New research from Cornell University and Rensselaer Polytechnic Institute shows a continually warming world is leading to extended, late-summer weeks of water stratification, which prompts oxygen deprivation in the water — provoking conditions called hypoxia (low oxygen) and anoxia (no oxygen) — and negative consequences for fish and other species.

The work published Dec. 6 in the journal Global Change Biology.

“Lakes with dissolved oxygen losses strongly outnumber those with gains,” said lead author Stephen Jane, a postdoctoral fellow at the Cornell Atkinson Center for Sustainability. “At large scales, aerobic organisms are losing available habitat as warming of lakes continues. This is particularly the case for organisms that rely on well-oxygenated cool waters deep in lakes to survive warm periods.”

Jane and his colleagues examined about 25 years of data available for more than 400 lakes — mostly from the United States — to identify dissolved oxygen loss. In addition to Rondaxe Lake, the group studied New York’s Neversink (Sullivan County) and Cannonsville (Delaware County) reservoirs, and Jockeybush and Sagamore lakes (Hamilton County).

In temperate climate lakes, the researchers found that the amount of low oxygen water is increasing by 0.9% to 1.7% per decade on average and found that the volume of lake water lacking oxygen has increased by more than 50% from three decades ago.

Reducing oxygen in lake water can have many effects. For example, anoxic portions of the water column might see a buildup of methane — a powerful greenhouse gas. Nutrients such as phosphorus from agricultural fertilizer, released from unsettled lake sediment, may enter the water column, which increases the likelihood of harmful algal blooms.

In a typical July or August, a lake surface may be about 70 degrees, while the lake bottom may be around 40 degrees. “Water temperature and density are related,” Jane said. “So it becomes a situation where basically you have oil and vinegar, where strong water temperature differences between layers causes resistance to mixing — which is stratification.”

The result is that oxygen from the atmosphere is prevented from replenishing dissolved oxygen in deep waters, Jane said. Because winter ends sooner than it did decades ago, seasonal stratification is starting earlier and ending later.

These stratification changes lead to more time for deoxygenation — the interruption of the natural oxygenation process — for deep-water habitats, he said.

“We show here that as warming is continuing, the amount of time that lakes exhibit stratification is increasing and this leads to increases in the amount of low-oxygen water in lakes,” said co-author Kevin Rose, associate professor at Rensselaer Polytechnic Institute, Troy, New York. “The bad news is that given projected warming rates, we’ll likely see even greater increases in the amount of oxygen-depleted water in lakes in the future.”

Funding was provided by the National Science Foundation and by Cornell Atkinson.

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Materials provided by Cornell University. Original written by Blaine Friedlander, courtesy of the Cornell Chronicle. Note: Content may be edited for style and length.

Anyone who has ever sent a voice message with a cell phone knows how much the volume matters: Shouting into the microphone results in a distorted and unclear recording. But whispering is not a good idea either — then the result is too quiet and also difficult to understand. That is why sound engineers ensure the perfect sound at every concert and talk show: They regulate each microphone’s gain to match the input signal.

The neurons in the brain can also fine-tune their sensitivity, and even do so autonomously. A new study led by the University of Bonn and the University Hospital Bonn shows how they do this. For this purpose, the participants investigated nerve cell networks that also play a role in vision, hearing and touch. The stimulus first travels to the so-called thalamus, a structure deep in the center of the brain. From there, it is then conducted to the cerebral cortex, where it is further processed.

Each neuron adjusts itself

“The neurons in the cerebral cortex are stimulated by the signals from the thalamus to generate action potentials,” explains Prof. Dr. Heinz Beck from the Institute of Experimental Epileptology and Cognition Research at the University Hospital Bonn. “These are short voltage pulses that are then transmitted to other sites in the brain. For that to work well, the neurons have to adjust to the intensity of the excitatory signals.”

