A role for the ubiquitin-proteasome system in activity-dependent presynaptic silencing

Chronic changes in electrical excitability profoundly affect synaptic transmission throughout the lifetime of a neuron. We have previously explored persistent presynaptic silencing, a form of synaptic depression at glutamate synapses produced by ongoing neuronal activity and by strong depolarization. Here we investigate the involvement of the ubiquitin-proteasome system (UPS) in the modulation of presynaptic function. We found that proteasome inhibition prevented the induction of persistent presynaptic silencing. Specifically, application of the proteasome inhibitor, MG-132, prevented decreases in the size of the readily releasable pool of vesicles and in the percentage of active synapses. Presynaptic silencing was accompanied by decreases in levels of the priming proteins, Munc13-1 and Rim1. Importantly, overexpression of Rim1α prevented the induction of persistent presynaptic silencing. Furthermore, strong depolarization itself increased proteasome enzymatic activity measured in cell lysates. These results suggest that modulation of the UPS by electrical activity contributes to persistent presynaptic silencing by promoting the degradation of key presynaptic proteins

Effect of 3d-doping on the electronic structure of BaFe2As2

The electronic structure of BaFe2As2 doped with Co, Ni, and Cu has been studied by a variety of experimental and theoretical methods, but a clear picture of the dopant 3d states has not yet emerged. Herein we provide experimental evidence of the distribution of Co, Ni, and Cu 3d states in the valence band. We conclude that the Co and Ni 3d states provide additional free carriers to the Fermi level, while the Cu 3d states are found at the bottom of the valence band in a localized 3d10 shell. These findings help shed light on why superconductivity can occur in BaFe2As2 doped with Co and Ni but not Cu.Comment: 18 pages, 8 figure

Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues

Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown “mito-protective” properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study

Rationale and Design of an Ecological Momentary Assessment Study Examining Predictors of Binge Eating Among Sexual Minority and Heterosexual Young Women: Protocol for the Health and Experiences in Real Life (HER Life) Study

Background: Previous research has identified health disparities between sexual minority and heterosexual women, including increased rates of obesity and binge eating in sexual minority women. Established predictors of binge eating behavior include negative emotions and sociocultural processes; however, these studies are generally conducted in samples of young women where sexual identity is not known or reported. There is a dearth of research evaluating how sexual minority–specific factors (eg, minority stress and connectedness to the lesbian, gay, bisexual, transgender, and queer community) may affect binge eating in sexual minority women. In addition, no studies have examined these processes in racially diverse samples or considered how intersecting minority identities (eg, Black and sexual minority) may affect eating behaviors. Objective: The Health and Experiences in Real Life (HER Life) Project aims to clarify real-world predictors of binge eating in young heterosexual and sexual minority women using ecological momentary assessment. The role of affective, social, and health behavior factors in binge eating will be examined for all women (aim 1), and sexual minority–specific predictors will also be considered for sexual minority women participants (aim 2). Person-level moderators of race, body- and eating-related factors, and sexual minority–specific factors will also be examined to better understand how real-world binge eating predictors may differ for various demographic groups (aim 3). Methods: Researchers aim to recruit 150 sexual minority and 150 heterosexual women from across the United States, including at least 50 Black women for each group, using web-based recruitment methods. The eligibility criteria include identifying as a woman, being aged between 18 and 30 years, and having had at least two binge eating episodes in the last 2 weeks. Participants must endorse being only or mostly attracted to men (considered heterosexual) or only or mostly attracted to women or having a current or most recent female partner (considered sexual minority). Eligible participants complete an initial web-based baseline survey and then 14 days of ecological momentary assessment involving the completion of a morning and before-bed survey and 5 prompted surveys per day as well as a user-initiated survey after binge eating episodes. The data will be analyzed using a series of multilevel models. Results: Data collection started in February 2021. We have currently enrolled 129 sexual minority women and 146 heterosexual women. Data collection is expected to conclude in fall 2022. Conclusions: The Health and Experiences in Real Life Project aims to elucidate potential differences between sexual minority and heterosexual women in within-person factors predicting binge eating and inform eating disorder interventions for sexual minority women. The challenges in recruiting sexual minority women, including the determination of eligibility criteria and considerations for remote data collection, are discussed. International Registered Report Identifier (IRRID): DERR1-10.2196/4119

Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions and cardiac remodeling

To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy

Electronic structure of Co_xTiSe_2 and Cr_xTiSe_2

The results of investigations of intercalated compounds Cr_xTiSe_2 and Co_xTiSe_2 by X-ray photoelectron spectroscopy (XPS) and X-ray emission spectroscopy (XES) are presented. The data obtained are compared with theoretical results of spin-polarized band structure calculations. A good agreement between theoretical and experimental data for the electronic structure of the investigated materials has been observed. The interplay between the M3d--Ti3d hybridization (M=Cr, Co) and the magnetic moment at the M site is discussed. A 0.9 eV large splitting of the core Cr2p{3/2} level was observed, which reveals a strong exchange magnetic interaction of 3d-2p electrons of Cr. In the case of a strong localization of the Cr3d electrons (for x<0.25), the broadening of the CrL spectra into the region of the states above the nominal Fermi level was observed and attributed to X-ray re-emission. The measured kinetic properties are in good accordance with spectral investigations and band calculation results.Comment: 14 pages, 11 figures, submitted to Phys.Rev.

Spectroscopic investigation of the deeply buried Cu In,Ga S,Se 2 Mo interface in thin film solar cells

The Cu In,Ga S,Se 2 Mo interface in thin film solar cells has been investigated by surface sensitive photoelectron spectroscopy, bulk sensitive X ray emission spectroscopy, and atomic force microscopy. It is possible to access this deeply buried interface by using a suitable lift off technique, which allows to investigate the back side of the absorber layer as well as the front side of the Mo back contact. We find a layer of Mo S,Se 2 on the surface of the Mo back contact and a copper poor stoichiometry at the back side of the Cu In,Ga S,Se 2 absorber. Furthermore, we observe that the Na content at the Cu In,Ga S,Se 2 Mo interface as well as at the inner grain boundaries in the back contact region is significantly lower than at the absorber front surfac

Mapping the Two-Component Atomic Fermi Gas to the Nuclear Shell-Model

The physics of a two-component cold fermi gas is now frequently addressed in laboratories. Usually this is done for large samples of tens to hundreds of thousands of particles. However, it is now possible to produce few-body systems (1-100 particles) in very tight traps where the shell structure of the external potential becomes important. A system of two-species fermionic cold atoms with an attractive zero-range interaction is analogous to a simple model of nucleus in which neutrons and protons interact only through a residual pairing interaction. In this article, we discuss how the problem of a two-component atomic fermi gas in a tight external trap can be mapped to the nuclear shell model so that readily available many-body techniques in nuclear physics, such as the Shell Model Monte Carlo (SMMC) method, can be directly applied to the study of these systems. We demonstrate an application of the SMMC method by estimating the pairing correlations in a small two-component Fermi system with moderate-to-strong short-range two-body interactions in a three-dimensional harmonic external trapping potential.Comment: 13 pages, 3 figures. Final versio

Effect of race on prediction of brain amyloidosis by plasma Aβ42/Aβ40, phosphorylated tau, and neurofilament light

BACKGROUND AND OBJECTIVES: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups. METHODS: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, RESULTS: There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were DISCUSSION: Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals