Culture

Detailed analysis of immune response to SARS-CoV-2 bodes well for COVID-19 vaccine

image: Alba Grifoni, Ph.D., a postdoctoral researcher in the Sette lab and study first co-author, tests the T cell response in blood samples collected from individuals who have recovered from COVID-19.

Image: 
La Jolla Institute for Immunology

LA JOLLA, CA--Scientists around the world are racing to develop a vaccine to protect against COVID-19 infection, and epidemiologists are trying to predict how the coronavirus pandemic will unfold until such a vaccine is available. Yet, both efforts are surrounded by unresolved uncertainty whether the immune system can mount a substantial and lasting response to SARS-CoV-2 and whether exposure to circulating common cold coronaviruses provides any kind of protective immunity.

A collaboration between the labs of Alessandro Sette, Dr. Biol. Sci. and Shane Crotty, Ph.D., at La Jolla Institute for Immunology is starting to fill in the massive knowledge gap with good news for vaccine developers and is providing the first cellular immunology data to help guide social distancing recommendations.

Published in today's online edition of Cell, the study documents a robust antiviral immune response to SARS-CoV-2 in a group of 20 adults who had recovered from COVID-19. The findings show that the body's immune system is able to recognize SARS-CoV-2 in many ways, dispelling fears that the virus may elude ongoing efforts to create an effective vaccine.

"If we had seen only marginal immune responses, we would have been concerned," says Sette, a professor in the Center for Infectious Disease and Vaccine Research, and adds, "but what we see is a very robust T cell response against the spike protein, which is the target of most ongoing COVID-19 efforts, as well as other viral proteins. These findings are really good news for vaccine development."

"All efforts to predict the best vaccine candidates and fine-tune pandemic control measures hinge on understanding the immune response to the virus," says Crotty, also a professor in the Center for Infectious Disease and Vaccine Research. "People were really worried that COVID-19 doesn't induce immunity, and reports about people getting re-infected reinforced these concerns, but knowing now that the average person makes a solid immune response should largely put those concerns to rest."

In an earlier study, Sette and his team had used bioinformatics tools to predict which fragments of SARS-CoV-2 are capable of activating human T cells. The scientists then, in this newest research, tested whether T cells isolated from adults who had recovered from COVID-19 without major problems, recognized the predicted protein fragments, or so-called peptides, from the virus itself. The scientists pooled the peptides into two big groups: The first so-called mega-pool included peptides covering all proteins in the viral genome apart from SARS-CoV-2's "spike" protein. The second mega-pool specifically focused on the spike protein that dots the surface of the virus, since almost all of the vaccines under development right now target this coronavirus spike protein.

"We specifically chose to study people who had a normal disease course and didn't require hospitalization to provide a solid benchmark for what a normal immune response looks like, since the virus can do some very unusual things in some people," says Sette.

The researchers found that all COVID-19 patients had a solid CD4, or "helper", T cell response, which helps antibody production. Almost all patients had produced virus-specific CD8, or "killer", T cells, which eliminate virus-infected cells. "Our data show that the virus induces what you would expect from a typical, successful antiviral response," says Crotty.

And, although these results don't preclude that the immune response to SARS-CoV-2 may be detrimental, they provide an important baseline against which individuals' immune responses can be compared; or, as Sette likes to put it, "if you can get a picture of something, you can discuss whether you like it or not but if there's no picture there's nothing to discuss."

"We have a solid starting foundation to now ask whether there's a difference in the type of immune response in people who have severe outcomes and require hospitalization versus people who can recover at home or are even asymptomatic," adds Sette. "But not only that, we now have an important tool to determine whether the immune response in people who have received an experimental vaccine resembles what you would expect to see in a protective immune response to COVID-19, as opposed to an insufficient or detrimental response."

The teams also looked at the T cell response in blood samples that had been collected between 2015 and 2018, before SARS-CoV-2 started circulating. Many of these individuals had significant T cell reactivity against SARS-CoV-2, although they had never been exposed to SARS-CoV-2. But everybody has almost certainly seen at least three of the four common cold coronaviruses, which could explain the observed crossreactivity.

It is still unclear, though, whether the observed crossreactivity provides at least some level of preexisting immunity to SARS-CoV-2 and therefore could explain why some people or geographical locations are hit harder by COVID-19.

¬¬"Given the severity of the ongoing COVID-19 pandemic, any degree of cross-reactive coronavirus immunity could have a very substantial impact on the overall course of the pandemic and is a key detail to consider for epidemiologists as they try to scope out how severely COVID-19 will affect communities in the coming months," says Crotty.

Credit: 
La Jolla Institute for Immunology

Social good creates economic boost

image: QUT's Professor Per Davidsson and Professor Martin Obschonka

Image: 
QUT

As unemployment rates skyrocket around the world in response to the COVID-19 pandemic, a world-first study has found social venture start-ups not only alleviate social problems but also are much more important for job creation than previously thought.

Written by Professor Martin Obschonka, Director of QUT's Australian Centre for Entrepreneurship Research, and its founding director, Professor Per Davidsson, along with collaborators from Sweden, the paper - The regional employment effects of new social firm entry - has just been published on Springer Open Access.

They contend the impact of social venture start-ups on regional job creation has been largely overlooked. They also argue the first-of-its-kind investigation could provide important input to employment policy, especially as global governments scramble to prop up ailing economies.

"It has long been acknowledged that the entry and growth of new firms contribute a large share of job creation in most countries. Social venture start-ups, however, are mostly celebrated for their worth in helping the disadvantaged or solving social concerns - their role in job creation has not really been considered," said Professor Obschonka.

