Culture

A patient and family walk into a doctor's office. They hope that the latest tests will reveal what is causing the patient's illness and end the diagnostic odyssey they have been going through for years. Having an accurate diagnosis also means that maybe there is a treatment that at least can alleviate the patient's condition.

At Baylor College of Medicine, Dr. Sarah Elsea and her colleagues have been working on improving their ability to identify the genetic cause of undiagnosed conditions. Their study appears in the journal Genetics in Medicine.

"About nine of every 10 patients that are referred to us have neurological conditions, such as developmental delay and intellectual disability, for which they don't have a diagnosis," said Elsea, professor of molecular and human genetics at Baylor and corresponding author of the work.

To identify the genetic cause of undiagnosed conditions, the researchers look for potentially defective genes in the patient's genome. They use whole-exome sequencing, which analyzes all the genes that encode proteins. A gene may have many variants that encode slightly different versions of the same protein that still carry their function normally. But some variants may encode defective proteins that can cause disease. The challenging part is determining whether the variant of a particular gene that is found in a patient is causing the disease.

"In some cases, the variant is missing all or a large portion of the gene, which results in a non-functional protein. This suggests that the variant is involved in the disease. However, most genetic variants involve changes in a single building block of the DNA. That one 'misspelled' gene sequence may or may not result in a defective or less functional protein, and we need other mechanisms, such as untargeted metabolomics, to determine if that genetic change causes disease," said Elsea, who also is the senior director of biochemical genetics at Baylor Genetics.

Enter untargeted metabolomics

Elsea and her colleagues used untargeted metabolomics to provide an additional level of information to help them determine whether the genetic variant they found in the patient was actually causing the condition.

"Untargeted metabolomics lets us look at the function of the protein encoded by the gene variant in the patient to explore metabolic abnormalities that may be associated with the variant," Elsea said.

In the current study, the researchers integrated whole-exome sequencing and targeted metabolomics to analyze the data of a group of 170 patients. They were pleased to find that the metabolomics data informed 44 percent of the cases.

"The analysis let us reclassify nine variants as likely benign, 15 variants as likely causing disease and three as disease-causing variants. Metabolomics data confirmed a clinical diagnosis in 21 cases," Elsea said. "Our analysis is extremely helpful not only for confirming that a variant causes the condition, but also to rule out variants as the cause of disease. Having a more accurate diagnosis may help identify a better treatment for the condition and also provides important information for the family regarding recurrence risk."

This analysis also aids with the diagnosis of patients that may have a mild form of a disease, because the analysis is broad and very sensitive and shows the effects of the variant in entire metabolic pathways.

"We have been able to identify a few cases with milder diseases. Before our integrated analysis, we would not have diagnosed those cases with the disease, but we can now because metabolomics revealed metabolic abnormalities that we could link to the gene variant in the patient," Elsea said. "This approach has improved diagnostics substantially and also increased our understanding of these conditions and the range of clinical manifestations that we might see in patients."

The researchers hope that their integrated multi-omics analysis will help other patients by providing a diagnosis, clarifying previous suspected diagnoses or monitoring their treatment.

Researchers from the University of Houston, in collaboration with others, have designed a "catch and kill" air filter that can trap the virus responsible for COVID-19, killing it instantly.

Zhifeng Ren, director of the Texas Center for Superconductivity at UH, collaborated with Monzer Hourani, CEO of Medistar, a Houston-based medical real estate development firm, and other researchers to design the filter, which is described in a paper published in Materials Today Physics.

The researchers reported that virus tests at the Galveston National Laboratory found 99.8% of the novel SARS-CoV-2, the virus that causes COVID-19, was killed in a single pass through a filter made from commercially available nickel foam heated to 200 degrees Centigrade, or about 392 degrees Fahrenheit. It also killed 99.9% of the anthrax spores in testing at the national lab, which is run by the University of Texas Medical Branch.

"This filter could be useful in airports and in airplanes, in office buildings, schools and cruise ships to stop the spread of COVID-19," said Ren, MD Anderson Chair Professor of Physics at UH and co-corresponding author for the paper. "Its ability to help control the spread of the virus could be very useful for society." Medistar executives are is also proposing a desk-top model, capable of purifying the air in an office worker's immediate surroundings, he said.

Ren said the Texas Center for Superconductivity at the University of Houston (TcSUH) was approached by Medistar on March 31, as the pandemic was spreading throughout the United States, for help in developing the concept of a virus-trapping air filter.

Luo Yu of the UH Department of Physics and TcSUH along with Dr. Garrett K. Peel of Medistar and Dr. Faisal Cheema at the UH College of Medicine are co-first authors on the paper.

The researchers knew the virus can remain in the air for about three hours, meaning a filter that could remove it quickly was a viable plan. With businesses reopening, controlling the spread in air conditioned spaces was urgent.

And Medistar knew the virus can't survive temperatures above 70 degrees Centigrade, about 158 degrees Fahrenheit, so the researchers decided to use a heated filter. By making the filter temperature far hotter - about 200 C - they were able to kill the virus almost instantly.

Ren suggested using nickel foam, saying it met several key requirements: It is porous, allowing the flow of air, and electrically conductive, which allowed it to be heated. It is also flexible.

But nickel foam has low resistivity, making it difficult to raise the temperature high enough to quickly kill the virus. The researchers solved that problem by folding the foam, connecting multiple compartments with electrical wires to increase the resistance high enough to raise the temperature as high as 250 degrees C.

By making the filter electrically heated, rather than heating it from an external source, the researchers said they minimized the amount of heat that escaped from the filter, allowing air conditioning to function with minimal strain.

A prototype was built by a local workshop and first tested at Ren's lab for the relationship between voltage/current and temperature; it then went to the Galveston lab to be tested for its ability to kill the virus. Ren said it satisfies the requirements for conventional heating, ventilation and air conditioning (HVAC) systems.

"This novel biodefense indoor air protection technology offers the first-in-line prevention against environmentally mediated transmission of airborne SARS-CoV-2 and will be on the forefront of technologies available to combat the current pandemic and any future airborne biothreats in indoor environments," Cheema said.

Hourani and Peel have called for a phased roll-out of the device, "beginning with high-priority venues, where essential workers are at elevated risk of exposure (particularly schools, hospitals and health care facilities, as well as public transit environs such as airplanes)."

That will both improve safety for frontline workers in essential industries and allow nonessential workers to return to public work spaces, they said.

Microalgae could provide an alternative source of healthy omega-3 fatty acids for humans while also being more environmentally friendly to produce than popular fish species. This is the result of a new study by scientists from Martin Luther University Halle-Wittenberg (MLU). The study was recently published in the Journal of Applied Phycology and offers an initial indication of the environmental effects of producing microalgae in Germany.

Microalgae have been the focus of several decades of research - initially as a raw material for alternative fuels, but more recently as a source of nutrients in the human diet. They are mainly produced in open ponds in Asia; however, these ponds are at risk of potential contamination. Also, some species of algae are easier to cultivate in closed systems, so-called photobioreactors. "We wanted to figure out whether microalgae produced in photobioreactors in Germany could provide a more environmentally friendly source of essential nutrients than fish," says Susann Schade from the Institute of Agricultural and Nutritional Sciences at MLU. Up to now, photobioreactors had usually only been compared to pond cultivation and they often scored worse due to their higher environmental impacts. "However, little research has been done on the precise extent of the environmental impacts of algae produced for human consumption, especially under climatic conditions such as those found in Germany," adds Schade.

For their study, the researchers developed a model to determine location-specific environmental impacts. "One of the things we did was to compare the carbon footprint of nutrients from microalgae and fish. We also analysed how much both food sources increase the acidification and eutrophication in water bodies," explains Dr Toni Meier, head of the Innovation Office nutriCARD at MLU. The researchers were able to show that microalgae farming has a similar impact on the environment as fish production. "However, if we compare the environmental effects in relation to the amount of omega-3 fatty acids produced, fish from aquaculture comes off far worse," says Schade. One advantage of algae cultivation is its low land consumption; even infertile soils can be used. In contrast, both open ponds and the cultivation of feed for aquaculture require very large areas of land. In particular, fish species that are popular in Germany, such as salmon and pangasius, are primarily produced through aquaculture and therefore put the environment under a considerable amount of pressure. However, even fishing wild Alaska pollack had poorer values than microalgae for all environmental indicators.

"Microalgae should not and cannot completely replace fish as a food source. But if microalgae could be established as a common food, it would be another excellent environmentally friendly source of long-chain omega-3 fatty acids," explains Meier. Several algae are already used as a food supplement in powder or tablet form and as an additive to foods such as pasta or cereals. It would be a way to reduce the current gap in the global supply of omega-3 fatty acids. At the same time, it would provide considerable relief to the world's oceans.

Washington, DC - July 7, 2020 - According to findings published this week in mBio, Nissle, a strain of Escherichia coli, is harmless to intestinal tissue and may protect the gut from enterohemorrhagic E. coli, a pathogen that produces Shiga toxin.

E. coli has gotten a bad rap because a few pathogenic strains can cause severe, even life-threatening, symptoms. But for more than a century, the commensal strain Nissle has been used as a probiotic and, more recently, to treat intestinal disorders including ulcerative colitis.

Researchers at the University of Cincinnati wanted to understand whether Nissle could also protect intestinal tissue against EHEC and other pathogens. They studied the probiotic's protective effects using human intestinal organoids, or HIOs, which are experimental models of real tissue derived from stem cells.  

The researchers first injected the HIOs with Nissle and observed that the bacterium was harmless: It did not damage the epithelial barrier, formed by the protective outer layer of the organoid. Next, in separate experiments, they injected HIOs with enterohemorrhagic E. coli or EHEC. This pathogen produces Shiga toxin, which sickens millions and kills thousands of people--mainly children--every year. The EHEC quickly broke down the epithelial barrier in the HIOs.  

