Paedomorphic Facial Expressions Give Dogs a Selective Advantage

How wolves were first domesticated is unknown. One hypothesis suggests that wolves underwent a process of self-domestication by tolerating human presence and taking advantage of scavenging possibilities. The puppy-like physical and behavioural traits seen in dogs are thought to have evolved later, as a byproduct of selection against aggression. Using speed of selection from rehoming shelters as a proxy for artificial selection, we tested whether paedomorphic features give dogs a selective advantage in their current environment. Dogs who exhibited facial expressions that enhance their neonatal appearance were preferentially selected by humans. Thus, early domestication of wolves may have occurred not only as wolf populations became tamer, but also as they exploited human preferences for paedomorphic characteristics. These findings, therefore, add to our understanding of early dog domestication as a complex co-evolutionary process.     

Akt regulates glutamate receptor trafficking and postsynaptic membrane elaboration at the Drosophila neuromuscular junction

The Akt family of serine‐threonine kinases integrates a myriad of signals governing cell proliferation, apoptosis, glucose metabolism, and cytoskeletal organization. Akt affects neuronal morphology and function, influencing dendrite growth and the expression of ion channels. Akt is also an integral element of PI3Kinase‐target of rapamycin (TOR)‐Rheb signaling, a pathway that affects synapse assembly in both vertebrates and Drosophila. Our recent findings demonstrated that disruption of this pathway in Drosophila is responsible for a number of neurodevelopmental deficits that may also affect phenotypes associated with tuberous sclerosis complex, a disorder resulting from mutations compromising the TSC1/TSC2 complex, an inhibitor of TOR (Dimitroff et al., 2012). Therefore, we examined the role of Akt in the assembly and physiological function of the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse that displays developmental and activity‐dependent plasticity. The single Drosophila Akt family member, Akt1 selectively altered the postsynaptic targeting of one glutamate receptor subunit, GluRIIA, and was required for the expansion of a specialized postsynaptic membrane compartment, the subsynaptic reticulum (SSR). Several lines of evidence indicated that Akt1 influences SSR assembly by regulation of Gtaxin, a Drosophila t‐SNARE protein (Gorczyca et al., 2007) in a manner independent of the mislocalization of GluRIIA. Our findings show that Akt1 governs two critical elements of synapse development, neurotransmitter receptor localization, and postsynaptic membrane elaboration. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 73: 723–743, 2013     

Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle

Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES) for 1 or 4 weeks following muscle-derived stem cell (MDSC) transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation) presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle.     

Population genetics and relatedness in a critically endangered island raptor, Ridgway’s Hawk Buteo ridgwayi

Many island avian populations are of conservation interest because they have a higher risk of extinction than mainland populations. Susceptibility of island birds to extinction is primarily related to human induced change through habitat loss, persecution, and introduction of exotic species, in combination with genetic factors. We used microsatellite profiles from 11 loci to assess genetic diversity and relatedness in the critically endangered hawk Buteo ridgwayi endemic to the island of Hispaniola in the Caribbean. Using samples collected between 2005 and 2009, our results revealed a relatively high level of heterozygosity, evidence of a recent genetic bottleneck, and the occurrence of inbreeding within the population. Pair relatedness analysis found 4 of 7 sampled breeding pairs to be related similar to that of first cousin or greater. Pedigree estimates indicated that up to 18 % of potential pairings would be between individuals with relatedness values similar to that of half-sibling. We discuss our findings in the context of conservation genetic management suggesting both carefully managed translocations and the initiation of a captive population as a safeguard of the remaining genetic diversity.     

Mortality and Potential Years of Life Lost Attributable to Alcohol Consumption by Race and Sex in the United States in 2005

Background

Alcohol has been linked to health disparities between races in the US; however, race-specific alcohol-attributable mortality has never been estimated. The objective of this article is to estimate premature mortality attributable to alcohol in the US in 2005, differentiated by race, age and sex for people 15 to 64 years of age.

Methods and Findings

Mortality attributable to alcohol was estimated based on alcohol-attributable fractions using indicators of exposure from the National Epidemiologic Survey on Alcohol and Related Conditions and risk relations from the Comparative Risk Assessment study. Consumption data were corrected for undercoverage (the observed underreporting of alcohol consumption when using survey as compared to sales data) using adult per capita consumption from WHO databases. Mortality data by cause of death were obtained from the US Department of Health and Human Services. For people 15 to 64 years of age in the US in 2005, alcohol was responsible for 55,974 deaths (46,461 for men; 9,513 for women) representing 9.0% of all deaths, and 1,288,700 PYLL (1,087,280 for men; 201,420 for women) representing 10.7% of all PYLL. Per 100,000 people, this represents 29 deaths (29 for White; 40 for Black; 82 for Native Americans; 6 for Asian/Pacific Islander) and 670 PYLL (673 for White; 808 for Black; 1,808 for Native American; 158 for Asian/Pacific Islander). Sensitivity analyses showed a lower but still substantial burden without adjusting for undercoverage.

