Sensory drive mediated by climatic gradients partially explains divergence in acoustic signals in two horseshoe bat species, Rhinolophus swinnyi and Rhinolophus simulator

Geographic variation can be an indicator of still poorly understood evolutionary processes such as adaptation and drift. Sensory systems used in communication play a key role in mate choice and species recognition. Habitat-mediated (i.e. adaptive) differences in communication signals may therefore lead to diversification. We investigated geographic variation in echolocation calls of African horseshoe bats, Rhinolophus simulator and R . swinnyi in the context of two adaptive hypotheses: 1) James' Rule and 2) the Sensory Drive Hypothesis. According to James' Rule body-size should vary in response to relative humidity and temperature so that divergence in call frequency may therefore be the result of climate-mediated variation in body size because of the correlation between body size and call frequency. The Sensory Drive Hypothesis proposes that call frequency is a response to climate-induced differences in atmospheric attenuation and predicts that increases in atmospheric attenuation selects for calls of lower frequency. We measured the morphology and resting call frequency (RF) of 111 R . simulator and 126 R . swinnyi individuals across their distributional range to test the above hypotheses. Contrary to the prediction of James' Rule, divergence in body size could not explain the variation in RF. Instead, acoustic divergence in RF was best predicted by latitude, geography and climate-induced differences in atmospheric attenuation, as predicted by the Sensory Drive Hypothesis. Although variation in RF was strongly influenced by temperature and humidity, other climatic variables (associated with latitude and altitude) as well as drift (as suggested by a positive correlation between call variation and geographic distance, especially in R . simulator ) may also play an important role

Preservation of glaciochemical time-series in snow and ice from the Penny Ice Cap, Baffin Island

A detailed investigation of major ion concentrations of snow and ice in the summit region of Penny Ice Cap (PIC) was performed to determine the effects of summer melt on the glaciochemical time-series. While ion migration due to meltwater percolation makes it difficult to confidently count annual layers in the glaciochemical profiles, time-series of these parameters do show good structure and a strong one year spectral component, suggesting that annual to biannual signals are preserved in PIC glaciochemical records

Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum.

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one\u27s own body

Clipless management of the renal vein during hand-assist laparoscopic donor nephrectomy

BACKGROUND: Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can occur, and is often due to interference from previously placed clips. We report our experience with a clipless technique in which no vascular clips are placed on tributaries of the renal vein at or near the renal hilum in order to avoid laparoscopic stapling device misfires. METHODS: From December 20, 2002 to April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor nephrectomy (LDN) at our institution. Clipless management of the renal vein tributaries was used in all patients, and these vessels were divided using either a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO). The medical and operative records of the donors and recipients were reviewed to evaluate patient outcomes. RESULTS: The mean follow-up time was 14 months. Of the 50 LDN procedures, there were no laparoscopic stapling device malfunctions and no vascular complications. All renal allografts were functioning at the time of follow-up. CONCLUSION: Laparoscopic stapling device failure due to deployment across previously placed surgical clips during laparoscopic live donor nephrectomy can be prevented by not placing clips on the tributaries of the renal vein. In our series, there were no vascular complications and no device misfires. We believe this clipless technique improves the safety of laparoscopic donor nephrectomy

The Feasibility and Impact of Delivering a Mind-Body Intervention in a Virtual World

Introduction: Mind-body medical approaches may ameliorate chronic disease. Stress reduction is particularly helpful, but face-to-face delivery systems cannot reach all those who might benefit. An online, 3-dimensional virtual world may be able to support the rich interpersonal interactions required of this approach. In this pilot study, we explore the feasibility of translating a face-to-face stress reduction program into an online virtual setting and estimate the effect size of the intervention. Methods and Findings: Domain experts in virtual world technology joined with mind body practitioners to translate an existing 8 week relaxation response-based resiliency program into an 8-week virtual world-based program in Second Life™ (SL). Twenty-four healthy volunteers with at least one month's experience in SL completed the program. Each subject filled out the Perceived Stress Scale (PSS) and the Symptom Checklist 90- Revised (SCL-90-R) before and after taking part. Participants took part in one of 3 groups of about 10 subjects. The participants found the program to be helpful and enjoyable. Many reported that the virtual environment was an excellent substitute for the preferred face-to-face approach. On quantitative measures, there was a general trend toward decreased perceived stress, (15.7 to 15.0), symptoms of depression, (57.6 to 57.0) and anxiety (56.8 to 54.8). There was a significant decrease of 2.8 points on the SCL-90-R Global Severity Index (p<0.05). Conclusions: This pilot project showed that it is feasible to deliver a typical mind-body medical intervention through a virtual environment and that it is well received. Moreover, the small reduction in psychological distress suggests further research is warranted. Based on the data collected for this project, a randomized trial with less than 50 subjects would be appropriately powered if perceived stress is the primary outcome

The Viral Interferon Regulatory Factors of Kaposi's Sarcoma-Associated Herpesvirus Differ in Their Inhibition of Interferon Activation Mediated by Toll-Like Receptor 3

