Saturday, May 23, 2020

Now closer to reality: Prosthetics that can feel

Now closer to reality: Prosthetics that can feel
A prosthetic hand with fingertip sensors designed by Jacob Segil in collaboration with researchers at Case Western Reserve University. Credit: CU Boulder College of Engineering and Applied Science
Humans do a lot of things with their hands: We squeeze avocados at the grocery story, scratch our dogs behind the ears and hold our significant others' hands. They are things that many people who have lost limbs can't do.
CU Boulder biomedical engineer Jacob Segil is working to bring back that sense of touch for amputees, including veterans of the wars in Iraq and Afghanistan.
Segil, an instructor in the Engineering Plus Program and program director for the Center for Translational Research at CU Boulder, is part of a long-running effort to achieve the stuff of science fiction: designing  that may one day allow amputees to feel the world around them through electronic sensors. Picture Luke Skywalker twitching after he gets poked in his robotic hand.
"In my field, we have a gold standard, which is the physiological hand," said Segil, also a research healthcare scientist at the U.S. Department of Veterans Affairs. "We're trying to recreate it, and we're still so far off."
Far off, but closer than you might think. Through an effort led by Case Western Reserve University and the VA, Segil and his colleagues have used a unique "neural interface" to give a small number of amputees back the sense of touch in their missing fingers. In a new study, published this month in the journal Scientific Reports, the team demonstrated just how effective this sensory restoration technology can be—helping one amputee to feel his hand adopt a series of postures, such as a gesture resembling the thumbs-up sign.
For Segil, who recently received a $1 million Career Development Award from the VA to continue his work, the project is a chance to use his engineering skills to help real people.
"A lot of us engineers would just be happy building stuff," Segil said. "But as a VA researcher, your work can help the people who served our country. It's a powerful motivator."
Body sense
Segil grew up in a family of physicians and had long been fascinated by the idea of studying the human body as a machine—albeit a pretty complicated one.
Now closer to reality: Prosthetics that can feel
A display of fingertip sensors. Credit: CU Boulder College of Engineering and Applied Science
"It's really just a bunch of wires and actuators, with a huge microprocessor in your head," Segil said.
That interest led him to earn his Ph.D. in  from CU Boulder and to take on a postdoctoral research position split between two VA centers: the Louis Stokes Cleveland VA Medical Center in Ohio and the Rocky Mountain Regional VA Medical Center in Aurora, Colorado. In Cleveland, Segil worked with biomedical engineer Dustin Tyler and explored the benefit of prosthetic limbs that can feel.
In the 2000s, Tyler invented a way to, essentially, hotwire the human nervous system.
His interface, called a nerve cuff electrode, surrounds the nerves and zaps them with electronic pulses. Adjust those signals just right, and they will travel to the brain, tricking it into thinking that it can feel fingers, even if there are no fingers to feel.
"We're tapping into that wire before it gets to the brain, and then the brain can't tell whether it's coming from the finger or from our artificial system," said Tyler, a professor at Case Western and a VA researcher.
To date, only four patients have undergone the surgery needed to receive that sensory feedback. But the project is a huge breakthrough in prosthetics, Segil said. He explained that while artificial hands have grown more high-tech in recent years, many amputees still choose not to use them—in large part, because these devices are numb.
"All prosthetic devices that have ever been used are 'disembodied,'" he said. "They are a tools, external to the body. They're the equivalent of a tennis player and their racket."
In the recently published , Segil and his colleagues began to probe whether sensing prosthetics could do more—becoming a meaningful part of a person's body.
The researchers worked with one volunteer, a man in his 40s who had lost his arm below his elbow six years before. They fed his neural interface varying patterns of sensory information—say, cues that he was picking up a penny. The group then asked the man to, while his prosthetic was hidden from view, decide what position his hand was in from a menu of seven postures.
The interface did the trick. With enough practice, the man was able to identify the seven postures with up to 95% accuracy.
"When you have five points of information, the user is able to synthesize those to get a broader view of what the state of the hand is," Tyler said.
The team is still a long way from their Star Wars moment. But it's a good start.
"I think we need to go further into this embodiment space where the artificial and the physical are blurred," Segil said. "That's the stuff the goes beyond prosthetic limbs and redefines the interface between man and machine."
Stories to tell
Segil is planning to push his mind-bending research further with his new funding, which will be split between the VA centers in Ohio and Colorado. His current work will focus on the psychology of prosthetics as much as the engineering—what will it take for amputees to think of their artificial limbs as real body parts? He also hopes that patients in Colorado will soon be able to receive their own neural interfaces.
For now, the engineer takes his inspiration from people like the (anonymous) human subject who volunteered to participate in his recent study.
"Every amputee has a story," he said. "Everyone has their physical scars, but also emotional triumphs, how they get through their day-to-day. It's a wonderful environment to work in."
New fingertip sensors to help veterans feel through their prosthetics