Conclusions

The burden of mortality attributable to alcohol in the US is unequal among people of different races and between men and women. Racial differences in alcohol consumption and the resulting harms explain in part the observed disparities in the premature mortality burden between races, suggesting the need for interventions for specific subgroups of the population such as Native Americans.     

Investigation of Genetic Structure between Deep and Shallow Populations of the Southern Rock Lobster,Jasus edwardsii in Tasmania,Australia

The southern rock lobster, Jasus edwardsii, shows clear phenotypic differences between shallow water (red coloured) and deeper water (pale coloured) individuals. Translocations of individuals from deeper water to shallower waters are currently being trialled as a management strategy to facilitate a phenotypic change from lower value pale colouration, common in deeper waters, to the higher value red colouration found in shallow waters. Although panmixia across the J. edwardsii range has been long assumed, it is critical to assess the genetic variability of the species to ensure that the level of population connectivity is appropriately understood and translocations do not have unintended consequences. Eight microsatellite loci were used to investigate genetic differentiation between six sites (three shallow, three deep) across southern Tasmania, Australia, and one from New Zealand. Based on analyses the assumption of panmixia was rejected, revealing small levels of genetic differentiation across southern Tasmania, significant levels of differentiation between Tasmania and New Zealand, and high levels of asymmetric gene flow in an easterly direction from Tasmania into New Zealand. These results suggest that translocation among Tasmanian populations are not likely to be problematic, however, a re-consideration of panmictic stock structure for this species is necessary.     

Modeling Long-Term Host Cell-Giardia lamblia Interactions in an In Vitro Co-Culture System

Globally, there are greater than 700,000 deaths per year associated with diarrheal disease. The flagellated intestinal parasite, Giardia lamblia, is one of the most common intestinal pathogens in both humans and animals throughout the world. While attached to the gastrointestinal epithelium, Giardia induces epithelial cell apoptosis, disrupts tight junctions, and increases intestinal permeability. The underlying cellular and molecular mechanisms of giardiasis, including the role lamina propria immune cells, such as macrophages, play in parasite control or clearance are poorly understood. Thus far, one of the major obstacles in ascertaining the mechanisms of Giardia pathology is the lack of a functionally relevant model for the long-term study of the parasite in vitro. Here we report on the development of an in vitro co-culture model which maintains the basolateral-apical architecture of the small intestine and allows for long-term survival of the parasite. Using transwell inserts, Caco-2 intestinal epithelial cells and IC-21 macrophages are co-cultured in the presence of Giardia trophozoites. Using the developed model, we show that Giardia trophozoites survive over 21 days and proliferate in a combination media of Caco-2 cell and Giardia medium. Giardia induces apoptosis of epithelial cells through caspase-3 activation and macrophages do not abrogate this response. Additionally, macrophages induce Caco-2 cells to secrete the pro-inflammatory cytokines, GRO and IL-8, a response abolished by Giardia indicating parasite induced suppression of the host immune response. The co-culture model provides additional complexity and information when compared to a single-cell model. This model will be a valuable tool for answering long-standing questions on host-parasite biology that may lead to discovery of new therapeutic interventions.     

Seasonal variation in grey crowned crane (Balearica regulorum) abundance in the Ngorongoro Crater,Tanzania

There are few quantitative estimates of numbers of Africa's endangered grey crowned cranes (Balearica regulorum), yet conservation of this species will depend on such estimates. We used line-transect distance sampling on multiple 2-km segments of an existing road network to estimate the abundance of grey crowned cranes in a portion of the Ngorongoro Crater, Tanzania, during the wet (April) and dry (August) seasons of 2016. We analysed data from 106 transects on which we observed 174 groups of 1–61 cranes (median and mode = 2). Abundance and density estimates on the areas surveyed were best modelled without group size as a covariate and indicated that mean crane densities were significantly lower in the wet season (2.4/km²) than in the dry season (20.2 cranes/km²). Even based on survey areas of different size, minimum estimated numbers of cranes in the Crater (wet season: 108–133; dry season: 362–401) likely reflect the concentration of cranes in the nonbreeding (dry) season in the perennial wetlands of the Crater and reinforce the notion of the Crater being a key seasonal habitat for crane populations in northern Tanzania, as previously suggested in the literature.     