"Yet using an established method for tracking direct and indirect job creation effects across 67 regions in Sweden over an eight-year period from start-up entry into the marketplace, our findings show the average job creation effect per firm was larger for social start-ups than for their commercial counterparts.

"Job creation is often a major focus of the social mission of these start-ups, especially for marginalised groups including people with disabilities and long-term unemployed individuals."

Professor Davidsson said the findings were contrary to the reliance on volunteers by many social endeavours.

"There appear to be a number of reasons social ventures create more jobs. First up, most 'commercial' start-ups represent individuals choosing self-employment which can mean they have no burning desire to grow and take on employees," Professor Davidsson said.

"Commercial start-ups also often operate in crowded markets with little room for growth. So even the high growth firms among the commercial category do not raise the average to high levels; partly because they outcompete or acquire some of their peers.

"By contrast, social ventures address underserved 'markets' of social problems, such as homelessness, substance abuse, domestic violence, refugees, environmental concerns, animal shelters, foodbanks, crisis centres, youth unemployment and so on.

"This creates room for growth without pushing out other social ventures. And being passionate about solving as much of 'their' social issue as they possibly can, social entrepreneurs are motivated to grow.

"They can also benefit from lower costs due to tax breaks and partial reliance on volunteers to have a growth advantage over commercial firms offering competing products or services."

The authors of the study acknowledge that as the commercial firm sector is much larger than the social sector, total job creation is greater overall.

The study compared regions in Sweden in terms of their social and commercial start-ups between 1990 to 2014 and their net job creation effects in each up to eight years after they entered the market.

"Similar comparisons for Australia or other countries do not yet exist," said Professor Obschonka.

"However, total employment in the social sector has grown recently in other countries, so our findings would most likely be valid in Australia and elsewhere along with Sweden."

Credit: 
Queensland University of Technology

How cells decide the way they want to recycle their content

image: Genotoxic stress induces Ulk1 dephosphorylation at Ser637 in a p53/PPM1D-dependent manner. The dephosphorylated Ulk1 is then phosphorylated at Ser746 by a necroptosis initiator, RIPK3, and translocates to the Golgi, which results in alternative autophagy (left). TNF signaling induces necroptosis but not alternative autophagy (right).

Image: 
Department of Pathological Cell Biology, Medical Research Institute,TMDU

Researchers from Tokyo Medical and Dental University (TMDU) identify a novel phosphorylation site of the protein Ulk1 to be an essential regulating factor for alternative autophagy, but not canonical autophagy.

Tokyo, Japan - Autophagy is a housekeeping process through which cells remove dysfunctional contents to balance energy sources during times of stress. Now, researchers from Tokyo Medical and Dental University (TMDU) identified a novel molecular mechanism by which a type of autophagy, called alternative autophagy, is activated. In a new study published in Nature Communications, they showed how a specific phosphorylation site of the protein Unc51-like kinase 1 (Ulk1) is essential for the cell to go down the alternative autophagy path.

As living structures, cells ensure homeostasis by carrying out specific processes by which they build and degrade their contents. Particularly at times of stress, for example during exposure to toxins, autophagy helps to ensure an orderly turnover process by which cells can recycle their contents to survive. Interestingly, the process of autophagy can take place by several distinct molecular mechanisms, two of which are canonical and alternative autophagy. While the protein Ulk1 is known to initiate both types of autophagy, the mechanism by which Ulk1 differentially regulates them has remained unclear.

"Autophagy is a very elaborate process by which cells recycle their contents," says the corresponding author of the study Shigeomi Shimizu. "The goal of our study was to understand how Ulk1 that has control over two types of autophagy, differentially regulates them."

To achieve their goal, the researchers used mouse embryonic fibroblasts (MEFs) deficient in the protein Atg5 to turn off canonical autophagy. By exposing them to etoposide, a DNA-damaging reagent, they then induced alternative autophagy. Using mass spectrometry, the researchers found that Ulk1 carried an additional phosphoryl group at its amino acid serine in position 746 (Ser746; p-Ulk1746), also called phosphorylation, when exposed to etoposide but not when left untreated. By developing a new antibody against p-Ulk1746, the researchers then showed that the protein localized to the Golgi complex within the cells. The Golgi complex is an organelle participating in many cellular processes, including alternative autophagy.

"While these were already exciting findings, our goal was to understand whether the specific phosphorylation of Ulk1 at the serine 746 site is required for alternative autophagy and which kinase is responsible for this phosphorylation step," says lead and the corresponding author of the study Satoru Torii.

To analyze the causal relationship between Ulk1 Ser746 phosphorylation and alternative autophagy, the researchers used a fluorescent tandem protein consisting of red fluorescent protein (RFP) and green fluorescent protein (GFP). Because GFP does not fluoresce within acidic environments, the tandem protein made autolysosomes, cellular compartments that are created during autophagy, become red. While the red fluorescence appeared after etoposide treatment, it was not generated in cells producing Ulk1 nonphosphorylated mutant, indicating that p-Ulk1746 is required for alternative autophagy. Next, the researchers demonstrated that receptor-interacting protein kinase 3 (RIPK3), a protein that phosphorylates other proteins involved in necroptosis, is responsible for the generation of p-Ulk1746 by showing that p-Ulk1746 and alternative autophagy occurred in normal cells but not in cells deficient in RIPK3. Intriguingly in MEFs that expressed Atg5, canonical autophagy was not affected by RIPK3-deficiency, indicating that p-Ulk1746 is not involved in canonical autophagy.

