Heat stress but not inbreeding affects offensive sperm competitiveness in Callosobruchus maculatus

Environmental and genetic stress have well‐known detrimental effects on ejaculate quality, but their concomitant effect on male fitness remains poorly understood. We used competitive fertilization assays to expose the effects of stress on offensive sperm competitive ability in the beetle Callosobruchus maculatus, a species where ejaculates make up more than 5% of male body mass. To examine the effects of environmental and genetic stress, males derived from outcrosses or sib matings were heat shocked at 50°C for 50 min during the pupal stage, while their siblings were maintained at a standard rearing temperature of 28°C. Heat‐shocked males achieved only half the offensive paternity success of their siblings. While this population exhibited inbreeding depression in body size, sperm competitiveness was unaffected by inbreeding, nor did the effect of heat shock stress on sperm competitiveness depend on inbreeding status. In contrast, pupal emergence success was increased by 34% among heat‐stressed individuals, regardless of their inbreeding status. Heat‐shocked males' ejaculate size was 19% reduced, but they exhibited 25% increased mating duration in single mating trials. Our results highlight both the importance of stress in postcopulatory sexual selection, and the variability among stressors in affecting male fitness.     

Automated,High Accuracy Classification of Parkinsonian Disorders: A Pattern Recognition Approach

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process.     

Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes

Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.     

Impact of Low Dose Prenatal Ethanol Exposure on Glucose Homeostasis in Sprague-Dawley Rats Aged up to Eight Months

Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring’s health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.     

Ocular-Motor Profile and Effects of Memantine in a Familial Form of Adult Cerebellar Ataxia with Slow Saccades and Square Wave Saccadic Intrusions

Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°–18°) and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly), but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich’s, in which saccadic intrusions are prominent.     

International EcoHealth One Health Congress 2016

We provide an overview of terrestrial animal translocations carried out for conservation purposes in Britain, summarising what has been achieved in recent decades and discussing the issues raised by this approach to conservation. In the last 40 years, at least nine species have been reintroduced following extinction in Britain (or at least one country within Britain), including five birds, one mammal, one amphibian and two invertebrates. Many more species have been translocated within Britain to establish additional populations in order to improve conservation status. We discuss the guidelines and protocols used to assess translocation projects in Britain, notably the IUCN guidelines, most recently revised in 2013. We also discuss the likely use of species translocations in future and suggest that, in our increasingly fragmented landscapes, they will have an important role to play in conservation restoration, especially for animals with limited mobility. Moving species around is a complex undertaking and our understanding of the inherent risks involved, including the risks from disease, has improved significantly in recent years. Conservation translocations should be considered in the context of species recovery targets and high standards should be maintained so that disease risks and other potentially negative impacts are minimised.

     

Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications

In this study, we investigate the translational potential of a novel combined construct using an FDA-approved decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) seeded with human or porcine mesenchymal stem cells (MSCs) for cardiovascular indications. With the emerging success of individual component in various clinical applications, the combination of SIS-ECM with MSCs could provide additional therapeutic potential compared to individual components alone for cardiovascular repair. We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes. Additionally, we evaluated the ability of porcine MSCs to modulate recipient graft-specific response towards SIS-ECM in a porcine cardiac patch in vivo model. Specifically, we determined: 1) in vitro loading-capacity of human MSCs on SIS-ECM, 2) effect of cell seeding on SIS-ECM structure, compositions and mechanical properties, 3) effect of SIS-ECM seeding on human MSC phenotypes and differentiation potential, and 4) optimal orientation and dose of porcine MSCs seeded SIS-ECM for an in vivo cardiac application. In this study, histological structure, biochemical compositions and mechanical properties of the FDA-approved SIS-ECM biomaterial were retained following MSCs repopulation in vitro. Similarly, the cellular phenotypes and differentiation potential of MSCs were preserved following seeding on SIS-ECM. In a porcine in vivo patch study, the presence of porcine MSCs on SIS-ECM significantly reduced adaptive T cell response regardless of cell dose and orientation compared to SIS-ECM alone. These findings substantiate the clinical translational potential of combined SIS-ECM seeded with MSCs as a promising therapeutic candidate for cardiac applications.     

Does the circadian clock drift when pilots fly multiple transpacific flights with 1- to 2-day layovers?

On trips with multiple transmeridian flights, pilots experience successive non-24 h day/night cycles with circadian and sleep disruption. One study across a 9-day sequence of transpacific flights (no in-flight sleep, 1-day layovers between flights) reported an average period in the core body temperature rhythm of 24.6 h (circadian drift). Consequently, pilots were sometimes flying through the circadian performance nadir and had to readapt to home base time at the end of the trip. The present study examined circadian drift in trip patterns with longer flights and in-flight sleep. Thirty-nine B747-400 pilots (19 captains, 20 first officers, mean age = 55.5 years) were monitored on 9- to 13-day trips with multiple return flights between East Coast USA and Japan (in 4-pilot crews) and between Japan and Hawaii (in 3-pilot crews), with 1-day layovers between each flight. Measures included total in-flight sleep (actigraphy, log books) and top of descent (TOD) measures of sleepiness (Karolinska Sleepiness Scale), fatigue (Samn–Perelli Crew Status Check) and psychomotor vigilance task (PVT) performance. Circadian rhythms of individual pilots were not monitored. To detect circadian drift, mixed-model analysis of variance examined whether for a given flight, total in-flight sleep and TOD measures varied according to when the flight occurred in the trip sequence. In addition, sleep propensity curves for pre-trip and post-trip days were examined (Chi-square periodogram analyses). Limited data suggest that total in-flight sleep of relief crew at landing may have decreased across successive East Coast USA–Japan (flights 1, 3, 5 or 7; median arrival 03:45 Eastern Daylight Time (EDT)). However, PVT response speed at TOD was faster on East Coast USA–Japan flights later in the trip. On these flights, circadian drift would result in flights later in the trip landing closer to the evening wake maintenance zone, when sleep is difficult and PVT response speeds are fastest. On Japan–East Coast USA flights (flights 2, 4, 6 or 8; median arrival time 14:52 EDT), PVT response speeds were slower on flight 8 than on flight 2. Circadian drift would move these arrivals progressively earlier in the SCN pacemaker cycle, where PVT response speeds are slower. Across the five post-trip days, 12 pilots (Group A) immediately resumed their pre-trip sleep pattern of a single nocturnal sleep episode; 9 pilots (Group B) had a daytime nap on most days that moved progressively earlier until it merged with nocturnal sleep and 17 pilots (Group C) had nocturnal sleep and intermittent naps. Chi-square periodogram analyses of the sleep propensity curves for each group across baseline and post-trip days suggest full adaptation to EDT from post-trip day 1 (dominant period = 24 h). However, in Groups B and C, the patterns of split sleep post-trip compared to pre-trip suggest that this may be misleading. We conclude that the trends in total in-flight sleep and significant changes in PVT performance speed at TOD provide preliminary evidence for circadian drift, as do persistent patterns of split sleep post-trip. However, new measures to track circadian rhythms in individual pilots are needed to confirm these findings.