Earth

New study by the ICTA-UAB shows that residents and visitors highlight the natural and biodiversity values of the Llobregat Delta, in Barcelona.

A new study undertaken by researchers at the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) supports protestors' concerns about damage to the Llobregat Delta in airport expansion plans.

The research, carried out in 2019, found that the well-maintained and unique natural environment of the Llobregat Delta is important or very important to 100% residents and 98.8% of visitors who responded to the survey.

The recently published article in Environmental Science and Policy found that the greatest frustrations that residents and visitors expressed related to the expansion of the airport and urban areas. Participants surveyed expressed concern about future airport expansion plans, and expressed their desire that these plans be modified.

"What is remarkable about the results is the amount of agreement among residents and visitors about the importance of the natural values of the Llobregat Delta. Even though the airport is nearby, people value being able to be able to access a protected natural area so close to Barcelona", explains Dr Sonia Graham, the researcher leading the project. Dr Graham recalls that, "during the interviews, a Barcelona resident told researchers that they would not like the airport to grow larger, and to have an impact on the area. They stated that the impact on the beach area by a possible expansion would be quite a hard blow, horrific". The wetlands, birdwatching huts and walking paths are highly valued ecosystem services and infrastructure that enable residents and visitors to experience and appreciate this unique area.

Beatrice Meo, the lead author of the article, explains that not only are people concerned about the expansion of the airport, they are also worried about the impacts of climate change. "About 90% of residents and visitors are very or fairly concerned about the impacts of climate change on the Llobregat Delta. More than 60% of respondents believe we are already feeling the effects of climate change now", she says.

The work took place between March and June 2019. It involved in-depth interviews and a survey of residents and visitors to the Llobregat Delta. The interviews and survey collected data on what residents and visitors value about the natural environment, and how concerned they are about the impacts of climate change on the delta.

New classes of drugs are biologic disease-modifying anti-rheumatic drugs (bDMARDs) and Januskinase inhibitors (JAKi). At the 2021 EULAR congress, Strangfeld and colleagues shared new data assessing the effects of these medications on the risk of serious infections in elderly people with RA. RA is an inflammatory autoimmune disease that causes pain, swelling, and stiffness in the joints, but it also affects other organ systems through underlying systemic inflammation, causing for example cardiovascular diseases or fatigue.

RABBIT is a prospective, observational cohort study in Germany. Patients with RA are enrolled when they start a new DMARD after failing at least one conventional synthetic treatment (csDMARD). This analysis included 2,274 people over the age of 70. In total, 626 serious infections were observed in 425 of these people.

Adjusted for those differences, serious infections were less likely in patients receiving bDMARDs or JAKi compared to csDMARDs, but this was not statistically significant. Associations with an increased risk of serious infections were seen for glucocorticoid use, higher disease activity, and having another underlying disease such as chronic pulmonary or kidney disease, or diabetes. The authors also found that better physical capacity was associated with a decreased risk of having a serious infection.

Overall, the results suggest that treatment with these new classes of drugs is not associated with an increased risk of serious infection in elderly RA patients above 70 years of age.

Professor Konstantin Arutyunov of the HSE Tikhonov Moscow Institute of Electronics and Mathematics (MIEM HSE), together with Chinese researchers, has developed a graphene-based mechanical resonator, in which coherent emission of sound energy quanta, or phonons, has been induced. Such devices, called phonon lasers, have wide potential for application in information processing, as well as classical and quantum sensing of materials. The study is published in the journal Optics Express.

Using an analogy with photons, quanta of the electromagnetic spectrum, there are also particles of sound energy, phonons. In fact, these are artificially introduced objects in physics - quasi-particles, which correspond to vibrations of the crystal lattice of matter.

Some substances, when irradiated, emit photons of the same wavelength, phase, and polarisation. This process, called stimulated emission, was predicted by Albert Einstein over a century ago and is the basis of the device we all know - the laser. The first lasers were constructed about sixty years ago, and they have become firmly established in our lives in various fields.

A similar process, involving the emission of 'identical' phonons, underlies a device called, by analogy, a phonon laser, or saser. In fact, it was predicted at the same time as lasers, but only a few experimental realisations have been developed over a long period of time, and none of them have been widely used in the industry.

Magnesium ions, semiconductors, composite systems with microcavities, electromechanical resonators, nanoparticles, and many other substances and systems have been used as active media for phonon lasers over the last decade. Unlike previous studies, the present study used graphene to create coherent acoustic excitations. Due to the unique properties of graphene, such resonators can potentially be widely used.

