Development of StressCheck: A telehealth motivational enhancement therapy to improve voluntary engagement for PTSD treatment among active-duty service members

Background: Rates of PTSD in active-duty military are high relative to the general population. Although efficacious treatments exist, they are underutilized. Many service members with PTSD do not present for treatment and, of those who do, many do not receive sufficient doses of the interventions to receive full benefits. Motivational Enhancement Therapy (MET) “check-ups”, are brief interventions designed to elicit treatment engagement for those who are not treatment-seeking. Methods: StressCheck is an MET for nontreatment seeking Army and Air Force personnel. StressCheck aims to improve PTSD and increase treatment engagement, especially around evidence-based interventions, as well as to decrease stigma about seeking mental health services and improve knowledge about treatment options. This paper describes the intervention components and process of treatment development. The paper also describes next steps in testing the effectiveness of the intervention. Conclusion: PTSD is associated with deleterious health, occupational, and psychological effects. If effective, this innovative intervention will bridge the gap between those who are not treatment seeking and existing services, thereby enhancing reach and impact of existing services

Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells

Angiogenesis is regulated by hyperglycemic conditions, which can induce cellular stress responses, reactive oxygen species (ROS), and anti-oxidant defenses that modulate intracellular signaling to prevent oxidative damage. The RUNX2 DNA-binding transcription factor is activated by a glucose-mediated intracellular pathway, plays an important role in endothelial cell (EC) function and angiogenesis, and is a target of oxidative stress. RUNX2 DNA-binding and EC differentiation in response to glucose were conserved in ECs from different tissues and inhibited by hyperglycemia, which stimulated ROS production through the aldose reductase glucose-utilization pathway. Furthermore, the redox status of cysteine and methionine residues regulated RUNX2 DNA-binding and reversal of oxidative inhibition was consistent with an endogenous Methionine sulfoxide reductase-A (MsrA) activity. Low molecular weight MsrA substrates and sulfoxide scavengers were potent inhibitors of RUNX2 DNA binding in the absence of oxidative stress, but acted as antioxidants to increase DNA binding in the presence of oxidants. MsrA was associated with RUNX2:DNA complexes, as measured by a sensitive, quantitative DNA-binding ELISA. The related RUNX2 protein family member, RUNX1, which contains an identical DNA-binding domain, was a catalytic substrate of recombinant MsrA. These findings define novel redox pathways involving aldose reductase and MsrA that regulate RUNX2 transcription factor activity and biological function in ECs. Targeting of these pathways could result in more effective strategies to alleviate the vascular dysfunction associated with diabetes or cancer

Intermittent search strategies

This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. We first show that intermittent search strategies are actually widely observed at various scales. At the macroscopic scale, this is for example the case of animals looking for food ; at the microscopic scale, intermittent transport patterns are involved in reaction pathway of DNA binding proteins as well as in intracellular transport. Second, we introduce generic stochastic models, which show that intermittent strategies are efficient strategies, which enable to minimize the search time. This suggests that the intrinsic efficiency of intermittent search strategies could justify their frequent observation in nature. Last, beyond these modeling aspects, we propose that intermittent strategies could be used also in a broader context to design and accelerate search processes.Comment: 72 pages, review articl

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

Localizing transcripts to single cells suggests an important role of uncultured deltaproteobacteria in the termite gut hydrogen economy

Identifying microbes responsible for particular environmental functions is challenging, given that most environments contain an uncultivated microbial diversity. Here we combined approaches to identify bacteria expressing genes relevant to catabolite flow and to locate these genes within their environment, in this case the gut of a “lower,” wood-feeding termite. First, environmental transcriptomics revealed that 2 of the 23 formate dehydrogenase (FDH) genes known in the system accounted for slightly more than one-half of environmental transcripts. FDH is an essential enzyme of H_2 metabolism that is ultimately important for the assimilation of lignocellulose-derived energy by the insect. Second, single-cell PCR analysis revealed that two different bacterial types expressed these two transcripts. The most commonly transcribed FDH in situ is encoded by a previously unappreciated deltaproteobacterium, whereas the other FDH is spirochetal. Third, PCR analysis of fractionated gut contents demonstrated that these bacteria reside in different spatial niches; the spirochete is free-swimming, whereas the deltaproteobacterium associates with particulates. Fourth, the deltaproteobacteria expressing FDH were localized to protozoa via hybridization chain reaction-FISH, an approach for multiplexed, spatial mapping of mRNA and rRNA targets. These results underscore the importance of making direct vs. inference-based gene– species associations, and have implications in higher termites, the most successful termite lineage, in which protozoa have been lost from the gut community. Contrary to expectations, in higher termites, FDH genes related to those from the protozoan symbiont dominate, whereas most others were absent, suggesting that a successful gene variant can persist and flourish after a gut perturbation alters a major environmental niche

