Earth

HUNTINGTON, W.Va. - During development, brain cells may find different ways to connect with each other based on sex, according to researchers at the Marshall University Joan C. Edwards School of Medicine.

The study, recently published in eNeuro, an open access journal for the Society of Neuroscience, showed a significantly more robust synaptogenic response in male-derived cells compared to female-derived cells when exposed to factors secreted from astrocytes, which are non-neuronal cells found throughout the central nervous system. This difference was driven largely by how neurons responded to thrombospondin-2 (TSP2), a protein with cell adhesion properties that is normally secreted by astrocytes. In the study, TSP2 prompted a strong increase in synapses in male neurons while showing no effect on female neurons.

This work provides strong evidence that synapses, which serve as the basic building blocks for brain connectivity, may be formed by vastly different mechanisms during early development.

"Our goal is to better understand at a basic cellular level if there are sex differences in how cellular networks form in the brain," said W. Christopher Risher, Ph.D., an assistant professor of biomedical sciences at the Joan C. Edwards School of Medicine and corresponding author on the study. "In this study, for the first time, we see evidence that events which were always assumed to be occurring in the same manner, regardless of sex, may actually be completely different in males compared to females. The fact that these differences involve astrocytes, which have traditionally been ignored in neuroscience but have recently become a hot topic for study, makes them all the more intriguing."

Risher's team, led by first author Anna Mazur, Ph.D., isolated brain cells (neurons and astrocytes) from male and female newborn rats for this study. Once the cells were isolated, they were cultured for up to two weeks in various combinations with each other and then imaged on a fluorescent microscope to determine how many synapses were formed at the end of the experiment. In addition, the cells were treated with TSP2 as well as numerous regulators of estrogen signaling, in order to determine the effect of each of these factors on synapse formation in male- and female-derived cultures.

"The fact that we have identified molecular pathways present in males that are either absent or less prominent in females indicates that there may be much that researchers have missed in the area of synaptic development, simply because we weren't looking separately at males and females," Risher said.

Risher and his team continue to research the presence and impact of differences in cellular networks. Ultimately, findings from their work could help pave the way for sex-specific therapies for neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia, that present with strong sex biases in humans.

Since the beginning of the pandemic, several reports have indicated that SARS-CoV-2 spillover events have occurred from humans to animals, as evidenced by the transmission of the virus between keepers and tigers and lions in the Bronx Zoo in New York. However, to date, the full range of animal species that are susceptible to SARS-CoV-2 infection remains unclear. Typically, such information could be obtained by experimentally infecting a large variety of animal species with SARS-CoV-2 to see if they are susceptible. However, in order to reduce and refine such animal experiments, the researchers at the University of Bern and at the IVI set out to answer this question using a different, and more animal friendly approach.

Building an in vitro zoo

The authors used their knowledge on advanced in vitro cell culture models for the human respiratory tract, to create a large collection of similar models from various domesticated and wildlife animal species. For this the team isolated airway epithelial cells (AEC) from tracheobronchial tissue from deceased animals and created a cell biobank from different animal species that can be used to establish well-differentiated AEC culture models to determine whether these animals can be infected with SARS-CoV-2. Because the cells are isolated from deceased animals and the number of isolated cells can be increased in a petri dish, the researchers do not have to perform any animal experiments. To date, the cell biobank contains primary cells from 12 different animal species; rhesus macaque, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two neotropical bat species. "Our collection is unique, and thus far we are the first that have used such a large collection of advanced in vitro cell culture models from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2 infection", says Ronald Dijkman from the Institute for Infectious Diseases (IFIK) at the University of Bern.

Rhesus macaques and cats as potential spillback reservoirs for SARS-CoV-2

In these experiments, the researchers found that the in vitro results agreed well with previously published studies using animal experimentation to assess the susceptibility of different animals to SARS-CoV-2 infection. Using whole viral genome sequencing, the researchers also observed that SARS-CoV-2 replicated in the in vitro models of monkey and cats, without the need for the virus to adapt. These findings suggest that certain species of monkeys and cats may be particularly vulnerable to SARS-CoV-2 infection. "Our findings, together with the reports from previously documented spillover events, indicate that close surveillance of these animals and other close relatives, whether they live in the wild, captivity or households, is necessary", says Dijkman.

This information can be used by the responsible authorities such as the Swiss Federal Office for Public Health and the Federal Food Safety and Veterinary Office, for SARS-CoV-2 surveillance at the human - animal interface. Specifically, it helps them to establish and tailor early detection surveillance programs to monitor animals that can act as potential spillback reservoirs for SARS- CoV-2. Dijkman added, "This will benefit the general public since it will help prevent new SARS- CoV-2 variants from developing in animal reservoirs and potentially being reintroduced into the human population, to which the current vaccines may not be protective."

Implementing the 3R (Replace, Reduce, Refine) principles in coronavirus research

The findings of the study also show that advanced in vitro cell culture models of cells lining the airways from different mammals can be used as an alternative method, circumventing traditional in vivo experimental constraints, to evaluate and provide insight into the host spectrum of SARS-CoV- 2. "Our study shows that there is a lot of potential to replace, reduce and refine animal experimentation in the near future, and I hope that for basic fundamental research questions our results will convince researchers, pharmaceutical companies, and drug administration agencies to use advanced biologically relevant in vitro models prior to conducting animal experiments", says Dijkman.

FINDINGS

A chemical modification that occurs in some RNA molecules as they carry genetic instructions from DNA to cells' protein-making machinery may offer protection against non-alcoholic fatty liver, a condition that results from a build-up of fat in the liver and can lead to advanced liver disease, according to a new study by UCLA researchers.

The study, conducted in mice, also suggests that this modification -- known as m6A, in which a methyl group attaches to an RNA chain -- may occur at a different rate in females than it does in males, potentially explaining why females tend to have higher fat content in the liver. The researchers found that without the m6A modification, differences in liver fat content between the sexes were reduced dramatically.

In addition, in a preclinical model, the investigators demonstrated that gene therapy can be used to enhance or add modifications to key RNAs to slow down or reduce the severity of liver disease.

BACKGROUND

Fatty liver can develop when liver fat content increases due to dietary or genetic factors, potentially leading to advanced liver scarring and disease, as seen in cirrhosis and other conditions. High liver fat content is also associated with increased risk of cardiovascular disease.

In recent years, scientists have identified hundreds of chemical modifications like m6A that can occur in RNA molecules, altering the RNA's instructions for making proteins without affecting the core DNA. Some modifications can be beneficial, as in the case of liver disease; others can have a detrimental effect.

METHOD

Using a unique mouse model missing m6A RNA modifications in the liver and a control model that included the modifications, the authors compared the effects of diets with differing fat contents to assess the effects of the modifications on fatty liver disease. In addition, they used measurements from human patients who had undergone liver biopsies during bariatric surgery to correlate markers of m6A RNA modifications with liver fat content and inflammation.

IMPACT

A key question moving forward is how genetic and environmental factors affect the body's natural ability to create RNA modifications. Because m6A appears to act as a protective checkpoint that slows the accumulation of fat in the liver, the investigators hope their findings will spur future research on the development of therapies to enhance chemical modifications as a way to protect against liver disease and similar disorders.

WOODS HOLE, Mass. – What’s a hungry marine microbe to do when the pickings are slim? It must capture nutrients – nitrogen, phosphorus, or iron – to survive, yet in vast expanses of the ocean, nutrients are extremely scarce. And the stakes are high: Marine microbial communities drive many of the elemental cycles that sustain all life on Earth.

One ingenious solution to this challenge is reported this week in Proceedings of the National Academy of Sciences. In low-nutrient environments, marine microbes can clump together and hook up with even tinier cells that have vibrating, hairlike appendages (cilia) on their surface. The beating cilia create microcurrents that can pull up to 10 times more nutrients within the microbes’ reach – thereby serving up a meal through cooperative work.

Even if the ocean is wildly turbulent, microbes can piggyback into consortia for division of labor, says senior corresponding author John H. Costello of Providence College and the Marine Biological Laboratory (MBL), Woods Hole, where much of the research was conducted.

“For all conditions but the most radically extreme mixing, these microbial cells live in fluid spaces that are smaller than the eddies caused by ocean mixing,” Costello says. “In their world, the surrounding fluid is always viscous and they do not experience turbulent eddies as humans feel them.”

The team used a technology called Particle Image Velocimetry (PIV) to measure the direction and magnitude of fluid flows around a photosynthetic marine diatom, Coscinodiscus wailesii, with and without an attached ciliate “partner,” Pseudovorticella coscinodisci. They found that fluid flows generated by ciliary beating can increase nutrient flux to the diatom’s cell surface 4-10 times greater than fluxes to the diatom alone.

This cooperative solution is one way microbes can cope in low-nutrient environments. Another previously known tactic for individual cells is sinking to greater depths, which creates relative motion between the cell and surrounding water and increases its exposure to higher nutrient concentrations.

“Sinking might work well in low-nutrient conditions where mixing will recirculate the cells back up from the depths to the sunlit layers,” Costello says. “That way, the risk to the diatom of sinking might be countered by the probability of being returned to high-light environments. But in low-mixing conditions, forming consortia with ciliates could be a more favorable solution to low nutrient availability.”

Diatoms are among the most important groups of single-celled photosynthesizers for removing carbon dioxide from the atmosphere. Thus, the study helps to illuminate ocean-atmospheric exchanges that have become increasingly important for understanding climate change.

“We have described a collaborative solution – consortium formation – that has evolved on the microscopic scale to allow this large diatom species to successfully persist in low-nutrient waters that would otherwise appear to restrict its success,” Costello says.

COLUMBUS, Ohio - When COVID-19 hit, affluent Columbus residents responded by taking significantly fewer trips to large grocery and big-box stores, apparently ordering more online and stocking up when they did go out to shop.

