STAT5b: A master regulator of key biological pathways

The Signal Transducer and Activator of Transcription (STAT)-5 proteins are required in immune regulation and homeostasis and play a crucial role in the development and function of several hematopoietic cells. STAT5b activation is involved in the expression of genes that participate in cell development, proliferation, and survival. STAT5a and STAT5b are paralogs and only human mutations in STAT5B have been identified leading to immune dysregulation and hematopoietic malignant transformation. The inactivating STAT5B mutations cause impaired post-natal growth, recurrent infections and immune dysregulation, whereas gain of function somatic mutations cause dysregulated allergic inflammation. These mutations are rare, and they are associated with a wide spectrum of clinical manifestations which provide a disease model elucidating the biological mechanism of STAT5 by studying the consequences of perturbations in STAT5 activity. Further, the use of Jak inhibitors as therapy for a variety of autoimmune and malignant disorders has increased substantially heading relevant lessons for the consequences of Jak/STAT immunomodulation from the human model. This review summarizes the biology of the STAT5 proteins, human disease associate with molecular defects in STAT5b, and the connection between aberrant activation of STAT5b and the development of certain cancers

Quantum Melting and Absence of Bose-Einstein Condensation in Two-Dimensional Vortex Matter

We demonstrate that quantum fluctuations suppress Bose-Einstein condensation of quasi-two-dimensional bosons in a rapidly-rotating trap. Our conclusions rest in part on an effective-Lagrangian description of the triangular vortex lattice, and in part on microscopic Bogoliubov equations in the rapid-rotation limit. We obtain analytic expressions for the collective-excitation dispersion, which, in a rotating system, is quadratic rather than linear. Our estimates for the boson filling factor at which the vortex lattice melts at zero temperature due to quantum fluctuations are consistent with recent exact-diagonalization calculations.Comment: 4 pages, 1 figures, version to appear in Phys. Rev. Let

Exact solutions for interacting boson systems under rotation

We study a class of interacting, harmonically trapped boson systems at angular momentum L. The Hamiltonian leaves a L-dimensional subspace invariant, and this permits an explicit solution of several eigenstates and energies for a wide class of two-body interactionsComment: 8 pages, error corrected (concerns generalization of subspace structure

Quantum Phases of Vortices in Rotating Bose-Einstein Condensates

We investigate the groundstates of weakly interacting bosons in a rotating trap as a function of the number of bosons, $N$, and the average number of vortices, $N_V$. We identify the filling fraction $\nu\equiv N/N_V$ as the parameter controlling the nature of these states. We present results indicating that, as a function of $\nu$, there is a zero temperature {\it phase transition} between a triangular vortex lattice phase, and strongly-correlated vortex liquid phases. The vortex liquid phases appear to be the Read-Rezayi parafermion states

A Systematic Analysis of Temporal Trends in the Handgrip Strength of 2,216,320 Children and Adolescents Between 1967 and 2017

Objective: To estimate national and international temporal trends in handgrip strength for children and adolescents, and to examine relationships between trends in handgrip strength and trends in health-related and sociodemographic indicators. Methods: Data were obtained through a systematic search of studies reporting temporal trends in the handgrip strength for apparently healthy 9–17 year-olds, and by examining large national fitness datasets. Temporal trends at the country-sex-age level were estimated by sample-weighted regression models relating the year of testing to mean handgrip strength. International and national trends were estimated by a post-stratified population-weighting procedure. Pearson’s correlations quantified relationships between trends in handgrip strength and trends in health-related/sociodemographic indicators. Results: 2,216,320 children and adolescents from 13 high-, 5 upper-middle-, and 1 low-income countries/special administrative regions between 1967 and 2017 collectively showed a moderate improvement of 19.4% (95%CI: 18.4 to 20.4) or 3.8% per decade (95%CI: 3.6 to 4.0). The international rate of improvement progressively increased over time, with more recent values (post-2000) close to two times larger than those from the 1960s/1970s. Improvements were larger for children (9–12 years) compared to adolescents (13–17 years), and similar for boys and girls. Trends differed between countries, with relationships between trends in handgrip strength and trends in health-related/sociodemographic indicators negligible-to-weak and not statistically significant. Conclusions: There has been a substantial improvement in absolute handgrip strength for children and adolescents since 1967. There is a need for improved international surveillance of handgrip strength, especially in low- and middle-income countries, to more confidently determine true international trends. PROSPERO registration number: CRD42013003657

Fragmented Condensate Ground State of Trapped Weakly Interacting Bosons in Two Dimensions

The ground state and its structure for a rotating, harmonically trapped N-Boson system with a weak repulsive contact interaction are studied as the angular momentum L increases up to 3N. We show that the ground state is generally a fragmented condensate due to angular momentum conservation. In response to an (arbitrarily weak) asymmetric perturbation of the trap, however, the fragmented ground state can be transformed into a single condensate state. We manifest this intrinsic instability by calculating the conditional probability distributions, which show patterns analogous to the boson density distributions predicted by mean-field theory.Comment: 4 pages, 4 ps figure

Differential response of three large mammal species to human recreation in the Rocky Mountains of Colorado, USA