An Alternative Yukawa Unified SUSY Scenario

Supersymmetric SO(10) Grand Unified Theories with Yukawa unification represent an appealing possibility for physics beyond the Standard Model. However Yukawa unification is made difficult by large threshold corrections to the bottom mass. Generally one is led to consider models where the sfermion masses are large in order to suppress these corrections. Here we present another possibility, in which the top and bottom GUT scale Yukawa couplings are equal to a component of the charged lepton Yukawa matrix at the GUT scale in a basis where this matrix is not diagonal. Physically, this weak eigenstate Yukawa unification scenario corresponds to the case where the charged leptons that are in the 16 of SO(10) containing the top and bottom quarks mix with their counterparts in another SO(10) multiplet. Diagonalizing the resulting Yukawa matrix introduces mixings in the neutrino sector. Specifically we find that for a large region of parameter space with relatively light sparticles, and which has not been ruled out by current LHC or other data, the mixing induced in the neutrino sector is such that $sin^2 2\Theta_{23} \approx 1$, in agreement with data. The phenomenological implications are analyzed in some detail.Comment: 32 pages, 22 Figure

Effective killing of the human pathogen Candida albicans by a specific inhibitor of non-essential mitotic kinesin Kip1p

Kinesins from the bipolar (Kinesin-5) family are conserved in eukaryotic organisms and play critical roles during the earliest stages of mitosis to mediate spindle pole body separation and formation of a bipolar mitotic spindle. To date, genes encoding bipolar kinesins have been reported to be essential in all organisms studied. We report the characterization of CaKip1p, the sole member of this family in the human pathogenic yeast Candida albicans. C. albicans Kip1p appears to localize to the mitotic spindle and loss of CaKip1p function interferes with normal progression through mitosis. Inducible excision of CaKIP1 revealed phenotypes unique to C. albicans, including viable homozygous Cakip1 mutants and an aberrant spindle morphology in which multiple spindle poles accumulate in close proximity to each other. Expression of the C. albicans Kip1 motor domain in Escherichia coli produced a protein with microtubule-stimulated ATPase activity that was inhibited by an aminobenzothiazole (ABT) compound in an ATP-competitive fashion. This inhibition results in ‘rigor-like’, tight association with microtubules in vitro. Upon treatment of C. albicans cells with the ABT compound, cells were killed, and terminal phenotype analysis revealed an aberrant spindle morphology similar to that induced by loss of the CaKIP1 gene. The ABT compound discovered is the first example of a fungal spindle inhibitor targeted to a mitotic kinesin. Our results also show that the non-essential nature and implementation of the bipolar motor in C. albicans differs from that seen in other organisms, and suggest that inhibitors of a non-essential mitotic kinesin may offer promise as cidal agents for antifungal drug discovery

A measurement of the W boson mass using large rapidity electrons

We present a measurement of the W boson mass using data collected by the D0 experiment at the Fermilab Tevatron during 1994--1995. We identify W bosons by their decays to e-nu final states where the electron is detected in a forward calorimeter. We extract the W boson mass, Mw, by fitting the transverse mass and transverse electron and neutrino momentum spectra from a sample of 11,089 W -> e nu decay candidates. We use a sample of 1,687 dielectron events, mostly due to Z -> ee decays, to constrain our model of the detector response. Using the forward calorimeter data, we measure Mw = 80.691 +- 0.227 GeV. Combining the forward calorimeter measurements with our previously published central calorimeter results, we obtain Mw = 80.482 +- 0.091 GeV