With fewer options available to them, low-income people had to double down on what they had always done: regular trips to the local dollar stores and small groceries to get their family's food.

That's the conclusion of a new study that analyzed traffic to Columbus grocery sellers before, during and after the COVID-19 lockdown.

Dollar stores and small local grocers in neighborhoods housing mostly low-income people of color didn't see as much of a decline in customers during the lockdown as did large grocery and big-box stores, said Armita Kar, lead author of the study and a doctoral student in geography at The Ohio State University.

"Most low-income people still had to shop for groceries in person during the COVID lockdowns and may not have had the economic ability to stock up on food," Kar said.

"They took fewer trips to mid- and high-end grocery stores outside their neighborhood and continued to go regularly to the stores that were nearest to them, which were the dollar stores and local grocers."

The problems faced by poor people during the pandemic lockdown were not new, said study co-author Huyen Le, assistant professor of geography at Ohio State.

"COVID-19 exacerbated the existing problems of unequal access to food for low-income people," Le said.

The study was published online recently in the journal Applied Geography.

The researchers used anonymized and aggregated cell phone location data to analyze 2020 travel patterns to nearly all Columbus area grocery stores (393 in total) during pre-lockdown (Jan 6 - March 15), lockdown (March 16 - April 19) and initial reopening (April 20 - May 31).

The goal was to find out how different kinds of grocery stores were affected by the lockdown and how travel to stores differed between high- and low-income neighborhoods.

Results showed that mid- and high-end grocery stores and big-box food retailers in the city saw their in-person customer levels plunge when COVID-19 lockdowns began, presumably because their mostly affluent clientele could shop online and stock up on supplies, so they went to stores less often.

But dollar stores and smaller independent grocers, particularly in low-income neighborhoods and those housing people of color, saw only a small decline in their customer levels during the lockdown.

When the initial reopening occurred in April, the larger grocery stores and big-box retailers saw their customer numbers recover quickly - with an important caveat.

Most of the returning customers lived in the immediate area, results showed. Customers who used to come from longer distances - often from low-income neighborhoods - did not return in the same numbers, Kar said.

"We believe the transportation options for people in low-income neighborhoods were limited," she said. "Public transit was still less regular, and some may not have been able to combine work and shopping trips as they once did."

COVID-19 exposed many of the inequalities in our food system in a way that made them harder to ignore, said study co-author Harvey Miller, professor of geography and director of Ohio State's Center for Urban and Regional Analysis.

"The rich and poor were mostly shopping at different food stores before COVID-19, and those differences became even more stark when the lockdown came," Miller said.

And these results point to the need to support better food shopping options for low-income people living in food deserts, Le said, so they don't have to rely on dollar stores.

"Dollar stores mostly offer packaged and highly processed foods that aren't healthy," Le said.
"Policymakers should examine ways to provide better shopping options for people in low-income areas, so they have better access to healthy foods."

Prof. LI Chuanfeng, Prof. XU Jinshi and their colleagues from Prof. GUO Guangcan's group, University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS), realized the high-contrast readout and coherent manipulation of a single silicon carbide divacancy color center electron spin at room temperature for the first time in the world, in cooperation with Prof. Adam Gali, from the Wigner Research Centre for Physics in Hungary. This work was published in National Science Review on July 5, 2021.

Solid-state spin color centers are of utmost importance in many applications of quantum technologies, the outstanding one among which is the nitrogen-vacancy (NV) center in diamond. Since the detection of individual NV defect centers in diamond with room-temperature was reported in 1997, the NV centers in diamond have been applied to versatile fields, including quantum computing, quantum networking and quantum sensing.

Recently, to take advantage of more mature material processing and device integration technologies, researchers seek similar color centers in other semiconductor materials. Among them, the spin color centers in silicon carbide, including silicon vacancies (missing a silicon atom) and divacancies (missing a silicon atom and an adjacent carbon atom), have attracted broad interest due to excellent optical and spin properties.

However, the typical readout contrast via room-temperature coherent manipulation of the single silicon vacancy color centers is only 2%, and the photon count rate is also as low as 10 kilo counts per second. These shortages restrict the practical application of the coherent manipulation of the single silicon vacancy color centers at room temperature.

Researchers from USTC implanted defect color centers in SiC with their ion implantation technique [ACS Photonics 6, 1736-1743 (2019); PRL 124, 223601 (2020)] to manufacture a divacancy color center array. They achieved spin-coherent manipulation of the single divacancy color center at room temperature with the optically detected magnetic resonance (ODMR), at the same time, they found that one type of divacancy color centers (called PL6) had a 30% spin readout contrast, whose single-photon emission rate was up to 150 kilo counts per second.

These two important parameters are an order of magnitude higher than the silicon vacancy color center in SiC. For the first time, the spin color centers of SiC showed excellent properties comparable to the diamond NV color center at room temperature. Especially, the coherence time of the electron spin at room temperature was extended to 23 microseconds. Moreover, the research team also realized the coupling and detection of a single electron spin and a nearby nuclear spin in SiC color centers.

