disease present. These were investigated using an advanced technology known as capillary electrophoresis mass spectrometry, that separated out protein components in the urine at a molecular level. Following a two-step validation analysis, the researchers found fifty peptides associated with liver fibrosis in patients, mainly fragments of a protein called collagen.

When they tested a new set of patients for these fifty peptides, they correctly identified liver fibrosis patients in 84.2% of cases (sensitivity), and correctly identified those without it in 82.4% of cases (specificity).

While the results require further validation by other research teams, the researchers hope that their findings could form the basis of a simple and cost effective urine test that could spot those who have liver fibrosis before it progresses, although it may be many years before this is seen in clinical practice.

Dr Ayman Bannaga, a PhD student at Warwick Medical School, said: "A urine test is an attractive tool because it is easy to collect from patients, and so this approach can be easily applied in hospitals and GP practices. The ideal potential vision for this test would be to check the condition in people who do not have symptoms to tackle it early, through education, monitoring and medications if needed.

"There are a number of causes of liver fibrosis including viruses such as hepatitis B and C, excessive alcohol consumption, a build-up of fat in the liver, and some auto-immune diseases."

When the liver becomes fibrotic, proteins called collagens shrink the liver, causing the liver to become smaller and stiffer and affecting its function. Fragments of these proteins, which scientists term peptides, find their way into the blood, where they will be filtrated into the kidneys and leave the body via the urine. Currently detecting these protein changes would have to be done using a biopsy, but a urine test would be much easier and less invasive for patients.

Dr Bannaga adds: "Liver fibrosis affects people who are productive, those who drink lots of alcohol, people with sedentary lifestyles. A recent UK study done by a Bristol group showed that 1 in 40 people around the age of 24 years have fibrosis."

Professor Ramesh Arasaradnam OBE, Consultant Gastroenterologist and Dr Bannaga's PhD supervisor at Warwick Medical School, said: "Analysing urine for the purposes of diagnostics is a promising research area, and this new study builds on existing work in my research group looking at urine peptides in colon cancer. While we are unlikely to see this in clinical practice for some time, it provides an avenue for further investigation that could help in the prevention of this terrible condition."

Credit: 
University of Warwick

Tiny cave snail with muffin-top waistline rolls out of the dark in Laos

image: The new transparent "muffin-topped" snail, Laoennea renouardi.

Image: 
Estée Bochud

A new species of tiny cave snail that glistens in the light and has a muffin-top-like bulge, was discovered by Marina Ferrand of the French Club Etude et Exploration des Gouffres et Carrie?res (EEGC), during the Phouhin Namno caving expedition in Tham Houey Yè cave in Laos in March 2019. The new species, Laoennea renouardi, is 1.80 mm tall and is named after the French caver, Louis Renouard, who explored and mapped the only two caves in Laos known to harbor this group of tiny snails. Only two species of Laoennea snail are known so far, L. carychioides and now, L. renouardi.

Caver and scientist, Dr. Adrienne Jochum, affiliated with the Natural History Museum Bernand University of Bern (Switzerland), as well as the Senckenberg Research Institute and Natural History Museum (Frankfurt, Germany) described the new species and its cave habitat together with co-authors: Estée Bochud, Natural History Museum Bern; Quentin Wackenheim, Laboratoire de Géographie Physique (Meudon, France) and Laboratoire Trajectoires (Nanterre, France); Marina Ferrand, EEGC; and Dr. Adrien Favre, Senckenberg Research Institute and Natural History Museum, in the open-access, peer-reviewed journal Subterranean Biology.

"The discovery and description of biodiversity before it disappears is a major priority for biologists worldwide. The caves in Laos are still largely underexplored and the snails known from them remain few in number," points out Dr. Jochum.

The fact that two species of tiny cave snails of the same group were found in two caves located in two independent karstic networks 3.4 km apart, caused the authors to question evolutionary processes in these underground hotspots of biodiversity. The authors hypothesise that the two caves might have been connected during the Quaternary, around 100-200 thousand years ago. In time, the river Yè might have formed a barrier, thus disconnecting the cave systems and separating the populations. As a result, the snails evolved into two different species.

Credit: 
Pensoft Publishers

Scientists discover a new mineral

image: Petrovit

Image: 
SPbU

For more than 40 years, Stanislav Filatov, Professor at St Petersburg University, together with colleagues from other research institutions in Russia, has been studying the mineralogy of scoria cones and lava flows of fumaroles in Kamchatka. They were formed after two major eruptions of Tolbachik Volcano - in 1975-1976 and 2012-2013. This territory is unique in its mineralogical diversity. In recent years, researchers have discovered dozens of new minerals here, many of which are one-of-a-kind in the world.

The recent find by the scientists from St Petersburg University, petrovite, Na10CaCu2(SO4)8, occurs as blue globular aggregates of tabular crystals with gaseous inclusions. 'The copper atom in the crystal structure of petrovite has an unusual and very rare coordination of seven oxygen atoms. Such coordination is characteristic of only a couple of compounds, as well as of saranchinaite, which was discovered by our colleagues from St Petersburg University - the research team of Professor Oleg Siidra,' said the project manager, Professor Stanislav Filatov.