"These are striking results that shed new light on how cells regulate the complex process of autophagy," says Shimizu. "We hope that our findings will be helpful in understanding the role of alternative autophagy in normal biology and disease."

Credit: 
Tokyo Medical and Dental University

Researchers reveal common origin of fermi bubbles and galactic center x-ray outflows

A pair of gigantic gamma-ray bubbles centered on the core of the Milky Way galaxy were discovered by the Fermi Gamma-ray Space Telescope 10 years ago. But how these so-called "Fermi bubbles" arose was a mystery.

Recently, however, researchers at the Shanghai Astronomical Observatory (SHAO) of the Chinese Academy of Sciences have presented a new model that for the first time simultaneously explains the origins of both the Fermi bubbles and the Galactic center biconical X-ray structure, which was discovered in 2003.

According to this model, the two structures are essentially the same phenomenon and was caused by the forward shock driven by a pair of jets emanating from Sagittarius A* (Sgr A*) - the supermassive black hole lurking at the Galactic center - about five million years ago. The study was published in The Astrophysical Journal.

Fermi bubbles are two colossal blobs filled with very hot gas, cosmic rays and magnetic fields. Although they cannot be seen with the naked eye, they are very bright in diffuse gamma-ray emissions. In gamma rays, the Fermi bubbles have very sharp edges and the edges coincide well with an X-ray structure called the Galactic center biconical X-ray structure.

Seeing the very similar edges of Fermi bubbles and the Galactic center biconical X-ray structure, the SHAO researchers realized these structures might share the same origin. Furthermore, the biconical X-ray structure could be naturally explained by the shock-compressed thin shell of hot thermal gas driven by a past energy outburst from the Galactic center.

In previous theoretical models and computer simulations of the Fermi bubbles, two major competing energy sources were proposed, i.e., star formation at the Galactic center and Sgr A*. However, in both models, the Fermi bubbles are explained as ejecta bubbles, while the forward shock is always located much further away from the edge of the Fermi bubbles. In other words, these models could not explain the Fermi bubbles and the Galactic center biconical X-ray structure simultaneously.

In contrast, the theoretical model in this study, proposed by GUO Fulai and his graduate student ZHANG Ruiyu from SHAO, used computer simulations to demonstrate for the first time that the Fermi bubbles and the Galactic center biconical X-ray structure are the same phenomenon.

In this model, the edge of the Fermi bubbles is the forward shock driven by a pair of jets emanating from Sgr A* about five million years ago. "One good thing about this model is that the energy and age of the Fermi bubbles can be constrained by the X-ray observations quite well," said corresponding author GUO Fulai. The age of the bubbles inferred in this study is also consistent with that derived from recent ultraviolet observations of some high velocity clouds along many sightlines towards the bubble region.

The new model indicates that the total energy injected during the Fermi bubble event by the supermassive black hole is close to that released by about 20,000 supernovae. The total matter consumed by Sgr A* during this event is about 100 solar masses.

"Another very interesting thing that we found in our study is that if the bubbles and the biconical X-ray structure share the same origin, they are very unlikely to be produced by star formation or black hole winds," said GUO. Near the Galactic center, the biconical X-ray structure has a very narrow base, while the forward shock produced by star formation or black hole winds can easily propagate to large distances, leading to a base much wider than observed.

In contrast, collimated jets deposit most of the energy quickly to large distances along the jet direction, naturally leading to a narrow base for the shock front near the Galactic plane. The supermassive black hole in our own Galaxy has been very quiescent in recent years without any evidence of current jet activities, but "our study strongly suggests that a pair of powerful jets emanated from it about five million years ago, lasted for about one million years, and produced the gigantic Fermi bubbles still seen today," added GUO.

Credit: 
Chinese Academy of Sciences Headquarters

Metagenomics reveals distinct microbiotypes in the giant clams Tridacna maxima

image: Different assemblages of corals and giant clams

Image: 
Dr. Lauric Thiault

New research conducted at CRIOBE and ENTROPIE research units, with the collaboration of the Swire institute of Marine Science of The University of Hong Kong, The Cawthron Institute and James Cook University, highlights the impacts of benthic species assemblages on the giant clams Tridacna maxima. The findings were recently published in the journal Microbiome.

The researchers explored for the first time the influence of benthic species-assemblages on giant clams health, with or without increasing temperature. To do so, they created artificial benthic assemblages using two coral species (Pocillopora damicornis and Acropora cytherea) and one giant clam species (Tridacna maxima). The results showed that the health status of giant clams depended on the neighbouring species. Moreover, using cutting-edge DNA multiplexing-metabarcoding technology adapted by Dr. Xavier Pochon, the team studied the microbial community of the giant clams. The researchers newly discovered distinct microbiotypes (group of specific bacteria) in the studied T. maxima population, one of which was linked to clam mortality.

Giant clams are less studied by scientists, yet they are important members of coral reefs and play numerous ecological roles. They are the largest living bivalves and serve as food for fish and human. Like coral, they contribute to primary production through photosynthesis by hosting unicellular algae. They also host a large community of bacteria as well as animals such as shrimps or crabs. However, all of the 12 currently recognised species are under threat and more than 50% of the wild population are either locally extinct or severely depleted.