The graphene resonator was produced by microlithography: a photo-sensitive polymer film is deposited on a silicon substrate. Using ultraviolet light, a certain structure is 'drawn' on the substrate, which subsequently allows the formation of a repeating system of micro-cavities by means of plasma treatment. The treated substrate is covered with a layer of graphene, and this system of 'drums' behaves like a resonator, i.e. it amplifies external vibrations if they are generated with a certain frequency.

If such a 'drum' is irradiated with laser light at a specific wavelength, photons are repeatedly reflected between the silicon backing and the graphene, thereby forming optical cavities where mechanical vibrations of the appropriate frequency are produced.

'Experimentally, we have examined a nanostructure, which is a fixed membrane made of a monatomic layer of carbon, or a graphene. Vibrations of atoms, or phonons, were activated in it through exposure to external optical radiation,' says Konstantin Arutyunov. 'The research is expected to continue, as it is of considerable interest both for physics of ultra small objects and has the potential to create a new generation of quantum optomechanical sensors and transducers.'

Geologic activity on Earth appears to follow a 27.5-million-year cycle, giving the planet a "pulse," according to a new study published in the journal Geoscience Frontiers.

"Many geologists believe that geological events are random over time. But our study provides statistical evidence for a common cycle, suggesting that these geologic events are correlated and not random," said Michael Rampino, a geologist and professor in New York University's Department of Biology, as well as the study's lead author.

Over the past five decades, researchers have proposed cycles of major geological events--including volcanic activity and mass extinctions on land and sea--ranging from roughly 26 to 36 million years. But early work on these correlations in the geological record was hampered by limitations in the age-dating of geologic events, which prevented scientists from conducting quantitative investigations.

However, there have been significant improvements in radio-isotopic dating techniques and changes in the geologic timescale, leading to new data on the timing of past events. Using the latest age-dating data available, Rampino and his colleagues compiled updated records of major geological events over the last 260 million years and conducted new analyses.

The team analyzed the ages of 89 well-dated major geological events of the last 260 million years. These events include marine and land extinctions, major volcanic outpourings of lava called flood-basalt eruptions, events when oceans were depleted of oxygen, sea-level fluctuations, and changes or reorganization in the Earth's tectonic plates.

They found that these global geologic events are generally clustered at 10 different timepoints over the 260 million years, grouped in peaks or pulses of roughly 27.5 million years apart. The most recent cluster of geological events was approximately 7 million years ago, suggesting that the next pulse of major geological activity is more than 20 million years in the future.

The researchers posit that these pulses may be a function of cycles of activity in the Earth's interior--geophysical processes related to the dynamics of plate tectonics and climate. However, similar cycles in the Earth's orbit in space might also be pacing these events.

"Whatever the origins of these cyclical episodes, our findings support the case for a largely periodic, coordinated, and intermittently catastrophic geologic record, which is a departure from the views held by many geologists," explained Rampino.

The visual thalamus is classically known to relay visual stimuli coming from the retina to the cerebral cortex. Researchers from the Max Planck Institute of Neurobiology now show that although neurons in the mouse visual thalamus connect to both eyes, they establish strong functional connections only with one retina. These results settle partly contradictory results of earlier studies and demonstrate how important it can be to complement structural data with functional analyses.

We have two eyes, but perceive the tree in front of us only once. Our brain therefore has the complicated task of combining the information of both eyes in a meaningful way. To do so, visual stimuli first travel from the retina via so-called ganglion cells to the visual thalamus. There, the information does end up in clearly defined areas - depending on the type and eye-of-origin of retinal ganglion cells transporting the visual stimuli. Signals from the right and left eye are thus clearly separated in the visual thalamus and independently transmitted to the visual cortex. Only in this brain region, the incoming information is combined - at least according to a long-standing theory.

However, recent anatomical studies describe that a surprising number of neurons in the mouse visual thalamus has contact to both eyes. Does the separation of 'left eye' and 'right eye' information channels not hold true in mice? Scientists from Tobias Bonhoeffer's department wanted to shed more light on this newly raised question. They further developed an optogenetic method, so that they could activate ganglion cells of both eyes successively with light of different colors and measure the corresponding electrical responses in a thalamic cell.