More information: Jacob L. Segil et al. Combination of Simultaneous Artificial Sensory Percepts to Identify Prosthetic Hand Postures: A Case Study, Scientific Reports (2020). DOI: 10.1038/s41598-020-62970-4
Journal information: Scientific Reports 

A 'sole' mate to prevent diabetic foot ulcers




A sole mate to prevent diabetic foot ulcersCredit: UT Southwestern Medical Center

THIS IS HOW I LOST MY FOOT 

A new cooling insole developed by UT Southwestern scientists reduced the foot temperature of patients with diabetic neuropathy by several degrees, diminishing a significant risk factor for diabetic foot ulcers. This new device, detailed in an article published online ahead of print May 6 in The Journal of Foot & Ankle Surgery, could eventually prevent thousands of amputations that take place worldwide each year because of this condition.
Just in the U.S., more than 100,000 lower extremity amputations take place every year, many of them prompted by diabetic  ulcers. These ulcers are associated with numerous quality-of-life and , including a mortality rate of 50 percent within five years for patients who develop them. Although the exact cause of this common diabetes complication is unclear, high foot pressure has long been considered a prevailing cause. Consequently, the most prescribed preventive treatment for  is pressure-relieving insoles.
However, says Metin Yavuz, D.Eng., an associate professor in the School of Health Professions' Division of Prosthetics and Orthotics at UT Southwestern Medical Center, this prophylactic intervention isn't accomplishing its goal, since diabetic amputation rates have been on the rise despite widely available pressure-reliving insoles. "Even when patients receive therapeutic shoes and insoles, education, and close monitoring," he says, "30 to 40 percent of patients who have had one diabetic foot ulcer will still develop another within a year."
Hoping to decrease these numbers, Yavuz and his colleagues focused on another risk factor for these ulcers: foot . Animal studies have shown that skin maintained between 25 and 30 degrees C is less likely to break down under pressure than skin at . The feet of diabetic patients already tend to be warmer due to inflammation associated with the disease, Yavuz explains, compounded by friction from walking and the stiff therapeutic shoes that patients wear, which are usually made of synthetic materials that act as heat insulators.
"We thought, why don't we break that vicious cycle by cooling the foot?" he says.
To do that, Yavuz and his lab, aided by a pilot grant from UTSW's Center for Translational Medicine, developed a system that circulates  into pressure-relieving insoles. The device, which the researchers named Temperature and Pressure Monitoring and Regulating Insoles (TAPMARI), consists of a small box strapped to the wearer's calf that houses a cooling unit, a small water pump, a battery pack, and a thermostat. The cooling unit harnesses a type of thermoelectric cooling called the Peltier effect to chill water to a desired temperature that's then pumped into insoles placed in the wearer's shoes. Yavuz later teamed up with the engineering company Vivonics Inc. and obtained funding from the National Institutes of Health to improve the design.
The researchers tested the improved device in eight volunteers: one man and seven women of a median age of 45 years. Five of these volunteers were healthy and three had .
Using an infrared thermal camera, the researchers took photos of the subjects' feet at baseline before wearing the insoles, then placed a cooling  in only their right shoes. They took more thermal photos after the subjects walked five minutes on a treadmill and again after they wore the insoles an additional two hours and walked five minutes on the treadmill again.
Results showed that the mean baseline foot temperature in the group was 28.1 degrees C. Mean foot temperatures at the end of the study were 31.7 degrees C for the left foot and 25.9 degrees C for the right, which was cooled by TAPMARI. Although the diabetics' feet got warmer than those of the healthy volunteers during walking, they still maintained a mean temperature of 27.5 degrees C in the right foot, suggesting that the insoles could maintain temperature in a range that protects against skin breakdown.
Cool temperatures from the insoles didn't cause vasoconstriction (narrowing of blood vessels) in the foot, which could have damaged tissue, Yavuz says. However, sole temperatures reached as high as 30.8 degrees C in some regions of the cooled feet, particularly in the midfoot, suggesting that the design of the insole needs to be improved. Other design elements could also be tweaked, he says, such as reducing the size of the unit worn on the calf.
Eventually, Yavuz says, these devices could change the course for patients with diabetes, preventing this common and often serious complication.
"Diabetic foot ulcers can be a major burden on patients, their families, caregivers, and the health system," he says. "What we're doing now to prevent these ulcers or simply maintain the status quo isn't working. TAPMARI could be the start of a whole new approach."
Other researchers who contributed to this study include Ali Ersen and Lawrence A. Lavery of UTSW; Aakshita Monga and Yasser Salem of the University of North Texas Health Science Center; Alan Garrett of the John Peter Smith Hospital; and Gordon B. Hirschman and Ryan Myers of Vivonics Inc.
How to avoid foot amputation in diabetic patients