"For decades we have been focusing on the effect of climate change on single species but this doesn't reflect what could happen within coral reef as a whole. This is why we decided to explore the effect of neighbouring species on the giant clam. We were extremely surprised to discover that the presence of some corals, particularly Acropora cytherea, led to an acute sensitivity of giant clams to increasing temperature which therefore exhibited a high death rate." explains Dr. Isis Guibert.

Microbiomes are an integral part of multicellular organisms, contributing to their health and physiological performance. The scientists noted that despite a surge of interest in this research focus, very few invertebrate microbiomes have been studied. The microbiome of giant clams is particularly interesting because clams are exposed to an extreme abundance and diversity of microbes through filter feeding. The discovery of specific microbiome structure, detectable from the genus level, is the first description of microbiotypes in invertebrates. "The results of our study suggest that, similarly to humans, genetic factors might drive the microbiotype of a giant clam." said Dr. Isis Guibert.

Interestingly, the clams with compromised health were characterised by a prominence of vibrio and therefore a distinct microbiome. "The relative proportion of Vibrionaceae could be used as an early indicator of clam health in natural populations." explains Dr.Véronique Berteaux-Lecellier, who supervised the study, "We hypothesise that A. cytherea could secrete metabolites that might have weakened the clams' defenses against Vibrio infection; future research should explore this possibility." The findings of this study suggest that the composition of the coral reef benthos, together with increasing water temperatures, could negatively impact the health of giant clams and potentially other reef organisms. Therefore, the findings support the idea that, like terrestrial conservation and restoration, taking account of the entire benthic assemblages should be the goal of marine conservation strategies.

Credit: 
The University of Hong Kong

'Cell pores' discovery gives hope to millions of brain and spinal cord injury patients

video: 'Cell pores' discovery gives hope to millions of brain and spinal cord injury patients.

Image: 
Aston University

Scientists have discovered a new treatment to dramatically reduce swelling after brain and spinal cord injuries, offering hope to 75 million victims worldwide each year.

The breakthrough in treating such injuries - referred to as central nervous system (CNS) edema - is thought to be hugely significant because current options are limited to putting patients in an induced coma or performing risky surgery.

Brain and spinal cord injuries affect all age groups. Older people are more at risk of sustaining them from strokes or falls, while for younger age groups, major causes include road traffic accidents and injuries from sports such as rugby, US-style football and other contact games.

The high-profile example of Formula 1 racing driver Michael Schumacher demonstrates the difficulties physicians currently face in treating such injuries. After falling and hitting his head on a rock while skiing in Switzerland in 2013, Schumacher developed a swelling on his brain from water rushing into the affected cells. He spent six months in a medically-induced coma and underwent complex surgery, but his rehabilitation continues to this day.

The new treatment, developed by an international team of scientists working at Aston University (UK), Harvard Medical School (US), University of Birmingham (UK), University of Calgary (Canada), Lund University (Sweden), Copenhagen University (Denmark) and University of Wolverhampton (UK), features in the latest edition of the scientific journal Cell.

The researchers used an already-licensed anti-psychotic medicine - trifluoperazine (TFP) - to alter the behaviour of tiny water channel 'pores' in cells known as aquaporins.

Testing the treatment on injured rats, they found those animals given a single dose of the drug at the trauma site recovered full movement and sensitivity in as little as two weeks, compared to an untreated group that continued to show motor and sensory impairment beyond six weeks after the injury.

The treatment works by counteracting the cells' normal reaction to a loss of oxygen in the CNS - the brain and spinal cord - caused by trauma. Under such conditions, cells quickly become 'saltier' because of a build-up of ions, causing a rush of water through the aquaporins which makes the cells swell and exerts pressure on the skull and spine. This build-up of pressure damages fragile brain and spinal cord tissues, disrupting the flow of electrical signals from the brain to the body and vice versa.

But the scientists discovered that TFP can stop this from happening. Focusing their efforts on important star-shaped brain and spinal cord cells called astrocytes, they found TFP prevents a protein called calmodulin from binding with the aquaporins. Normally, this binding effect sends the aquaporins shooting to the surface of the cell, letting in more water. By halting this action, the permeability of the cells is reduced.

Traditionally, TFP has been used to treat patients with schizophrenia and other mental health conditions. Its long-term use is associated with adverse side effects, but the researchers said their experiments suggested that just a single dose could have a significant long-lasting impact for CNS edema patients.

Since TFP is already licensed for use in humans by the US Federal Drug Administration (FDA) and UK National Institute for Health and Care Excellence (NICE) it could be rapidly deployed as a treatment for brain injuries. But the researchers stressed that further work would allow them to develop new, even better medicines based on their understanding of TFP's properties.

According to the World Health Organisation (WHO), each year around 60 million people sustain a traumatic brain or spinal cord injury and a further 15 million people suffer a stroke. These injuries can be fatal or lead to long-term disability, psychiatric disorders, substance abuse or self-harm.

Professor Roslyn Bill of the Biosciences Research Group at Aston University said:

"Every year, millions of people of all ages suffer brain and spinal injuries, whether from falls, accidents, road traffic collisions, sports injuries or stroke. To date, their treatment options have been very limited and, in many cases, very risky.

"This discovery, based on a new understanding of how our cells work at the molecular level, gives injury victims and their doctors hope. By using a drug already licensed for human use, we have shown how it is possible to stop the swelling and pressure build-up in the CNS that is responsible for long-term harm.

"While further research will help us to refine our understanding, the exciting thing is that doctors could soon have an effective, non-invasive way of helping brain and spinal cord injury patients at their disposal."