Then, the researchers pre-treated HIOs with Nissle and, 12 hours later, injected them with EHEC. This is where the Nissle proved to be protective: Even though the EHEC proliferated in the organoid tissue, it did not destroy the epithelial barrier. During the same time, the Nissle population declined rapidly in the tissue. The researchers observed the same effects when they injected pre-treated HIOs with uropathogenic E. coli, the strain responsible for the majority of urinary tract infections.  

"Basically, the Nissle was killed by the pathogenic bacteria, but it made the intestine able to withstand damage better," said molecular geneticist Alison Weiss, Ph.D., who worked on the study together with Suman Pradhan, Ph.D., a research associate in Weiss's lab.  

The results suggest Nissle may confer benefits not by inhibiting the pathogenic strains directly, but instead by harnessing defense mechanisms in the cell itself, and that the probiotic may help prevent severe EHEC infections. However, the results also suggest that Nissle can be vulnerable to phages from the Shiga toxin, which would limit the probiotic's usefulness as a therapeutic. Weiss cautioned that more studies are needed to better understand the complex interactions of bacterial species in a real-world setting.  

Weiss's research focuses on bacteria that produce the Shiga toxin, like EHEC. "It's really bad," she said. "My whole career, I've been interested in preventing pediatric pathogens. Once these kids get EHEC, all you can do is give them fluids and support them. There's nothing else we can do."  

Weiss is excited by the potential of using HIOs as a model for better understanding intestinal conditions. "They're a huge breakthrough," she said. "A lot of intestinal pathogens are species-specific, and organoids are really good for looking at early events."  

Organoids offer at least one other major advantage over mice, she added. "Mice are awful. They pee and bite and scratch," she said. "The little organoids don't complain at all."

A simple measuring tape could be the key to identifying which children could develop
neurological and developmental abnormalities from Zika virus exposure during gestation.
This is according to an invited commentary published July 7 in JAMA Network Open and
written by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Division of
Prenatal Pediatrics at Children's National Hospital.

Zika virus (ZIKV), first isolated in 1947 in the Ziika Forest in Uganda, made headlines in
2015-2016 for causing a widespread epidemic that spread through parts of North and
South America, several islands in the Pacific and parts of Southeast Asia. Although
previously linked with no or mild symptoms, researchers discovered during this epidemic
that Zika can cross from a pregnant woman to her gestating fetus, leading to a syndrome
marked by microcephaly (decreased brain growth), abnormal neurologic tone, vision and
hearing abnormalities, and joint contractures.

"For the 90% to 95% of ZIKV-exposed infants who fortunately were not born with severe
abnormalities at birth and were normocephalic, our hope was that these children would
have normal neurodevelopmental outcomes," Dr. Mulkey writes in the commentary.
"Unfortunately, this has not been the case."

Her commentary expands on a study in the same issue entitled "Association between
exposure to antenatal Zika virus and anatomic and neurodevelopmental abnormalities in
children" by Cranston et al. In this study, the researchers find that head circumference --
a simple measure taken regularly at postnatal appointments in the U.S. -- can provide
insight into which children were most likely to develop neurologic abnormalities. Their
findings show that 68% of those whose head circumference was in the "normal" range at
birth developed neurologic problems. Those whose head circumference was at the
upper end of this range were significantly less likely to have abnormalities than those at
the lower end.

Just this single measurement offers considerable insight into the risk of developing
neurologic problems after Zika exposure. However, notes Dr. Mulkey, head
circumference growth trajectory is also key. Of the 162 infants whose heads were initially
in the normocephalic range at birth, about 10.5% went on to develop microcephaly in the
months after birth.

"Because early head growth trajectory is associated with cognitive outcomes in early
childhood," Dr. Mulkey writes, "following the head circumference percentile over time can
enable recognition of a child with increased risk for poor outcome who could benefit from
early intervention therapies."

This simple assessment could be significantly augmented with neuroimaging, she adds.
The study by Cranston et al., as well as others in the field, have shown that brain
imaging often reveals problems in ZIKV-exposed children, such as calcifications and
cerebral atrophy, even in those with normal head circumferences. This imaging doesn't
necessarily need to take place at birth, Dr. Mulkey says. Postnatal development of
microcephaly, failure to thrive or developmental delay can all be triggers for imaging later
on.

Together, Dr. Mulkey says, the study by Cranston et al. and others that focus on ZIKVexposed children support the need for following these patients long term. Children
exposed to ZIKV in the epidemic nearly five years ago are now approaching school age,
a time fraught with more complicated cognitive and social demands. Through her own
research at Children's National's Congenital Zika Virus Program and collaboration with
colleagues in Colombia, Dr. Mulkey is following multiple cohorts of ZIKV exposed
children as they grow. She recently published a study on neurological abnormalities in
one of these cohorts in JAMA Pediatrics in January 2020.

"It's really important to follow these children as long as possible so we'll really know the
outcomes of this virus," Dr. Mulkey says.

Archaeologists from Cardiff University and the University of Sheffield have combined the latest scientific methods to offer new insights into life during the Norman Conquest of England.

Until now, the story of the Conquest has primarily been told from evidence of the elite classes of the time. But little has been known about how it affected everyday people's lives.