Outdoor recreation benefits local economies, environmental education, and public health and wellbeing, but it can also adversely affect local ecosystems. Human presence in natural areas alters feeding and reproductive behaviors, physiology, and population structure in many wildlife species, often resulting in cascading effects through entire ecological communities. As outdoor recreation gains popularity, existing trails are becoming overcrowded and new trails are being built to accommodate increasing use. Many recreation impact studies have investigated effects of the presence or absence of humans while few have investigated recreation effects on wildlife using a gradient of disturbance intensity. We used camera traps to quantify trail use by humans and mid- to large-sized mammals in an area of intense outdoor recreation–the Upper East River Valley, Colorado, USA. We selected five trails with different types and intensities of human use and deployed six cameras on each trail for five weeks during a COVID-enhanced 2020 summer tourism season. We used occupancy models to estimate detectability and habitat use of the three most common mammal species in the study area and determined which human activities affect the habitat use patterns of each species. Human activities affected each species differently. Mule deer (Odocoileus hemionus) tended to use areas with more vehicles, more predators, and greater distances from the trailhead, and they were more likely to be detected where there were more bikers. Coyotes (Canis latrans) and red foxes (Vulpes vulpes) were most likely to use areas where their prey species occurred, and foxes were more likely to be detected where the vegetation was shorter. Humans and their recreational activities differentially influence different species. More generally, these results reinforce that it is unlikely that a single management policy is suitable for all species and management should thus be tailored for each target species

Longitudinal Analysis of Memory B and T Cell Responses to Dengue Virus in a 5-Year Prospective Cohort Study in Thailand

Prior exposure to dengue virus (DENV) has a profound impact on the outcome of infection, which varies according to the interval between infections. Antibodies secreted by B cells and cytokines secreted by T cells are thought to contribute both to protective immunity against DENV and the pathogenesis of dengue disease. We analyzed peripheral blood mononuclear cells (PBMC) collected from Thai children over a 5-year prospective cohort study to define the dynamics of DENV-specific memory B and T cell responses and the impact of symptomatic or subclinical DENV infections. To measure B cell responses, PBMC were stimulated with IL-2 plus R848 and culture supernatants were tested for DENV-binding antibodies by ELISA. To measure T cell responses, PBMC were stimulated in dual-color ELISPOT assays with overlapping peptide pools of structural and non-structural proteins from the four DENV types. B cell responses were low to one or more DENV types prior to symptomatic infection and increased with reactivity to all four types after infection. Subjects who had a subclinical infection or who did not experience a DENV infection during the study period showed strong memory B cell responses to all four DENV types. T cell responses to DENV peptides demonstrated a cytokine hierarchy of IFN-γ \u3e IL-2 \u3e IFN-γ/IL-2. T cell responses were low or absent prior to secondary infections. The trends in T cell responses to DENV peptides over 3 year post-infection were highly variable, but subjects who had experienced a secondary DENV1 infection showed higher cytokine responses compared to subjects who had experienced a secondary DENV2 or subclinical infection. The longitudinal nature of our study demonstrates persistent memory B cell responses over years and a lasting but variable impact of secondary DENV infection on DENV-specific T cell responses

Structural Controls on Shallow Cenozoic Fluid Flow in the Otago Schist, New Zealand

The Otago Schist in the South Island of New Zealand represents an exhumed Mesozoic accretionary prism. Two coastal areas (Akatore Creek and Bruce Rocks) south of Dunedin preserve structural and geochemical evidence for the development of postmetamorphic hydrothermal systems that involved widespread fluid-rock reaction at shallow crustal depths. The Jurassic to Triassic pumpellyite-actinolite (Akatore Creek) to upper greenschist facies (Bruce Rocks) metamorphic fabrics were crosscut by sets of regionally extensive Cretaceous exhumation joints. Many of the joints were subsequently reactivated to form networks of small-displacement (<metres) strike-slip faults containing cemented fault breccias and veins composed of hydrothermal calcite, siderite, and ankerite. Paleostress analysis performed on infrequent fault slickenlines indicates an overall strike-slip paleostress regime and a paleo-σ1 orientation (azimuth 094°) similar to the contemporary σ1 orientation in Otago and Canterbury (azimuth c. 110°-120°). High δ18O values in vein calcite (δ18OVPDB=21 to 28‰), together with the predominance of Type I calcite twins, suggest that vein formation occurred at low temperatures (<200°C) in the shallow crust and was associated with strongly channelized fluid flow along the joint and fault networks. Mass-balance calculations performed on samples from carbonate alteration zones show that significant mobilisation of elements occurred during fluid flow and fluid-rock reaction. Whole-rock and in situ carbonate 87Sr/86Sr data indicate varying degrees of interaction between the hydrothermal fluids and the host rock schists. Fluids were likely derived from the breakdown of metamorphic Ca-rich mineral phases with low 87Rb in the host schists (e.g., epidote or calcite), as well as more radiogenic components such as mica. Overall, the field and geochemical data suggest that shallow fluid flow in the field areas was channelized along foliation surfaces, exhumation joints, and networks of brittle faults, and that these structures controlled the distribution of fluid-rock reactions and hydrothermal veins. The brittle fault networks and associated hydrothermal systems are interpreted to have formed after the onset of Early Miocene compression in the South Island and may represent the manifestation of fracturing and fluid flow associated with reverse reactivation of regional-scale faults such as the nearby Akatore Fault