This analysis shows that indeed a multitude of neurons in the visual thalamus receive input from both retinas. But interestingly, there are only very few cells in which the signal strengths of both eyes are similar. In most cells, one eye dominates with a much higher input strength. The weak signals from the non-dominant eye did not trigger an action potential in the experiment and thus seem to not play a major role in the processing of visual information. "With these results, we can explain the contradictory findings of previous research," says Tobias Rose, who led the study. "The neurons in the visual thalamus do form connections with both eyes, but are functionally monocular or, so to speak, one-eyed. That means that only the signal strength of one eye is high enough for the cells to respond."

Selection of input

The spatial arrangement of retinal and thalamic cells and the resulting connection possibilities alone cannot explain the functional monocularity. Instead, the scientists showed that even with equal access to both eyes, thalamic cells establish functional connections with only one eye. Accordingly, there is a clear selection of the input source. In addition, the contact sites with the dominant eye seem to strengthen, while those of the non-dominant eye remain in an immature state.

Future studies aim to reveal how the dominant eye is determined and whether this mechanism also applies to different retinal ganglion cell types. Another interesting research topic are the immature contact sites. At first glance without obvious function, the question arises whether they could be activated when needed - and thus play a role, for example in amblyopia, a form of visual impairment.

With their study, the researchers prove that the mouse visual thalamus indeed transfers visual information in separate channels - presumably similar to humans. In addition, it becomes clear that anatomical data sets may be interpreted with caution: Just because neurons are in contact with each other does not mean that they communicate extensively.

BIRMINGHAM, Ala. - A comprehensive health-screening program in rural northern KwaZulu-Natal, South Africa, has found a high burden of undiagnosed or poorly controlled non-communicable diseases, according to a study published in The Lancet Global Health.

Researchers found that four out of five women over the age of 30 were living with a chronic health condition, and that the HIV-negative population and older people -- especially those over 50 -- bore the higher burden of undiagnosed or poorly controlled non-communicable diseases such as diabetes and hypertension.

The study was co-led by Emily Wong, M.D., a resident faculty member at the Africa Health Research Institute, or AHRI, in Durban, KwaZulu-Natal, South Africa. Wong is also an assistant professor in the Division of Infectious Diseases, University of Alabama at Birmingham Department of Medicine and an associate scientist in the UAB Center for AIDS Research.

"The data will give AHRI researchers and the Department of Health critical indicators for where the most urgent interventions are needed," Wong said. "The research was done before COVID-19, but it has highlighted the urgency of diagnosing and treating people with non-communicable diseases -- given that people with uncontrolled diabetes and hypertension are at higher risk of getting very ill with COVID."

Durban lies in the worldwide epicenter for HIV-associated tuberculosis infections. Wong works there to understand the impact of HIV infection -- the virus that causes AIDS -- on tuberculosis pathogenesis, immunity and epidemiology. She collaborates closely with another UAB researcher who also works at AHRI, Andries "Adrie" Steyn, Ph.D., professor in the UAB Department of Microbiology.

"We are working hard to strengthen ties and collaborations between the two institutions and create a UAB-AHRI Tuberculosis Center that further facilitates multi-disciplinary collaborations," Wong said. Wong joined UAB last year, and she will spend about 80 percent of her time at AHRI and 20 percent at UAB when travel resumes from its COVID-19 hiatus.

As background to the study, 15 years of intense public health efforts that increased access to anti-retroviral therapy in sub-Saharan Africa has beneficially decreased mortality from AIDS and increased life expectancy. As a result, there is an increasing priority to address other causes of disease, including tuberculosis and non-communicable diseases.

In the 18-month Lancet Global Health study, health workers screened 17,118 people age 15 years and older via mobile camps within 1 kilometer of each participant's home in the uMkhanyakude district. They found high and overlapping burdens of HIV, tuberculosis, diabetes and hypertension among men and women.

While the HIV cases were, for the most part, well diagnosed and treated, some demographic groups, including men in their 20s and 30s, still had high rates of undiagnosed and untreated HIV. The majority of people with tuberculosis, diabetes or hypertension were either undiagnosed or not well controlled. Tuberculosis remains one of the leading causes of death in South Africa, and the high rates of undiagnosed and asymptomatic tuberculosis that health workers found is a concern.

"Our findings suggest that the massive efforts of the past 15 years to test and treat for HIV have done very well for that one disease," Wong said. "But in that process, we may have neglected some of the other important diseases that are highly prevalent."

The mobile camps screened for diabetes, high blood pressure, nutritional status (obesity and malnutrition), and tobacco and alcohol use, as well as HIV and tuberculosis. The tuberculosis screening component included high-quality digital chest X-rays and sputum tests for people who reported symptoms or had abnormal X-rays. Clinical information was layered onto 20 years of population data from AHRI's health and demographic surveillance research. Through a sophisticated data system and the use of artificial intelligence to interpret the chest X-rays, AHRI's clinical team examined the information in real time and referred people to the public health system as needed.