Dr Zubair Ahmed of the University of Birmingham's Institute of Inflammation and Ageing said:

"This is a significant advance from current therapies, which only treat the symptoms of brain and spinal injuries but do nothing to prevent the neurological deficits that usually occur as a result of swelling. The re-purposed drug offers a real solution to these patients and can be fast-tracked to the clinic."

Dr Alex Conner of the University of Birmingham's Institute of Clinical Sciences said:

"It is amazing that our work studying tiny water channels in the brain can tell us something about traumatic brain swelling that affects millions of people every year."

Dr Mootaz Salman, Research Fellow in Cell Biology at Harvard Medical School, said:

"This novel treatment offers new hope for patients with CNS injuries and has huge therapeutic potential. Our findings suggest it could be ready for clinical application at a low cost in the very near future".

Credit: 
Aston University

Assessment of deaths from COVID-19, seasonal influenza

What The Viewpoint Says: Publicly available data were used to analyze the number of deaths from seasonal influenza deaths compared with deaths from COVID-19.

Authors: Jeremy Samuel Faust, M.D., M.S., of Harvard Medical School and Brigham and Women's Hospital in Boston, is the corresponding author.

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

(doi:10.1001/jamainternmed.2020.2306)

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

Credit: 
JAMA Network

Examining association between weight loss before bariatric surgery, risk of death after surgery

What The Study Did: Researchers looked at whether a patient's body weight and weight loss before bariatric surgery were associated with risk of death within 30 days after surgery using data from nearly 500,000 patients in the U.S. and Canada.

Authors: Wei Bao, M.D., Ph.D., of the University of Iowa College of Public Health in Iowa City, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.4803)

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

Credit: 
JAMA Network

New research into stem cell mutations could improve regenerative medicine

New research from the University of Sheffield into stem cells could help make regenerative medicine safer

Regenerative medicine involves using pluripotent stem cells to repair damaged or diseased tissues in the body

The new research has suggested ways to reduce the likelihood of mutations occurring in these cells when cultured.

Research from the University of Sheffield has given new insight into the cause of mutations in pluripotent stem cells and potential ways of stopping these mutations from occurring.

The findings, published in Stem Cell Reports, show that pluripotent stem cells are particularly susceptible to DNA damage and mutations compared to other cells, and this could cause genetic mutations.

Pluripotent stem cells are able to develop into any cell type in the body, and there is considerable interest in using them to produce cells to replace diseased or damaged tissues in applications referred to as regenerative medicine.

One concern for the safety of this is that these cells often acquire recurrent mutations which might lead to safety issues if used in patients.

The researchers have found that these mutations are more likely to occur in a certain point during their cell cycle and have suggested ways of growing the cells to dramatically reduce the susceptibility to DNA damage and potentially the mutations that arise.

Peter Andrews, Professor of Biomedical Science at the University of Sheffield, said: "Clinical trials of regenerative medicine using cells derived from pluripotent stem cells are now beginning around the world, but there are concerns that mutations in the pluripotent stem cells may risk patient safety. Our results may allow us to significantly reduce that risk.

"Understanding the genetic stability of human pluripotent stem cells is an area developed at the University of Sheffield and one in which we are an international lead."

The Department of Biomedical Science at the University of Sheffield carries out world-leading research to understand disease, improve treatments, and find potential cures. Researchers work in areas ranging from cell biology and developmental biology to neuroscience and regenerative medicine, with expertise in topics including stem cells and cancer.

Credit: 
University of Sheffield

Reptile poaching in Balochistan (Pakistan) is on a decreasing trend but still troublesome

image: A topographic map of southwestern Balochistan showing visit sites in Chagai, Nushki, Panjgur, Kharan and Washuk districts.

Image: 
Rafaqat Masroor

Since 2013, following strict enforcement of provincial wildlife legislation in the less studied regions of Asia, the overall trend of illegal reptile poaching is steadily decreasing. But it's too early to claim that the issue is solved. Poached reptiles are largely destined not only for the pet trade, but also folk medicines and snake charmer shows, according to the recent study led by the scientists from the Pakistan Museum of Natural History and the University of Peshawar published in the open-access journal Herpetozoa.

For the first time, the exploitation of reptiles for the pet trade has come to the attention of the public in the late 1960s. In general, illegal poaching is one of the problems we still face a lot all over the world, despite strict restrictions which are coming in force massively over the last decades. The wildlife trade leads not only to biodiversity loss (through the capture of protected species), but also threatens with a possible spread of animal-borne diseases, due to interspecies contact at pet and folk medicine markets. The case of the recent COVID-19 pandemic gives a lesson to learn, and in order to stop further occurrences, a focus on law-enforcement activities should be brought to wildlife trade hotspots.

In the particular case of Pakistan, a country with high species diversity of reptiles, still very little is known about the links between illegal wildlife trade and wildlife decline. The illegal poaching and trade in Pakistan are largely undocumented and it's difficult to bring accurate data since the trade involves many channels and follows informal networks. There is marginal information available about the medicinal use of wild flora and fauna for some parts of Pakistan, but there is no report on the commercialisation, harvest, market dynamics and conservation impact of these activities.

Since 2013, a number of confiscations of different reptile species and their parts from Pakistani nationals have been reported widely from across the country, which resulted in the enforcement of legislations regarding the wildlife trade in Pakistan.

An international team of researchers, led by Dr. Rafaqat Masroor from Pakistan Museum of Natural History investigated the extent of illegal reptile collection in southwestern Balochistan. Scientists tried to determine what impact these activities might have on the wild populations.