For example, they need to dial down their sensitivity if the incoming stimuli were very strong. “We have now discovered that a specific enzyme called SLK plays a role in this process,” says Beck, who is also spokesperson for the Transdisciplinary Research Area “Life and Health” at the University of Bonn. “It enables neurons to individually calibrate their own excitability.” Which is somewhat like having no sound engineer: Instead, the microphones would automatically adjust their sensitivity so that the recording is neither too quiet nor overamplified.

“In this mechanism, special nerve cells play an essential role, the so-called interneurons,” explains Dr. Pedro Royero from Beck’s research group. He earned his doctorate with this study in the Max Planck International Graduate School and performed most of the experiments. Interneurons send inhibitory action potentials to excited neurons. In a way, they turn the knob that reduces their sensitivity. “The SLK now determines how much this regulator can be adjusted by the interneurons, that is, how strong their inhibitory effect is.”

There are two different types of interneurons. Some are activated directly by incoming impulses from the thalamus. They already inhibit the neurons while these are simultaneously excited by the thalamus. Another type, in contrast, is only switched on by the activity of the neurons in the cerebral cortex — i.e. the very neurons they are supposed to inhibit afterwards. So they are part of a negative feedback loop. “Interestingly, the SLK is not active in this feedback inhibition, but only in the first case,” Royero points out.

New insights into the development of diseases

The researchers were also able to show that certain genes are activated during sensitivity adjustment. They now want to investigate their role in the process in more detail. This is also interesting because the balance between excitation and inhibition is extremely important for brain function. This can be seen, for example, in epilepsy: The characteristic seizures result from overexcitation of large areas of nerve cells. In fact, studies show that in some epilepsy patients, less SLK is found in neurons than normal. Perhaps the study will therefore also contribute to a better understanding of the disease mechanisms.

Participating institutions and funding:

In addition to the University of Bonn and the University Hospital Bonn, the German Center for Neurodegenerative Diseases (DZNE), the Max Planck Institute for Behavioral Neurobiology — caesar and the University of Sidney were involved in the work. The study was funded by the German Research Foundation (DFG), the European Research Council (ERC) and the Bonfor Fellowship Program of the University Hospital Bonn.

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A team of researchers led by Dr. Yasutaka Kakui from Waseda Institute for Advanced Study, Waseda University; Frank Uhlmann at the Chromosome Segregation Laboratory, The Francis Crick Institute; and Toru Hirota, from the Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, set out to decode this enigma.

How did it all start? For Kakui, it was his fascination for chromosomes that motivated him to take up this research. “How is genomic DNA stored within cells? This is an ancient, unsolved question. To expand our knowledge of how cells accurately pass on genetic information to successive generations, we need to understand the molecular basis for chromosome formation.” And that is what drove this study, the findings of which have been published in Cell Reports.

During mitosis, DNA undergoes significant compaction to form chromosomes. A large protein ring complex called condensin plays a key role in the compaction process. It binds at specific sites on DNA and compresses it by forming loops. So, scientists know that condensin is crucial for DNA compaction, which is closely related to chromosomal dimensions — with thicker chromosomes being more compacted. They also know that the pattern of condensin-binding sites is species-specific. But the exact role of condensin and chromatin contacts in determining chromosomal dimensions is, as yet, unclear.

The researchers explored various facets of condensin and chromatin contacts to address the questions at hand. They employed Hi-C and super-resolution microscopy to analyze the correlation between mitotic chromatin contacts and chromosomal arm length in both budding and fission yeasts, S. cerevisiae and S. pombe, respectively. Conclusive evidence was found indicating that the distance between chromatin contacts is directly proportional to arm length in both interphase and mitosis. Hence, shorter arms have short range contacts and longer arms have long range contacts. This was found to be species-specific.

