Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.Corinne Caillaud, Mie Mechta, Heidi Ainge, Andreas N Madsen, Patricia Ruell, Emilie Mas, Catherine Bisbal, Jacques Mercier, Stephen Twigg, Trevor A Mori, David Simar and Romain Barrè

Sprint Training Increases Muscle Oxidative Metabolism During High-Intensity Exercise in Patients With Type 1 Diabetes

OBJECTIVE—To investigate sprint-training effects on muscle metabolism during exercise in subjects with (type 1 diabetic group) and without (control group) type 1 diabetes

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

<p>Abstract</p> <p>Background</p> <p>Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications.</p> <p>Methods</p> <p>During the first 150 days after allogeneic HSTC, thirty patients were monitored weekly for active CMV infection by <it>pp65 </it>antigenemia, nested-PCR and real-time PCR assays. Receiver operating characteristic (ROC) plot analysis was performed to determine a threshold value of the CMV DNA load by real-time PCR.</p> <p>Results</p> <p>Using ROC curves, the optimal cutoff value by real-time PCR was 418.4 copies/10⁴PBL (sensitivity, 71.4%; specificity, 89.7%). Twenty seven (90%) of the 30 analyzed patients had active CMV infection and two (6.7%) developed CMV disease. Eleven (40.7%) of these 27 patients had acute GVHD, 18 (66.7%) had opportunistic infection, 5 (18.5%) had chronic rejection and 11 (40.7%) died - one died of CMV disease associated with GVHD and bacterial infection.</p> <p>Conclusions</p> <p>The low incidence of CMV disease in HSCT recipients in our study attests to the efficacy of CMV surveillance based on clinical routine assay. The quantification of CMV DNA load using real-time PCR appears to be applicable to the clinical practice and an optimal cutoff value for guiding timely preemptive therapy should be clinically validated in future studies.</p

Estimating density and detection of bobcats in fragmented midwestern landscapes using spatial capture–recapture data from camera traps

Camera‐trapping data analyzed with spatially explicit capture–recapture (SCR) models can provide a rigorous method for estimating density of small populations of elusive carnivore species. We sought to develop and evaluate the efficacy of SCR models for estimating density of a presumed low‐density bobcat (Lynx rufus) population in fragmented landscapes of west‐central Illinois, USA. We analyzed camera‐trapping data from 49 camera stations in a 1,458‐km2 area deployed over a 77‐day period from 1 February to 18 April 2017. Mean operational time of cameras was 52 days (range = 32–67 days). We captured 23 uniquely identifiable bobcats 113 times and recaptured these same individuals 90 times; 15 of 23 (65.2%) individuals were recaptured at ≥2 camera traps. Total number of bobcat capture events was 139, of which 26 (18.7%) were discarded from analyses because of poor image quality or capture of only a part of an animal in photographs. Of 113 capture events used in analyses, 106 (93.8%) and 7 (6.2%) were classified as positive and tentative identifications, respectively; agreement on tentative identifications of bobcats was high (71.4%) among 3 observers. We photographed bobcats at 36 of 49 (73.5%) camera stations, of which 34 stations were used in analyses. We estimated bobcat density at 1.40 individuals (range = 1.00–2.02)/100 km 2. Our modeled bobcat density estimates are considerably below previously reported densities (30.5 individuals/100 km 2) within the state, and among the lowest yet recorded for the species. Nevertheless, use of remote cameras and SCR models was a viable technique for reliably estimating bobcat density across west‐central Illinois. Our research establishes ecological benchmarks for understanding potential effects of colonization, habitat fragmentation, and exploitation on future assessments of bobcat density using standardized methodologies that can be compared directly over time. Further application of SCR models that quantify specific costs of animal movements (i.e., least‐cost path models) while accounting for landscape connectivity has great utility and relevance for conservation and management of bobcat populations across fragmented Midwestern landscapes

Embracing Dynamic Models for Gene Drive Management

Robust methods of predicting how gene drive systems will interact with ecosystems is essential for safe deployment of gene drive technology. We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology development and implementation. Gene drive technologies, although diverse in design and mode of action, are molecular architectures that promote the transmission of genetic information between generations. In theory, the release of one gene-drive-modified organism (GDMO) has the potential to irreversibly alter species, ecosystems, and environmental processes at a global scale (although in practice numerous mechanisms can limit invasiveness) [1]. This alarming and tremendous potential is an unprecedented challenge to biotechnology management that demands a different scope of oversight and coordination between public stakeholders, developers, and regulators [2,3]. Responsible management of GDMOs needs robust methods of risk assessment that account for and reduce uncertainties across different geographic and ecological contexts [1–3]

Fine-scale local adaptation in life histories along a continuous environmental gradient in Trinidadian guppies

&lt;p&gt;1. Theoretical models of life-history evolution predict a continuum of fast to slow life histories, yet most of empirical support for this theory comes from studies that have considered dichotomous environments (i.e. high vs. low food, presence or absence of major predators). Although this approach has been very successful in identifying the signature of local adaptation, it might limit our ability to identify the causes of underlying patterns of phenotypic variation. By studying the variation in life-history traits along continuous gradients, we can gain better insight into the diversity of adaptations exhibited by natural populations.&lt;/p&gt; &lt;p&gt;2. We studied the evolution of life-history traits along a gradient of predation pressure in the Trinidadian guppy (Poecilia reticulata). Six localities along the Guanapo–Caroni River drainage were selected with respect to their predator community, going from upstream localities where guppies only coexist with a single gape-limited fish predator, to lowland sites where guppies coexist with a complex fish community. Along this gradient, we characterized the field pattern of phenotypic variation in age and size at maturity and reproductive effort. Further, to determine the genetic basis of this variation, we measured these traits in second-generation laboratory-born fish from the same localities sampled in the wild.&lt;/p&gt; &lt;p&gt;3. In nature, we found a fine-scale pattern of phenotypic variation in most life-history traits that paralleled the continuous predation gradient. In the laboratory, we observed that reproductive allocation and brood size progressively decrease while age at maturity and interbrood interval progressively increase with a reduction in the predator community, suggesting a genetic basis to the parallel patterns observed in the field for reproductive allocation and offspring number.&lt;/p&gt; &lt;p&gt;4. However, there were some exceptions to the observed pattern of variation. Females from one low-predation locality matured younger and reproduced more frequently than expected based upon the simple nature of the fish community. We also found significant differences between our field and laboratory results for embryo size, suggesting that this trait is highly plastic.&lt;/p&gt; &lt;p&gt;5. Our results imply that local adaptation in guppies occurs at a finer scale than has previously been shown. Furthermore, while our results are consistent with predator-driven life-history variation, we also find patterns of plasticity that would not be apparent in the traditional dichotomous approach.&lt;/p&gt