Unconventional life history in a migratory shorebird: desegregating reproduction and migration.

Conventional life-history theory predicts that energy-demanding events such as reproduction and migration must be temporally segregated to avoid resource limitation. Here, we provide, to our knowledge, the first direct evidence of 'itinerant breeding' in a migratory bird, an incredibly rare breeding strategy (less than 0.1% of extant bird species) that involves the temporal overlap of migratory and reproductive periods of the annual cycle. Based on GPS-tracking of over 200 female American woodcock, most female woodcock (greater than 80%) nested more than once (some up to six times) with short re-nest intervals, and females moved northwards on average 800 km between first and second nests, and then smaller distances (ca 200+ km) between subsequent nesting attempts. Reliance on ephemeral habitat for breeding, ground-nesting and key aspects of life history that reduce both the costs of reproduction and migration probably explain the prevalence of this rare phenotype in woodcock and why itinerant breeding so rarely occurs in other bird species.

Exploring Early-Stage Retinal Neurodegeneration in Murine Pigmentary Glaucoma: Insights From Gene Networks and miRNA Regulation Analyses.

Purpose: Glaucoma is a group of heterogeneous optic neuropathies characterized by the progressive degeneration of retinal ganglion cells. However, the underlying mechanisms have not been understood completely. We aimed to elucidate the genetic network associated with the development of pigmentary glaucoma with DBA/2J (D2) mouse model of glaucoma and corresponding genetic control D2-Gpnmb (D2G) mice carrying the wild type (WT) Gpnmb allele. Methods: Retinas isolated from 13 D2 and 12 D2G mice were subdivided into 2 age groups: pre-onset (1-6 months: samples were collected at approximately 1-2, 2-4, and 5-6 months) and post-onset (7-15 months: samples were collected at approximately 7-9, 10-12, and 13-15 months) glaucoma were compared. Differential gene expression (DEG) analysis and gene-set enrichment analyses were performed. To identify micro-RNAs (miRNAs) that target Gpnmb, miRNA expression levels were correlated with time point matched mRNA expression levels. A weighted gene co-expression network analysis (WGCNA) was performed using the reference BXD mouse population. Quantitative real-time PCR (qRT-PCR) was used to validate Gpnmb and miRNA expression levels. Results: A total of 314 and 86 DEGs were identified in the pre-onset and post-onset glaucoma groups, respectively. DEGs in the pre-onset glaucoma group were associated with the crystallin gene family, whereas those in the post-onset group were related to innate immune system response. Of 1329 miRNAs predicted to target Gpnmb, 3 miRNAs (miR-125a-3p, miR-3076-5p, and miR-214-5p) were selected. A total of 47 genes demonstrated overlapping with the identified DEGs between D2 and D2G, segregated into their time-relevant stages. Gpnmb was significantly downregulated, whereas 2 out of 3 miRNAs were significantly upregulated (P < 0.05) in D2 mice at both 3-and 10-month time points. Conclusions: These findings suggest distinct gene-sets involved in pre-and post-glaucoma in the D2 mouse. We identified three miRNAs regulating Gpnmb in the development of murine pigmentary glaucoma.

Gene-by-environment modulation of lifespan and weight gain in the murine BXD family.

How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a low-fat chow diet (CD, n = 663) or a high-fat diet (HFD, n = 685). We further generate key metabolic data in a parallel cohort euthanized at four time points. HFD feeding shortens lifespan by 12%: equivalent to a decade in humans. Initial body weight and early weight gains account for longevity differences of roughly 4-6 days per gram. At 500 days, animals on a HFD typically gain four times as much weight as control, but variation in weight gain does not correlate with lifespan. Classic serum metabolites, often regarded as health biomarkers, are not necessarily strong predictors of longevity. Our data indicate that responses to a HFD are substantially modulated by gene-by-environment interactions, highlighting the importance of genetic variation in making accurate individualized dietary recommendations.

Identification of a Functional Non-coding Variant in the GABA A Receptor α2 Subunit of the C57BL/6J Mouse Reference Genome: Major Implications for Neuroscience Research.