This work lays the foundation for building room-temperature solid-state quantum storage and scalable solid-state quantum networks which are based on the SiC spin color center system. It is essential for the next generation of hybrid quantum devices to integrate spin defects with a high readout contrast and a high photon count rate into high-performance SiC electron devices.

Oncotarget published "Ex vivo analysis of DNA repair targeting in extreme rare cutaneous apocrine sweat gland carcinoma" which reported a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population.

As PALB2 exhibits functions in the BRCA1/2-RAD51-dependent homologous DNA recombination repair pathway, we sought to use ex vivo functional screening to explore sensitivity of the tumor cells to therapeutic targeting of DNA repair.

Drug screening suggested sensitivity of the PALB2 deficient cells to BET-bromodomain inhibition, and modest sensitivity to DNA-PKi, ATRi, WEE1i and PARPi.

A phenotypic RNAi screen of 300 DNA repair genes was undertaken to assess DNA repair targeting in more detail.

RNAi inhibition of RAD52-dependent HR on the other hand potentiated the efficacy of a novel BETi ODM-207.

Together these Oncotarget results describe the first ever CAC case with a BRCAness genetic background, evaluate combinatorial DNA repair targeting, and provide a data resource for further analyses of DNA repair targeting in PALB2 deficient cancers.

Together these Oncotarget results describe the first ever CAC case with a BRCAness genetic background

Dr. Juha K. Rantala from The University of Sheffield as well as The Misvik Biology Oy said, "Metastatic cutaneous apocrine gland carcinoma (CAC) is an extreme rare malignancy arising from a sweat gland with "

The tumorigenesis of these rare cancers is largely unclear, but histologically cutaneous apocrine gland carcinomas mimic metastatic apocrine breast cancer or apocrine carcinomas arising in ectopic breast tissue.

Given the rarity of metastatic CAC tumors and the heterogeneity of the treatments used, the survival benefits of cytotoxic agents in treatment of metastatic CAC remains unclear, as does the use of targeted therapies, which have been reported for a few individual patients.

The authors used multiomics methods for ex vivo analysis of the patient derived tumor cells with the aim to inform the treatment of the patient after relapse following 9 previous treatment regimens.

Of these, two different BET-bromodomain inhibitors; JQ1 and ODM-207 were the most potent drugs with known DNA repair targeting mechanisms. To assess DNA repair pathways essential for the tumor cells and contributing to sensitivity/resistance of the tumor cells to BETi, we use ex vivo functional RNAi screening to discover biological insights on the different DNA repair pathways with the PALB2 deficient cells.

To extend the analysis beyond the patient derived cells, the authors go on to assess with publicly available drug screening data the correlation between efficacy of PARP inhibitors Olaparib, Talazoparib and BETi on 800 model cell lines divided to unaltered or PALB2 altered cell lines.

The Rantala Research Team concluded in their Oncotarget Research Outlet that although the efforts here ultimately did not result in successful treatment of the patient, the significance of this study is its demonstration that this type of functional ex vivo analyses if performed in the early stages of disease could provide valuable insights into treatment of rare cancers where there is limited data available to base treatment decisions on.

Their analyses of sensitivity of PALB2 deficient cancer cells to inhibition of the different DNA repair pathways also offer a valuable data resource for testing and building new hypothesis on.

In summary, by interrogating the patient-derived cells, they identify a potential therapeutic opportunity for targeting PALB2 deficient cells through inhibition of DNA repair with BETi or PARPi.

Moreover, they identify the PALB2 c.1592delT mutation as a potential susceptibility factor for non-melanoma skin cancer in the high cancer risk families carrying this founder mutation.

Tokyo, Japan - Researchers from Tokyo Metropolitan University have analyzed long-term precipitation radar data from satellites and found significantly enhanced rainfall over the most recent decade during the annual Meiyu-Baiu rainy season in East Asia. The data spans 23 years and gives unprecedented insight into how rainfall patterns have changed. They showed that the increased rainfall was driven by the decadal increased transport of moisture from the tropics and frequent occurrence of the upper tropospheric trough over the front.

From the second half of June to the first half of July every year, East Asia is subject to a particularly rainy spell known as the Meiyu (in China) or Baiu (in Japan) season or "plum rains," from the ripening of plums along the Yangtze River. They are triggered by the so-called Meiyu-Baiu front, where the flow of moist air around the Asian monsoon region meets anti-cyclonic flows around the rim of the western North Pacific subtropical high (WNPSH). Though they bring much needed water to the region, recently, it seems that the floods they trigger have taken a deadly turn, with widespread destruction; flooding in China and Japan in 2020 was particularly devastating. For scientists and policymakers, it is vital that this be put within the framework of a bigger picture: are these simply anomalies, or are they here to stay?