Researchers found that:

Half of the people 15 years or older had at least one active disease, and 12 percent had two or more diseases. The incidences of diabetes and high blood pressure were 8.5 percent and 23 percent, respectively.

One-third of the people were living with HIV, but this was mostly well diagnosed and treated. Women bore a particularly high burden of HIV, high blood pressure and diabetes.

For tuberculosis, 1.4 percent of the people had active disease, and 22 percent had lifetime disease. About 80 percent of the undiagnosed tuberculosis was asymptomatic, and men had higher rates of active tuberculosis.

Researchers also identified several disease patterns by geographical location -- for example, the highest burden of HIV was seen near main roads, while higher rates of tuberculosis and non-communicable diseases were seen in more remote areas.

Cancer cells can develop resistance to therapy through both genetic and non-genetic mechanisms. But it is unclear how and why one of these routes to resistance prevails. Understanding this 'choice' by the cancer cells may help us devise better therapeutic strategies. Now, the team of Prof. Jean-Christophe Marine (VIB-KU Leuven Center for Cancer Biology) shows that the presence of certain stem cells correlates with the development of nongenetic resistance mechanisms. Their study is published in the prestigious journal Cancer Cell.

Two routes to resistance

Even though cancer therapy has made great strides in the last few years, resistance remains a major problem. When cancer cells develop resistance against the drugs targeting them, they can continue to spread, even when the patient is going through therapy.

Until recently, it was thought that this resistance arises exclusively through mutations - genetic alterations - in the cancer cells. However, new studies have suggested that resistance against cancer drugs can also arise via non-genetic mechanisms that change the expression of certain genes without altering the DNA sequence.

Prof. Jean-Christophe Marine (VIB-KU Leuven Center for Cancer Biology): "The importance of nongenetic reprogramming as a driver of therapy resistance is not yet widely accepted in the field. Although my group has demonstrated that drug tolerance can be driven by nongenetic mechanisms, strong evidence that resistance can be acquired in absence of a genetic cause is still lacking."

In their study, the team of Prof. Marine firmly establishes that nongenetic mechanisms contribute to resistance to therapy in melanoma. The key question has become: "How do cancer cells 'choose' between the different routes to resistance?"

Neural crest stem cells as key

Surprisingly, the team demonstrates that the road to resistance is predetermined and not randomly selected. They show that the presence of a specific group of cells, neural crest stem cells, leads to non-genetic rather than genetic drug resistance in melanoma. A possible reason for this is that these neural crest stem cells exhibit 'epigenetic plasticity', which means that these cells have an increased ability to select which genes they express and how much. These cells literally reprogram themselves to evade the therapeutic pressure.

The researchers also identified the signaling pathway that drives the emergence of the neural crest stem cells and promotes their survival. This signaling pathway depends crucially on the protein Focal Adhesion Kinase (or FAK). By blocking the activity of this protein, the team was able to drastically reduce the occurrence of non-genetic drug resistance in patient-derived xenografts - tumor cells from human patients that were implanted in mice.

This combination of new basic insights into tumor cell biology and recently discovered non-genetic resistance mechanisms to cancer drugs has far-reaching clinical consequences.

Florian Rambow, senior postdoc who contributed to the study, explains: "These findings have several important clinical implications. Not only did we show a viable way to suppress non-genetic resistance, but we also demonstrated that the presence of specific cells dictates which resistance mechanism is likely to occur. This observation is the key to predicting potential resistance routes in patients and developing personalized therapies."

Southeast Asian monsoon region falls in the warm and humid tropics modulated by Asian monsoon. It is home to nearly 15% of the world's tropical forests and one of the biodiversity hotspots in the world.

With the unprecedented urbanization and population growing rate, water scarcity issues have already posed a serious challenge for sustainable development in Southeast Asian monsoon region. However, the impact of anthropogenic forcing, such as greenhouse gases and anthropogenic aerosols, on extreme drought events in the region is still unclear.

Scientists from the Institute of Atmospheric Physics (IAP) of the Chinese Academy of Sciences investigated the observed drought changes over Southeast Asian monsoon region and impacts of anthropogenic forcing using the Coupled Model Intercomparison Project phase 6 (CMIP6) models.

Their findings were published in Geophysical Research Letters on June 1.

