Publisher Health

An international research team succeeded in identifying global factors that explain the diversity of form and function in plants. Led by the University of Zurich, the Max Planck Institute for Biogeochemistry in Jena and the University of Leipzig, the researchers collected and analyzed plant data from around the world. For the first time, they showed for characteristics such as plant size, structure, and life span how strongly these are determined by climate and soil properties. Insights derived from this could be crucial to improving Earth system models with regard to the role of plant diversity.
At first glance, the diversity of plant form and function seems difficult to comprehend. However, it can be described in terms of morphological, physiological, and biochemical characteristics. It has been shown previously that traits across species fall into two main categories within which each plant must maintain a balance: first, size and second, economy of metabolism. In a recent study in Nature Ecology and Evolution, a team of researchers has now confirmed for the first time, using a greatly enlarged global dataset for 17 different plant traits, that these two main categories apply to all plants studied worldwide.
In the size category, plants balance height, leaf size, and seed size, among other traits. These traits are also influenced by hydraulic components of water transport in plants. The economics category describes how quickly and effectively the plant gains energy and biomass through photosynthesis, balanced against how long it survives. This category is determined by measurable characteristics such as the structure and composition of the leaves in terms of leaf area, as well as their elemental composition (nitrogen, phosphorus and carbon). The team showed that life strategies of the plant species collected worldwide in the TRY database are well explained by these two main categories.
Characteristics of over 20,000 species analyzed
Plant traits are influenced by a wide variety of external factors, such as climate, soil conditions, and human intervention. It has not yet been possible to determine which factors are decisive at the global level. To answer this question, the research team, led by Julia Joswig at the University of Zurich and the Max Planck Institute for Biogeochemistry in Jena, analyzed the characteristics of over 20,000 species. Information on climate and soil conditions at the location of each plant was included in the analysis.
“Our study clearly demonstrates that plant traits worldwide can be explained by joint effects of climate and soil,” Joswig said, adding, “This suggests that aspects of climate change and soil erosion, both of which occur as a result of land use change, for example, should be researched together.”
Many of the relationships described here were already known from small-scale, local studies. “But the fact that these processes could now be shown globally and their significance quantified is an important milestone,” adds Prof. Miguel Mahecha of the University of Leipzig. “Studies of this kind can guide global Earth system models to represent the complex interaction of climate, soil and biodiversity, which is an important prerequisite for future predictions,” Mahecha adds.
As expected, the study shows how the height of plant species changes along latitudes, due to differences in climate. However, the economic traits of plants do not show this gradient. Similarly, soil quality is only partially affected by climate, so there is a latitude-independent component in information about soil. Joswig and her colleagues show that this soil information is also relevant for the economic traits. Besides climate, soil-forming factors include organisms living in the soil, geology and topography, and of course time. Global change affects climate, organisms, and to some extent topography. Therefore, the study suggests that global risks to plant life should be explored especially in relation to climate change and soil erosion.
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LMU researchers have developed a method that allows resting human immune cells to be genetically analyzed in detail for the first time.
CD4+ T cells are important parts of the immune system and play a key role in defending the body against pathogens. As they possess a great variety of defense mechanisms against HIV in their resting state, they are infected only very rarely — but these few infected cells form a latent reservoir for HIV in the body that currently cannot be reached by antiviral drugs. Consequently, the virus can spread again from there after activation of the CD4+ T cells. Understanding how HIV interacts with resting CD4+ T cells is essential for finding new therapeutic approaches. Scientists led by Prof. Oliver T. Keppler from the Max von Pettenkofer Institute at LMU have now developed a method that for the first time allows these specific immune cells to be genetically manipulated under physiological conditions in an efficient and uncomplicated manner. As the authors report in the journal Nature Methods, this permits previously unobtainable insights into the biology of these cells.
Resting CD4+ T cells had been scarcely amenable to genetic manipulations, because the available methods generally presuppose dividing cells, as Keppler explains. “And resting cells do not divide by definition.” As the first step in the development of the new method, the team of scientists optimized the cultivation conditions. As a result, the researchers were able to keep these cells alive in the laboratory after extracting them from the blood of healthy donors not just for 3-4 days as before, but for up to six weeks. The decisive progress came with an advance in nucleofection, a special method that allows reagents to be delivered into the nucleus of a cell. Using this technique, the researchers introduced the genetic scissors CRISPR-Cas into resting CD4+ T cells, enabling them to make targeted modifications to the genome of the host cells — for example, by eliminating genes by means of so-called knockouts. “This combination worked very efficiently, and we were able to reach and genetically manipulate around 98 percent of the cells. Moreover, we did this without activating the CD4+ T cells,” says Keppler. “What was particularly exciting was that we were able to eliminate up to six genes simultaneously with high efficiency by means of a single nucleofection. Nobody had managed to do that in primary cells before — and we did it with cells isolated from an intact organ.”