Though studied in much depth, the majority of studies use rainfall gauge measurements and observations of cloud activity around land. An overall picture of rainfall throughout the region was lacking, particularly analyses which spanned long periods of time. Now, a team led by Assistant Professor Hiroshi Takahashi have examined satellite data featuring radar measurements of precipitation. They combined two sets of data, the Tropical Rainfall Measuring Mission (TRMM) and the Global Precipitation Measurement Mission (GPM). The full set of data spans 23 years and covers both the sea and the land with equal precision. Through careful analysis of the time series, they confirmed a significant elevation in rainfall over the past decade. In particular, they showed that there has been a clear increase in the number of extreme precipitation events, the kind that can trigger natural disasters.

The question is why it has changed. The team focused on two aspects of the development of rainfall, the transport of moisture and changes in the flow of air in the upper troposphere. Firstly, they showed that there has been increased transport of water vapor along the rim of the WNPSH, largely due to decreased tropical cyclone activity, a trend seen both in decade-to-decade comparisons and the devastating season of 2020. Furthermore, they showed there were anomalous circulations in the upper troposphere, creating a "trough" that drove air upwards around the western edge of the Meiyu-Baiu front, strongly correlated with enhanced rainfall.

Through a full analysis of data encompassing a far larger area and a longer time span than before, the team's findings put the recent changes in the Meiyu-Baiu season in East Asia within the framework of a globally changing climate. They hope that new standards for average rainfall are reflected in new standards of disaster prevention.

Researchers at UC San Francisco are zeroing in on how the immune system may play a role in miscarriage, which affects about a quarter of pregnancies.

Working in mice, the researchers have found that a recently discovered subset of cells in the immune system may prevent the mother's immune system from attacking the placenta and fetus. If the research is confirmed in further animal studies, and the cells play a similar role in people, they could point the way toward new therapies for pregnancies that are threatened by defects in immune tolerance.

The researchers showed that pregnant mice who did not have this subset of cells, known as extrathymic Aire-expressing cells, were twice as likely to miscarry, and in many of these pregnancies fetal growth was severely restricted.

"When you're pregnant, the immune system is seeing the placenta for the first time in decades - not since the mother made a placenta when she herself was a fetus," said Eva Gillis-Buck, MD, a UCSF surgery resident and first author of the paper in Science Immunology.

"Our research suggests that this subset of immune cells is carrying out a sort of 'secondary education' - sometimes many years after the better-known population of the educator cells have carried out the primary education in the thymus - teaching T cells not to attack the fetus, the placenta and other tissues involved in pregnancy."

The immune system has to be educated not to attack one's own tissues and organs to prevent autoimmune disease. But pregnancy presents a unique challenge, since the fetus expresses proteins found in the placenta as well as proteins whose genetics are distinct from the mother.

"It was a conceptual leap to link Aire-expressing cells, which are critical for preventing autoimmune disease, to pregnancy," said Tippi Mackenzie, MD, professor of surgery and Co-director of the UCSF Center for Maternal Fetal Precision Medicine and a senior author of the paper. "This work hints at a mechanism for the known association between autoimmune disease and pregnancy complications."

Like the better-known educator cells in the thymus, the rare subset - originally discovered by James Gardner, MD, PhD, an assistant professor of surgery, investigator in the UCSF Diabetes Center, and a senior author of the study - is known for their ability to express a unique protein called the Autoimmune Regulator, or Aire. Aire has been extensively studied in the thymus, where it helps define the curriculum of this "high school" for the immune system.

But the Aire-expressing cells under study reside outside the thymus in the lymph nodes and spleen, so they are called extrathymic Aire-expressing cells, or eTACs. Their role in the immune system is not fully known, although the UCSF scientists suspect they provide a mechanism for "continuing education."

The pregnancy finding is the first evidence that eTACs play a role in the maintenance of normal immune tolerance. In the thymus, Aire-expressing cells begin interacting with other immune cells very early in life to teach them what not to attack. The thymus begins to shrink and is nearly gone by adulthood, by which time most immune cells have been educated.

But as the thymus shrinks, the population of eTACs in lymph nodes and the spleen expands. The study suggests a healthy pregnancy may depend on having these cells around.

To tease apart the normal role of this outlier population of Aire-expressing cells, the researchers used genetically engineered mice from the Gardner lab to delete eTACs selectively during pregnancy.

"Understanding how the immune system normally gets educated to distinguish 'self' from 'non-self' is a very fundamental problem in biology," Gardner said. "Once we know the basic wiring of this self-education system, we hope to do all kinds of powerful things - like modify the curriculum to improve pregnancy outcomes, prevent autoimmunity, or promote tolerance of transplanted organs."

Great leaps in science and technology have been propelled by recent advances in seeing fast evolving physical phenomena, as they happen. Femtosecond lasers from the infrared to the X-ray region have enabled us to 'watch', in real time, atoms dance in molecules and solids on femtosecond and picosecond timescales. Watching such fascinating motions not just in real time but at the spatial locations where they happen, is a bigger challenge.