The research team, which also included academics from the University of Bristol, used a range of bioarchaeological techniques to compare human and animal bones recovered from sites across Oxford, along with ceramics used for cooking. Their results suggest only short-term fluctuations in food supplies following the Conquest which didn't adversely affect the population's overall health.

There is evidence the Norman invasion led to more controlled and standardised mass agricultural practices. Pork became a more popular choice and dairy products were used less. But on the whole, a diet dominated by vegetables, cereals beef and mutton remained largely unchanged.

Dr Elizabeth Craig-Atkins of the University of Sheffield's Department of Archaeology said: "Examining archaeological evidence of the diet and health of ordinary people who lived during this time gives us a detailed picture of their everyday experiences and lifestyles. Despite the huge political and economic changes that were happening, our analysis suggests the Conquest may have only had a limited impact on most people's diet and health.

"There is certainly evidence that people experienced periods where food was scarce. But following this, an intensification in farming meant people generally had a more steady food supply and consistent diet. Aside from pork becoming a more popular food choice, eating habits and cooking methods remained unchanged to a large extent."

Researchers used a technique called stable isotope analysis on bones to compare 36 humans found in various locations around Oxford, including Oxford Castle, who had lived between the 10th and 13th centuries. Signals from food we consume are archived as chemical tracers in our bones, allowing scientists to investigate the quality and variety of a person's diet long after they have died.

The team found that there wasn't a huge difference between the health of the individuals, who were alive at different points before and after the Conquest. Levels of protein and carbohydrate consumption were similar in the group and evidence of bone conditions related to poor diet - such as rickets and scurvy - were rare. However, high resolution analysis of teeth showed evidence of short-term changes in health and diet in early life during this transitional phase.

Isotope analysis was also used on 60 animals found at the same sites, to ascertain how they were raised. Studies of pig bones found their diets became more consistent and richer in animal protein after the Conquest, suggesting pig farming was intensified under Norman rule. They were likely living in the town and being fed scraps instead of natural vegetable fodder.

Fragments of pottery were examined using organic residue analysis. When food is cooked in ceramic pots, fats are absorbed into the vessel, allowing researchers to extract them. Analysis showed that pots were used to cook vegetables like cabbage as well as meat such as lamb, mutton or goat across the conquest. Researchers say the use of dairy fats reduced after the Conquest and that pork or chicken became more popular.

Dr Richard Madgwick, based in Cardiff University's School of History, Archaeology and Religion, said: "To our knowledge, this is the very first time globally that human osteology, organic residues analysis and isotope analysis of incremental dentine and bone have been combined in a single study.

"It is only with this innovative and diverse suite of methods that we have been able to tell the story of how the Conquest affected diet and health in the non-elite, a somewhat marginalised group until now."

The dietary impact of the Norman Conquest: A multiproxy archaeological investigation of Oxford, UK, is published in the journal PLOS ONE.

What The Study Did: How the prescription of hydroxychloroquine and chloroquine to outpatients has changed in the United States during the COVID-19 pandemic is examined in this study.

Authors: Daniel S. Budnitz, M.D., M.P.H., of the Centers for Disease Control and Prevention COVID-19 Response Team in Atlanta, 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.2020.2594)

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

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WOODS HOLE, Mass. -- Deserts of the U.S. Southwest are extreme habitats for most plants, but, remarkably, microscopic green algae live there that are extraordinarily tolerant of dehydration. These tiny green algae (many just a few microns in size) live embedded in microbiotic soil crusts, which are characteristic of arid areas and are formed by communities of bacteria, lichens, microalgae, fungi, and even small mosses. After completely drying out, the algae can become active and start photosynthesizing again within seconds of receiving a drop of water.

How are they so resilient? That question is at the core of research by Elena Lopez Peredo and Zoe Cardon of the Marine Biological Laboratory (MBL), published this week in Proceedings of the National Academy of Sciences. Given the intensified droughts and altered precipitation patterns predicted as the global climate warms, understanding the adaptations that facilitate green plant survival in arid environments is pressing.

Working with two particularly resilient species of green microalgae (Acutodesmus deserticola and Flechtneria rotunda), Peredo and Cardon studied up- and down-regulation of gene expression during desiccation, and added a twist. They also analyzed gene expression in a close aquatic relative (Enallax costatus) as it dried out and ultimately died. Surprisingly, all three algae - desiccation tolerant or not - upregulated the expression of groups of genes known to protect even seed plants during drought. But the desiccation-tolerant algae also ramped down expression of genes coding for many other basic cellular processes, seemingly putting the brakes on their metabolism. The aquatic relative did not.

Peredo's and Cardon's research suggests this new perspective on desiccation tolerance warrants investigation in green plants more broadly. Upregulation of gene expression coding for protective proteins may be necessary but not sufficient; downregulation of diverse metabolic genes may also be key to survival.

Coconut oil production may be more damaging to the environment than palm oil, researchers say.

The issue of tropical forests being cut down for palm oil production is widely known, but the new study says coconut oil threatens more species per ton produced than palm or other vegetable oils.

The researchers use this example to highlight the difficulties of "conscientious consumption".