GABA type-A (GABA-A) receptors containing the α2 subunit (GABRA2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J. Here we demonstrate a global reduction of GABRA2 brain protein and mRNA in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J. The mutation is a single base pair deletion located in an intron adjacent to a splice acceptor site that only occurs in the B6J reference genome. The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines. Repair of the deletion using CRISPR-Cas9-mediated gene editing on a B6J genetic background completely restored brain levels of GABRA2 protein and mRNA. Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum. These results suggest that naturally occurring variation in GABRA2 levels between B6J and other substrains or inbred strains may also explain strain differences in anxiety-like or alcohol and drug response traits related to striatal function. Characterization of the B6J private mutation in the Gabra2 gene is of critical importance to molecular genetic studies in neurobiological research because this strain is widely used to generate genetically engineered mice and murine genetic populations, and is the most widely utilized strain for evaluation of anxiety-like, depression-like, pain, epilepsy, and drug response traits that may be partly modulated by GABRA2 function.

Ethanol's Effect on Coq7 Expression in the Hippocampus of Mice.

Coenzyme Q (CoQ) is a well-studied molecule, present in every cell membrane in the body, best known for its roles as a mitochondrial electron transporter and a potent membrane anti-oxidant. Much of the previous work was done in vitro in yeast and more recent work has suggested that CoQ may have additional roles prompting calls for a re-assessment of its role using in vivo systems in mammals. Here we investigated the putative role of Coenzyme Q in ethanol-induced effects in vivo using BXD RI mice. We examined hippocampal expression of Coq7 in saline controls and after an acute ethanol treatment, noting enriched biologic processes and pathways following ethanol administration. We also identified 45 ethanol-related phenotypes that were significantly correlated with Coq7 expression, including six phenotypes related to conditioned taste aversion and ethanol preference. This analysis highlights the need for further investigation of Coq7 and related genes in vivo as well as previously unrecognized roles that it may play in the hippocampus.

Genetic cartography of longevity in humans and mice: Current landscape and horizons.

Aging is a complex and highly variable process. Heritability of longevity among humans and other species is low, and this finding has given rise to the idea that it may be futile to search for DNA variants that modulate aging. We argue that the problem in mapping longevity genes is mainly one of low power and the genetic and environmental complexity of aging. In this review we highlight progress made in mapping genes and molecular networks associated with longevity, paying special attention to work in mice and humans. We summarize 40 years of linkage studies using murine cohorts and 15 years of studies in human populations that have exploited candidate gene and genome-wide association methods. A small but growing number of gene variants contribute to known longevity mechanisms, but a much larger set have unknown functions. We outline these and other challenges and suggest some possible solutions, including more intense collaboration between research communities that use model organisms and human cohorts. Once hundreds of gene variants have been linked to differences in longevity in mammals, it will become feasible to systematically explore gene-by-environmental interactions, dissect mechanisms with more assurance, and evaluate the roles of epistasis and epigenetics in aging. A deeper understanding of complex networks-genetic, cellular, physiological, and social-should position us well to improve healthspan.

Miniature environmental chambers for temperature humidity bias testing of microelectronics.

Environmental chambers are commonly used for reliability testing of microelectronics and other products and materials. These chambers are large, expensive, and limit electrical connectivity to devices under test. In this paper, we present a collection of ten small, low-cost environmental chambers, with humidity control based on mixtures of water and glycerol placed inside the chambers. We demonstrate relative humidities from 44% to 90%, at temperatures from 30 to 85 °C, enabling industry-standard testing at 85% humidity and 85 °C. The division of samples between ten separate chambers allows different conditions to be applied to each sample, in order to quickly characterize the effects of the environment on device reliability, enabling extrapolation to estimate lifetimes in working conditions.

Highly-stable silver nanobelts joined via diffusion-free attachment.