It is precisely this advance that has been made by a team of researchers at the Tata Institute of Fundamental Research, Mumbai, York University and the Rutherford Appleton Laboratories, UK [1]. They exploded a solid surface with an ultrahigh intensity (10^19 W/sq.cm), 25 femtosecond laser pulse (pump) creating a hot, dense plasma and monitored its ultra-rapid motion by reflecting a weak second femtosecond pulse (probe). The Doppler shifts in the wavelength imposed on the reflected probe pulse by the fast evolving plasma give away the outward (blue shift) and inward (red shift) motions of the plasma.

No previous study captured the motion on the entire plasma surface -- the 'dance floor' -- in a single experiment. This team coupled femtosecond time resolution with micrometre space resolution, thereby capturing the ultra-rapid twists and turns of the plasma at different transverse locations.

The experiments devised a novel 2-D Doppler monitor with sixteen independent, single shot, high resolution spectrometers all triggered by the pump laser pulse and capturing the instantaneous velocity of the plasma at different spatial locations. They show that different portions of the plasma move in and out at different times, contrary to the usual expectation of a somewhat uniform motion. This new method can prove very useful for tracking the flow of heat and energy along the surface and watching the growth of plasma instabilities, very important for understanding laser plasma science and pushing forward applications of high intensity, femtosecond laser driven laser plasmas in imaging and laser fusion.

The team's findings, with important implications for ocean biogeochemistry and climate science, have been published by Nature Communications in a paper by Associate Professor Mark Holzer from UNSW Science's School of Mathematics & Statistics, with co-authors Tim DeVries (UCSB) and Casimir de Lavergne (LOCEAN).

"The deep North Pacific is a vast reservoir of remineralized nutrients and respired carbon that have accumulated over centuries," says A/Prof. Holzer. "When these deep waters are returned to the surface, their nutrients support biological production and their dissolved CO2 can be released into the atmosphere. As such, the deep Pacific plays a key role in the earth's climate system."

But what are the pathways of the ocean circulation that supply newly ventilated surface water to the deep Pacific? And how and where does this old water eventually return to the surface? To date, there were two competing theories for the role that the overturning circulation plays in this.

One theory - the 'standard conveyor' - envisions broad overturning with Antarctic Bottom Water upwelling to around 1.5 km depth before flowing back south to the Southern Ocean. The other theory - the 'shadowed conveyor' - argues that the overturning is compressed to lie below about 2.5 km with a largely stagnant "shadow zone" above it.

"Our work reconciles these two theories: the shadowed conveyor correctly captures vertically compressed overturning beneath a shadow zone, while the standard view must be broadly interpreted in terms of water paths diffusing through the shadow zone. Because the shadow zone is largely shielded from the overturning circulation the question becomes how exactly does water get into and out of it," A/Prof. Holzer says.

Using novel mathematical analyses applied to a state-of-the-art ocean circulation model that optimally fits the circulation to observed tracer distributions and surface forcings, the authors were able to quantify in detail the pathways and timescales with which the shadow zone exchanges water with the surface ocean.

"Our analyses allowed us to come up with a new schematic of the large-scale deep circulation in the Pacific. We find that diffusive transport both along and across density surfaces plays a leading role in ventilating the shadow zone."

Contrary to the widely held view that Pacific deep waters exclusively follow density surfaces to upwell in the Southern Ocean, the authors found that only about half of the water in the shadow zone follows this route, with the other half returning to the surface in low latitudes and in the subarctic Pacific, helping to explain the high biological production there.

The scientists say this new understanding of the deep Pacific circulation and transport pathways will help interpret observed tracer distributions and biogeochemical processes.

"An exciting direction for future research is to understand how the shadow zone, already low in oxygen and sensitive to increased oxygen demand, shapes the response of the ocean's biological pump to climate change," A/Prof. Holzer says.

Central nervous system (CNS) diseases such as Alzheimer's disease (AD) manifest early at the microscopic (i.e. cellular) level, deep in the brain. Yet, optical microscopes that can see cells in the living brain are superficial or invasive. Whole brain imaging techniques such as magnetic resonance imaging are deep and non-invasive, but lack cellular resolution.

In a new paper published in Light Science & Application, a team of scientists, led by Professor Vivek J. Srinivasan from the Departments of Ophthalmology and Radiology and Tech4Health Institute, NYU Langone Health, USA, and co-workers have developed a label-free optical microscopy approach that has a unique ability to image deep, with high resolution and minimal invasiveness. Specifically, they demonstrated an in vivo high numerical aperture optical coherence microscopy (OCM) approach that utilizes the 1700 nm water absorption window, where attenuation of light by scattering and absorption is minimized.

The 1700 nm water absorption window, also known as the third near-infrared (NIR) window, boasts a local water absorption minimum and relatively low scattering. In OCM, a broader spectrum provides a finer axial resolution, and with it, a stronger ability to reject multiply scattered light that causes image blur. Yet the entire 1700 nm window, which spans from 1560 to 1820 nm, is often not used:

"The transition from standard wavelengths to 1700 nm OCM, while optimally using the entire water absorption window (not just a portion of the window), has been very difficult to date due to the numerous optical engineering challenges." the scientists mentioned.

These challenges include noisy detectors and light sources, severe chromatic dispersion, and lack of standardized optical components. The scientists addressed these issues through the choice of a low noise supercontinuum light source, a custom numerical dispersion compensation method, and optical system design. With these technical advances, neuronal cell and myelin architecture across the entire depth of the mouse neocortex, and some sub-cortical regions, can be imaged through a thinned-skull preparation that preserves intracranial space.

"The results represent unprecedented depths for cellular-scale brain imaging through a minimally invasive preparation. We next investigated the 5xFAD mouse model of Alzheimer's disease (AD), which is expected to show a gradation of pathology with cortical depth. The imaging results confirmed the appearance of severe pathology in deep but not superficial cortex, which would be missed by more superficial imaging techniques."

Another important feature of the method is that the image contrast arises from intrinsic properties of the brain itself. OCM does not require transgenic mice or administration of compounds. Neuronal cell body loss, demyelination of axons, plaques, and local tissue changes can all be imaged.

"Now disease can be visualized deep in the mouse brain with a simple surgical preparation, without exogenous labeling. The 1700 nm optical window can also quantify tissue water and lipid content in vivo, which may provide further insights into disease progression." the scientists forecast.

Shizuoka, Japan - At Shikine Island, Japan, kelp forests and abalone fisheries were once common, but over the last twenty years they have disappeared. Now, researchers from Japan have discovered that these temperate coastal marine ecosystems are becoming more "simple", losing biodiversity, complexity and their aesthetic values.

In a study published this month, researchers from the University of Tsukuba and international collaborators explored how the combined effects of ocean warming and acidification are changing temperate coastal marine ecosystems.

Tropical coastal seas are synonymous with coral reefs. As ocean temperatures cool toward the poles, corals give way to kelp as the main habitat-forming species. The shift from coral to kelp can clearly be seen along the 2000 km coastline of Japan, and changes to these ecosystems are already underway.

"Kelp forests are being lost globally as a result of warmer sea surface temperatures and heatwaves," says lead author, Dr Sylvain Agostini. "In Japan, this "isoyake", or "burnt seashore", is widespread. As ocean temperatures continue to increase, warm water corals are shifting northward into temperate reefs and could replace cold-water species."

There are three possible scenarios as coastal species shift. Temperate reefs could become more tropicalized and dominated by warm water corals, fishes, and other species. Alternatively, reefs may become dominated by tropical seaweeds or turf algae.

But another effect of increasing greenhouse gas emissions--ocean acidification--complicates matters. Acidification reduces the amount of carbonate in the ocean, which is needed by reef-building corals to create their structure. Decreases in carbonate ion concentrations could limit the colonization of new areas by fast-growing coral species.

To examine possible changes along the coast of Japan, the team used three locations at a similar latitude that represent three different scenarios (present, ocean warming, and ocean warming plus acidification). They examined the existing communities, and then transplanted kelp and coral species and measured their growth and survival at the different sites.

The team found that with both ocean warming and acidification, coastal ecosystems are likely to lose kelp forests but may not gain reef-building corals. The result is a simplified turf-dominated habitat.

"Warmer waters facilitate the growth and colonization of reef-building corals," explains Dr Ben Harvey. "But ocean acidification appears to negate these benefits. And kelp transplants did not survive in warmer waters, largely because they were eaten by warm water fishes."

"The consequences of these changes is that warm temperate coastal waters are facing major simplification which is clearly seen in the degradation of the seascape" as noted and documented by Prof. Nicolas Floc'h, co-author of the study and artist at the Ecole Européenne Supérieure d'Art de Bretagne. Lost kelp forests are likely to be replaced by simpler turf-dominated communities that provide a fraction of the ecosystem services of more biodiverse tropical reefs. Overall, the results highlight the urgent need for control of carbon emissions and limit the drivers of ocean change.

From the vocal cords that produce our voice, to our heartbeat, our body's cells are constantly subjected to mechanical forces that steadily change their response to these stimuli, regulating vital processes, in healthy individuals and in diseases such as cancer alike. Nevertheless, despite their importance, we remain largely ignorant of how cells sense and respond to these forces.

Now, an international team co-led by the researcher Pere Roca-Cusachs, from the Institute for Bioengineering of Catalonia (IBEC), and Isaac Almendros, a researcher at the Respiratory Diseases Networking Biomedical Research Centre (CIBERES) and IDIBAPS, both professors at the Faculty of Medicine and Health Sciences of the University of Barcelona (UB), has proved that what determines mechanical sensitivity in cells is the rate at which the force is applied, in other words, how fast the force is applied. The paper has been published in the prestigious journal Nature Communications and shows, for the first time in vivo, the predictions of the "molecular clutch" model.

These results open the door to a better understanding of how a cancerous tumour proliferates, as well as how the heart, the vocal cords or the respiratory system respond to the constant variation of forces to which they are repeatedly exposed.

A constant cellular "push and pull":

The researchers observed that there are two responses to the force applied to a cell, using state-of-the-art techniques such as Atomic Force Microscopy (AFM) or so-called "optical tweezers".