They say consumers lack objective guidance on the environmental impacts of crop production, undermining their ability to make informed decisions.

"The outcome of our study came as a surprise," said lead author Erik Meijaard, of Borneo Futures in Brunei Darussalam.

"Many consumers in the West think of coconut products as both healthy and their production relatively harmless for the environment.

"As it turns out, we need to think again about the impacts of coconut."

Co-author Dr Jesse F. Abrams, of the Global Systems Institute and the Institute for Data Science and Artificial Intelligence, both at the University of Exeter, added: "Consumers, especially those striving to be more responsible in their consumption, rely heavily on information that they receive from the media, which is often supplied by those with vested interests.

"When making decisions about what we buy, we need to be aware of our cultural biases and examine the problem from a lens that is not only based on Western perspectives to avoid dangerous double standards."

According to the study, production of coconut oil affects 20 threatened species (including plants and animals) per million tons of oil produced. This is higher than other oil-producing crops, such as palm (3.8 species per million tons), olive (4.1) and soybean (1.3).

The study shows that the main reason for the high number of species affected by coconut is that the crop is mostly grown on tropical islands with rich diversity and many unique species.

Impact on threatened species is usually measured by the number of species affected per square hectare of land used - and by this measure palm's impact is worse than coconut.

Coconut cultivation is thought to have contributed to the extinction of a number of island species, including the Marianne white-eye in the Seychelles and the Solomon Islands' Ontong Java flying fox.

Species not yet extinct but threatened by coconut production include the Balabac mouse-deer, which lives on three Philippine islands, and the Sangihe tarsier, a primate living on the Indonesian island of Sangihe.

The authors, however, emphasise that the objective of the study is not to add coconut to the growing list of products that consumers should avoid.

Indeed, they note that olives and other crops raise also raise concerns.

Co-author Professor Douglas Sheil, of the Norwegian University of Life Sciences, said: "Consumers need to realise that all our agricultural commodities, and not just tropical crops, have negative environmental impacts.

"We need to provide consumers with sound information to guide their choices."

The researchers argue for new, transparent information to help consumers.

"Informed consumer choices require measures and standards that are equally applicable to producers in Borneo, Belgium and Barbados," they write.

"While perfection may be unattainable, improvements over current practices are not."

Cyanobacteria, commonly referred to as blue-green algae, are the first organisms on earth that learned to extract electrons from water and convert sunlight to usable energy through photosynthesis. Using cyanobacteria as a model organism, the details of photosynthesis--the key process that supports all forms of advanced lives on earth--have been studied for many decades. And all studies, despite their differences, reveal one thing: that it is an astonishingly precise process, consisting of numerous small reactions run by many proteins and their combinations. However, the molecular-level details of many of these steps are still not understood very well.

The initial energy capture and transmission is one such step that still holds many unanswered questions. At the start of a photosynthetic cycle, special proteins on the membrane of cyanobacteria absorb the solar energy and then transfer this energy to other cellular proteins. This is the "light-harvesting" process. As excess energy can harm the cell, some proteins take part in the dissipation of excess energy, a process known as "energy quenching." These are closely coordinated processes, with energy transfer between different molecules taking place very quickly, within a few tens of picosecond (1 picosecond = 1 × 10-12 second). In cyanobacteria, two reaction-systems, the Photosystems (PS) I and II, work together to capture the energy from sunlight.

Now, in a new study published in Communications Biology, a team of scientists led by Associate Professor Fusamichi Akita of Okayama University, Japan, has investigated the structure of PSI of the cyanobacterium Thermosynechococcus vulcanus, formed under an iron-deficient condition, to decipher the role of a key protein called iron-stress inducible A protein or "IsiA" in photosynthesis.

In the cyanobacterial membrane, IsiA appears in low iron level conditions, and combines with a trimeric core of PSI to perform the light-harvesting step. Much akin to a runner in a relay race, IsiA "donates" or transfers the captured energy to the trimeric core of PSI that performs the subsequent step in the photosynthesis process. It has been believed that in addition to functioning an "energy harvester," IsiA also works as a "quencher" that gets rid of excess energy as heat when light intensity is too high for the cells to grow.

Dr Akita explains what made them interested in the IsiA's function, stating "While IsiA has been considered as both the energy donor and quencher for a long time, the path of these processes is not clear. Moreover, the data accumulated so far suggests a different story, indicating a contrasting possibility that in reality IsiA is involved either in the energy transfer or quenching processes but not in both steps."

To answer the first question, the team first used a technique called "single-particle cryogenic electron microscopy," and determined the structure of the "supercomplex" that IsiA forms with the trimeric PSI core and many other molecules in the absence of iron. They found that 18 copies of IsiA come together to form a ring encircling the trimeric PSI core. As a result of this arrangement, several possible energy transfer pathways from IsiA to the PSI core were formed, and a pathway that had the fastest rate of energy transfer was determined to serve as the main route through which the energy moves from IsiA to the PSI core.