More information: Metin Yavuz et al, Temperature- and Pressure-Regulating Insoles for Prevention of Diabetic Foot Ulcers, The Journal of Foot and Ankle Surgery (2020). DOI: 10.1053/j.jfas.2019.05.009
Disinfecting effect of copper on SARS-CoV-2 and other viruses 
https://www.physicsforums.com/threads/disinfecting-effect-of-copper-on-sars-cov-2-and-other-viruses.989075/

May 14, 2020

 When researchers reported last month that the novel coronavirus causing the COVID-19 pandemic survives for days on glass and stainless steel but dies within hours after landing on copper, the only thing that surprised Bill Keevil was that the pathogen lasted so long on copper 

https://www.smithsonianmag.com/science-nature/copper-virus-kill-180974655/

 Keevil, a microbiology researcher at the University of Southampton (U.K.), has studied the antimicrobial effects of copper for more than two decades. He has watched in his laboratory as the simple metal slew one bad bug after another. He began with the bacteria that causes Legionnaire's Disease and then turned to drug-resistant killer infections like Methicillin-resistant Staphylococcus aureus (MRSA). He tested viruses that caused worldwide health scares such as Middle East Respiratory Syndrome (MERS) and the Swine Flu (H1N1) pandemic of 2009. In each case, copper contact killed the pathogen within minutes. "It just blew it apart," he says.

 https://www.nih.gov/news-events/news-releases/new-coronavirus-stable-hours-surfaces 

The virus that causes coronavirus disease 2019 (COVID-19) is stable for several hours to days in aerosols and on surfaces, according to a new study from National Institutes of Health, CDC, UCLA and Princeton University scientists in The New England Journal of Medicine. The scientists found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel. The effect of copper seems to be independently verified. One should continue to use hand sanitizer and wear a protective face cover/mask.

https://www.physicsforums.com/threads/disinfecting-effect-of-copper-on-sars-cov-2-and-other-viruses.989075/

Friday, May 22, 2020

Handwashing 6-10 times a day linked to lower infection risk

Handwashing 6-10 times a day linked to lower infection risk
Credit: ivabalk from Pixabay
Moderate frequency handwashing six to ten times a day is linked to a lower risk of seasonal coronavirus infection, according to a new UCL study.
The research, published in Wellcome Open Research and awaiting , is the first empirical evidence that regular handwashing can reduce personal risk of acquiring seasonal coronavirus infection. It draws on data from three successive winter cohorts (2006 to 2009) of the England-wide Flu Watch study.
Sarah Beale (UCL Institute of Health Informatics), Ph.D. researcher and first author on the study, said: "Given that COVID-19 appears to demonstrate similar transmission mechanisms to seasonal coronaviruses, these findings support clear public health messaging around the protective effects of handwashing during the pandemic."
"It's important to highlight that frequency of handwashing is only one aspect of hand hygiene. We also know that both longer duration of handwashing and the context of handwashing e.g. upon returning home or before eating—have been associated with lower overall risk of influenza or influenza-like-illness.
"Good hand hygiene should be practiced at all times regardless of whether you show symptoms or not. This will help protect yourself and prevent unwittingly spreading the virus to others around you."
For this study, 1,633 participants provided baseline estimates of hand hygiene behavior and coronavirus infections were identified from nasal swabs. The majority of participants (almost 80%) were adults over sixteen years of age.
To assess overall handwashing frequency participants were asked the start of each season to "Estimate how many times you washed your hands yesterday." Frequency of daily handwashing was subsequently categorized as low (≤5 times daily), moderate (6-10 times daily), or high (>10 times daily) guided by literature around influenza-like illness in Western community settings.
Moderate-frequency handwashing was associated with significantly reduced overall risk of contracting coronavirus (36% reduction in the risk of infection compared to those who washed their hands 0-5 times per day). For higher intensity  there was no significant dose-response effect.
The analysis was adjusted for age and healthcare worker status due to their relationship both with  practices and with risk of contracting coronavirus infections.
Ellen Fragaszy, (UCL Institute of Health Informatics and the London School of Hygiene and Tropical Medicine), Senior Research Fellow and last author on the study, concluded: "Something as simple as washing our hands regularly can help us to keep the  rate low and reduce transmissions.New study finds two billion people without proper sanitation at high risk for coronavirus
More information: Sarah Beale et al. Hand Hygiene Practices and the Risk of Human Coronavirus Infections in a UK Community Cohort, Wellcome Open Research (2020). DOI: 10.12688/wellcomeopenres.15796.1

