West Nile Virus and Ferruginous Hawks (Buteo Regalis) in the Northern Great Plains

Emerging infectious diseases (EID) present significant threats to the conservation of global biodiversity (Daszak et al. 2000). Evaluating impacts (spatial, temporal and demographic) of EIDs on sensitive and declining wildlife populations is challenging because quantitative information is usually dependent on estimates rather than counts (Wobeser 2007) and mortality rates are seldom quantified with conventional monitoring (Naugle et al. 2005)

WEST NILE VIRUS AND FERRUGINOUS HAWKS (BUTEO REGALIS) IN THE NORTHERN GREAT PLAINS

Emerging infectious diseases (EID) present significant threats to the conservation of global biodiversity (Daszak et al. 2000). Evaluating impacts (spatial, temporal and demographic) of EIDs on sensitive and declining wildlife populations is challenging because quantitative information is usually dependent on estimates rather than counts (Wobeser 2007) and mortality rates are seldom quantified with conventional monitoring (Naugle et al. 2005). West Nile virus (WNv), a mosquito-borne Flavivirus (family Flaviviridae; Komar 2001), was discovered in northwest Uganda in 1937 (Smithburn et al. 1940). First encountered in the western hemisphere in New York in 1999 (Nash et al. 2001), WNv has become enzootic in all 48 contiguous states, and has been reported from 96% of counties to date (Centers for Disease Control and Prevention [CDC] 2013). West Nile virus has been detected in 65 species of mosquito in the United States (CDC 2012) and its ability to establish and persist across ecosystems and hosts is illustrated by its extensive distribution (CDC 2013). West Nile virus infection has been reported in 326 avian species (CDC 2013). Among a more scarcely occurring avian guild like the raptors, the CDC Arbornet Surveillance System (1999 to 2004) have documented infection in 36 species (Nemeth et al. 2006), approximately 70% of all raptor species occurring in North America

Shared decision making in patients with low risk chest pain: prospective randomized pragmatic trial.

OBJECTIVE: To compare the effectiveness of shared decision making with usual care in choice of admission for observation and further cardiac testing or for referral for outpatient evaluation in patients with possible acute coronary syndrome. DESIGN: Multicenter pragmatic parallel randomized controlled trial. SETTING: Six emergency departments in the United States. PARTICIPANTS: 898 adults (aged \u3e17 years) with a primary complaint of chest pain who were being considered for admission to an observation unit for cardiac testing (451 were allocated to the decision aid and 447 to usual care), and 361 emergency clinicians (emergency physicians, nurse practitioners, and physician assistants) caring for patients with chest pain. INTERVENTIONS: Patients were randomly assigned (1:1) by an electronic, web based system to shared decision making facilitated by a decision aid or to usual care. The primary outcome, selected by patient and caregiver advisers, was patient knowledge of their risk for acute coronary syndrome and options for care; secondary outcomes were involvement in the decision to be admitted, proportion of patients admitted for cardiac testing, and the 30 day rate of major adverse cardiac events. RESULTS: Compared with the usual care arm, patients in the decision aid arm had greater knowledge of their risk for acute coronary syndrome and options for care (questions correct: decision aid, 4.2 v usual care, 3.6; mean difference 0.66, 95% confidence interval 0.46 to 0.86), were more involved in the decision (observing patient involvement scores: decision aid, 18.3 v usual care, 7.9; 10.3, 9.1 to 11.5), and less frequently decided with their clinician to be admitted for cardiac testing (decision aid, 37% v usual care, 52%; absolute difference 15%; P CONCLUSIONS: Use of a decision aid in patients at low risk for acute coronary syndrome increased patient knowledge about their risk, increased engagement, and safely decreased the rate of admission to an observation unit for cardiac testing.Trial registration ClinicalTrials.gov NCT01969240