Environmental Influences on Dall's Sheep Survival

Understanding how species respond to environmental conditions can assist with conservation strategies and harvest management, especially in arctic and boreal regions that are experiencing rapid climate change. Although climatic influences on species distributions have been studied, broad-scale effects of climate on survival are less well known. We examined the interactive effects of meteorological and remotely sensed environmental variables on survival of Dall's sheep (Ovis dalli dalli) lambs and adults by synthesizing radio-telemetry data across their range. We used data from 9 studies of adult sheep and 2 studies of lambs that were conducted between 1997 and 2012 at sites spanning the species' range in Alaska, USA, and northwestern Canada. We obtained environmental variables throughout the range of Dall's sheep, including the normalized difference vegetation index (NDVI) from optical remote sensing, freeze-thaw frequency (FTF) from passive microwave remote sensing, and gridded climate variables such as snow water equivalent, temperature, and precipitation. We used Cox proportional hazard regression to investigate the effects of environmental variables recorded during summer, winter, and the previous winter on annual survival rates of Dall's sheep lambs and adults. Summer NDVI was the most influential environmental factor affecting lamb survival, with improved lamb survival occurring in years with a high maximum NDVI. Also, lamb predation by coyotes (Canis latrans) and golden eagles (Aquila chrysaetos) decreased substantially with increasing NDVI. The previous winter FTF had the strongest effect on adult survival, with decreased survival occurring after winters with high FTF. In addition, these remotely sensed environmental factors interacted with meteorological factors to affect survival, such that effects of winter temperature depended on summer NDVI and winter FTF. Warm winters increased lamb survival only when preceded by summers with high NDVI, and warm winters increased adult survival only when winter FTF was low. Thus, potential benefits of climate warming may be counteracted if wintertime freeze-thaw events markedly increase. Correlations among environmental variables across sites were low, and regional climate cycles such as the Pacific Decadal Oscillation (PDO) had weak effects, indicating substantial local variability in climatic conditions experienced by Dall's sheep across their range. These findings can help managers anticipate how Dall's sheep populations will respond to changes in local environmental conditions. Our results also highlight the utility of multiple remotely sensed environmental conditions for ungulate management, especially passive microwave products that provide valuable information on winter icing events. © 2020 The Wildlife Society.     

9-Phenanthrol and flufenamic acid inhibit calcium oscillations in HL-1 mouse cardiomyocytes

It is well established that intracellular calcium ([Ca²⁺]_i) controls the inotropic state of the myocardium, and evidence mounts that a “Ca²⁺ clock” controls the chronotropic state of the heart. Recent findings describe a calcium-activated nonselective cation channel (NSC_Ca) in various cardiac preparations sharing hallmark characteristics of the transient receptor potential melastatin 4 (TRPM4). TRPM4 is functionally expressed throughout the heart and has been implicated as a NSC_Ca that mediates membrane depolarization. However, the functional significance of TRPM4 in regards to Ca²⁺ signaling and its effects on cellular excitability and pacemaker function remains inconclusive. Here, we show by Fura2 Ca-imaging that pharmacological inhibition of TRPM4 in HL-1 mouse cardiac myocytes by 9-phenanthrol (10 μM) and flufenamic acid (10 and 100 μM) decreases Ca²⁺ oscillations followed by an overall increase in [Ca²⁺]_i. The latter occurs also in HL-1 cells in Ca²⁺-free solution and after depletion of sarcoplasmic reticulum Ca²⁺ with thapsigargin (10 μM). These pharmacologic agents also depolarize HL-1 cell mitochondrial membrane potential. Furthermore, by on-cell voltage clamp we show that 9-phenanthrol reversibly inhibits membrane current; by fluorescence immunohistochemistry we demonstrate that HL-1 cells display punctate surface labeling with TRPM4 antibody; and by immunoblotting using this antibody we show these cells express a 130–150 kDa protein, as expected for TRPM4. We conclude that 9-phenanthrol inhibits TRPM4 ion channels in HL-1 cells, which in turn decreases Ca²⁺ oscillations followed by a compensatory increase in [Ca²⁺]_i from an intracellular store other than the sarcoplasmic reticulum. We speculate that the most likely source is the mitochondrion.