In the future, the researchers will thus be able to eliminate individual genes and whole signaling pathways and analyze their functions. By knocking out the corresponding genes, they have already managed to clarify whether four previously controversial cellular factors play a role in infection with HIV or not.
On top of this, they pursued a second “knock-in” approach, whereby additional or slightly modified genes are inserted, such as a gene for green fluorescent protein (GFP). With the help of this protein, researchers can analyze how the activity of a target gene changes under certain conditions, or they can mark specific proteins. “All these things together give us the opportunity for the first time to investigate the interaction of HIV with human resting CD4+ T cells under physiological conditions,” explains Adrian Ruhle, co-lead author of the study. “But we can also investigate these cells better in their general role as immune cells beyond HIV.” In the long term, the researchers hope that having a better understanding of the biology of these cells will lead to new approaches for the total elimination of HIV from the bodies of patients, as there are still around 37 million people worldwide infected with the virus.
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Engineers at the University of California San Diego have developed a powerful new tool that monitors the electrical activity inside heart cells, using tiny “pop-up” sensors that poke into cells without damaging them. The device directly measures the movement and speed of electrical signals traveling within a single heart cell — a first — as well as between multiple heart cells. It is also the first to measure these signals inside the cells of 3D tissues.
The device, published Dec. 23 in the journal Nature Nanotechnology, could enable scientists to gain more detailed insights into heart disorders and diseases such as arrhythmia (abnormal heart rhythm), heart attack and cardiac fibrosis (stiffening or thickening of heart tissue).
“Studying how an electrical signal propagates between different cells is important to understand the mechanism of cell function and disease,” said first author Yue Gu, who recently received his Ph.D. in materials science and engineering at UC San Diego. “Irregularities in this signal can be a sign of arrhythmia, for example. If the signal cannot propagate correctly from one part of the heart to another, then some part of the heart cannot receive the signal so it cannot contract.”
“With this device, we can zoom in to the cellular level and get a very high resolution picture of what’s going on in the heart; we can see which cells are malfunctioning, which parts are not synchronized with the others, and pinpoint where the signal is weak,” said senior author Sheng Xu, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering. “This information could be used to help inform clinicians and enable them to make better diagnoses.”
The device consists of a 3D array of microscopic field effect transistors, or FETs, that are shaped like sharp pointed tips. These tiny FETs pierce through cell membranes without damaging them and are sensitive enough to detect electrical signals — even very weak ones — directly inside the cells. To evade being seen as a foreign substance and remain inside the cells for long periods of time, the FETs are coated in a phospholipid bilayer. The FETs can monitor signals from multiple cells at the same time. They can even monitor signals at two different sites inside the same cell.
“That’s what makes this device unique,” said Gu. “It can have two FET sensors penetrate inside one cell — with minimal invasiveness — and allow us to see which way a signal propagates and how fast it goes. This detailed information about signal transportation within a single cell has so far been unknown.”
To build the device, the team first fabricated the FETs as 2D shapes, and then bonded select spots of these shapes onto a pre-stretched elastomer sheet. The researchers then loosened the elastomer sheet, causing the device to buckle and the FETs to fold into a 3D structure so that they can penetrate inside cells.

Scientists at Scripps Research, University of Chicago and Icahn School of Medicine at Mount Sinai have identified a new Achilles’ heel of influenza virus, making progress in the quest for a universal flu vaccine. Antibodies against a long-ignored section of the virus, which the team dubbed the anchor, have the potential to recognize a broad variety of flu strains, even as the virus mutates from year to year, they reported Dec. 23, 2021 in the journal Nature.
“It’s always very exciting to discover a new site of vulnerability on a virus because it paves the way for rational vaccine design,” says co-senior author Andrew Ward, PhD, professor of Integrative Structural and Computational Biology at Scripps Research. “It also demonstrates that despite all the years and effort of influenza vaccine research there are still new things to discover.”