Mate Replacement and Alloparental Care in Ferruginous Hawk

Alloparental care (i.e., care for unrelated offspring) has been documented in various avian species (Maxson 1978, Smith et al. 1996, Tella et al. 1997, Lislevand et al. 2001, Literak and Mraz 2011). A male replacement mate that encounters existing broods has options, which include alloparental care or infanticide. Infanticide may be beneficial in some species (Rohwer 1986, Kermott et al. 1990), but in long-lived avian species, like the ferruginous hawk (Buteo regalis) that do not renest within a season, infanticide might be detrimental. Adoption and rearing success likely provide direct evidence of competence of replacement mates as potential parents for future seasons, a benefit that might outweigh the investment of time and effort associated with adoption and rearing (after Rohwer 1986). Anticipated mating opportunity at the cost of adoption (Gori et al. 1996, Rohwer et al. 1999) may explain step-parental benevolence and therefore, in such a scenario would enhance individual fitness through subsequent recruitment of related young

C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility

Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper’-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.This work was supported by BFU_2014-59307-R, MEIONet and JCyLe (CSI052U16). LGH and NFM are supported by European Social Fund/JCyLe grants (EDU/1083/2013 and EDU/310/2015). ORD is a Sir Henry Dale Fellow jointly funded by the Wellcome Trust and Royal Society (Grant Number 104158/Z/14/Z). RB is funded by DFG (grant Be1168/8-1). AT and ID were supported by DFG grants TO421/8-2 and TO421/6-1, respectively.Peer reviewe

The effect of black cohosh extract and risedronate coadministration on bone health in an ovariectomized rat model

Preparations of black cohosh extract are sold as dietary supplements marketed to relieve the vasomotor symptoms of menopause, and some studies suggest it may protect against postmenopausal bone loss. Postmenopausal women are also frequently prescribed bisphosphonates, such as risedronate, to prevent osteoporotic bone loss. However, the pharmacodynamic interactions between these compounds when taken together is not known. To investigate possible interactions, 6-month-old, female Sprague-Dawley rats underwent bilateral ovariectomy or sham surgery and were treated for 24 weeks with either vehicle, ethinyl estradiol, risedronate, black cohosh extract or coadministration of risedronate and black cohosh extract, at low or high doses. Bone mineral density (BMD) of the femur, tibia, and lumbar vertebrae was then measured by dual-energy X-ray absorptiometry (DEXA) at weeks 0, 8, 16, and 24. A high dose of risedronate significantly increased BMD of the femur and vertebrae, while black cohosh extract had no significant effect on BMD individually and minimal effects upon coadministration with risedronate. Under these experimental conditions, black cohosh extract alone had no effect on BMD, nor did it negatively impact the BMD-enhancing properties of risedronate

Genetically enhanced asynapsis of autosomal chromatin promotes transcriptional dysregulation and meiotic failure

During meiosis, pairing of homologous chromosomes and their synapsis are essential prerequisites for normal male gametogenesis. Even limited autosomal asynapsis often leads to spermatogenic impairment, the mechanism of which is not fully understood. The present study was aimed at deliberately increasing the size of partial autosomal asynapsis and analysis of its impact on male meiosis. For this purpose, we studied the effect of t12 haplotype encompassing four inversions on chromosome 17 on mouse autosomal translocation T(16;17)43H (abbreviated T43H). The T43H/T43H homozygotes were fully fertile in both sexes, while +/T43H heterozygous males, but not females, were sterile with meiotic arrest at late pachynema. Inclusion of the t12 haplotype in trans to the T43H translocation resulted in enhanced asynapsis of the translocated autosome, ectopic phosphorylation of histone H2AX, persistence of RAD51 foci, and increased gene silencing around the translocation break. Increase was also on colocalization of unsynapsed chromatin with sex body. Remarkably, we found that transcriptional silencing of the unsynapsed autosomal chromatin precedes silencing of sex chromosomes. Based on the present knowledge, we conclude that interference of meiotic silencing of unsynapsed autosomes with meiotic sex chromosome inactivation is the most likely cause of asynapsis-related male sterility

Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase

Meiotic crossovers are produced when programmed double-strand breaks (DSBs) are repaired by recombination from homologous chromosomes (homologues). In a wide variety of organisms, meiotic HORMA-domain proteins are required to direct DSB repair towards homologues. This inter-homologue bias is required for efficient homology search, homologue alignment, and crossover formation. HORMA-domain proteins are also implicated in other processes related to crossover formation, including DSB formation, inhibition of promiscuous formation of the synaptonemal complex (SC), and the meiotic prophase checkpoint that monitors both DSB processing and SCs. We examined the behavior of two previously uncharacterized meiosis-specific mouse HORMA-domain proteins-HORMAD1 and HORMAD2-in wild-type mice and in mutants defective in DSB processing or SC formation. HORMADs are preferentially associated with unsynapsed chromosome axes throughout meiotic prophase. We observe a strong negative correlation between SC formation and presence of HORMADs on axes, and a positive correlation between the presumptive sites of high checkpoint-kinase ATR activity and hyper-accumulation of HORMADs on axes. HORMADs are not depleted from chromosomes in mutants that lack SCs. In contrast, DSB formation and DSB repair are not absolutely required for depletion of HORMADs from synapsed axes. A simple interpretation of these findings is that SC formation directly or indirectly promotes depletion of HORMADs from chromosome axes. We also find that TRIP13 protein is required for reciprocal distribution of HORMADs and the SYCP1/SC-component along chromosome axes. Similarities in mouse and budding yeast meiosis suggest that TRIP13/Pch2 proteins have a conserved role in establishing mutually exclusive HORMAD-rich and synapsed chromatin domains in both mouse and yeast. Taken together, our observations raise the possibility that involvement of meiotic HORMA-domain proteins in the regulation of homologue interactions is conserved in mammals

Making sense of diabetes medication decisions: a mixed methods cluster randomized trial using a conversation aid intervention.

PURPOSE: To determine the effectiveness of a shared decision-making (SDM) tool versus guideline-informed usual care in translating evidence into primary care, and to explore how use of the tool changed patient perspectives about diabetes medication decision making. METHODS: In this mixed methods multicenter cluster randomized trial, we included patients with type 2 diabetes mellitus and their primary care clinicians. We compared usual care with or without a within-encounter SDM conversation aid. We assessed participant-reported decisions made and quality of SDM (knowledge, satisfaction, and decisional conflict), clinical outcomes, adherence, and observer-based patient involvement in decision-making (OPTION12-scale). We used semi-structured interviews with patients to understand their perspectives. RESULTS: We enrolled 350 patients and 99 clinicians from 20 practices and interviewed 26 patients. Use of the conversation aid increased post-encounter patient knowledge (correct answers, 52% vs. 45%, p = 0.02) and clinician involvement of patients (Mean between-arm difference in OPTION12, 7.3 (95% CI 3, 12); p = 0.003). There were no between-arm differences in treatment choice, patient or clinician satisfaction, encounter length, medication adherence, or glycemic control. Qualitative analyses highlighted differences in how clinicians involved patients in decision making, with intervention patients noting how clinicians guided them through conversations using factors important to them. CONCLUSIONS: Using an SDM conversation aid improved patient knowledge and involvement in SDM without impacting treatment choice, encounter length, medication adherence or improved diabetes control in patients with type 2 diabetes. Future interventions may need to focus specifically on patients with signs of poor treatment fit. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov: NCT01502891

HSP70-binding protein HSPBP1 regulates chaperone expression at a posttranslational level and is essential for spermatogenesis

Molecular chaperones play key roles during growth, development, and stress survival. The ability to induce chaperone expression enables cells to cope with the accumulation of nonnative proteins under stress and complete developmental processes with an increased requirement for chaperone assistance. Here we generate and analyze transgenic mice that lack the cochaperone HSPBP1, a nucleotide-exchange factor of HSP70 proteins and inhibitor of chaperone-assisted protein degradation. Male HSPBP1(−/−) mice are sterile because of impaired meiosis and massive apoptosis of spermatocytes. HSPBP1 deficiency in testes strongly reduces the expression of the inducible, antiapoptotic HSP70 family members HSPA1L and HSPA2, the latter of which is essential for synaptonemal complex disassembly during meiosis. We demonstrate that HSPBP1 affects chaperone expression at a posttranslational level by inhibiting the ubiquitylation and proteasomal degradation of inducible HSP70 proteins. We further provide evidence that the cochaperone BAG2 contributes to HSP70 stabilization in tissues other than testes. Our findings reveal that chaperone expression is determined not only by regulated transcription, but also by controlled degradation, with degradation-inhibiting cochaperones exerting essential prosurvival functions