The field trips, conducted in 2013-2017, targeted Chagai, Nushki, Panjgur, Kharan and Washuk districts in Balochistan province. Over those years, scientists interviewed 73 illegal collectors. Most of the collectors worked in groups, consisting of males aged between 14 to 50 years.

"They were all illiterate and their sole livelihood was based on reptile poaching, trade, and street shows. These collectors were well-organized and had trapping equipment for the collection of reptiles. [...] These groups were locally known as "jogeez", who mainly originated from Sindh Province and included snake charmers, having their roots deep with the local hakeems (herbal medicine practitioners) and wildlife traders, businessmen and exporters based at Karachi city. [...] We often observed local people killing lizards and snakes, mostly for fear of venom and part for fun and centuries-old myths", share Dr. Masroor.

A total number of illegally poached reptiles, recorded during the investigation, results in 5,369 specimens representing 19 species. All of them had already been declared Protected under Schedule-III of the Balochistan Provincial Wildlife Act.

Amongst the reasons for the province of Balochistan to remain unexplored might have been the lack of government environmental and wildlife protection agencies, lack of resources and specialists of high qualification in the provincial wildlife, forest and environment departments, as well as geopolitical position and remoteness of vast tracts of areas.

Scientists call for the provincial and federal government to take action and elaborate a specific strategy for the conservation of endemic and threatened species as a part of the country's natural heritage both in southwestern Balochistan and whole Pakistan. The conservation plan needs to be consulted with specialists in the respective fields, in order to avoid incompetence.

Also, the research group suggests to strictly ban illegal poaching of venomous snakes for the purpose of venom extraction.

What is important to remember is that Balochistan represents one of the most important areas of Asia with a high number of endemic reptile species. The illegal capture of these species presents a threat to the poorly documented animals. Even though the current trend for captured reptiles is decreasing, more actions are needed, in order to ensure the safety of the biodiversity of the region.

Credit: 
Pensoft Publishers

TRAPPIST-1 planetary orbits not misaligned

image: Artist's impression of the TRAPPIST-1 exoplanet system.

Image: 
NAOJ

Astronomers using the Subaru Telescope have determined that the Earth-like planets of the TRAPPIST-1 system are not significantly misaligned with the rotation of the star. This is an important result for understanding the evolution of planetary systems around very low-mass stars in general, and in particular the history of the TRAPPIST-1 planets including the ones near the habitable zone.

Stars like the Sun are not static, but rotate about an axis. This rotation is most noticeable when there are features like sunspots on the surface of the star. In the Solar System, the orbits of all of the planets are aligned to within 6 degrees with the Sun's rotation. In the past it was assumed that planetary orbits would be aligned with the rotation of the star, but there are now many known examples of exoplanet systems where the planetary orbits are strongly misaligned with the central star's rotation. This raises the question: can planetary systems form out of alignment, or did the observed misaligned systems start out aligned and were later thrown out of alignment by some perturbation? The TRAPPIST-1 system has attracted attention because it has three small rocky planets located in or near the habitable zone where liquid water can exist. The central star is a very low-mass and cool star, called an M dwarf, and those planets are situated very close to the central star. Therefore, this planetary system is very different from our Solar System. Determining the history of this system is important because it could help determine if any of the potentially habitable planets are actually inhabitable. But it is also an interesting system because it lacks any nearby objects which could have perturbed the orbits of the planets, meaning that the orbits should still be located close to where the planets first formed. This gives astronomers a chance to investigate the primordial conditions of the system.

Because stars rotate, the side rotating into view has a relative velocity towards the viewer, while the side rotating out of view has a relative velocity away from the viewer. If a planet transits, passes between the star and the Earth and blocks a small portion of the light from the star, it is possible to tell which edge of the star the planet blocks first. This phenomenon is called the Rossiter-McLaughlin effect. Using this method, it is possible to measure the misalignment between the planetary orbit and the star's rotation. However, until now those observations have been limited to large planets such as Jupiter-like or Neptune-like ones.

A team of researchers, including members from the Tokyo Institute of Technology and the Astrobiology Center in Japan, observed TRAPPIST-1 with the Subaru Telescope to look for misalignment between the planetary orbits and the star. The team took advantage of a chance on August 31, 2018, when three of the exoplanets orbiting TRAPPIST-1 transited in front of the star in a single night. Two of the three were rocky planets near the habitable zone. Since low-mass stars are generally faint, it had been impossible to probe the stellar obliquity (spin-orbit angle) for TRAPPIST-1. But thanks to the light gathering power of the Subaru Telescope and high spectral resolution of the new infrared spectrograph IRD, the team was able to measure the obliquity. They found that the obliquity was low, close to zero. This is the first measurement of the stellar obliquity for a very low-mass star like TRAPPIST-1 and also the first Rossiter-McLaughlin measurement for planets in the habitable zone.

However the leader of the team, Teruyuki Hirano at the Tokyo Institute of Technology, cautions, "The data suggest alignment of the stellar spin with the planetary orbital axes, but the precision of the measurements was not good enough to completely rule out a small spin-orbit misalignment. Nonetheless, this is the first detection of the effect with Earth-like planets and more work will better characterize this remarkable exoplanet system."

Credit: 
National Institutes of Natural Sciences

Beads made of boa bones identified in lesser Antilles

image: The vertebrae found in this study are the first identification of Boa on these islands.

Image: 
Corentin Bochaton

Today Boa snakes have a patchy distribution in the islands that form the Lesser Antilles in the Caribbean Sea, but the constrictors are nearly absent from archaeological deposits in the region. Whether this scarcity is due to past species distribution, poor preservation conditions, or a lack of interaction with human communities, remains unknown.

