Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.

The rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized.

Perceived stigma, mental health, and campus support among Latina/o and White college students.

College campuses can play a pivotal role in promoting mental health awareness and reducing stigma among college students. This study examines the effect of Latina/o and White students' mental health on their perceived self stigma and public stigma and the moderating role of college and university campuses' support toward perceived stigma. Survey responses of 51,821 Latina/o and White college students were examined.

Longitudinal evidence for the emergence of multiple intelligences in assistance dog puppies.

Cognitive test batteries suggest that adult dogs have different types of cognitive abilities that vary independently. In the current study, we tested puppies repeatedly over a crucial period of development to explore the timing and rate at which these different cognitive skills develop. Service dog puppies (n = 113), raised using two different socialization strategies, were either tested longitudinally (n =91) or at a single time point (n = 22).

Structures of human PTP1B variants reveal allosteric sites to target for weight loss therapy.

Protein Tyrosine Phosphatase 1B (PTP1B) is a negative regulator of leptin signaling whose disruption protects against diet-induced obesity in mice. We investigated whether structural characterization of human PTP1B variant proteins might reveal precise mechanisms to target for weight loss therapy. We selected 12 rare variants for functional characterization from exomes from 997 people with persistent thinness and 200,000 people from UK Biobank.

Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.

The rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized.

Native dynamics and allosteric responses in PTP1B probed by high-resolution HDX-MS.

Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for obesity, diabetes, and certain types of cancer. In particular, allosteric inhibitors hold potential for therapeutic use, but an incomplete understanding of conformational dynamics and allostery in this protein has hindered their development. Here, we interrogate solution dynamics and allosteric responses in PTP1B using high-resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), an emerging and powerful biophysical technique.

Native dynamics and allosteric responses in PTP1B probed by high-resolution HDX-MS.

Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for obesity, diabetes, and certain types of cancer. In particular, allosteric inhibitors hold potential for therapeutic use, but an incomplete understanding of conformational dynamics and allostery in this protein has hindered their development. Here, we interrogate solution dynamics and allosteric responses in PTP1B using high-resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), an emerging and powerful biophysical technique.

A 16-Channel Low-Power Neural Connectivity Extraction and Phase-Locked Deep Brain Stimulation SoC.

Growing evidence suggests that phase-locked deep brain stimulation (DBS) can effectively regulate abnormal brain connectivity in neurological and psychiatric disorders. This letter therefore presents a low-power SoC with both neural connectivity extraction and phase-locked DBS capabilities. A 16-channel low-noise analog front-end (AFE) records local field potentials (LFPs) from multiple brain regions with precise gain matching.

Engineered cord blood megakaryocytes evade killing by allogeneic T-cells for refractory thrombocytopenia.

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both and ; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated β-2 microglobulin (β2M) gene knockout (KO).

Flexible, high-resolution thin-film electrodes for human and animal neural research.

Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans.

Comparison of near-background concentrations of Argon-37 and Xenon-133 in the atmosphere.

Radioisotopes of the noble gases xenon and argon can be important indicators of underground nuclear explosions. The Comprehensive Nuclear-Test-Ban Treaty (CTBT) includes monitoring capabilities to identify potential nuclear explosions conducted in violation of the CTBT. This monitoring currently focuses on measurement of the xenon isotopes Xe, Xe, Xe, and Xe.

Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates.

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes.

Migration of noble gas tracers at the site of an underground nuclear explosion at the Nevada National Security Site.

As part of an underground gas migration study, two radioactive noble gases (Ar and Xe) and two stable tracer gases (SF and PFDMCH) were injected into a historic nuclear explosion test chimney and allowed to migrate naturally. The purpose of this experiment was to provide a bounding case (natural transport) for the flow of radioactive noble gases following an underground nuclear explosion. To accomplish this, soil gas samples were collected from a series of boreholes and a range of depths from the shallow subsurface (3 m) to deeper levels (~160 m) over a period of eleven months.

Long-term recording reliability of liquid crystal polymer µECoG arrays.

Objective: The clinical use of microsignals recorded over broad cortical regions is largely limited by the chronic reliability of the implanted interfaces.

Approach: We evaluated the chronic reliability of novel 61-channel micro-electrocorticographic (µECoG) arrays in rats chronically implanted for over one year and using accelerated aging. Devices were encapsulated with polyimide (PI) or liquid crystal polymer (LCP), and fabricated using commercial manufacturing processes.

Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity.

Forest-based Therapy: Research Letter of a Novel Regime for Improved Respiratory Health.

Nature-based therapies are well documented. However, forest-based therapy for respiratory health is still an innovative treatment. Our subject reports respiratory problems and forest walking, suggesting that improved respiratory health may be another positive outcome of forest-based therapies, when associated with activities that increase parasympathetic activity.

Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution.

Hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (HDXMS) is a rapid and effective method for localizing and determining protein stability and dynamics. Localization is routinely limited to a peptide resolution of 5 to 20 amino acid residues. HDXMS data can contain information beyond that needed for defining protein stability at single amide resolution.

In vitro assessment of long-term reliability of low-cost μECoG arrays.

Micro-electrocorticographic (μECοG) electrode arrays provide a minimally invasive, high-resolution neural interface with broad cortical coverage. Previously, we fabricated μECoG arrays at a lower cost than commercially available devices using low-cost industrial processes [1], [2]. Here, we report the in vitro electrical performance of five μECoG designs undergoing an accelerated aging protocol.

Production and release rate of Ar from the UT TRIGA Mark-II research reactor.

Air samples were taken at various locations around The University of Texas at Austin's TRIGA Mark II research reactor and analyzed to determine the concentrations of Ar, Ar, and Xe present. The measured ratio of Ar/Ar and historical records of Ar releases were then utilized to estimate an annual average release rate of Ar from the reactor facility. Using the calculated release rate, atmospheric transport modeling was performed in order to determine the potential impact of research reactor operations on nearby treaty verification activities.

Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen.

Hepatitis C virus (HCV) is a major cause of liver disease, affecting over 2% of the world's population. The HCV envelope glycoproteins E1 and E2 mediate viral entry, with E2 being the main target of neutralizing antibody responses. Structural investigations of E2 have produced templates for vaccine design, including the conserved CD81 receptor-binding site (CD81bs) that is a key target of broadly neutralizing antibodies (bNAbs).

A low-cost, multiplexed μECoG system for high-density recordings in freely moving rodents.

Objective: Micro-electrocorticography (μECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely behaving rodents challenging. We report a novel high-density 60-electrode system for μECoG recording in freely moving rats.