The mineral consists of oxygen atoms, sodium sulphur and copper, which form a porous framework. The voids are connected to each other by channels through which relatively small sodium atoms can move. The scientists have therefore established that the structural type of petrovite is promising for ionic conductivity and can be used as a cathode material for sodium ion batteries.

'At present, the biggest problem for this use is the small amount of a transition metal - copper - in the crystal structure of the mineral. It might be solved by synthesising a compound with the same structure as petrovite in the laboratory,' said Stanislav Filatov.

Credit: 
St. Petersburg State University

Scientists discover new mechanism controlling brain size

image: The research team used stem cells and zebrafish to investigate the role of RRP7A in brain development. The picture shows the brain of a normal zebrafish larvae (left) and a larvae with microcephaly (right).

Image: 
Assist. Prof. Canan Doganli, University of Copenhagen

Under the leadership of Professor Lars Allan Larsen and Professor Søren Tvorup Christensen at University of Copenhagen (UCPH), Denmark, an international research team has taken an important step forward in understanding the complex mechanisms that control development of the so-called cerebral cortex, which is the part of the brain that play a key role in attention, perception, awareness, thought, memory, language, and consciousness. The results have just been published in the internationally recognized journal Nature Communications.

The scientists started with genetic analyses of a large family in which children were born with primary microcephaly; a rare congenital brain disorder characterized by a reduction in the size of the cerebral cortex and varying degree of cognitive dysfunction. The scientists found that the children were carriers of a mutation in both copies of the gene, RRP7A, and by the use of stem cell cultures as well as zebrafish as model organism, RRP7A was shown to play a critical role for brain stem cells to proliferate and form new neurons. This process is extremely complex and slight disturbances may have serious consequences, which may explain why the mutation affects the brain and no other tissues and organs.

- "Our discovery is surprising, because it reveals hitherto unknown mechanisms involved in the development of the brain. In addition, it highlights the value of research in rare disorders, which is important both for the patients and family affected by the disease but also beneficial for society in the form of new knowledge about human biology", states Lars Allan Larsen, Department of Cellular and Molecular Medicine.

The researchers further discovered that the mutation in RRP7A affects the function of the so-called primary cilia, which project in a single copy as antenna-like structures on the surface of cells to register environmental cues and control the formation of new neurons in the developing brain.

- "Our results open a new avenue for understanding how primary cilia control developmental processes, and how certain mutations at these antenna-like structures compromise the formation of tissues and organs during development. To this end, we have already initiated a series of investigations to understand the mechanisms by which RRP7A regulates ciliary signaling to control formation and organization of neurons in the brain, and how defects in this signaling may lead to brain malformation and cognitive disorders, says Søren Tvorup Christensen at Department of Biology.

Credit: 
University of Copenhagen - Faculty of Science

Pesticides commonly used as flea treatments for pets are contaminating English rivers

Researchers at the University of Sussex have found widespread contamination of English rivers with two neurotoxic pesticides commonly used in veterinary flea products: fipronil and the neonicotinoid imidacloprid. The concentrations found often far exceeded accepted safe limits.

These chemicals are banned for agricultural use due to the adverse environmental effects, but there is minimal environmental risk assessment for pesticides used on domestic cats and dogs. This is due to the assumption that there are likely to be fewer environmental impacts due to the amount of product used.

But there is growing concern that this assumption may be incorrect. To investigate this, Professor Dave Goulson and Rosemary Perkins from the University of Sussex analysed data gathered by the Environment Agency in English waterways between 2016-18. They found that fipronil was detected in 98% of freshwater samples, and imidacloprid in 66%.

Rosemary Perkins, a PhD student at Sussex and a qualified vet, said: "The use of pet parasite products has increased over the years, with millions of dogs and cats now being routinely treated multiple times per year".

"Fipronil is one of the most commonly used flea products, and recent studies have shown that it degrades to compounds that are more persistent in the environment, and more toxic to most insects, than fipronil itself. Our results, showing that fipronil and its toxic breakdown products are present in nearly all of the freshwater samples tested, are extremely concerning."

According to the Veterinary Medicines Directorate (VMD), who funded the research, there are 66 licensed veterinary products containing fipronil in the UK, and 21 containing imidacloprid, either alone or in combination with other parasiticides. These include spot-on solutions, topical sprays and collars impregnated with the active ingredient.

While some of these products can be purchased only with a veterinary prescription, others can be bought without a prescription from pet shops, supermarkets, pharmacies and online. Many pet owners receive year-round preventative flea and/or tick treatment from their vet practice via healthcare plans.

Fipronil has a history of very limited agricultural use prior to its ban in 2017. It is also licensed for use in ant and cockroach baits, however only one product is licensed for use by non pest-control professionals. Use on pets seems to be the most plausible source of the widespread contamination of rivers.

The paper, co-authored with Martin Whitehead from the Chipping Norton Veterinary Hospital and Wayne Civil at the Environment Agency, examines the occurrence of fipronil and imidacloprid in English rivers as indicators of the potential contamination of waterways from the use of pet flea treatments.

They found that the average fipronil concentration across the rivers sampled by the Environment Agency exceeded chronic safety thresholds five-fold. The overall pollution levels in English rivers indicate that fipronil and its toxic breakdown products pose a high risk to aquatic ecosystems.