To find out why boas occur sparsely in the Lesser Antilles today but hardly at all in archaeological contexts, Corentin Bochaton of the Max Planck Institute for the Science of Human History and the University of Bordeaux, conducted a multidisciplinary study combining archaeological evidence with historical and biological data sources. The study, published in Journal of Island and Coastal Archaeology, describes eight archaeological Boa finds on islands where the reptiles have never previously been identified and provides insights into the relationship between Amerindian groups and Boa before Western colonization.

Boas had a special status in pre-Columbian Lesser Antilles

To conduct the study, Bochaton investigated the animal remains from three sites: Dizac Beach on Martinique, Basse-Terre Cathedral on Basse-Terre (Guadeloupe) and Pointe Gros Rampart on La Désirade (Guadeloupe). Using a binocular microscope, Bochaton observed the surface condition and taxonomic features of the finds, eventually identifying eight vertebrae from the Boa genus.

Despite the presence of many other snake species in the archeological assemblages of the Lesser Antilles, these Boa remains are the only snake bones that appear to have been made into beads, an important clue as to their cultural significance. "The extreme scarcity of Boa in zooarchaeological assemblages, combined with the fact that these are the only snake bones to be modified, reflects the prominent status Boa had in Pre-Columbian Amerindian communities," says Bochaton.

The fact that Boa are largely absent from archaeological finds suggests they probably weren't hunted or eaten by human populations, at least not near their settlements, and evidence from historical records further points to an elevated status of Boa snakes. A chronicle of a 17th century voyage to the Caribbean in a document known as Carpentras Anonymous describes the indigenous people of the islands as unwilling to kill Boas, believing the harm they did to the snakes would also be done to their grandchildren. Further, an account by Charles de Rochefort (1658) retells a story told by the people of Dominica of a monstrous snake who carried on its head a stone of great worth that would glow when it drank or moved in the abyss.

"These documents show us that Boa snakes had, among all snakes, a special status and were especially feared and respected, which could help explain their scarcity in archaeological deposits," says Bochaton.

Multiple lines of evidence help to reconstruct lost past

The islands of the Lesser Antilles were first colonized by Amerindian groups between 7,000 and 5,500 years ago, but molecular evidence and the presence of Boa in fossil deposits show that the snakes colonized these islands thousands, if not millions of years before. Approximately 2,500 years ago, ceramic producing cultures arrived and evolved until the first European contact. At this point a ceramic style known as Cayo emerges.

Western colonization in the 17th century almost completely depopulated the Lesser Antilles of Amerindians and wiped out indigenous cultural practices. It also brought about the extinctions of a long list of species, ranging from terrestrial and flying mammals to birds and scaled reptiles - a list this paper shows to remain incomplete.

"Because of their absence in the archaeological record, Boa snakes were presumed absent from Guadeloupe," Bochaton explains. "These remains not only show that Boas were here, they remind us how much of the cultural and natural history of these islands has been lost, and how important it is to use different lines of evidence to discover and interpret the past."

Credit: 
Max Planck Institute of Geoanthropology

New functions of a protein may improve biocontrol methods in sustainable agriculture

image: NEW FUNCTIONS OF A PROTEIN MAY IMPROVE BIOCONTROL METHODS IN SUSTAINABLE AGRICULTURE

Image: 
University of Malaga

The laboratory of the UMA "BacBio" has proved that Bacillus subtilis cells, when deprived of an amyloid protein (TasA), exhibit a range of cytological anomalies and dysfunctions leading to their premature death. A discovery that enables progress to be made in understanding the role of these proteins, widely distributed in the microbial world, and helps improve biological control methods in sustainable agriculture. This research has been recently published in the scientific journal Nature Communications.

The UMA research team has particularly evidenced how this amyloid protein TasA, required for the assembly of the bacterial communities known as "biofilms", also prevents bacterial cell death, but preserving cell membrane integrity. "That is: we observed a complementary role in these proteins in addition to their merely structural role", explains the main author of this study, the researcher Diego Romero, who is also a member of the Institute for Mediterranean and Subtropical Horticulture "La Mayora" (IHSM), a joint research institute of the Spanish National Research Council (CSIC) and the UMA.

According to the expert, this dual functionality is reflected in bacterial attachment to plant surfaces, where the protein contributes to combat pathogen attack and improve bacterial fitness. "We aim to boost its use in sustainable models of crop production and protection", says the Professor of the UMA Department of Microbiology.

Thus, this study has worked on the bacterium Bacillus subtilis placing emphasis on two aspects: the study of its molecular bases, that lead to the formation of bacterial communities known as "biofilms", and how these biofilms contribute to the beneficial activity of Bacillus as biocontrol agents in sustainable agriculture models.

The amyloids: dual functionality

Amyloids are proteins primarily known for its relation to degenerative diseases in human beings. In fact, "amyloidosis", an ailment caused by amyloid accumulation in organs or tissues, is named after them. However, as noted by this research, amyloid proteins (TasA among them) have the ability to adopt a great variety of purposes in nature, reason why they are called functional amyloids.

"The fact that these proteins are widely distributed in the microbial world entails the possibility that they might play a role in other bacterial species stabilizing cell integrity, or at least a different and complementary role to that initially observed in each of these systems", clarifies Romero.