“By identifying sites of vulnerability to antibodies that are shared by large numbers of variant influenza strains we can design vaccines that are less affected by viral mutations,” says study co-senior author Patrick Wilson, MD, who was previously at the University of Chicago and recently recruited to Weill Cornell Medicine as a professor of pediatrics and a scientist in the institution’s Gale and Ira Drukier Institute for Children’s Health. “The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications.”
In a typical year, influenza affects more than 20 million people in the United States and leads to more than 20,000 deaths. Vaccines against influenza typically coax the immune system to generate antibodies that recognize the head of hemagglutinin (HA), a protein that extends outward from the surface of the flu virus. The head is the most accessible regions of HA, making it a good target for the immune system; unfortunately, it is also one of the most variable. From year to year, the head of HA often mutates, necessitating new vaccines.
Researchers have designed experimental influenza vaccines to be more universal, spurring the body to create antibodies against the less-variable stalk region of HA, which extends like a stem between the influenza virion and the HA head. Some of these universal flu vaccines are currently in early clinical trials.
In the new study, a collaborative team of scientists characterized 358 different antibodies present in the blood of people who had either been given a seasonal influenza vaccine, were in a phase I trial for an experimental, universal influenza vaccine, or had been naturally infected with influenza.

The SARS-CoV-2 Alpha (B.1.1.7) variant mutated to evade our ‘innate immune system’, helping establish it as the world’s first ‘Variant of Concern’, finds a new study led by researchers at UCL and the Quantitative Biosciences Institute, University of California San Francisco.
Published in Nature, the study shows the Alpha variant, first identified in the UK, evolved to make more of its ‘antagonism proteins’ that nullify the body’s first line of defence, known as the ‘innate immune system’.
Every cell in the nose, throat and lungs (airways) have a network of sensors that detect incoming viruses. When this happens the cells produce the protein interferon, which acts like a ‘burglar alarm’ and orchestrates a blanket anti-viral response, across both non-immune and immune cells (T cells and antibodies) to avert infection. But antagonism proteins can help the virus to evade these sensors.
This novel discovery is the first to identify evolution of enhanced antagonism protein expression in any virus and the first to implicate mutations in SARS-CoV-2 that increase infectiousness but do not involve the ‘spike’ protein
Scientists say the breakthrough findings provide a powerful insight into how SARS-CoV-2 is evolving, and offer a fresh clue to help identify new and emerging Variants of Concern, which are both highly transmissible and infectious.
Co-first author Dr Lucy Thorne (UCL Division of Infection & Immunity) said: “We wanted to know what made the SARS-CoV-2 Alpha variant special. How had it evolved from the first wave strain identified in Wuhan, China, and what features did it have that allowed it to spread around the world and become the first variant of concern?

NEW HOPE, Minn. — Pfc. Shina Vang and his fellow soldiers in the Minnesota National Guard have had an exceptionally busy year. They helped process Afghan refugees fleeing Kabul for the United States, provided security at American military bases across the Horn of Africa and stood sentinel in Washington, D.C., following the Jan. 6 attacks on the U.S. Capitol. They also deployed across Minnesota during the civil unrest prompted by the police killings of George Floyd in Minneapolis and Daunte Wright in nearby Brooklyn Center.But none of those experiences prepared Private Vang and his fellow Guard members for their latest deployment: collecting bedpans, clipping toenails and feeding residents at North Ridge Health and Rehab, a sprawling nursing home in suburban Minneapolis that is the largest in the state.“I’ve had protesters throw apples and water bottles at me but that doesn’t compare to the challenge of giving someone a bed bath,” Private Vang said.Over the past two weeks, 30 Guard members have been working as certified nursing assistants at North Ridge, which has been so badly hobbled by an exodus of employees that administrators have been forced to mothball entire wings, severely limiting new admissions.As a result, hospitals cannot send patients to long-term care centers like North Ridge, creating a backup that is eroding Minnesota’s capacity to treat people with Covid-19 and other medical emergencies. Similar backlogs are choking health systems across the country.“It’s beyond a crisis,” said Katie Smith Sloan, the president of LeadingAge, an association of nonprofit long-term care facilities.On Tuesday, President Biden announced that 1,000 military medical professionals would be dispatched to hospitals across the country this winter to help overwhelmed doctors and nurses.Public health experts fear the worst is yet to come as the highly transmissible Omicron variant spreads to communities where health care workers are already straining to handle the surge of patients sickened by Delta. Maine, New Hampshire, Indiana and New York have deployed the National Guard to overburdened hospitals and nursing homes in recent weeks, but Minnesota’s initiative may be the most ambitious, with 400 guard members who have no previous nursing experience going through rapid-fire training before being sent to long-term care facilities across the state.