New study finds two billion people without proper sanitation at high risk for coronavirus


coronavirus
Credit: CC0 Public Domain
Without access to soap and clean water, more than 2 billion people in low- and middle-income nations—a quarter of the world's population—have a greater likelihood of acquiring and transmitting the coronavirus than those in wealthy countries.
That's the conclusion of a new study by the Institute for Health Metrics and Evaluation at the University of Washington's School of Medicine.
More than 50% of the people in sub-Saharan Africa and Oceania lacked access to effective handwashing, according to the study published last week in the journal Environmental Health Perspectives.
"Handwashing is one of the key measures to prevent COVID transmission, yet it is distressing that access is unavailable in many countries that also have limited health care capacity," said Dr. Michael Brauer, a professor at IHME, which currently has one of the world's leading models of the coronavirus of the pandemic.
In 46 countries, more than half of people lacked access to soap and . In Nigeria, China, Ethiopia, Democratic Republic of the Congo, Bangladesh, Pakistan, India, and Indonesia, more than 50 million persons in each were estimated to be without handwashing access.
"Temporary fixes, such as hand sanitizer or water trucks, are just that—temporary fixes," Brauer said. "But implementing long-term solutions is needed to protect against COVID and the more than 700,000 deaths each year due to poor handwashing access," Brauer said.
Even with 25 percent of the world's population lacking access to effective handwashing facilities, there have been "substantial improvements in many countries" between 1990 and 2019, Brauer said. Those countries include Saudi Arabia, Morocco, Nepal, and Tanzania, which have improved their nations' sanitation.
The paper does not estimate access to handwashing facilities in non-household settings such as schools, workplaces, , and other public locations such as markets.
Earlier this month, the World Health Organization predicted 190,000 people in Africa could die of COVID-19 in the first year of the pandemic, and that upward of 44 million of the continent's 1.3 billion people could be infected with the coronavirus.For washing your hands, is it more effective to use soap and water or an alcohol-based sanitizer?
More information: Michael Brauer et al, Global Access to Handwashing: Implications for COVID-19 Control in Low-Income Countries, Environmental Health Perspectives (2020). DOI: 10.1289/EHP7200
Journal information: Environmental Health Perspectives 

First human trial of COVID-19 vaccine finds it is safe and induces rapid immune response