They revealed an increasing drought risk for 1951-2018 due to more frequent and wide-spread droughts over the Southeast Asian monsoon region.

They also detected the influence of anthropogenic forcing, which has increased the likelihood of the extreme droughts in historical simulation by reducing precipitation and enhancing evapotranspiration.

The time of emergence (ToE) of anthropogenic forcing in extreme drought frequency and affected area firstly appeared around the 1960s. Even though drought risk will start to decrease since the 2030s in the future under the lowest emission scenario of CMIP6, the projected drought risks are still beyond the changes caused by nature alone.

"The impact of anthropogenic forcing on drought risk over Southeast Asia has already exceeded internal climate variability in the late 20th century. It is urgent to take actions to reduce anthropogenic aerosol loading and greenhouse gas emissions to reduce drought risks in Southeast Asia." Said Dr. Lixia Zhang, the lead author of the study.

Tissue-engineering scaffolds built around ultrashort peptides provide a new platform for studying bone regeneration in the lab.

The peptides developed at KAUST self-assemble into a cartilage-like hydrogel that mimics the natural matrix that underpins bone formation in the body. Its physiologically relevant properties enable this cell-friendly biomaterial to support the growth and development of bone marrow precursor cells. It also enables tubular blood vessels to take shape, which is a critical part of bone health and repair.

"Our system is a simple, efficient and robust model that closely resembles the complex architecture of native bone tissue," says Ph.D. student Salwa Alshehri. "Using these peptide-based hydrogels, we can now build 3D disease models for tissue engineering, biomedical research and drug testing."

KAUST researchers, led by bioengineering professor Charlotte Hauser, had previously shown that their ultrashort peptides could be mixed with cells in the nozzle of a 3D printer to create a type of bioink that, once ejected, would instantly solidify into desired forms2. But it was unclear if the synthetic material could sustain the full complexity of bone development, which includes the adhesion, spread and differentiation of bone-specific stem cells, along with the incursion of blood vessels needed for nutrient transfer and metabolic-waste removal.

Alshehri put the platform to the test. She and Hauser, together with Ph.D. student Hepi Hari Susapto, fine-tuned the stiffness of their hydrogels by altering the concentration of peptides in their mix. Once they had the right mechanical properties for bone growth, the researchers seeded the scaffolds with bone marrow-derived mesenchymal stem cells. Inside these 3D constructs, the cells maintained their capacity for self-renewal and, under appropriate conditions, could convert into bone-forming osteocyte cells.

The KAUST team then went one step further. The researchers added cells taken from human umbilical veins to their mini-bone scaffolds and found that the material could support a dense network of blood vessel formation as well. "Our model successfully accommodated more than one cell type without any compromise on their viability," says Alshehri, who now hopes to develop even more sophisticated bone tissue models for evaluation in animal models and, eventually, as a regenerative therapy for patients with bone disease.

Alshehri, Hauser and their colleagues are also looking to extend the platform into other medical applications, not just bone regeneration. "Since blood vessels are an integral part of native tissues," Alshehri says, "the successful culture of endothelial cells in 3D within these hydrogels holds a great promise for tissue engineering applications in general."

Living beings are continuously exposed to harmful agents, both exogenous (ultraviolet radiation, polluting gases, etc.) and endogenous (secondary products of cellular metabolism) that can affect DNA integrity. That's why cells are endowed with a series of molecular mechanisms whose purpose is to identify and signpost possible damage to the genetic material for speedy repair. These mechanisms are precisely regulated because they are key to cell survival. In extreme situations of massive and irreparable damage, cells enter a phase of controlled dismantling called "programmed cell death". Among the events that take place during this process is the massive delivery to the cytoplasm of a mitochondrial protein called cytochrome C. Under homeostatic conditions, this protein plays a role in energy metabolism within the mitochondria. However, in situations of irreparable damage, it directs the controlled and orchestrated destruction of the cell from the cytoplasm.

The authors of this paper suggest that extramitochondrial cytochrome C plays a dual role in response to cell damage. In the initial stages of damage, a limited amount of cytochrome C is able to reach the cell nucleus without accumulating in the cytoplasm and, therefore, without triggering programmed cell death. Once in the nucleus, cytochrome C interacts with the protein ANP32B, a histone chaperone that helps maintain DNA structure and inhibits the activity of the enzyme (phosphatase) PP2A, a major promoter of DNA damage repair. Thus, cytochrome C "hijacks" ANP32B as a means of activating PP2A and facilitating DNA repair. When damage to the genetic material cannot be repaired by the cellular mechanisms, cytochrome C "floods" both the cytoplasm and the nucleus, leading to the irremediable death of the cell. "What's the point of continuing to build a house that's going to be demolished?".