Now, longer distances of chromatin contacts lead to larger chromatin loops, both of which are indicators of wider chromosomal arms. The authors thus investigated both budding and fission yeasts to conclude that within a species, longer chromosomal arms were always wider. Motivated by the successful observation in the yeasts, they extended their study to human cells, to find the same correlations. “We made the unexpected discovery that longer chromosomal arms are always thicker throughout eukaryotic species, which helps us understand how mitotic chromosomes form during cell divisions,” explains Kakui. Their study would be the first to conclusively establish that chromosomal arm length determines mitotic chromosome width.

This study has provided unique insights into mitotic chromosomal structure that challenge the current perspectives on mitotic chromosome formation. Kakui summarizes, “Our findings would open a novel way to avoid chromosome miscarriage, a probable cause for the formation of cancer cells and/or birth defects such as Down syndrome, through controlling mitotic chromosome structure. This can potentially change medical treatments for cancer therapy and/or fertility treatments.”

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Now, studying mice with an autoimmune disease similar to multiple sclerosis (MS), researchers at Washington University School of Medicine in St. Louis have shown that the same approach can be used to eliminate unwanted cells that cause autoimmunity. The findings, available online in Science Immunology, extend the powerful tool of immunotherapy to a class of diseases that are often debilitating and difficult to treat.

“We were able to use CAR-T cells to eliminate just the immune cells that are causing the autoimmunity and not other immune cells you might need to protect against viruses or other infection,” said co-senior author Chyi-Song Hsieh, MD, PhD, the Alan A. and Edith L. Wolff Professor of Rheumatology and a professor of medicine and of pathology & immunology. “Our CAR-T cells were very effective at treating mice that have an MS-like disease.”

At the heart of CAR-T therapy are the immune system’s T cells, crucial elements of the body’s defense force. T cells respond to threats such as bacteria, viruses and cancerous cells by coordinating an immune assault and killing foreign organisms and infected or cancerous cells.

But every once in a while, T cells mistake healthy cells for infected cells and turn their weapons on the body’s own cells and tissues, triggering an autoimmune disease. MS is marked by rogue T cells that trigger the destruction of myelin, the protective covering over nerves. As myelin is eaten away, communication between the brain and spinal cord and the rest of the body becomes unreliable, and people begin experiencing symptoms such as fatigue, pain, tingling, vision problems and loss of coordination. Immunosuppressive drugs can quash the self-destructive activity of rogue T cells, but such drugs also suppress helpful T cells and put people at risk of severe infections.

In CAR-T cancer therapies, doctors take a patient’s own T cells, modify them to recognize and vigorously attack his or her specific cancer, and then put them back in the body on a seek-and-destroy mission. Inspired by this approach, the researchers set out to create CAR-T cells equipped to seek out and destroy the rogue T cells that cause MS. The idea was to make CAR-T cells that would function akin to a police department’s internal affairs office, rooting out the bad apples in the T cells defense force while leaving good T cells in place to protect the body.

“Having MS can really erode your quality of life, and while current therapies slow down the course of the disease, they don’t cure it and they have side effects,” said co-senior author Gregory F. Wu, MD, PhD, an associate professor of neurology and of pathology & immunology. “I believe that this is a fully treatable disease, and CAR-T cells may be the way toward much better therapeutics.”

Along with Hsieh and Wu, the research team included co-authors Nathan Singh, MD, an assistant professor of medicine, and Takeshi Egawa, MD, PhD, an associate professor of pathology & immunology.

First, the researchers made some bait. They designed a molecule by combining a fragment of a protein found in myelin with a protein that activates T cells. Only T cells that target myelin — the bad apples, so to speak — would respond to this hybrid molecule. Then, they loaded the bait molecule onto a kind of T cell known as killer T cells. Any rogue T cells that took the bait would be eliminated by the killer T cells.

That was the idea, at least. To see whether it worked, the researchers turned to mice with an MS-like condition. Treating such mice with the engineered CAR-T cells prevented disease in those that had yet to develop problems, and reduced signs of disease in those that were already showing neurological effects.