While, in most rivers, imidacloprid was found to pose a moderate risk, in seven out of the 20 rivers sampled there was a high environmental risk.

Co-author Professor Dave Goulson said "Fipronil and imidacloprid are both highly toxic to all insects and other aquatic invertebrates. Studies have shown both pesticides to be associated with declines in the abundance of aquatic invertebrate communities. The finding that our rivers are routinely and chronically contaminated with both of these chemicals and mixtures of their toxic breakdown products is deeply troubling."

The paper, published in Science of the Total Environment, notes that the highest levels of pollution were found immediately downstream of wastewater treatment works, supporting the hypothesis that significant quantities of pesticide may be passing from treated pets to the environment via household drains.

Bathing of pets treated with spot-on fipronil flea products has been confirmed as a potentially important route to waterways for fipronil via sewers, and the washing of hands, pet bedding or other surfaces that have come into contact with treated pets are potential additional pathways for entry to sewers. Other pathways for contamination of waterways includes swimming and rainfall wash-off from treated pets. The strong correlation between fipronil and imidacloprid levels across the river sites tested suggest that they may be coming from a common source.

Rosemary Perkins added: "We've identified a number of steps that can be taken to minimise or avoid environmental harm from pet flea and/or tick treatments. These range from introducing stricter prescription-only regulations, to considering a more judicious and risk-based approach to the control of parasites in pets, for example by moving away from blanket year-round prophylactic use.

"We'd recommend a re-evaluation of the environmental risks posed by pet parasite products, and a reappraisal of the risk assessments that these products undergo prior to regulatory approval."

Credit: 
University of Sussex

Parasite infection discovery could assist mental health treatments

image: T.gondii parasites

Image: 
plos.org

New research into how a common parasite infection alters human behaviour could help development of treatments for schizophrenia and other neurological disorders.

Scientists say behaviour changes in those infected with T. gondii, which currently infects 2.5 billion people worldwide and causes the disease Toxoplasmosis, could be linked to lowered amounts of norepinephrine, a chemical released in the brain as part of the stress response. Norephinephrine also controls neuroinflammation, the activation of the brain's immune system against infection.

Norepinephrine and neuroinflammation are associated with neuropsychological disorders such as schizophrenia, Alzheimer's disease, and ADHD.

Although usually considered asymptomatic in humans, T. gondii infection can cause headache, confusion and seizures in others as well as an increased susceptibility to schizophrenia - and can be fatal to immunocompromised patients.

T. gondii can only sexually reproduce in cats. It forms cysts which are shed in the cat's faeces. It makes its way into new hosts through ingestion of anything contaminated by these cysts, such as water, soil or vegetables; through blood transfusions, from unpasteurised goat's milk; eating raw or undercooked meat, or from mother to foetus.

After a few weeks, the infection enters a dormant phase, whereupon cysts form in the brain. They can remain there for many years, possibly for life. It is during this stage that infection decreases the regulator of the brain's immune response norepinephrine.

The mechanisms by which the parasite affects brain function have been poorly understood. But research led by the University of Leeds and Université de Toulouse now suggests that the parasite's ability to reduce norepinephrine interrupts control of immune system activation, enabling an overactive immune response which may alter the host's cognitive states.

The findings - Noradrenergic Signaling and Neuroinflammation Crosstalk Regulates Toxoplasma gondii-Induced Behavioral Changes - have been published in Trends in Immunology.

Glenn McConkey, Associate Professor of Heredity, Disease, and Development at Leeds' School of Biology, who published the research, said: "Our insight connects the two opposing theories for how Toxoplasma alters host behaviour and this may apply to other infections of the nervous system. One school believes that behaviour changes are invoked by the immune response to infection and the other that changes are due to altered neurotransmitters."

"This research will contribute to the great need in understanding how brain inflammation is connected to cognition, which is essential for the future development of antipsychotic treatments."

Credit: 
University of Leeds

Obese people found to be at increased risk of COVID-19

A new study led by researchers at Queen Mary University of London uses a novel approach to investigate the effects of cardiovascular risk factors on the risk of COVID-19 infection.

Several observational studies have reported the link between cardiovascular risk factors (such as obesity, high blood pressure, diabetes and high cholesterol) and COVID-19 severity. However, these studies could not ascertain the cause and effect relationship due to the observational design.

The new study, published in the science journal Frontiers in Genetics, used a novel approach called 'Mendelian Randomisation', which leveraged on the individual genetic information, to investigate the effects of cardiovascular risk factors on the risk of COVID-19 infection.

Lead author Dr Nay Aung from Queen Mary University of London said: "Our results show that individuals with high body mass index (BMI), a marker of obesity, and high low-density lipoprotein (LDL) cholesterol (also known as 'bad' cholesterol) are at an increased risk of getting COVID-19. Other cardiovascular risk factors (high blood pressure and diabetes) do not appear to elevate the COVID-19 risk.

"Our findings support the use of BMI and LDL cholesterol as important metrics alongside other known characteristics (such as age and ethnicity) in the risk assessment of vulnerability to COVID-19 infection."