This project received funding from the Ramón Areces Foundation and the Spanish Association Against Cancer (AECC), as well as from the Spanish Government and the Andalusian Regional Government.

Below please find a summary for a new article that will be published today in Annals of Internal Medicine. The summary is not intended to substitute for the full article as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

FDA advisory panelist outlines numerous issues with aducanumab's accelerated approval for Alzheimer's disease
Abstract: https://www.acpjournals.org/doi/10.7326/M21-2603
URL goes live when the embargo lifts

Despite near unanimous objection from its advisory panel, the U.S. Food and Drug Administration (FDA) granted aducanumab approval to treat Alzheimer's disease on June 7, 2021. In a commentary published in Annals of Internal Medicine, a member and former Chair of the advisory panel and an aducanumab site investigator explain why this unprecedented "accelerated approval" is problematic for clinical research and patient care.

Under accelerated approval, a drug is approved based on its effect on a surrogate marker of a disease rather than clinical outcomes. The product is expected to provide a meaningful advantage over other available therapies for a serious disease. Aducanumab's phase 1 study indicates the drug reduces beta-amyloid (the surrogate marker of disease), but whether beta-amyloid alone is a valid surrogate for the treatment of Alzheimer's is notably unclear and still a topic of ongoing important study. With the surprising approval, treating an amyloid level becomes clinical practice.

The authors express grave concern that aducanumab's approval will have important consequences for drug development, regulation, and patient care. While the world waits for the results of randomized and controlled clinical trials required to confirm aducanumab's clinical benefits (or not), insurers and payers will have to use the scant information available to determine which patients should take it and how to cover it. The copays for aducanumab, which may be as much as 20% of the total cost, will be added to the already substantial financial burden many American families face due to Alzheimer's disease. Also, clinicians will have to address with patients, uncertainty regarding whether the drug is even beneficial or safe.

According to the authors, the effect of aducanumab's approval will reverberate for years. Patients, caregivers, providers, and scientists must navigate treatment of Alzheimer's disease with an uncertain treatment. Time will tell whether or not it is safe and effective.

June 17, 2021 - Nutley, NJ - Tiny genetic markers, circulating in the blood, have shown great promise in diagnosing and treating disease. Yet identifying and harvesting these extracellular vesicles (EVs) have been a major challenge for science.

Now a laboratory at the Hackensack Meridian Center for Discovery and Innovation (CDI) has discovered a highly sensitive methodology that can efficiently find and harness EVs - particularly exosomes and the micro RNAs they carry. These could be crucial clues to identifying diseases such as cancer early on in its development.

The scientists have now unveiled the Extracellular Vesicle Capture by AnTibody of CHoice and 1 Enzymatic Release, or EV-CATCHER, in the Journal of Extracellular Vesicles.

"We are establishing the threshold of detection," said Olivier Loudig, Ph.D., an associate member of the CDI. "The EV-CATCHER is really intended to push the envelope."

"This work shows us a new dimension to the study of circulating and exhaled biomarkers," said David Perlin, PhD., the chief scientific officer and senior vice president of the CDI. "The Loudig laboratory is elevating the field with this novel work which has great promise."

The EV-CATCHER was designed by Loudig as a high-throughput test to find and quantify tiny amounts of micro RNAs detected through next-generation sequencing. The technology uses targeted antibodies to bind to the molecules in plasma. It was developed after Loudig and his team tested 11 other methodologies, including magnetic beads, which were found to be inexact.

Testing the EV-CATCHER involved taking mouse-derived extracellular EVs that were spiked into human plasma. The results showed the EV-CATCHER caught the mouse-derived material - and the researchers were able to successfully extract the intact micro RNAs within.

Other analyses assessed samples from COVID-19 patients.

The first comparison used sequences from samples purified with the EV-CATCHER, in contrast to whole-serum samples. Loudig and his team were able to show which exosomes were hallmarks of hospitalized patients with serious disease, and which showed up in more moderate cases.

Separately, a test on convalescent plasma of recovered COVID-19 patients showed that high levels of anti-spike IgG antibodies demonstrated neutralizing properties against the SARS-CoV-2 virus, in vitro.

Furthermore, the testing showed that the COVID-19 patients' exosomes themselves had neutralizing properties on the virus - meaning it could have therapeutic value in convalescent plasma, and other potential treatments of the future.