“We’re working on improving the CAR-T cells, to get them to kill more efficiently and last longer so that we can get better treatment outcomes,” Hsieh said. “Right now, there’s no way to tell who is going to get MS or when, so preventing disease in people isn’t realistic, but we could treat it, and I think the CAR-T approach looks very promising.”

The beauty of the CAR-T approach is that by swapping out the protein fragment in the bait molecule, killer T cells can be redirected toward different rogue immune cells to treat different diseases.

“I see patients in the clinic who have a rare disease known as myelin oligodendrocyte glycoprotein (MOG) antibody disease that is very similar to MS,” Wu said. “Unlike MS, which is complicated, we know exactly what the target is in MOG antibody disease. I wish I could just get rid of these self-reactive cells for my patients, but we’ve had no way to do that. Now, we are working toward using the patient’s own immune cells to create CAR-T cells that would eliminate those self-reactive T cells.”

A new study by scientists at University of California — Berkeley, has found that 39 out of 43 coastal airports in California have assets exposed to projected flooding that could disrupt their operations in the next 20 to 40 years. Sarah Lindbergh of University of California, Berkeley, will present her team’s findings during the Society for Risk Analysis Annual Meeting, Dec. 4-8 in Tampa, Florida.

Lindbergh and her colleagues at UC Berkeley conducted a statewide assessment of California’s airport infrastructure exposure to projected coastal flooding (from storm surge and sea-level rise) up to the year 2100. Their research combines a novel coastal flooding exposure assessment of the airports with a policy review of more than 100 state legislature and planning documents to address the importance of collaborative climate adaptation.

The flooding exposure assessment is the first of its kind, using geospatial tools to look beyond each airport’s perimeter to include its entire interconnected infrastructure — including road access, ground-based navigation, and communications systems. “It’s important to recognize that critical assets for airport operations may lie outside airport boundaries,” explains Lindbergh.

The analysis indicates that 39 out of 43 public coastal California airports have assets exposed to coastal flooding by 2100. (This number is much higher than traditional risk assessments that have only considered assets within an airport’s perimeters.) “Although we do not know how these newly identified exposures translate into impact,” says Lindbergh, “we were surprised to see that most of the airport assets could see a flooding event sooner than 2100 — in the next 20 years.”

Sixteen of the 39 airports have assets exposed within their boundaries (i.e. runways and taxiways), while the remaining 23 have assets outside of their jurisdiction that are at risk from flooding (such as road access to the airport and navigation systems). The list includes Los Angeles International Airport (LAX), ranked among the top five busiest airports in the world.

The researchers also examined how airport assets exposed to flooding transfer risks to nine of the state’s key multimodal, interregional transportation corridors (which include connected highways and railways). The ripple effects on the transportation of both goods and people could include delays, congestion, and cancellations. Their report identifies critical airports within these corridors to be prioritized for adaptation, particularly those within the San Francisco Bay — Central Valley — Los Angeles corridor (such as San Francisco International Airport and Oakland International Airport) and also Murray Field Airport in Eureka within the San Francisco Bay — North Coast transportation corridor.

The team’s state policy review revealed that market and regulatory incentives for airport infrastructure (maintenance, upgrade, and replacement) are mostly bound to an airport’s perimeters. This limits the ability for diverse infrastructure stakeholders to understand and act on their collective exposure to hazards such as coastal flooding. “Most policies are still being designed to mitigate risk and promote adaptation at the single asset level — for example, one airport at a time,” says Lindbergh.

She and her colleagues argue that measuring the exposure of interconnected infrastructure can help direct state-level policies that promote collaborative climate adaptation plans. “Our study pushes people to think beyond their boundaries and jurisdictions,” says Lindbergh.

Her presentation, “Cross-sectoral and multiscalar exposure assessment to advance climate adaptation policy: the case of future coastal flooding of California’s airports” on Monday, December 5th at 3:30 is part of a session on “Risk from Extreme Storm Events.”

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