To solve the rest of the puzzle as to whether IsiA works as a quencher too, the scientists used a spectroscopic technique called "femtosecond time-resolved fluorescence decay." The result of this study ruled out the possibility of any energy-quenching taking place in the IsiA-PSI core supercomplex, confirming IsiA's role as an energy harvester and donor.

Highlighting the significance of this exciting study, Dr Akita states, "These structural and spectroscopic findings provide important insights into the molecular arrangement and energy-transfer mechanisms in the photosystems of cyanobacteria. A deeper understanding of how photosynthetic energy transfer takes place will help to develop new energy devices based on photosynthesis."

Further studies comparing the inter-species differences in PSI systems are required before we can generalize these findings, but for now, the results of this study have laid to rest a polarizing debate on the function of IsiA.

250 years ago, over one-fifth of Londoners had contracted syphilis by their 35th birthday, historians have calculated.

The same study shows that Georgian Londoners were over twice as likely to be treated for the disease as people living in the much smaller city of Chester at the same time (c.1775), and about 25 times more likely than those living in parts of rural Cheshire and north-east Wales.

The study, offers the first robust estimate of the amount of syphilis infection in London's population in the later eighteenth century.

Following years of painstaking archival research and data analysis, historians Professor Simon Szreter from the University of Cambridge, and Professor Kevin Siena from Canada's Trent University, have just published their disturbing findings in the journal Economic History Review.

They may not have surprised James Boswell, the celebrated biographer of Samuel Johnson, who recorded up to 19 episodes of venereal disease in his diary between 1760 and 1786. Boswell left a candid record of his many sexual exploits with prostitutes in London in this period, as well as the pain caused by contracting STIs. Today, however, the revelation could help to transform our understanding of the capital's population structure, sexual habits and wider culture as it became the world's largest metropolis.

Cambridge's Simon Szreter said: "It isn't very surprising that London's sexual culture differed from that of rural Britain in this period. But now it's pretty clear that London was in a completely different league to even sizeable provincial cities like Chester."

The researchers are confident that one-fifth represents a reliable minimum estimate, consistent with the rigorously conservative methodological assumptions they made at every stage. They also point out that a far greater number of Londoners would have contracted gonorrhea (or, indeed, chlamydia) than contracted syphilis in this period.

"Our findings suggest that Boswell's London fully deserves its historical reputation," Szreter said. "The city had an astonishingly high incidence of STIs at that time. It no longer seems unreasonable to suggest that a majority of those living in London while young adults in this period contracted an STI at some point in their lives."

"In an age before prophylaxis or effective treatments, here was a fast-growing city with a continuous influx of young adults, many struggling financially. Georgian London was extremely vulnerable to epidemic STI infection rates on this scale."

On experiencing initial signs of discomfort, such as a rash or pain in urination, most people in Georgian England hoped that they only had 'the clap' (gonorrhea) rather than 'the pox' (syphilis), and would have begun by self-medicating with various pills and potions. But for many, the symptoms got worse, leading to debilitating pain and fevers which they couldn't ignore.

Mercury salivation treatment was considered a reliable and permanent cure for syphilis but it was debilitating and required at least five weeks of residential care. This was provided, for free, by London's largest hospitals, at least two specialist hospitals, and many poor law infirmaries, as well as privately for those who could afford it.

To maximise the accuracy of their estimates, Szreter and Siena drew on large quantities of data from hospital admission registers and inspection reports, and other sources to make numerous conservative estimates including for bed occupancy rates and duration of hospital stays. Along the way, they excluded many patients to avoid counting the false positives that arise from syphilis's notoriously tricky diagnosis.

Of particular value to the researchers were surviving admissions registers from the late 1760s through to the 1780s for St Thomas's and Guy's Hospitals which consistently housed 20-30 per cent of their patients in 'foul' wards reserved for residential treatment for the pox. But the researchers also drew on evidence for St Bartholomew's hospital; workhouse infirmaries; and two subscription hospitals, the Lock and the Misericordia, which also cared for 'Foul' men and women.

Patients in London's foul wards often battled their diseases for six months or more before seeking hospitalization. This helped the researchers, making it highly likely that the majority of patients they were counting in the records were suffering from significant protracted symptoms more characteristic of secondary syphilis than of gonorrhea, soft chancre, or chlamydia.

After making careful adjustments, Szreter and Siena reached a final conservative estimate of 2,807 inpatients being treated for pox annually across all institutions c.1775. By dividing this figure by London's population, falling within the catchment area of the hospitals and workhouses studied, they arrived at a crude annual rate of treatment per capita.

By then comparing this with existing data for Chester - and making further adjustments to account for demographic and social differences between the two cities - they converted London's crude rate into a comparable cumulative probability rate. This suggested that while about 8% of Chester's population had been infected by age 35, the figure for London was well over 20%.

Why was Georgian London so syphilitic?

A major factor is likely to be the increasing movement of people through London in this period, combined with the financial precarity experienced by young adults aged 15-34. Young women were particularly well represented among new arrivals to the city, and they were often placed in positions of domestic and economic dependence on mostly male employers.