"This paper demonstrates that the technology not only helps us detect and diagnose disease in its early stages - it can also potentially be used to help treat disease, as well," said Megan Mitchell, Ph.D., a postdoctoral research fellow in the Loudig lab, and a co-author of the paper.

A new article, published as a Perspective in the journal Conservation Science and Practice, introduces a rapid assessment framework that can be used as a guide to make conservation and nature-based solutions more robust to future climate.

Climate change poses risks to conservation efforts, if practitioners assume a future climate similar to the past or present. For example, more frequent and intense disturbances, such as wildfire or drought-induced tree mortality, can threaten projects that are designed to enhance habitat for forest-dependent species and sequester carbon. Overlooking such climate-related risks can result in failed conservation investments and negative outcomes for people, biodiversity, and ecosystem integrity as well as lead to carbon-sink reversal. Drawing from lessons learned from a decade of funding over 100 adaptation initiatives through the WCS Climate Adaptation Fund, the authors offer a simple framework that enables users to rapidly assess how--and by what means--climate change will require innovation beyond business-as-usual conservation practice.

This tractable assessment encourages practitioners and funders to use the "what, when, where, why, and who"--or the "5Ws"--of climate-informed action as a tool in project design and implementation. The "what," for example, means considering whether climate variability and projected changes will require taking new actions or modifying existing actions. The "who" asks users to consider: by whom, with whom, who benefits and who might bear potential harm or tradeoffs from project implementation and anticipated outcomes.

Using the 5Ws in practice can result in doing conservation differently in the warming world and help practitioners achieve their desired objectives. They use available science and local knowledge to address climate risks to traditional investments in reforestation, fire management, watershed restoration, and habitat protection. Take reforestation as an example: a traditional approach might aim to enhance habitat and carbon sequestration using seed or seedlings from historically-dominant tree species. Tree mortality due to unsuitable climate conditions could then lead to unexpected habitat degradation and reductions in carbon sequestration. A climate-informed approach favors native species that are expected to thrive under future climate. Seed or seedlings can be sourced from warmer and/or drier locations to assist migration to climatically-suitable areas. The 5Ws facilitates this process of figuring out what, if anything, should be done differently from the status quo.

"There's such a pressing need for adaptation," notes Lauren E. Oakes, the article's lead author. "So, we need to mainstream strategic actions that are robust to future climate change into conservation efforts and nature-based solutions across the world." There is a breadth of rigorous tools available for adaptation practitioners, but the complexity cost and time required to use them can stall their broad uptake. Oakes says the "5Ws" offers an initial, less daunting entry into the climate-informed planning process for practitioners endeavoring to make their projects more robust to future conditions. The authors offer this rapid assessment as a pathway to broader adoption of adaptation planning, an urgent need as investments in nature-based solutions continue to ramp up.

With sorghum poised to become an important crop grown by Pennsylvania farmers, Penn State researchers, in a new study, tested more than 150 germplasm lines of the plant for resistance to a fungus likely to hamper its production.

Sorghum, a close relative to corn, is valuable for yielding human food, animal feed and biofuels. Perhaps its most notable attribute is that the grain it produces is gluten free. Drought resistant and needing a smaller amount of nutrients than corn to thrive, sorghum seems to be a crop that would do well in the Keystone State's climate in a warming world. But its susceptibility to fungal disease is problematic.

"In other locations where sorghum has been grown for a long time, it is attacked by a fungal pathogen that causes a disease called anthracnose leaf blight, which diminishes its yield," said study co-author Surinder Chopra, professor of maize genetics in the College of Agricultural Sciences. "We conducted a three-part experiment designed to evaluate the likelihood that anthracnose will be a problem with sorghum production in Pennsylvania, and what plants might resist the disease."

First, researchers carried out field surveys in 2011, 2012 and 2016 in six Pennsylvania locations to monitor the presence of the Colletotrichum fungus that causes anthracnose in commercial sorghum fields. They collected soil samples, plant samples and samples of the debris left by sorghum or corn, looking for the fungus at sites in Blair, Lancaster, Dauphin, Centre, Bedford and Lebanon counties.

Next, researchers grew 158 sorghum lines at Penn State's Russell E. Larson Agricultural Research Center at Rock Springs and tested them for vulnerability and resistance to the natural strains of anthracnose fungus. They obtained plant material for many of the sorghum lines from the International Crops Research Institute for the Semi-Arid Tropics, better known as ICRISAT, India.