The findings may have an impact on public health policy, whereby those who fall in the at risk obese category or those with extreme hyperlipidemia in the general population may require more rigorous social distancing or shielding.

Furthermore, studies assessing the role for cholesterol modification therapy during illness or hospital admission could be undertaken to assess potential impact on outcomes.

Credit: 
Queen Mary University of London

Scientists reduce levels of molecules that kill neurons in elderly mice with Alzheimer's

image: Antibidy fragment scFv-h3D6 is also effective in reducing Aβ levels in old mice

Image: 
UAB

Alzheimer's disease is the most common dementia worldwide and it is characterized by learning impairment, memory loss, disorientation, and anxiety, among other behavioral and psychological symptoms. Since Alois Alzheimer described the first case at the beginning of the 20th century, important advances have been achieved in terms of understanding physiopathology, but, unfortunately, an effective treatment has not been developed yet.

Although what triggers Alzheimer's disease it is not well established, several researches claim that the aggregation of the Aβ peptide and of the tau protein, both present in normal brains, plays a pivotal role in Alzheimer's progression. Moreover, it is worth noting that there is a crosstalk between both, Aβ peptide and tau protein, which means that a reduction or an increase in one of them could affect the other. Thus, therapies directed to reduce Aβ, and recently to reduce tau, have been explored. However, the use of full-length antibodies targeting Aβ has not been effective in ameliorating cognitive decline and produced severe side effects in terms of neuroinflammation.

In previous studies, the Protein Design and Immunotherapy Group at the Department of Biochemistry and Molecular Biology of the UAB, led by Prof. Sandra Villegas, developed an antibody fragment, scFv-h3D6, able to reduce the levels of Aβ and to ameliorate memory loss in young, model of Alzheimer's disease, mice. However, what happens in advanced stages of the disease has never been studied before.

In a recent study published in the International Journal of Molecular Sciences, the group has demonstrated that scFv-h3D6 is also effective in reducing Aβ levels in old mice, where the pathology is advanced the most. Interestingly, Aβ reduction because of scFv administration also produced a reduction in total tau levels and did not elicit any detectable side effect. Furthermore, a slight reduction in the neuroinflamatory extent featuring the AD brain was observed. Therefore, the treatment is efficient and safe.

"The main point of this study is that we have shown that therapy with antibody fragments works in the late phase of the disease, and not only decreases the main molecule in Alzheimer's, Aβ, but also reduces the levels of a second one, the tau protein, which ultimately kills the neuron and causes dementia", explains Sandra Villegas.
Future studies targeting both Aβ and tau pathologies in concert could show a putative pharmacological approach to treat this devastating disease.

Credit: 
Universitat Autonoma de Barcelona

A new diagnostic method predicts which cancer patients will respond to immunothe

image: Dr Banafshe Larijani, an Ikerbasque researcher seconded to the Biofisika Institute (UPV/EHU-University of the Basque Country, CSIC), leads the international group that has developed the new diagnostic method.

Image: 
Ikerbasque - UPV/EHU

Immunotherapy is a type of cancer treatment that helps the patient's immunological system to combat it and has a hugely positive impact in cancer treatments, even though it does not work in all cases: it is highly successful in some patients whereas in others it has little or no effect. Given the risks inherent in these procedures, a growing need has emerged to specify which patients are more likely to benefit from them, thus avoiding unnecessary exposure of those who will not benefit.

Fellow researchers from other centres in the Basque Country (Biocruces, PIE, BCAM), in Europe and the company FASTBASE Solutions Ltd have participated in the group led by Dr Larijani, who is also the director of the Centre for Therapeutic Innovation of the University of Bath (United Kingdom). The new predictive tool has been developed by using an advanced microscopy platform that identifies the interactions between the immune cells and the tumour cells and also informs about the activation state of the immune checkpoints that buffer the anti-tumour response.

The team has published its findings in the prestigious journal Cancer Research. Dr Larijani's team has analysed one immune checkpoint. In a healthy individual these checkpoints closely regulate the body's immune response, acting as a switch to prevent self-immune and inflammatory diseases.

Specifically, the immune checkpoint analysed comprises two proteins: PD-1 (present in immune cells known as T-lymphocytes) and PD-L1 (present in other types of immune cells and on the surface of many different types of tumours).

As a rule, when PD-1 on the surface of T-lymphocytes joins up with PD-L1 on the surface of other immune cells, it efficiently switches off the immune function of the T cell. And that is what tumour cells do: when PD-L1 is expressed on their surface, PD-1 is activated in the T-lymphocyte, so their anti-tumour function is deactivated and the tumour is allowed to survive and grow. The inhibitors used in immunotherapy function by interrupting the interaction between PD-L1 on the tumour and PD-1 in the T cell, thus restoring the patient's anti-tumour activity. This new tool determines the scope of the PD-1 / PD-L1 interaction in a tumour biopsy by predicting whether therapy using checkpoint inhibitors is likely to bring significant clinical benefits.

"Right now, decisions about whether to proceed with checkpoint inhibitor treatment are simply based on whether PD-1 and PD-L1 are present in the biopsies rather than in their functional state. However, our work has shown that it is much more important to know that the two proteins actually interact and, therefore, that they are likely to have a functional impact on the survival of the tumour," said Prof Larijani.

Credit: 
University of the Basque Country

Does the human brain resemble the Universe?

image: Left: section of cerebellum, with magnification factor 40x, obtained with electron microscopy (Dr. E. Zunarelli, University Hospital of Modena); right: section of a cosmological simulation, with an extension of 300 million light-years on each side (Vazza et al. 2019 A&A).

Image: 
University of Bologna

In their paper published in Frontiers of Physics, Franco Vazza (astrophysicist at the University of Bologna) and Alberto Feletti (neurosurgeon at the University of Verona) investigated the similarities between two of the most challenging and complex systems in nature: the cosmic network of galaxies and the network of neuronal cells in the human brain.

Despite the substantial difference in scale between the two networks (more than 27 orders of magnitude), their quantitative analysis, which sits at the crossroads of cosmology and neurosurgery, suggests that diverse physical processes can build structures characterized by similar levels of complexity and self-organization.

The human brain functions thanks to its wide neuronal network that is deemed to contain approximately 69 billion neurons. On the other hand, the observable universe can count upon a cosmic web of at least 100 billion galaxies. Within both systems, only 30% of their masses are composed of galaxies and neurons. Within both systems, galaxies and neurons arrange themselves in long filaments or nodes between the filaments. Finally, within both systems, 70% of the distribution of mass or energy is composed of components playing an apparently passive role: water in the brain and dark energy in the observable Universe.

Starting from the shared features of the two systems, researchers compared a simulation of the network of galaxies to sections of the cerebral cortex and the cerebellum. The goal was to observe how matter fluctuations scatter over such diverse scales.

"We calculated the spectral density of both systems. This is a technique often employed in cosmology for studying the spatial distribution of galaxies", explains Franco Vazza. "Our analysis showed that the distribution of the fluctuation within the cerebellum neuronal network on a scale from 1 micrometer to 0.1 millimeters follows the same progression of the distribution of matter in the cosmic web but, of course, on a larger scale that goes from 5 million to 500 million light-years".

The two researchers also calculated some parameters characterizing both the neuronal network and the cosmic web: the average number of connections in each node and the tendency of clustering several connections in relevant central nodes within the network.

"Once again, structural parameters have identified unexpected agreement levels. Probably, the connectivity within the two networks evolves following similar physical principles, despite the striking and obvious difference between the physical powers regulating galaxies and neurons", adds Alberto Feletti. "These two complex networks show more similarities than those shared between the cosmic web and a galaxy or a neuronal network and the inside of a neuronal body".

The encouraging results of this pilot study are prompting the researchers to think that new and effective analysis techniques in both fields, cosmology, and neurosurgery, will allow for a better understanding of the routed dynamics underlying the temporal evolution of these two systems.

Credit: 
Università di Bologna

Paleontologists uncover three new species of extinct walruses in Orange County

image: Map & Skulls

Image: 
Journal of Vertebrate Paleontology

Millions of years ago, in the warm Pacific Ocean off the coast of Southern California, walrus species without tusks lived abundantly.

But in a new study, Cal State Fullerton paleontologists have identified three new walrus species discovered in Orange County and one of the new species has "semi-tusks" -- or longer teeth.

The other two new species don't have tusks and all predate the evolution of the long iconic ivory tusks of the modern-day walrus, which lives in the frigid Arctic.

The researchers describe a total of 12 specimens of fossil walruses from Orange, Los Angeles and Santa Cruz counties, all estimated to be 5 to 10 million years old. The fossils represent five species, with two of the three new species represented by specimens of males, females and juveniles.

Their research, which gives insights on the dental and tusk evolution of the marine mammal, was published today in the Journal of Vertebrate Paleontology.

Geology graduate Jacob Biewer, and his research adviser James F. Parham, associate professor of geological sciences, are authors of the study, based on fossil skull specimens.

Parham and Biewer worked with Jorge Velez-Juarbe, an expert in marine mammals at the Natural History Museum of Los Angeles County, who is a co-author of the paper. Velez-Juarbe is a former postdoctoral scholar in Parham's lab and has collaborated on other CSUF fossil research projects. Parham is a research associate at the museum, which provides research opportunities for him and his students.

The researchers teamed to study and describe the anatomy of the specimens, most of which are part of the museum's collection.

"Orange County is the most important area for fossil walruses in the world," said Biewer, first author of the paper who conducted the research for his master's thesis. "This research shows how the walruses evolved with tusks."

Extinct Walrus Species Get Names

Today, there is only one walrus species and its scientific name is Odobenus.

For the new species found in Orange County, the researchers named the semi-tusked walrus, Osodobenus eodon, by combining the words Oso and Odobenus. Another is named Pontolis kohnoi in honor of Naoki Kohno, a fossil walrus researcher from Japan. Both of these fossils were discovered in the Irvine, Lake Forest and Mission Viejo areas.

Osodobenus eodon and Pontolis kohnoi are both from the same geological rock layer as the 2018 study by Parham and his students of another new genus and species of a tuskless walrus, Titanotaria orangensis, named after CSUF Titans. These fossils were found in the Oso Member of the Capistrano Formation, a geological formation near Lake Forest and Mission Viejo.