The full 20% chance of infection applies to individuals continuously resident in the capital from age 15 through to age 35. While this applies to most Londoners, among the sizeable mobile minority of the capital's population, who were probably at most risk, some came and went and so spent only part of that most vulnerable period of their lives exposed to this high level of risk.

The historians emphasise that STIs were particularly rife among young, impoverished, mostly unmarried women, either using commercial sex to support themselves financially or in situations that rendered them vulnerable to sexual predation and assault like domestic service. They were also rife among two sets of men: poor in-migrant men, many still unmarried and on the margins of London's economy; and, a range of more established men like James Boswell, who were able to pay for hospital or private treatment.

Why is the study important?

Szreter said: "Syphilis and other STIs can have a very significant effect on morbidity and mortality and also on fertility. So infection rates represent a serious gap in our historical knowledge, with significant implications for health, for demography and therefore for economic history. We hope that our work will help to change this."

"Understanding infection rates is also a crucial way to access one of the most private, and therefore historically hidden, of human activities, sexual practices and behaviours."

Proteins control many physiological functions that are essential for living things in vivo. There are over 20,000 types of proteins in humans, and each protein plays a different role by interacting with other proteins. Proximity-dependent biotin identification (BioID) technology is a technique for finding these interacting partner proteins. BioID can be used by expressing the BioID-fusion protein and adding biotin. In cells expressing BioID-fusion bait protein, proteins with which the bait protein interacts are biotinylated and can be comprehensively analyzed using precipitation with streptavidin followed by mass spectrometry.

Three types of BioID enzymes (BioID, BioID2, TurboID) have been developed so far. However, BioID and BioID2 require a long reaction time and TurboID also biotinylates non-interacting proteins. Further improvement of biotinylation enzymes is an important goal for enhancing the convenience of proximity biotinylation in cells.

In this research, we designed ancestral biotinylation enzymes using an ancestral enzyme reconstruction algorithm and metagenome data. The new enzyme, AirID (ancestral BirA for proximity-dependent biotin identification) showed higher activity, higher specificity, and less toxicity than the previous three types. AirID was applied in the evaluation of protein interaction inhibitors, analyzing complexes formed by three or more types of proteins, and analyzing interactions through compounds called Molecular Glue. In addition, we have succeeded in the comprehensive identification of proteins that interact with a target protein by identifying biotinylated proteins using mass spectrometry analysis in cultured cells which express the target protein fused with AirID. These results indicate that AirID is a suitable enzyme for analyzing comprehensive protein-protein interactions in cells.

Native to the Americas, the tequila bat (Leptonycteris yerbabuenae) lives in caves in some of the hottest desert areas in Mexico. Given that bats are highly mobile, and that migratory species tend to mix constantly with other bat populations, it is hard for conservationists to know whether they are protecting the best sites for the tequila bats to roost.

While known that some tequila bat populations migrate in Mexico's spring months to the Sonoran Desert to give birth to their pups and pollinate a variety of plants iconic to the region, including the economically important Blue Agave plant. Other tequila bat populations inhabit Southern Mexico year-round, forming large breeding colonies in the winter months.

This study aimed to help better inform conservationists of the species' breeding and migratory patterns by determining whether the bats inhabiting Southern Mexico year-round have a similar ancestral origin to those that migrate to the Sonoran Desert.

DNA analysis was necessary to understand how historical events may have shaped current tequila bat populations. But first, an international team, comprising researchers from the University of Bristol, the Centro de Investigación Científica y de Educación Superior de Ensenada and the Universidad Nacional Autónoma de México, had to track down the elusive creatures by travelling to remote caves in Mexico to collect DNA skin samples.

Bat expert, Angelica Menchaca (PhD) from Bristol's School of Biological Sciences who led the study, said: "Tequila bats are beautiful, especially after they arrive back from feeding as they return covered in pollen, completely yellow, a sign of how important they are to this ecosystem. They are easy to handle, not like other bat species that can be more aggressive.

"However, our expedition to the desert was not without hitches and dangers. We were often hiking in temperatures routinely exceeding 40°C and encountering desert wildlife such as rattle snakes, scorpions, hares, reptiles and ring-tailed cats along the way.

"Once we located the bat colony, our aim was to collect DNA skin samples from the bat's wing which heals quickly and doesn't harm them. We would wait until the bats went out to forage at around midnight and then enter the caves that were filled with thousands of baby bats, all packed together in nurseries, waiting for their mums to return."

Bats are subject to many threats around the world. Their populations are threatened by habitat loss, their roosts are often disturbed, and people fear them both from myths and as potential disease carriers. Bat-phobia is only increasing in our current climate. However, despite their often-negative press, bats are very valuable to ecosystems and the benefits they bring to our societies including the popular beverage tequila.

After analysing samples, the team were able to identify the bats' mitochondrial DNA and use this to trace the maternal line of the different populations to understand the ancestral descent of the species.

Explaining the findings, Dr Menchaca added: "Contrary to current practice, our study demonstrates that the species must be managed as two conservation units (CUs) in Mexico. We have shown that tequila bat populations that establish maternity colonies in the Sonoran Desert in northern Mexico show a distinct migratory behaviour, breed during the summer, have specific habitat requirements and belong to a maternal line distinct to their southern counterparts.