Silver nanobelts are demonstrated here to undergo inter-particle joining at relatively low temperatures of less than 180 °C. For surface-coated networks of nanobelts this joining reduced the network sheet resistance by 95%. The joining mechanism appears to be non-diffusional oriented attachment, caused by the thermal reactivation of the halted oriented attachment mechanism that occurred originally at room temperature during the rapid nanobelt synthesis. This self-assembly mechanism was explored by in situ electrical and calorimetric experiments, and supported by electron microscopy. Unlike pentagonal silver nanowires, silver nanobelts do not rely on diffusional instability to achieve workably low joining temperatures. The oriented attachment displayed by nanobelts represents a new approach to achieving valuable reductions in network resistance, disentangled from the instability and diffusion-driven failure by nanoparticle degradation displayed by competing silver nanoparticles.

Traditional East Asian medical pulse diagnosis: a preliminary physiologic investigation.

BACKGROUND: Toyohari Meridian Therapy (TMT) is a Japanese system of acupuncture that utilizes radial pulse diagnosis to diagnose and guide acupuncture treatment, including ascertaining when the treatment has concluded. The "root" treatment involves manipulation of the body's Qi without penetration of the needle. There has been little research into the physiologic correlates of the changes detected through pulse diagnosis by Traditional East Asian Medicine practitioners practicing TMT. OBJECTIVES: The study objective was to investigate whether there were any concurrent changes in physiologic cardiovascular variables, specifically the Central (Buckberg) Sub Endocardial Viability Ratio (SEVR) or Heart Rate (HR) adjusted Augmentation Index (AI), with changes in the radial pulses produced by a TMT "root treatment." MATERIALS AND METHODS: A parallel, single-blind, randomized controlled design was utilized. Sixty-two (62) healthy volunteers were randomized to receive either a TMT root treatment or a sham-treatment. Two (2) TMT practitioners participated, with the same practitioner conducting the needling in each case. The SEVR and HR-adjusted AI were measured by a third researcher. STATISTICAL ANALYSIS: Within-groups analysis (paired Student t-test) and between-groups analysis (analysis of covariance) were used; a p-value of 0.05 was designated as statistically significant. RESULTS: SEVR improved significantly within the treatment group but not in the control group. CONCLUSIONS: Results indicate that changes detected in the pulse by the TMT practitioners were associated with a measurable improvement in the SEVR. The findings of this study offer the possibility for further investigation into radial pulse diagnosis practices in an effort to find a physiologic understanding or basis of TMT practice and the system of pulse diagnosis it uses.

Investigating the reliability of Japanese toyohari meridian therapy diagnosis.

BACKGROUND: Toyohari meridian therapy (TMT) is a Japanese system of acupuncture. Acupoint selection follows diagnosis of the primary and secondary patterns of disharmony (sho) and disturbances in the yang channels. Pulse diagnosis and abdominal palpation diagnosis are the two main diagnostic methods used. Little is known about the reliability of pulse, abdominal, and pattern diagnosis in TMT. This is important since diagnosis of the sho determines acupoint treatment. If diagnosis is unreliable, there can be less confidence that the patient will receive optimal treatment. OBJECTIVE: The objective of this study is to assess the level of agreement between two TMT practitioners on pulse diagnosis, abdominal diagnosis, and diagnosis of the primary and secondary sho. METHODS: An inter-rater reliability study was conducted. Two (2) TMT practitioners separately conducted a TMT examination and completed an assessment form, choosing from a range of possible responses relating to pulse characteristics, abdominal diagnosis, and diagnosis of primary sho and secondary sho. The kappa coefficient was used as a measure of inter-rater reliability of the outcome variables. RESULTS: Sixty-two (62) Australians (22 males, 40 females) aged 20-65 years participated (mean age 49.2 +/- 12.2 years). Level of agreement for pulse diagnosis was 57%, 61%, and 77% for pulse depth, speed, and strength, respectively. For abdominal diagnosis, the level of agreement for involvement of the Lung, Kidney, Spleen, and Liver abdominal regions was 58%, 53%, 35%, and 10%, respectively. The overall level of agreement on primary sho diagnosis was 48% and for secondary sho diagnosis, 44%. CONCLUSIONS: Overall, there was a reasonable level of agreement on basic pulse characteristics and on abdominal diagnosis for two of the abdominal regions. Level of agreement on primary and secondary sho diagnosis suggests room for improvement. Further studies are required in order to gain a greater understanding of the reliability of diagnosis in TMT.