The third new walrus species, Pontolis barroni, was found in Aliso Viejo, near the 73 Toll Road. It is named after John Barron, a retired researcher from the U.S.Geological Survey and world expert on the rock layer where the specimens were found, Parham said.

Analysis of these specimens show that fossil walrus teeth are more variable and complex than previously considered. Most of the new specimens predate the evolution of tusks, Parham said.

"Osodobenus eodon is the most primitive walrus with tusk-like teeth," Parham said. "This new species demonstrates the important role of feeding ecology on the origin and early evolution of tusks."

Biewer explained that his work focused on getting a better understanding of the evolutionary history of the walrus in regards to its teeth.

"The importance of dental evolution is that it shows the variability within and across walrus species. Scientists assumed you could identify certain species just based on the teeth, but we show how even individuals of the same species could have variability in their dental setup," said Biewer, who earned a master's degree in geology in 2019.

"Additionally, everyone assumes that the tusks are the most important teeth in a walrus, but this research further emphasizes how tusks were a later addition to the history of walruses. The majority of walrus species were fish eaters and adapted to catching fish, rather than using suction feeding on mollusks like modern walruses."

Biewer, now a paleontologist in the Modesto area, also examined whether climate changes in the Pacific Ocean had an impact on ancient walruses. His work suggests that a rise in water temperature helped to boost nutrients and planktonic life, and played a role in the proliferation of walruses about 10 million years ago, which may have contributed to their diversity.

Sidebar:

For the fossil walrus research project, geology graduate Jacob Biewer spent hours in the lab measuring and describing the walrus bones.

"I sat many hours with a handy caliper taking notes on the lengths of teeth and width of skulls, among many other measurements," he said. "Describing bones is much more in depth and meticulous than it sounds. There are traits that the bones of each walrus species have -- the size, shape and number of teeth. I recorded how the bones are different from, or similar to, other extinct walrus species."

Biewer, a paleontologist who lives in Modesto, noted that despite the pandemic, he and Parham worked on the scientific paper with 300 miles of social distancing.

Completing his first journal publication, based on his master's work, and conducting the research project helped him to understand scientific methods and techniques that he now uses in his career, where he monitors construction sites for paleontological resources. He also teaches undergraduate geology courses at Cal State Stanislaus, where he earned a bachelor's degree in geology, and is considering pursuing a doctorate.

"The experiences I had in conducting this research, especially the presentations at national paleontological conferences, led to a big increase in my confidence in my scientific abilities," Biewer said. "I credit my time working with Dr. Parham directly to the achievements in my current employment -- from the skills he imparted to the doors he helped open."

Credit: 
Taylor & Francis Group

Deafening insects mask true biodiversity assessed via acoustic surveys in Japan

video: Samuel Ross explains the research

Image: 
Trinity College Dublin and Okinawa Institute of Science and Technology Graduate University

A collaborative team of ecologists, led by those from Trinity College Dublin, has been using recordings of animal noises to assess biodiversity in sub-tropical Japan. The team assessed how effective these acoustic surveys were for pinpointing Okinawa's wild and wonderful fauna in different sonic conditions--and discovered that the incessant choruses of the local cicadas disguise the true diversity of the region.

The work, just published in the journal Ecological Indicators, underlines the great potential that acoustic surveys have for characterising the biodiversity of habitats while also highlighting some major potential pitfalls.

Many scientists believe we are now living through the sixth mass extinction in Earth's history, which has largely been driven by human actions and our exploitation of the environment, but there is general consensus that it is not too late to halt declines in biodiversity if we act now. However, we need to know which species (and how many) are present in any given habitat before designing conservation programmes.

Acoustic surveys

Acoustic surveys--simple audio recordings of the animal sounds in a habitat--offer the potential to record large volumes of data. They can do this relatively cheaply and easily, given that recording devices can be left unattended once set up. This technique also means researchers need not spend lengthy periods in unhospitable or dangerous habitats, species are more likely to be accounted for as they won't be scared away by human presence, and the data can be very sensitive as each species makes unique sounds.

However, the new research shows that consideration must be given to ambient conditions, with the time of day, season, and proximity to urban areas and human activity all likely to interfere to varying extents with the recordings, such that some species cannot be heard.
Interestingly, on the sub-tropical island of Okinawa off the coast of Japan, it is the incessant noise of the cicada insects that have the biggest impact in masking the hoots, clicks and chirps of hundreds of native animals.

Lead author of the study, Samuel Ross, is a PhD Candidate in Trinity's School of Natural Sciences. He said:

"In total, we used about 230 hours of sound recordings from a wide range of habitats across Okinawa to gain insights into the biodiversity of the region, to characterise how it changes near urban areas, and most importantly, to assess how effective the various audio recording and assessment techniques are in extracting reliable information."

"As you'd expect the weather is important, with heavy winds and rain affecting the information we can get from recordings, and human noise pollution is also problematic. However, it's cicadas that really impact the quality of such assessments during Okinawa's summer months."

To date, most bio-acoustic surveys have been conducted in the Tropics but the field is developing quickly and these monitoring techniques will prove useful in Ireland, which provides homes to a number of iconic, endangered animals.

Many of Ireland's creatures have a cultural significance and the ability to soothe and inspire, while other research is opening our eyes to the power of the acoustic environment in influencing mental health.

Samuel Ross added:

"These methods are still relatively new and the prospect that we can monitor biodiversity using only audio recording equipment is really exciting. I see this as the next frontier in assessing the state of the world's ecosystems."

The study was led by Samuel Ross and Ian Donohue, Associate Professor in Zoology, at Trinity, working closely with colleagues at the Okinawa Institute of Science and Technology (OIST), including Professor Evan Economo and Dr Nick Friedman, who run an island-wide project to monitor Okinawa's ecosystems using sound.

Dr Friedman added:

"The forests in Okinawa are really noisy when the cicadas are out. The sound they make is so loud, it's at least annoying if not painful. It conceals a lot of different species that are in the forest because they don't really bother calling to each other while the cicadas are going. Knowing this helps us strategise how to use soundscape recordings to measure biodiversity or track the health of an ecosystem."

Credit: 
Trinity College Dublin

People in developing countries eat less bushmeat as they migrate from rural to urban areas

image: The yellow-footed tortoise (Chelonoidis denticulatus), also known as the Brazilian giant tortoise, can be found in the Amazon Basil of South America. (Photo credit: Thais Morcatty)

Image: 
Thais Morcatty

PRINCETON, N.J.-- People around the world, especially in developing countries in Africa, Asia, and South America, consume wild game, or bushmeat, whether out of necessity, as a matter of taste preference, or, in the case of particularly desirable wildlife species, to connote a certain social status. Bushmeat consumption, however, has devasted the populations of hundreds of wildlife species and been linked to the spread of zoological diseases such as the Ebola virus.

New Princeton University research finds that when people in developing countries move from rural areas to cities, they consume less bushmeat over time, perhaps because other sources of animal protein are more readily available. They also found that children in urban areas generally have less of a taste for wild game than their parents. In the long term, this could be good news for conservation.

The researchers traveled to Brazil -- one of many countries worldwide experiencing a dramatic migration from rural to urban areas -- and interviewed thousands of adults and children about their wildlife consumption habits.

The study, published in the journal Conservation Biology, is among the first to explore how the consumption of wildlife changes as countries become increasingly urbanized. The results have profound implications for the rapidly growing wildlife trade, which is a multi-billion-dollar industry that threatens human health, drives species extinction, and damages ecosystems.

"In the Amazon, as in most developing countries, people are leaving rural areas and moving into cities. We find -- for whatever reason -- they are reducing their consumption of wild animals over time, providing a needed break for overhunted wildlife," said study co-author David Wilcove, professor of ecology and evolutionary biology and public affairs and the High Meadows Environmental Institute.

"A decline in per capita consumption of wild animals by urban residents gives us hope that pressure on hunted species may decrease over time. At the same time, we don't know whether this decline will be large enough to compensate for an increasing human population in urban areas," said Willandia Chaves, the lead author of the study, who worked on the project as a postdoctoral researcher at Princeton and is now an assistant professor in the Department of Fish and Wildlife Conservation at Virginia Tech.

Wilcove and Chaves conducted the study with Denis Valle of the University of Florida, Aline S. Tavares of the Universidade Federal do Amazonas, and Thais Q. Morcatty of Oxford Brookes University.

The researchers surveyed six small towns, three large towns, and Manaus, the largest city in the Amazon Basin. This included 1,356 households and 2,776 school-age children. They studied the consumption of imperiled tortoises and freshwater turtles, as they are among the top five most consumed and traded species in urban areas in the Amazon. An estimated 1.7 million turtles were eaten in northwestern Brazil in 2018.

While subsistence hunting is permitted, most wildmeat consumption in Brazil is illegal. Moreover, the turtle species that were being consumed where this study took place are highly endangered. For this reason, the researchers had to design a survey that would allow interviewees to honestly answer questions without implicating themselves.

To do this, they used dominoes. The head of each household (whether male or female) was asked a series of questions about their consumption of turtles (illegal) versus cornmeal (legal).

When asked, "Do you consume this item in your house?" respondents would randomly choose a domino from a bag: one dot represented cornmeal, and two dots for turtles. Because the researchers knew the ratio of one-dot to two-dot dominoes in the bag, they could calculate the consumption rates of turtles while protecting participants' responses by not linking the behavior to an individual participant.

While the domino approach is not new, it has rarely been employed in conservation studies, making this study more cutting-edge. "It's also exciting because it gives us much more reliable answers about sensitive activities than direct questioning does," Wilcove said.

Next, the researchers randomly selected 49 middle and high schools (11 in Manaus, 13 in large towns, and 25 in small towns) to study any generational differences in how much they liked and consumed bushmeat compared to adults. At each school, they randomly selected four classrooms and asked the schoolchildren to complete an anonymous questionnaire, with parental consent. This accounted for 2,700 students in 146 classrooms, and schoolchildren varied from 11 to 18 years in age.

First, the researchers found people generally consumed fewer turtles in larger urban areas. This could be because turtles cost more in larger cities than in small towns, and law enforcement also is likely stronger in larger urban centers. In small towns, on the other hand, the rates of turtle consumption are much higher, perhaps because people living there have ready access to wilder areas where the turtles live or perhaps because enforcement of wildlife laws is lax.