A simple, marine-dwelling creature known as Trichoplax adhaerens has some remarkable properties. The organism can tolerate unusually high doses of radiation that would kill most other forms of life. T. adhaerens has another intriguing characteristic: the ability to resist cancer.
In a new study, Angelo Fortunato and his colleagues describe T. adhaerens’ unusual behavior, including its capacity to repair its DNA even after significant radiation damage and to extrude injured cells, which later die.
The findings advance scientific investigations of natural cancer-suppression mechanisms across life. Insights gleaned from these evolutionary adaptations may find their way into new and more effective therapies for this leading killer. Last year, over 600,000 people lost their lives to cancer in the US alone.
The unusual microorganism observed in the new study is rudimentary in form and easily cultured in the lab. This makes T. adhaerens an attractive model organism, enabling researchers to home in on fundamental processes of radiation tolerance as well as the underlying mechanisms guiding DNA repair, programmed cell death and other natural means of cancer resistance.
Fortunato is a researcher in the Arizona Cancer Evolution Center and the Biodesign Center for Biocomputing, Security and Society at Arizona State University. He is also a researcher in ASU’s School of Life Sciences.
Carlo Maley, a co-author of the new study is a researcher in the Biodesign Center for Biocomputing, Security and Society and the Center for Mechanisms of Evolution as well as ASU’s School of Life Sciences. He is the director of the Arizona Cancer Evolution Center.

Researchers have solved a decade-long mystery about a critical protein linked to Parkinson’s disease that could help to fast-track treatments for the incurable disease.
The research, published in Nature, has for the first time produced a ‘live action’ view of the protein, called PINK1, in exquisite molecular detail. The discovery explains how the protein is activated in the cell, where it is responsible for initiating the removal and replacement of damaged mitochondria. When the protein is not working correctly, it can starve brain cells of energy, causing them to malfunction and — in the long term — die, as happens to dopamine-producing cells in Parkinson’s disease.
The discovery is the culmination of a project spanning eight years and provides the first detailed blueprint for the discovery and development of therapeutic agents that could help to slow or even stop the progression of Parkinson’s disease.
Led by PhD student Mr Zhong Yan Gan and Professor David Komander, the multidisciplinary team at WEHI used innovative cryo-electron microscopy facilities and research to make the discovery.
At a glance WEHI researchers have, for the first time, visualised the entire process that leads to the activation of PINK1 — a protein directly linked to Parkinson’s disease. The team has been able to analyse each process that occurs from when PINK1 is initially made, to how defects in the protein lead to Parkinson’s disease. The enhanced understanding of the molecular basis of Parkinson’s disease created by the researchers has the potential to underpin new treatments.Turning the switch off
Parkinson’s disease is a progressive neurodegenerative disease caused by the death of dopamine-producing cells in the brain. More than 10 million people worldwide are living with Parkinson’s disease, including more than 80,000 Australians. Currently there are no approved drugs that can slow or stop the progression of Parkinson’s disease, with available therapies only able to treat and alleviate symptoms.

Researchers in Japan used magnetic resonance imaging to study the brains of secondary school students during a task focused on musical observation. They found that students trained to play music from a young age exhibited certain kinds of brain activity more strongly than other students. The researchers also observed a specific link between musical processing and areas of the brain associated with language processing for the first time.
Professor Kuniyoshi L. Sakai from the Graduate School of Arts and Sciences at the University of Tokyo is a keen musician, as are many of his colleagues. Although Sakai has studied human language through the lens of neuroscience for the last 25 years, it’s no surprise that he also studies the effect music has on the brain. Inspired by a mode of musical training known as the Suzuki method, which is based on ideas of natural language acquisition, Sakai and his team wanted to explore common neurological aspects of music and language.
“In the field of neuroscience, it is well established that there are areas of the brain that deal specifically with language, and even specialized regions that correspond to different parts of language processing such as grammar or syntax,” said Sakai. “We wondered if training under the Suzuki method might lead to activity in such areas, not when using language, but when engaging with music. Our study reveals this is indeed the case.”
