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Molecular mechanisms of insulin resistance

1. Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kDa (insulin receptor substrate 1 or IRS-1). IRS-1 fulfills the criteria of a direct substrate of the insulin receptor, and tyrosine phosphorylation of IRS-1 leads to another step in insulin action, i.e., an association of phosphorylated IRS-1 with the enzyme PI3-kinase activating this enzyme. Using antipeptide antibodies to insulin receptor, to IRS-1 and to PI 3-kinase together with anti-phosphotyrosine antibodies it is possible to study insulin-stimulated insulin receptor phosphorylation, IRS-1 phosphorylation and the association/activation of IRS-1/PI 3-kinase. 2. In this review we describe alterations in these three early steps of insulin action after binding in animal models of insulin resistance, i.e., streptozotocin-induced diabetes (STZ diabetes), fasting, spontaneously hypertensive rats, the ob/ob mice, dexamethasone-treated rats, and the chronic effect of insulin on Fao cells in culture. 3. In states of insulin resistance with hypoinsulinemia (STZ diabetes and fasting) there is an increase in these early steps of insulin action. In animal models of insulin resistance with hyperinsulinemia there is a decrease in these steps of insulin action, indicating molecular post-receptor defects. Since we could reproduce the decrease in these three early steps of insulin action in cells in culture by chronic treatment with insulin, we postulate that these defects may be a consequence of the hyperinsulinemia of these animals.

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Targeted Remediation of the Ipsilesional Arm in Chronic Stroke: A Randomized Clinical Trial

Among patients with chronic stroke and severe contralesional impairment, targeted ipsilesional arm training supported significant and sustained improvements in ipsilesional motor performance vs best practice therapy.

Importance Ipsilesional upper-limb motor deficits after stroke are functionally important yet largely neglected in rehabilitation. Remediation may improve motor outcomes in individuals with severe contralesional arm hemiparesis.

Objective To determine whether training of the ipsilesional arm improves motor performance in chronic stroke with severe contralesional impairment and significant ipsilesional arm motor deficits.

Design, Setting, and Participants This 2-site, parallel-group randomized clinical trial with blinded outcome assessment was conducted from February 2019 to August 2024, with follow-up through 6 months posttreatment. Data analysis was performed from August 2024 through August 2025. The trial was conducted at outpatient research laboratories at Penn State College of Medicine and the University of Southern California among adults with radiologically confirmed unilateral middle cerebral artery stroke, severe contralesional upper-extremity impairment (Fugl-Meyer score ≤28), and ipsilesional motor deficits. Participants were randomly assigned with equal probability to 2 treatment groups and stratified by sex.

Light-guided evolution creates proteins that can switch, sense, and compute

Researchers have created a method called optovolution that uses light to guide the evolution of proteins with dynamic behaviors. By engineering yeast cells so their survival depended on proteins switching states at the right time, scientists could rapidly select the best-performing variants. The technique produced new light-sensitive proteins that respond to different colors and improved optogenetic systems. It even evolved a protein that behaves like a tiny logic gate, activating genes only when two signals are present.

Atom-thin material could help solve chip manufacturing problem

Making computer chips smaller is not just about better design. It also depends on a critical step in manufacturing called patterning, where nanoscale structures are carved into materials to form the circuits inside everything from smartphones to advanced sensors.

To create these patterns, engineers use a hard mask, a thin, durable material layer that protects selected regions while the exposed areas are etched away.

“As chips get smaller, the manufacturing process becomes much more demanding,” said Saptarshi Das, Penn State Ackley Professor of Engineering Science and professor of engineering science and mechanics. “The mask used to define these patterns must survive extremely harsh processing conditions. If the mask degrades, the patterns cannot be transferred reliably.”

Brain-inspired device could lead to faster, more energy-efficient AI hardware

A team led by engineers at the University of California San Diego has developed a new brain-inspired hardware platform that could help computer hardware keep pace with the explosive growth of artificial intelligence. By combining memory and computation on the same chip—and allowing its components to interact collectively like neurons in the brain—the brain-inspired platform improved the speed, accuracy, and energy efficiency of pattern recognition in two simulated tasks: recognizing spoken digits and detecting epileptic seizures early from brain-wave recordings.

The approach could lead to the development of compact, energy-efficient hardware for smaller AI systems such as those used in wearable health monitors, smart sensors, and other autonomous devices.

The work, published on March 9 in Nature Nanotechnology, falls within the field of neuromorphic computing, which aims to build machines that mimic how the brain processes information. The researchers emphasize that the technology is brain-inspired, rather than brain-like; it draws ideas from how neural networks interact but does not attempt to replicate the brain itself.

Scientists create slippery nanopores that supercharge blue energy

Scientists have found a way to significantly boost “blue energy,” which generates electricity from the mixing of saltwater and freshwater. By coating nanopores with lipid molecules that create a friction-reducing water layer, they enabled ions to pass through much more efficiently while keeping the process highly selective. Their prototype membrane produced about two to three times more power than current technologies. The discovery could help bring osmotic energy closer to becoming a practical renewable power source.

Physicists finally see strange magnetic vortices predicted 50 years ago

A team of physicists has experimentally confirmed a long-predicted sequence of exotic magnetic phases in an atomically thin material. When cooled, the material forms tiny magnetic vortices before transitioning into a second ordered magnetic state—exactly as predicted by a famous theoretical model from the 1970s. Observing both phases together for the first time validates key ideas about how magnetism behaves in two dimensions. The findings could help inspire ultracompact technologies built on nanoscale magnetic control.

Golden lancehead genome reveals how genes responsible for venom toxins evolved

A research team led by scientists at the Butantan Institute in São Paulo, Brazil, has completed the most extensive genetic sequencing of a jararaca viper to date. The focus of the study was the genome of the golden lancehead (Bothrops insularis), particularly its venom genes. Since the species shares most of its genes with the other 48 species in the genus, the data serve as a reference for broader studies on the evolution of jararaca vipers and their toxins. The study is published in the journal Genome Biology and Evolution.

The golden lancehead was described in 1921 as a different species from the one known on the mainland, simply called jararaca (Bothrops jararaca). Isolated on Queimada Grande Island, off the coast of São Paulo, about 100,000 years ago, the population differed from its mainland counterparts to the point of separating into a new species.

In addition to having yellow skin, the golden lancehead is semi-arboreal and feeds on birds as an adult. Jararacas on the mainland, on the other hand, are dark in color and usually hunt small mammals, such as rats, on the ground. In 2021, B. jararaca became the first Brazilian snake to have its genome sequenced.

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