Second, children in urban areas are generally less likely to consume turtles than their parents. Social eating norms could play a role. If other children say it's "uncool" to eat turtles, then other kids might follow suit, or vice versa. Perhaps children consider the conservation implications of eating wildlife. Or perhaps it's simply because children's tastebuds haven't been fully developed. The researchers said more studies are needed to understand children's motivations.

"Is it a taste they will develop later in life, like children refusing to eat vegetables, or is it a lifelong switch?" Wilcove said. "We don't know yet, but the answer will mean a lot to the future of wildlife in the Amazon."

The researchers estimated that the overall consumption of endangered turtles in Amazonas state, the largest state in the Brazilian Amazon, is a very alarming 1.7 million turtles per year. Therefore, programs aimed at reducing consumption of illegal wildlife are urgently needed.

Certain towns seem to be "hotspots" for bushmeat consumption, so conservation efforts in those areas could be particularly important. Importantly, conservation education focused on schoolchildren, including increasing awareness regarding the plight of Amazonian turtles, could have long-term benefits if children forgo eating turtles as they become adults.

"Conservation efforts have focused on things like creating protected areas, working with rural communities to better manage wildlife, and improving enforcement - all important actions. However, unless we also target urban demand for wildlife, we will not be able to effectively address this issue," Chaves said.

"The bushmeat trade, both domestic and international has emerged as a massive threat to biodiversity, comparable to habitat destruction for some places. Yet, our knowledge of what drives this trade and how those drivers may change in the future is surprisingly weak. Until we better understand these issues, we are poorly equipped to solve this growing threat to wildlife," Wilcove said.

Credit: 
Princeton School of Public and International Affairs

Computer scientists launch counteroffensive against video game cheaters

image: Dr. Latifur Khan, professor of computer science in the Erik Jonsson School of Engineering and Computer Science

Image: 
The University of Texas at Dallas

University of Texas at Dallas computer scientists have devised a new weapon against video game players who cheat.

The researchers developed their approach for detecting cheaters using the popular first-person shooter game Counter-Strike. But the mechanism can work for any massively multiplayer online (MMO) game that sends data traffic to a central server.

Their research was published online Aug. 3 in IEEE Transactions on Dependable and Secure Computing.

Counter-Strike is a series of games in which players work in teams to counter terrorists by securing plant locations, defusing bombs and rescuing hostages. Players can earn in-game currency to buy more powerful weapons, which is a key to success. Various software cheats for the game are available online.

"Sometimes when you're playing against players who use cheats you can tell, but sometimes it may not be evident," said Md Shihabul Islam, a UT Dallas computer science doctoral student in the Erik Jonsson School of Engineering and Computer Science and lead author of the study, who plays Counter-Strike for fun. "It's not fair to the other players."

In addition to fair play, cheating also can have an economic impact when dissatisfied players leave to play other games, Islam said.

Cheating incidents also can have serious consequences in esports, a fast-growing industry with annual revenues close to $1 billion. Cheating can result in sanctions against teams and players, including disqualification, forfeiture of prize money and a ban on future participation, according to the Esports Integrity Commission based in the United Kingdom.

Detecting cheating in MMO games can be challenging because the data that goes from a player's computer to the game server is encrypted. Previous research has relied on decrypted game logs to detect cheating after the fact. The UT Dallas researchers' approach eliminates the need for decrypted data and instead analyzes encrypted data traffic to and from the server in real time.

"Players who cheat send traffic in a different way," said Dr. Latifur Khan, an author of the study, professor of computer science and director of the Big Data Analytics and Management Lab at UT Dallas. "We're trying to capture those characteristics."

For the study, 20 students in the UT Dallas class Cyber Security Essentials for Practitioners downloaded Counter-Strike and three software cheats: an aimbot, which automatically targets an opponent; a speed hack, which allows the player to move faster; and a wallhack, which makes walls transparent so players can easily see their opponent. The researchers set up a server dedicated to the project so the students' activity would not disrupt other online players.

The researchers analyzed game traffic to and from the dedicated server. Data travels in packets, or bundles, of information. The packets can be different sizes, depending on the contents. Researchers analyzed features, including the number of incoming and outgoing packets, their size, the time they were transmitted, their direction and the number of packets in a burst, which is a group of consecutive packets.

By monitoring the data traffic from the student players, researchers identified patterns that indicated cheating. They then used that information to train a machine-learning model, a form of artificial intelligence, to predict cheating based on patterns and features in the game data.

The researchers adjusted their statistical model, based on a small set of gamers, to work for larger populations. Part of the cheat-detection mechanism involves sending the data traffic to a graphics processing unit, which is a parallel server, to make the process faster and take the workload off the main server's central processing unit.

The researchers plan to extend their work to create an approach for games that do not use a client-server architecture and to make the detection mechanism more secure. Islam said gaming companies could use the UT Dallas technique with their own data to train gaming software to detect cheating. If cheating is detected, the system could take immediate action.

"After detection," Khan said, "we can give a warning and gracefully kick the player out if they continue with the cheating during a fixed time interval.

"Our aim is to ensure that games like Counter-Strike remain fun and fair for all players."

Credit: 
University of Texas at Dallas