"In the present context of an accelerated rate of habitat loss, increased fear of bats and decreased appreciation as ecosystem service providers, understanding how we can help support this important species survive these threats is even more relevant.

"We are studying other differences related to their behaviour and morphology that will also help us understand how these bats adapt to diverse habitats."

Importantly, this research will be used to help inform conservation management strategies, as the tequila bat is considered "Near Threatened" by the IUCN Red List of Endangered Species.

Human communication has evolved mechanisms that can be observed across all cultures and languages, including the use of communication history and the principle of least effort. These two factors enable us to use shared information about the past and present and to conserve energy, making communications as effective and efficient as possible. Given the remarkable sensitivity of dogs to human vocalizations, gestures and gazes, researchers have suggested that 30.000 years of domestication and co-evolution with humans may have caused dogs to develop similar principles of communication - a theory known as the domestication hypothesis.

On this basis, researchers designed an experiment that would examine the factors influencing the form, effort and success of dog-human interactions in a hidden-object task. Using 30 dog-owner pairs, researchers focused on a communicative behavior called showing, in which dogs gather the attention of a communicative partner and direct it to an external source.

While the owner waited in another room, an experimenter in view of a participating dog hid the dogs` favourite toy in one of four boxes. When the owner entered the room, the dog had to show its owner where the toy had been hidden. If the owner successfully located the toy, the pair were allowed to play as a reward. Participants were tested in two conditions: a close setup which required more precise showing and a distant setup which allowed for showing in a general direction.

The researchers found no evidence to suggest that dogs adhere to the principal of least effort, as they used as much energy in the easier far setup as they did in the more difficult close setup. However, this might have been a result of the owners influence on their dogs' effort. Secondly, dogs were not affected by different communication histories, as they performed similarly and used similar amounts of energy in both setups regardless of which condition they began with. Despite putting in similar amounts of effort, dogs adapted their showing strategies to be more or less precise, depending on the conditions.

The findings indicate that a crucial factor influencing the effort and accuracy of dogs' showing is the behaviour of the dog's owner. Owners who encouraged their dog to show where the toy was hidden increased their dog's showing effort but generally decreased their showing accuracy.

"We've seen in previous studies that if we keep eye contact with the dog or talk in a high-pitched voice, we seem to prompt a 'ready-to-obey attitude' which makes dogs very excited to follow our commands. So when owners asked their dogs 'Is the toy here?' and pointed at the boxes, they might have caused dogs to just show any box," says Melanie Henschel, main author of the study.

Although the researchers found no effects of communication history or the principal of least effort, the current study indicates for the first time that owners can influence their dog's showing accuracy and success.

"We were surprised that encouragement increased mistakes in dogs` showing accuracy. This could have impacts on the training of dogs and handlers in fields where dogs are working professionals. Future studies should focus on the complex effects of the owner's influence and the best strategies for handlers communicating with a dog." adds Juliane Bräuer, senior author and head of the DogStudies Lab at MPI-SHH in Jena.

Barcelona, 6 July 2020. Short, frequent walks in blue spaces--areas that prominently feature water, such as beaches, lakes, rivers or fountains--may have a positive effect on people's well-being and mood, according to a new study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation.

The study, conducted within the BlueHealth project and published in Environmental Research, used data on 59 adults. Over the course of one week, participants spent 20 minutes each day walking in a blue space. In a different week, they spent 20 minutes each day walking in an urban environment. During yet another week, they spent the same amount of time resting indoors. The blue space route was along a beach in Barcelona, while the urban route was along city streets. Before, during and after each activity, researchers measured the participants' blood pressure and heart rate and used questionnaires to assess their well-being and mood.

"We saw a significant improvement in the participants' well-being and mood immediately after they went for a walk in the blue space, compared with walking in an urban environment or resting," commented Mark Nieuwenhuijsen, Director of the Urban Planning, Environment and Health Initiative at ISGlobal and coordinator of the study. Specifically, after taking a short walk on the beach in Barcelona, participants reported improvements in their mood, vitality and mental health.

The authors did not identify any cardiovascular health benefits, although they believe this may be due to the design of the study. "We assessed the immediate effects of taking a short walk along a blue space," commented ISGlobal researcher Cristina Vert, lead author of the study. "Continuous, long-lasting exposure to these spaces might have positive effects on cardiovascular health that we were not able to observe in this study."

The Importance of the Environment on Health

"Our results show that the psychological benefits of physical activity vary according to the type of environment where it is carried out, and that blue spaces are better than urban spaces in this regard," commented Vert.

Numerous ISGlobal studies have identified health benefits associated with green spaces, including lower risk of obesity, better attention capacities in children and slower physical decline in older adults. The new study provides evidence showing that blue spaces are an environment favourable to mental health.

"According to the United Nations, 55% of the global population now lives in cities," explained Nieuwenhuijsen. "It is crucial to identify and enhance elements that improve our health--such as blue spaces--so that we can create healthier, more sustainable and more liveable cities."