The expert states that the importance of these results is twofold. From the agrobiotechnological point of view, it allows researchers to better understand the behaviour of beneficial bacteria, hence, improve and reinforce its use in sustainable production and protection programmes. On the other hand, from the microbial point of view, where amyloid proteins are highly distributed, a new target has been identified to be attacked should they wish to harm pathogenic microorganisms.

Credit: 
University of Malaga

Global spread of the multi-resistant pathogen Stenotrophomonas maltophilia

image: Scanning electron microscopic image of Stenotrophomonas maltophilia.

Image: 
E. Abda & I. Alio/ Mikrobiologie, Universität Hamburg

S. maltophilia strains occur in several natural and human associated ecosystems. The bacterium was long regarded as relatively unproblematic but is now considered to be one of the most feared hospital pathogens, as it frequently causes infections and is resistant to a number of antibiotics. This can be particularly dangerous for immune-compromised patients or for patients with underlying inflammatory lung diseases such as cystic fibrosis. Although almost any organ can be affected, infections of the respiratory tract, bacteraemia or catheter-related infections of the bloodstream are the most common. In view of the increasing importance of this pathogen and the often-severe clinical consequences of an infection, knowledge about the virulence factors and about the local and global transmission of S. maltophilia bacteria is urgently needed.

Scientists from a total of eight countries initially established a genotyping method that enables the standardised analysis of the different genomes of S. maltophilia strains. The DZIF teams around Prof. Stefan Niemann (FZB), Prof. Jan Rupp, (Clinic of Infectiology and Microbiology, Campus Lübeck) and Prof. Ulrich Nübel from the Leibniz Institute DSMZ (German Collection of Microorganisms and Cell Cultures GmbH ) in Braunschweig were involved.

The scientists found that the S. maltophilia complex can be divided into a total of 23 lineages with different prevalence levels. One particular line of descent appeared worldwide and had the highest rate of human-associated strains. This "Sm6" strain was also characterised by the presence of key virulence genes and resistance genes. "This suggests that a specific gene configuration may promote the spread of different S. maltophilia subtypes in the hospital setting, i.e. under antimicrobial treatment," says Matthias Gröschel, lead author of the study.

Transmission analysis also identified several potential outbreak events of genetically closely related strains that were isolated within days or weeks in the same hospitals. "Combined with studies on other pathogens, our results show how systematic genome-based monitoring of S. maltophilia and other pathogens in hospital settings can help detect transmission pathways and improve infection control," Thomas Kohl, senior author of the study at FZ Borstel, adds.

Credit: 
German Center for Infection Research

Scientists report on crucial reduction of Indian lion genome diversity

Modern bioinformatics allows us to take a look into the past and find out when certain species diverged during evolution, which of them still are genetically close to each other, and which are not. An international team of researchers, which, among others, includes the academic supervisor of ITMO University's Laboratory of Genomic Diversity and researchers from the University of Copenhagen, Barcelona Institute of Science and Technology, and other research centers from all over the world, analyzed the genomes of extinct and living lions. They managed to determine when the divergence took place, as well as come to several other conclusions on genetic diversity of the modern lion population in India. The results are published in the journal Proceedings of the National Academy of Sciences of the United States of America.

Lions are one of the most powerful and dangerous predators on the planet. Many cities and countries use lion images on their coats of arms as a symbol of power and strength.

However, according to scientists, nowadays lions are in great danger of extinction. In the last two centuries, a 90% reduction in the population took place. During the last 150 years, Cape and Barbary lions were exterminated. Today, apart from zoos, you can meet these animals only in Western and Central Africa, as well as in the Gir National Park and Wildlife Sanctuary, Gujarat, India. To comprehend the process of reduction in the lion population and prevent their extinction, scientists need to answer several questions considering their evolution history.

An international research team, which includes specialists from different countries and continents, as well as Stephen O'Brian, the academic supervisor of ITMO University's Laboratory of Genomic Diversity, has analyzed the remains of cave lions kept in museums and found during paleontological expeditions. The results of the analysis were compared with those of modern lions. It was concluded that cave lions and modern species diverged about 500,000 years ago.

The scientists have also discovered that lion ancestors which used to live in Central and Western Africa diverged from the ancestors of subspecies that used to inhabit Northern Africa, and now inhabit India, about 70,000 years ago. A quite popular myth about lions being artificially brought to India in the pre-colonial era is therefore proved to be false.

This research may have a direct impact on the attempts of the restoration of the Northern-African lion population. If the scientists manage to determine the closest relatives of Barbary subspecies, it will make the restoration more scientifically substantiated and possibly more successful. All the more so due to the fact that in various zoos there are animals which are considered to be derived from Barbary lions gifted to Moroccan rulers in the 19th century.

One of the important conclusions that the scientists came to is that there is no clear evidence that cave lions, which went extinct 10,000-15,000 years ago, or Cape and Barbary lions, which went extinct recently, had a problem with genetic diversity. It means that their extinction evidently was not caused by degeneration and accumulation of deleterious mutations in the population.

However, the reduction in genome diversity can be clearly detected in the modern population of Indian lions. As they have been living in a comparatively small area for centuries, inbreeding often took place. This resulted in cranial defects, low sperm count and testosterone levels, as well as smaller manes. These facts should be taken into consideration during the attempts to save the Indian lion population from extinction.

"The obtained results demonstrate the power given to us by the era of genome research. We can apply it to discover the secrets of the past by reading the fragments of DNA taken from modern species' ancestors. Apart from that, a troubling reduction in Indian lion genetic material was proved," Stephen O'Brien concludes.

Credit: 
ITMO University