Kaposi's sarcoma-associated herpesvirus (KSHV) infection is correlated with three human malignancies and can establish lifelong latent infection in multiple cell types within its human host. In order to establish and maintain infection, KSHV utilizes multiple mechanisms to evade the host immune response. One such mechanism is the expression of a family of genes with homology to cellular interferon (IFN) regulatory factors (IRFs), known as viral IRFs (vIRFs). We demonstrate here that KSHV vIRF1, -2, and -3 have a differential ability to block type I interferon signaling mediated by Toll-like receptor 3 (TLR3), a receptor we have previously shown to be activated upon KSHV infection. vIRF1, -2, and -3 inhibited TLR3-driven activation of IFN transcription reporters. However, only vIRF1 and vIRF2 inhibited increases in both IFN-β message and protein levels following TLR3 activation. The expression of vIRF1 and vIRF2 also allowed for increased replication of a virus known to activate TLR3 signaling. Furthermore, vIRF1 and vIRF2 may block TLR3-mediated signaling via different mechanisms. Altogether, this report indicates that vIRFs are able to block IFN mediated by TLRs but that each vIRF has a unique function and mechanism for blocking antiviral IFN responses

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

From McKinlay, C. J. D., Alsweiler, J. M., Ansell, J. M., Anstice, N. S., Chase, J. G., Gamble, G. D., … Harding, J. E. (2015). Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. New England Journal of Medicine, 373(16), 1507–1518. https://doi.org/10.1056/NEJMoa1504909 Copyright © 2015 Massachusetts Medical Society. Reprinted with permission.Neonatal hypoglycemia is a common and readily treatable risk factor for neurologic impairment in children. Although associations between prolonged symptomatic neonatal hypoglycemia and brain injury are well established,1 the effect of milder hypoglycemia on neurologic development is uncertain.2 Consequently, large numbers of newborns are screened and treated for low blood glucose concentrations, which involves heel-stick blood tests, substantial costs, and the possibility of iatrogenic harm. Under current guidelines,3 up to 30% of neonates are considered to be at risk for hypoglycemia, 15% receive a diagnosis of hypoglycemia, and approximately 10% require admission to a neonatal intensive care unit,4 costing an estimated $2.1 billion annually in the United States alone.5 Associated formula feeding and possible separation of mother and baby reduce breast-feeding rates,6 with potentially adverse effects on broader infant health and development. In addition, pain-induced stress in neonates, such as repeated heel sticks, may itself impair brain development.7 Thus, to determine appropriate glycemic thresholds for treatment, there have been repeated calls for studies of the effect of neonatal hypoglycemia on long-term development.2,8 We report the results of the Children with Hypoglycaemia and Their Later Development (CHYLD) study, a large prospective cohort study of term and late-preterm neonates born at risk for hypoglycemia. The study investigated the relation between the duration, frequency, and severity of low glucose concentrations in the neonatal period and neuropsychological development at 2 years.Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069622), the Health Research Council of New Zealand (10-399), and the Auckland Medical Research Foundation (1110009)

An Important Role for Mitochondrial Antiviral Signaling Protein in the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle

Kaposi's sarcoma-associated herpesvirus (KSHV) has been shown to be recognized by two families of pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Here we show that MAVS and RIG-I (retinoic acid-inducible gene 1), an RLR family member, also have a role in suppressing KSHV replication and production. In the context of primary infection, we show that in cells with depleted levels of MAVS or RIG-I, KSHV transcription is increased, while beta interferon (IFN-β) induction is attenuated. We also observed that MAVS and RIG-I are critical during the process of reactivation. Depletion of MAVS and RIG-I prior to reactivation led to increased viral load and production of infectious virus. Finally, MAVS depletion in latent KSHV-infected B cells leads to increased viral gene transcription. Overall, this study suggests a role for MAVS and RIG-I signaling during different stages of the KSHV life cycle

Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates

Trypanosoma cruzi, the agent of Chagas disease, probably infects tens of millions of people, primarily in Latin America, causing morbidity and mortality. The options for treatment and prevention of Chagas disease are limited and underutilized. Here we describe the discovery of a series of benzoxaborole compounds with nanomolar activity against extra- and intracellular stages of T. cruzi. Leveraging both ongoing drug discovery efforts in related kinetoplastids, and the exceptional models for rapid drug screening and optimization in T. cruzi, we have identified the prodrug AN15368 that is activated by parasite carboxypeptidases to yield a compound that targets the messenger RNA processing pathway in T. cruzi. AN15368 was found to be active in vitro and in vivo against a range of genetically distinct T. cruzi lineages and was uniformly curative in non-human primates (NHPs) with long-term naturally acquired infections. Treatment in NHPs also revealed no detectable acute toxicity or long-term health or reproductive impact. Thus, AN15368 is an extensively validated and apparently safe, clinically ready candidate with promising potential for prevention and treatment of Chagas disease

Performance of a multianalyte test as an aid for the diagnosis of ovarian cancer in symptomatic women

Background: Concomitant with the development of in vitro diagnostic multivariate index assays (IVDMIAs) to improve the diagnostic efficiency of ovarian cancer detection is the need to identify appropriate biostatistical approaches to assess improvements in risk predication. In this study, we assessed the utility of three different approaches for comparing diagnostic efficiency of an ovarian cancer multivariate assay in a retrospective case control phase 2 biomarker trial. The control cohort included both disease-free women and women with benign gynecological conditions to more accurately reflect the target population of symptomatic women