Other sorghum lines came from varieties Chopra's research group has been breeding in plots at Rock Springs for years and are being tested for stress tolerance in another study. Still others came from sources such as the U.S. Department of Agriculture's Agricultural Research Service stations in Griffin, Georgia, Lincoln, Nebraska, and Lubbock, Texas; the Grain, Forage and Bioenergy Research Center, Texas A&M Agrilife Sorghum Breeding Program; and the National Plant Germplasm System.

Lastly, researchers conducted experiments in greenhouses on the University Park campus. They chose 35 sorghum lines that demonstrated resistance to the fungus in field trials and tested their responses after inoculating them with the pathogen. The team evaluated and scored those plants for the severity of anthracnose leaf blight that developed.

In findings recently published in Crop Science, Chopra and colleagues reported that the anthracnose leaf blight symptoms were observed on the older and senescent leaves in Pennsylvania. After evaluating, in field and greenhouse tests, the performance of the 158 experimental lines and commercial hybrids, the researchers noted that they discovered sources of resistance to anthracnose leaf blight.

"Many of those sorghum lines we tested had been improved in several states in the U.S. and in other parts of the world," Chopra said. "These should be useful in breeding programs targeted for Pennsylvania and for northeastern U.S. climatic conditions. Several lines received from ICRISAT showed the high level of resistance in the field."

The research was done in preparation for widespread cultivation of sorghum in Pennsylvania, at which time anthracnose leaf blight is expected to become a problem for farmers, Chopra explained.

"Our study is the first to investigate the frequency, diversity and distribution of Colletotrichum fungi species on sorghum in Pennsylvania, and the first to look for disease-tolerant strains that will grow best in the Northeast," he said. "Our findings will help develop better recommendations for sorghum growers so they can manage and proactively prevent the buildup of inoculum and resulting disease outbreaks."

If the genome is the recipe of life, base pairs are the individual ingredients listed. These chemical structures form DNA, and every living organism on Earth has just four. The specific arrangements of these four base pairs -- A, T, C, G -- make us who and what we are.

So it was a big surprise when Scripps Research scientists revealed in 2014 that they could introduce two new, unnatural base pairs (they called them X and Y for short) into the genetic code of living bacteria in the lab. It was like two never-seen-before ingredients tossed into the recipe, hypothetically expanding the variety of dishes a cell can whip up.

Researchers immediately saw the potential applications: With more control and selection, they might be able to use cells as tiny kitchens to cook up new medicines and vaccines. But just because there are more letters in a genetic recipe doesn't mean the cell can read them, or knows what to do with them -- or that any of it works in the cells of organisms more complicated than bacteria.

In a study published June 17, 2021 in Nature Chemical Biology, a team led by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego helped address these hurdles.

The team revealed that yeast cell machinery seamlessly "reads" the unnatural X and Y ingredients, the way it would A, C, T and G, and translates them into RNA, which could eventually be translated into proteins, the basis for just about every part of the cell. Unlike bacteria, yeast are eukaryotes, part of the same multicellular class of life as animals, plants and fungi. (A note about safety: These synthetic cells can't survive without special liquid food provided in the lab.)

"Now we can see exactly how eukaryotic cell machinery interacts with unnatural base pairs, but it's not perfect, there's room to improve in terms of selectivity and efficiency," said senior author Dong Wang, PhD, professor in the Skaggs School of Pharmacy. "It's our hope that this finding will have a profound impact in the field by enabling the design of more effective, next-generation unnatural base pairs."

Wang's lab has long studied RNA polymerase II, an essential enzyme found in every fungal, plant and animal cell. RNA Pol II reads the DNA recipe and helps convert the genetic code into messenger RNA. (That mRNA then carries that genetic recipe out of the nucleus and into the cytoplasm, where it's translated and used to assemble proteins as instructed.) In the past, the team has studied the structure of RNA Pol II and how it responds to normal genetic recipe hiccups such as DNA damage caused by radiation.

In their latest study, Wang's team revealed for the first time step-by-step what it looks like, structurally speaking, when eukaryotic RNA Pol II picks up and incorporates unnatural base pairs as it transcribes a piece of DNA. In doing so, they discovered, for example, that RNA Pol II is selective -- it can bind X or Y on one strand of a double-stranded DNA genome, but not the other.

"What we have now is a unique view of what is and what is not well recognized by RNA Pol II," said Wang, who is also professor at UC San Diego School of Medicine and Department of Chemistry and Biochemistry. "This knowledge is important for us to design new unnatural base pairs that can be used by host RNA polymerases."