For their investigation, the team enlisted 98 Japanese secondary school students classified into three groups: Group S (Suzuki) was trained from a young age in the Suzuki method, Group E (Early) was musically trained from a young age but not in the Suzuki method, and Group L (Late) was either musically trained at a later age, but not in the Suzuki method, or were not musically trained at all. All the students had their brains scanned by functional magnetic resonance imaging (fMRI), which produced dynamic 3D models of their brains’ activity. During this time, they were given a musical exercise to identify errors in a piece of music played to them. The musical pieces played had errors in one of four musical conditions: pitch, tempo, stress and articulation.
During the exercises, groups S and E showed more overall brain activity than Group L, especially during the pitch and articulation conditions. Furthermore, groups S and E showed activity in very specific regions depending on the kind of error being tested for. Interestingly, Group S showed some unique patterns of activation mostly in areas of the right brain, associated with emotion and melody, during the tempo condition, supporting the ideas behind the Suzuki method.
“One striking observation was that regardless of musical experience, the highly specific grammar center in the left brain was activated during the articulation condition. This connection between music and language might explain why everyone can enjoy music even if they are not musical themselves,” said Sakai. “Other researchers, perhaps those studying neurological traits of artistic experts, may be able to build on what we’ve found here. As for ourselves, we wish to delve deeper into the connection between music and language by designing novel experiments to tease out more elusive details.”
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Researchers have presented a method that allows the heavier hydrogen ‘brother’ deuterium to be introduced specifically into many different molecules. The deuterated compounds obtained in this way are more stable against degradation by certain enzymes. Drugs produced using this method can be effective for longer, meaning they have to be taken in lower doses or less frequently.
Hydrogen (abbreviated “H”) is the lightest of all elements. It usually consists only of a positively charged proton and a negatively charged electron and is also called protium in this form. But there are also two heavier hydrogen isotopes, deuterium and tritium. The deuterium nucleus contains one neutron in addition to the proton, in the case of tritium there are even two. Both are very rare; tritium is also — in contrast to deuterium and protium — radioactive.
Deuterium has been the focus of pharmaceutical research for some years, because it can ensure that drugs are broken down 5, 10 or even 50 times more slowly. “We call this the kinetic isotope effect,” explains Prof. Dr. Andreas Gansäuer of the Kekulé Institute for Organic Chemistry and Biochemistry at the University of Bonn (Germany). The reason for this is that many reactions, including the degradation of active substances, do not occur spontaneously. They first need a slight “push,” the activation energy. This is somewhat like getting a model car to roll over a hill: That too only works if the car has sufficient momentum. “If you replace hydrogen with deuterium, the activation energy usually increases somewhat,” says Gansäuer. “As a result, reactions are slower. This also applies to the metabolism of pharmaceuticals in the liver.”
Triple rings under tension
This means that introducing deuterium instead of protium into drugs causes them to have a longer effect. They can therefore be taken in lower doses or less frequently. However, deuterium is rare and thus comparatively expensive. Consequently, deuterium should ideally only be introduced at the points where metabolization occurs primarily. This is where the new process comes in.
It is based on a class of substrates called epoxides, which can now be produced almost at will in many different ways. These groups can be visualized as a kind of “triangle” in which two corners are formed by carbon atoms and the third by an oxygen atom. Such three-membered rings are under great tension, which means they tear easily on one side. Epoxides therefore store energy like a taut spring, which can then be used for certain reactions.
Selective exchange
“We introduced epoxides into different test molecules and then opened the strained ring with our catalyst,” Gansäuer explains. “This contains a titanium atom to which deuterium is bonded.” To put it figuratively, when the epoxy ring is cut open, two reactive ends are created. The catalyst binds to one of them, which then transfers the deuterium to the remaining free end in a second step. “This allows us to introduce a deuterium atom at a single location and with a very specific and desired spatial orientation,” Gansäuer says. He is a member of the Transdisciplinary Research Area “Building Blocks of Matter and Fundamental Interactions” (TRA Matter) at the University of Bonn.
Another advantage of the method: For many complex molecules, there are two different ways of bonding that mirror each other. The new process can be used to create almost exclusively one of the two shapes. “Since compounds of mirror-image molecules are very difficult to separate and, moreover, they often have different properties in the human body, such stereoselectivity is very important,” comments Gansäuer.
The method developed has been used, for example, to produce deuterated precursors of the painkiller ibuprofen and the antidepressant venlafaxine. The authors are confident that it will be applied to many more pharmaceuticals in the future.
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