On the one hand, the cytoskeleton, the dense network of fibres (mainly actin), which has, among others, the function of maintaining the shape and structure of the cell, is reinforced when the cell is subjected to a moderate force. In this regard, the cell is able to sense and respond to mechanical force, and the reinforcement of the cytoskeleton leads to a stiffening of the cell, and the localisation of the YAP protein in the nucleus. When this occurs, the YAP protein controls and activates genes related to cancer development.

On the other hand, if the rate of force applied is repeatedly applied above a certain value, a reverse effect occurs; the cell no longer senses the mechanical forces. In other words, instead of the cytoskeleton and the cell becoming more rigid, a partial breakdown of the cytoskeleton occurs, leading to a softening of the cell.

"Like stretching and shrinking chewing gum, we have subjected cells to different forces in a controlled and precise manner, and we have seen that the rate at which the force is applied is of the utmost importance in determining the cellular response", explains Ion Andreu (IBEC), co-lead author of the study.

A model corroborated by in vivo experiments:

To understand how the reinforcement and softening effects of the cytoskeleton are related, the researchers developed a computational model that considers the effect of the progressive application of force on the cytoskeleton and the "couplings" (proteins involved in binding the cell to the substrate, such as talin and integrin). These "couplings" are somewhat akin to the effect of the clutch of a car, in tightening the mechanical connection between the engine and the wheels, which is why the model is known as the "molecular clutch".

Next, the scientists performed experiments on laboratory rats to prove that the results observed in single cells also occur in in-vivo whole organs. To do so, the researchers studied the lungs, which naturally undergo cyclical mechanical stretching during breathing. Specifically, the two lungs were ventilated at different rates, with one lung filling and emptying faster (hyperventilation) and the other more slowly, while maintaining a normal total ventilation rate.

After analysing and comparing cells from both lungs, they observed that the YAP protein increased its nuclear localisation only in cells from the lung subjected to hyperventilation. This increase in YAP in in-vivo samples, caused by the "cellular tug-of-war", was akin to that found in proliferating cancer tumours.

"Our results demonstrate, at organ level, the role of force application rate in the transduction of the ventilation-induced mechanical signal in the lungs", states Bryan Falcones (IBEC-UB), co-lead author of the study.

The paper sets out a mechanism by which cells respond, not only to direct forces, but also to other passive mechanical stimuli, such as the stiffness of the substrate on which they are located. The results give an insight into understanding how a priori opposite phenomena, such as reinforcing and softening of the cytoskeleton, can go hand in hand with controlling cell mechanics and respond specifically to different situations.

The article represents the transmission electron microscopy (TEM) and flow cytometry study of A-549 (human lung carcinoma) cellular uptake of Pr3+:LaF3 nanoparticles. The Pr3+:LaF3 nanoparticles are promising platforms for cell nano-sensors.

The objective of the work was to study the influence of nanoparticle morphology (nanoplates and nanospheres) on cytotoxicity and the dynamic of cellular uptake.

In the flow cytometry method, the cells go through a small tube (as a flow) and are irradiated by a laser. Cells scatter the laser light, and this scattering efficiency can give new information about some processes inside the cell. TEM method allows visualizing the cells with 0.2 nm (10-9 m) spatial resolution.

Both nanoplates and nanospheres are easily internalized by A-549 cells via macropinocytosis after 2, 10, and 24 hours of nanoparticle exposure. The nanoparticles were not observed in cell nuclei and other organelles. During macropinocytosis, relatively large vesicles (0.2-5 μm) are formed. The flow cytometry experiments revealed that the internalized nanoparticles increase the cells' optical inhomogeneity, which leads to an increase of side scattered light intensity by ~10% without any dynamic during 24 hours (for both morphotypes of nanoparticles). Probably, it can be explained by the fact that macropinocytosis is a dynamic process and some macropinosomes appear and move in the cytoplasm; in turn, other macropinosomes travel back to the cell surface of the membrane and release the content to the extracellular space; consequently, the equilibrium is achieved.

Finally, nanoplates and nanospheres have low tocixity and are easily internalized by cells. These facts pave the way toward creating nano-sensors for cells.

The luminescence of Pr3+:LaF3 nanoparticles (spectral shape) depends on the temperature in the physiological temperature range (20 to 60ºC). This fact, as well as nanosized dimensionality of Pr3+:LaF3 pave the way toward temperature sensing at cell level with spatial resolution less than one micrometer. Such temperature sensors are important in fundamental biology and pharmaceuticals. These sensors allow studying thermodynamic cell responses on external factors (drugs and physical conditions). This information is very important for pre-clinical studies of drugs.

For further development of the research, the authors plan to provide the targeted orientation of the nanoparticles to a specific cell organelle. This property can be achieved by creating a special bio-compatible shell around the Pr3+:LaF3 nanoparticle. This shell should contain special organic molecules which provide attachment to the specific cell organelle. There is also a plan to obtain a temperature map of the whole cell in the microscope.