From microbiomes to road kill: What DNA can tell us about the ecology of ticks

Knowledge of host species that maintain populations of Ixodes scapularis, the vector of Lyme disease in the eastern U.S., is needed to improve preventative strategies. The prevailing dogma of Lyme disease ecology is that the white-footed mouse (Peromyscus leucopus) is the most important host for juvenile ticks (i.e., larvae and nymphs; 1). The white-tailed deer (Odocoileus virginanus) is the primary host for adult ticks, however its role as a host for juveniles has not been rigorously studied. Here we provide both DNA and visual evidence that juveniles feed on O. virginanus. Our DNA-based host detection system may be more broadly applied in future studies to identify other important hosts of I. scapularis

XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner. The decrease in cell viability was due to an induction of apoptosis and cell cycle arrest. These results were recapitulated in in vivo studies where selinexor decreased tumor growth. Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. Cells expressing wildtype RB, a potent tumor suppressor that promotes growth arrest and apoptosis, were most susceptible to selinexor. Cell fractionation and immunofluorescence studies showed that selinexor treatment increased nuclear RB levels and mechanistic studies revealed that RB ablation curtailed the response to the drug. Conversely, limiting CDK4/6 dependent RB phosphorylation by palbociclib was additive with selinexor in reducing bladder tumor cell viability, confirming that RB activity has a role in the response to XPO1 inhibition. These results provide a rationale for XPO1 inhibition as a novel strategy for the treatment of bladder malignancies

A tight-binding potential for atomistic simulations of carbon interacting with transition metals: Application to the Ni-C system

We present a tight-binding potential for transition metals, carbon, and transition metal carbides, which has been optimized through a systematic fitting procedure. A minimal basis, including the s, p electrons of carbon and the d electrons of the transition metal, is used to obtain a transferable tight-binding model of the carbon-carbon, metal-metal and metal-carbon interactions applicable to binary systems. The Ni-C system is more specifically discussed. The successful validation of the potential for different atomic configurations indicates a good transferability of the model and makes it a good choice for atomistic simulations sampling a large configuration space. This approach appears to be very efficient to describe interactions in systems containing carbon and transition metal elements

Explaining racial and ethnic inequalities in postpartum allostatic load: Results from a multisite study of low to middle income woment

AbstractBackgroundRacial and ethnic inequalities in women's health are widely documented, but not for the postpartum period, and few studies examine whether neighborhood, psychosocial, and biological factors explain these gaps in women's health.MethodsUsing prospective longitudinal data collected from 1766 low to middle income women between 2008 and 2012 by the Community Child Health Network (CCHN), we tested the extent to which adjustment for neighborhood, economic, psychological, and medical conditions following a birth explained differences between African American, Latina, and White women in an indicator of physiological dysregulation allostatic load (AL), at one year postpartum as measured by 10 biomarkers: Body Mass Index, Waist Hip Ratio, systolic and diastolic blood pressure, high sensitivity C-reactive protein, Hemoglobin A1c, high-density lipoprotein and cholesterol ratio, and diurnal cortisol.ResultsMean postpartum AL scores were 4.65 for African American, 4.57 for Latina and 3.86 for White women. Unadjusted regression estimates for high AL for African American women (with White as the reference) were 0.80 (SD = 0.11) and 0.53 (SD = 0.15) for Latina women. Adjustment for household poverty, neighborhood, stress, and resilience variables resulted in a reduction of 36% of the excess risk in high AL for African Americans versus Whites and 42% of the excess risk for Latinas compared to Whites.ConclusionsRacial and ethnic inequalities in AL were accounted for largely by household poverty with additional contributions by psychological, economic, neighbourhood and medical variables. There remained a significant inequality between African American, and Latina women as compared to Whites even after adjustment for this set of variables. Future research into health inequalities among women should include a fuller consideration of the social determinants of health including employment, housing and prepregnancy medical conditions

Selinexor, a novel selective inhibitor of nuclear export, reduces SARS-CoV-2 infection and protects the respiratory system in vivo

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1β, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option

Phase and transport velocities in particle and electromagnetic beams

In a coherent monoenergetic beam of non-interacting particles, the phase velocity and the particle transport velocity are functions of position, with the strongest variation being in the focal region. These velocities are everywhere parallel to each other, and their product is constant in space. For a coherent monochromatic electromagnetic beam, the energy transport velocity is never greater than the speed of light, and can even be zero. The phase velocities (one each for the non-zero components of the electric and magnetic fields, in general) can be different from each other and from the energy transport velocity, both in direction and in magnitude. The phase velocities at a given point are independent of time, for both particle and electromagnetic beams. The energy velocity is independent of time for the particle beam, but in general oscillates (with angular frequency 2w) in magnitude and direction about its mean value at a given point in the electromagnetic beam. However, there exist electromagnetic steady beams, within which the energy flux, energy density and energy velocity are all independent of time.Comment: 9 pages, 12 figure

Use of migdut dissections and PCR blockers in the study of the eukaryotic microbiome of the black-legged tick

Bioinformatics is a field that can improve understanding of biological systems. In this study, DNA isolated from the black-legged tick (Ixodes scapularis) was analysed using QIIME2 microbiome bioinformatics software on the Cyverse platform. Use used PCR blockers and dissections were tested to reduce the amount of I. scapularis reads and thus allow for increased sequencing fungal and protist DNA reads