vaccine
Credit: CC0 Public Domain
The first COVID-19 vaccine to reach phase 1 clinical trial has been found to be safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans, according to new research published in The Lancet. The open-label trial in 108 healthy adults demonstrates promising results after 28 days—the final results will be evaluated in six months. Further trials are needed to tell whether the immune response it elicits effectively protects against SARS-CoV-2 infection.
"These results represent an important milestone. The trial demonstrates that a single dose of the new adenovirus type 5 vectored COVID-19 (Ad5-nCoV)  produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation," says Professor Wei Chen from the Beijing Institute of Biotechnology in Beijing, China, who is responsible for the study. "However, these results should be interpreted cautiously. The challenges in the development of a COVD-19 vaccine are unprecedented, and the ability to trigger these immune responses does not necessarily indicate that the vaccine will protect humans from COVID-19. This result shows a promising vision for the development of COVID-19 vaccines, but we are still a long way from this vaccine being available to all."
The creation of an effective vaccine is seen as the long-term solution to controlling the COVID-19 pandemic. Currently, there are more than 100 candidate COVID-19 vaccines in development worldwide.
The new Ad5 vectored COVID-19 vaccine evaluated in this trial is the first to be tested in humans. It uses a weakened common cold virus (adenovirus, which infects human cells readily but is incapable of causing disease) to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.
The trial assessed the safety and ability to generate an immune response of different dosages of the new Ad5-nCoV vaccine in 108 healthy adults between the ages of 18 and 60 years who did not have SARS-CoV-2 infection. Volunteers were enrolled from one site in Wuhan, China, and assigned to receive either a single intramuscular injection of the new Ad5 vaccine at a low dose (5 × 1010 viral particles/0·5ml, 36 adults), middle dose (1×1011 viral particles/1.0ml, 36 adults), or high dose (1.5 x 1011 viral particles/1.5ml, 36 adults).
The researchers tested the volunteers' blood at regular intervals following vaccination to see whether the vaccine stimulated both arms of the immune system: the body's 'humoral response' (the part of the immune system that produces neutralising antibodies which can fight infection and could offer a level of immunity), and the body's cell-mediated arm (which depends on a group of T cells, rather than antibodies, to fight the virus). The ideal vaccine might generate both antibody and T cell responses to defend against SARS-CoV-2.
The vaccine candidate was well tolerated at all doses with no serious adverse events reported within 28 days of vaccination. Most adverse events were mild or moderate, with 83% (30/36) of those receiving low and middle doses of the vaccine and 75% (27/36) in the high dose group reporting at least one adverse reaction within 7 days of vaccination.
The most common adverse reactions were mild pain at the injection site reported in over half (54%, 58/108) of vaccine recipients, fever (46%, 50/108), fatigue (44%, 47/108), headache (39%, 42/108), and muscle pain (17%, 18/108). One participant given the higher dose vaccine reported severe fever along with severe symptoms of fatigue, shortness of breath, and muscle pain—however these adverse reactions persisted for less than 48 hours.
Within two weeks of vaccination, all dose levels of the vaccine triggered some level of  in the form of binding antibodies (that can bind to the coronavirus but do not necessarily attack it—low-dose group 16/36, 44%; medium dose 18/36, 50%; high dose 22/36, 61%), and some participants had detectable neutralising antibodies against SARS-CoV-2 (low-dose group 10/36, 28%; medium dose 11/36, 31%; high dose 15/36, 42%).
After 28 days, most participants had a four-fold increase in binding antibodies (35/36, 97% low-dose group; 34/36 (94%) middle-dose group, and 36/36, 100% in high-dose group), and half (18/36) of participants in the low- and middle-dose groups and three-quarters (27/36) of those in the high-dose group showed neutralising antibodies against SARS-CoV-2.
Importantly, the Ad5-nCoV vaccine also stimulated a rapid T cell response in the majority of volunteers, which was greater in those given the higher and middle doses of vaccine, with levels peaking at 14 days after vaccination (low-dose group (30/36; 83.3%), medium (35/36, 97.2%), and high-dose group (35/36, 97.2%) at 14 days).
Further analyses showed that 28 days after vaccination, the majority of recipients showed either a positive T cell response or had detectable neutralising  against SARS-CoV-2 (low-dose group 28/36, 78%; medium-dose group 33/36, 92%; high-dose group 36/36, 100%).
However, the authors note that both the antibody and T-cell response could be reduced by high pre-existing immunity to adenovirus type 5 (the common cold virus vector/carrier)—in the study, 44%-56% of participants in the trial had high pre-existing immunity to adenovirus type 5, and had a less positive antibody and T-cell  to the vaccine.
"Our study found that pre-existing Ad5 immunity could slow down the rapid immune responses to SARS-CoV-2 and also lower the peaking level of the responses. Moreover, high pre-existing Ad5 immunity may also have a negative impact on the persistence of the vaccine-elicited immune responses," say Professor Feng-Cai Zhu from Jiangsu Provincial Center for Disease Control and Prevention in China who led the study.
The authors note that the main limitations of the trial are its small sample size, relatively short duration, and lack of randomised control group, which limits the ability to pick up rarer adverse reactions to the vaccine or provide robust evidence for its ability to generate an immune reaction. Further research will be needed before this trial vaccine becomes available to all.
A randomised, double-blinded, placebo-controlled phase 2 trial of the Ad5-nCoV vaccine has been initiated in Wuhan to determine whether the results can be replicated, and if there are any adverse events up to 6 months after vaccination, in 500 —250 volunteers given a middle dose, 125 given a low dose, and 125 given a placebo as a control. For the first time, this will include participants over 60 years old, an important target population for the vaccine.Investigational vaccine protects monkeys against COVID-19 pneumonia

More information: Feng-Cai Zhu et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. The Lancet. May 22, 2020 DOI: doi.org/10.1016/S0140-6736(20)31208-3
Journal information: The Lancet 

Algal genome provides insights into first land plants


Algal genome provides insights into first land plants
Penium margaritaceum. Credit: Cornell University
Cornell researchers have sequenced and analyzed the genome of a single-celled alga that belongs to the closest lineage to terrestrial plants and provides many clues to how aquatic plants first colonized land.
The report, "The Penium margaritaceum Genome: Hallmarks of the Origins of Land Plants," was published May 21 in the journal Cell.
Penium margaritaceum belongs to a group of freshwater algae called charophytes, and specifically to a subgroup called the Zygnematophyceae, which had a  with the first land plants some 600 million years ago. In order to shift from water to land—a transition that still puzzles scientists—plants had to protect themselves from drying out and from ultraviolet (UV) radiation, and they had to develop structures to support themselves without the buoyancy provided by water.
The researchers found footprints of all these adaptations in the Penium genome, providing insight into the mechanisms and genetics that early  required.
"We knew almost nothing about the genomes of the immediate ancestors of land plants," said senior author Jocelyn Rose, professor of plant biology in the College of Agriculture and Life Sciences.
"We now have exciting insights into the last common ancestor of algae and land plants," Rose said, "and that allows plant biologists to infer the origins of land plant molecular pathways, developmental systems and biological processes, and to place them in the context of land colonization in ways that have not previously been possible."
Though some algae of the charophyte group are branched and look like early land plants, molecular data reveals that the common ancestor had a simpler filament-like shape.
"We are very interested in why it is that the simple body plan might have been evolutionarily advantageous," Rose said. "Penium lives in the margins of fresh water and land, in habitats that expose it to periods of drying and rehydration and this was likely a key factor."
The Penium genome contains a great deal of repetitive and "junk" (non-coding) DNA, which created challenges for the researchers. They ended up extracting a clean set of DNA from purified nuclei and integrating many kinds of DNA sequencing techniques and assembly programs to cover the . They also conducted cutting-edge transcriptome (RNA) sequencing to complement the  and to understand which genes were turned on and off by different stresses.
"We found out that the genome is huge," said Zhangjun Fei, professor of bioinformatics at Boyce Thompson Institute and an adjunct associate professor in the Plant Pathology and Plant-Microbe Biology Section. Fei is a co-leading author of the study and handled the computational and sequencing work.
The genome of this tiny single-celled alga is even larger than the notoriously large maize genome and the human genome.
"One big result is that we found flavonoids, chemicals that can protect from UV light radiation," Fei said.
"Previously it was thought that these compounds only existed in land plants," Rose said. "We detected not only the flavonoids themselves, but also parts of the pathway for their biosynthesis."
The researchers also identified genes involved in regulatory systems and hormone signaling that have previously only been found in land plants, as well as mechanisms that keep  from drying out, including the production of mucilage.
They also found a large number of genes that contribute to cell wall biosynthesis and reorganization, which are necessary for structural support.
"Again, it's a single cell, but it has enormous families of cell wall modifying proteins," Rose said. "This suggests highly complex control of wall structure, dynamics and biomechanical properties that may be every bit as elaborate as in multicellular lands."
The researchers believe the Penium  will open up investigations into many areas of plant biology, including possible applications for modern crops. The team plans to investigate the genomes of other species of charophytes.

More information: Chen Jiao et al. The Penium margaritaceum Genome: Hallmarks of the Origins of Land Plants, Cell (2020). DOI: 10.1016/j.cell.2020.04.019
Journal information: Cell 

Insight into mechanism of treatment-resistant gonorrhea sets stage for new antibiotics

A research group at the Medical University of South Carolina examined an antibiotic-resistant strain of Neisseria gonorrhoeae and found a surprisingly new resistance mechanism that inhibits protein dynamics
MEDICAL UNIVERSITY OF SOUTH CAROLINA
IMAGE
IMAGE: DR. CHRISTOPHER DAVIES (LEFT) AND DR. AVINASH SINGH (RIGHT) OF THE MEDICAL UNIVERSITY OF SOUTH CAROLINA ARE CO-AUTHORS OF THE MAY 22, 2020 ARTICLE IN THE JOURNAL OF BIOLOGICAL CHEMISTRY.... view more 
CREDIT: MEDICAL UNIVERSITY OF SOUTH CAROLINA
Due to the spread of antibiotic-resistant strains of Neisseria gonorrhoeae, existing treatments for gonorrhea, the sexually transmitted infection caused by the bacterium, are no longer effective. In the absence of a vaccine, there is an urgent need to develop novel treatment options.
"It's becoming much more difficult to treat gonorrhea infections as a result of antibiotic resistance," said Christopher Davies, Ph.D., a professor in the Department of Biochemistry and Molecular Biology at the Medical University of South Carolina. "Antibiotics that used to work against the bug are no longer effective."
Davies and his team report surprising findings about antibiotic resistance in the May 22, 2020 issue of the Journal of Biological Chemistry, showing that mutations in an essential protein responsible for resistance affect the binding of the antibiotic to the microbe. Rather than directly blocking binding of the antibiotic, the mutations prevent movements in the protein that help form the binding site for the antibiotic. The findings could offer a strategy for developing new treatments that overpower antibiotic resistance. Avinash Singh, Ph.D., a postdoctoral fellow in the Davies laboratory, is lead author of the article.
N. gonorrhoeae acquires resistance to antibiotics via interactions with so-called commensal species of Neisseria that colonize mucosal surfaces, such as those in the throat and genital tract, but do not cause disease. These species develop resistance following exposure to antibiotics that someone has taken for an infection. The commensal bacteria then transfer sections of genes responsible for antibiotic resistance not only among themselves, but also to disease-causing N. gonorrhoeae during gonorrhea infections. Once N. gonorrhoeae have incorporated these genes, they develop resistance and are no longer treatable with current antibiotics.
Overpowering that resistance will require more than a genetic understanding of how resistance arises.
"We need to understand what that resistance means at the molecular level," said Davies. "Only then can we address antimicrobial resistance by designing new antimicrobials to replace those that are no longer effective."
In recent years, cephalosporins have been the main drugs used to treat gonorrhea. Like penicillin, they target essential bacterial proteins, called penicillin-binding proteins (PBPs), that are responsible for the construction of cell walls. Bacteria need their cell walls to maintain cell shape and integrity. When a PBP is inhibited by a cephalosporin, the bacterial wall develops holes, resulting in the death of the microbe.
Gonorrhea can become resistant to cephalosporins when the PBP drug target mutates. Davies' group looked at the effect of those mutations on the structure of a PBP called PBP2 from a cephalosporin-resistant strain of gonorrhea.
The researchers compared the molecular structure of PBP2 in the antibiotic-resistant strain to that of an antibiotic-susceptible strain.
To their surprise, they found that the mutations prevented changes in the shape of PBP2 that are necessary for the antibiotic to bind to the protein.
Typically, mutations that confer antibiotic resistance occur in the so-called active site of proteins and block binding. But in PBP2, several of the mutations are quite a distance away. These distant mutations seem to be restricting shape changes in PBP2 that normally allow the antibiotic to interact with the protein and kill the microbe.
Once scientists understand the molecular mechanisms behind antibiotic resistance, they will be able to create new generations of antibiotics designed to avoid or overpower these mechanisms.
Knowing the important mutations that cause resistance will also allow treatments to be tailored for specific strains of N. gonorrhoeae. Patterns of resistance mutations could then be used to develop diagnostic kits to identify the strain with which a patient is infected, enabling doctors to prescribe the most appropriate antibiotics.
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Past is prologue: Genetic 'memory' of ancestral environments helps organisms readapt


Past is prologue: Genetic 'memory' of ancestral environments helps organisms readapt
Top row: a male Tibetan chicken (left) and a female Tibetan chicken (right). Bottom row: a male lowland chicken (left) and a female lowland chicken (right). Credit: Diyan Li
Organisms carry long-term "memories" of their ancestral homelands that help them adapt to environmental change, according to a new study that involved raising chickens on the Tibetan Plateau and an adjacent lowland site.
The study provides new insights into how creatures adapt to changing environments, a topic that's especially relevant today in the context of rapid climate change, which is creating challenges for plants and animals worldwide.
The  was domesticated from the red jungle fowl in South Asia and Southeast Asia at least 4,000 to 4,500 years ago. It was brought to the Tibetan Plateau by about 1,200 years ago, where it acquired high-altitude adaptations such as an increase in oxygen-carrying red blood cells.
In a set of experiments by University of Michigan biologists and their Chinese colleagues, researchers hatched and reared hundreds of chickens on the Tibetan Plateau, at an elevation of nearly 11,000 feet, and at an adjacent lowland site in China's Sichuan Province. Some of the eggs from lowland chickens were hatched on the plateau, and some high-altitude eggs were hatched at a site 2,200 feet above sea level.
The goal was to assess the relative contributions of two types of phenotypic change—meaning changes to an organism's observable physical characteristics or traits—to the process of environmental adaptation. "Plastic" phenotypic changes involve altered gene activity but no rewriting of the genetic code in DNA molecules, while mutations cause altered gene activity by modifying the sequence of letters in the code itself.
Evolutionary biologists have debated the relative roles of plastic and mutation-induced changes in adaptation, and whether the former serve as stepping stones to the latter.
In the chicken study, researchers were specifically interested in how organisms readapt when reintroduced to ancestral environments. They found that plastic changes play a more prominent role when organisms return to an ancestral home than when they adapt to new environments.
"These findings reveal a mechanism by which past experience affects future evolution," said Jianzhi Zhang, the study's senior author and a professor in the U-M Department of Ecology and Evolutionary Biology.
"Our findings contribute to the recent debate on the relative roles of plastic and genetic changes in adaptation and reveal the importance of considering whether the environment is changing to a novel or ancestral one."
The findings are scheduled for publication May 22 in the journal Science Advances.
To study the relative roles of plastic and DNA-sequence changes, the researchers looked at gene-expression differences between lowland and Tibetan chickens in five tissue types: brain, liver, lung, heart and muscle. To do that, they analyzed RNA transcriptomes from cells in those tissues.
The genome is made of DNA that contains the instructions needed to build an organism. For those instructions to be carried out, DNA must be read and transcribed into messenger RNA molecules.
By analyzing the entire collection of RNA sequences in a cell, known as the transcriptome, researchers can determine when and where genes are turned on and off. Gene-expression studies provide snapshots of actively expressed genes under various conditions.
Changes in  alter an organism's phenotype, which includes its morphology, behavior and physiology. The term phenotypic plasticity refers to environmentally induced phenotypic changes that do not involve genetic mutations.
In the chicken study, the researchers found that while many mutation-induced phenotypic changes were necessary when the animals first adapted to the Tibetan Plateau, plastic changes largely transformed the transcriptomes to the preferred state when Tibetan chickens were brought back to the lowland.
A similar result was seen with egg "hatchability," the fraction of fertilized chicken eggs that hatched in the study.
When lowland eggs were incubated on the unfamiliar Tibetan Plateau, hatchability was significantly lower than that of Tibetan chicken eggs. But when Tibetan eggs were incubated in the lowland—an environment familiar from the distant past—there was no significant difference in hatchability between the two groups.
The egg result suggests that adaptive mutational changes are needed when an organism is brought to an unfamiliar environment for the first time, while plastic changes will do the trick when those same creatures return to an ancestral home.
Zhang's team also analyzed transcriptomes from previous studies of guppies and E. coli bacteria and found comparable results—regardless of whether the new environment was more stressful or less stressful than the ancestral environment.
"In summary, our work uncovers a phenomenon conserved from bacteria to vertebrates that organisms remember their ancestral environments in the form of phenotypic plasticity," the authors wrote.Comprehensive picture of vegetation and climate on Tibetan Plateau during Quaternary ice ages

More information: W.-C. Ho el al., "Phenotypic plasticity as a long-term memory easing readaptations to ancestral environments," Science Advances (2020). DOI: 10.1126/sciadv.aba3388 , advances.sciencemag.org/content/6/21/eaba3388
Journal information: Science Advances 
Provided by University of Michigan 

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