This paper evaluates results of a survey of electrostimulation models of myelinated nerve. Participants were asked to determine thresholds of excitation for 18 cases involving different ...characteristics of the neuron, the stimulation waveform, and the electrode arrangement. Responses were received from 7 investigators using 10 models. Excitation thresholds differed significantly among these models. For example, with a 2 ms monophasic stimulus pulse and an electrode/fiber distance of 1 cm, thresholds from the least to greatest value differed by a factor of 8.3; with a 5 μs pulse, thresholds differed by the factor 3.8. Significant differences in reported simulations point to the need for experimental validation. Additional efforts are needed to develop computational models for unmyelinated C-fibers, A-delta fibers, CNS neurons, and CNS Synapses.
H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain ...unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 Å resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal α-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.
Hoof care providers are pivotal for implementing biomechanical optimizations of the musculoskeletal system in the horse. Regular visits allow for the collection of longitudinal, quantitative ...information (“normal ranges”). Changes in movement symmetry, e.g., after shoeing, are indicative of alterations in weight-bearing and push-off force production. Ten Warmblood show jumping horses (7–13 years; 7 geldings, 3 mares) underwent forelimb re-shoeing with rolled rocker shoes, one limb at a time (“limb-by-limb”). Movement symmetry was measured with inertial sensors attached to the head, withers, and pelvis during straight-line trot and lunging. Normalized differences pre/post re-shoeing were compared to published test–retest repeatability values. Mixed-model analysis with random factors horse and limb within horse and fixed factors surface and exercise direction evaluated movement symmetry changes (p < 0.05, Bonferroni correction). Withers movement indicated increased forelimb push-off with the re-shod limb on the inside of the circle and reduced weight-bearing with the re-shod limb and the ipsilateral hind limb on hard ground compared to soft ground. Movement symmetry measurements indicate that a rolled rocker shoe allows for increased push-off on soft ground in trot in a circle. Similar studies should study different types of shoes for improved practically relevant knowledge about shoeing mechanics, working towards evidence-based preventative shoeing.
Mechanisms of sex chromosome dosage compensation (SCDC) differ strikingly among animals. In Drosophila flies, chromosome-wide transcription is doubled from the single X chromosome in hemizygous (XY) ...males, whereas in Caenorhabditis nematodes, expression is halved for both X copies in homozygous (XX) females 1, 2. Unlike other female-heterogametic (WZ female and ZZ male) animals, moths and butterflies exhibit sex chromosome dosage compensation patterns typically seen only in male-heterogametic species 3. The monarch butterfly carries a newly derived Z chromosome segment that arose from an autosomal fusion with the ancestral Z 4. Using a highly contiguous genome assembly, we show that gene expression is balanced between sexes along the entire Z chromosome but with distinct modes of compensation on the two segments. On the ancestral Z segment, depletion of H4K16ac corresponds to nearly halving of biallelic transcription in males, a pattern convergent to nematodes. Conversely, the newly derived Z segment shows a Drosophila-like mode of compensation, with enriched H4K16ac levels corresponding to doubled monoallelic transcription in females. Our work reveals that, contrary to the expectation of co-opting regulatory mechanisms readily in place, the evolution of plural modes of dosage compensation is also possible along a single sex chromosome within a species.
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•A new chromosome-level assembly is generated for the monarch butterfly•The neo-Z expression is upregulated by 2-fold in females (WZ)•The ancestral-Z expression is downregulated by nearly 2-fold in males (ZZ)•H4K16ac is enriched on neo-Z in females but depleted on ancestral-Z in males
Gu et al. use genomic, transcriptomic, and epigenomic tools to analyze sex chromosome dosage compensation in the monarch butterfly, which carries a neo Z chromosome. They find that the newly derived neo-Z and ancestral Z segments have evolved distinct modes of dosage compensation that mirror Drosophila flies and nematodes, respectively.
The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing ...research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.
The acidic (leucine‐rich) nuclear phosphoprotein 32 kDa (ANP32) family is composed of small, evolutionarily conserved proteins characterized by an N‐terminal leucine‐rich repeat domain and a ...C‐terminal low‐complexity acidic region. The mammalian family members (ANP32A, ANP32B, and ANP32E) are ascribed physiologically diverse functions including chromatin modification and remodelling, apoptotic caspase modulation, protein phosphatase inhibition, as well as regulation of intracellular transport. In addition to reviewing the widespread literature on the topic, we present a concept of the ANP32s as having a whip‐like structure. We also present hypotheses that ANP32C and other intronless sequences should not currently be considered bona fide family members, that their disparate necessity in development may be due to compensatory mechanisms, that their contrasting roles in cancer are likely context‐dependent, along with an underlying hypothesis that ANP32s represent an important node of physiological regulation by virtue of their diverse biochemical activities.
Horseshoes with modified contact surfaces combined with deformable ground substrates are used to change hoof orientation during mid-stance, for example, for therapeutic reasons.
To measure the effect ...of horseshoes and ground substrates on sagittal and transverse plane hoof orientation at mid-stance using a dorsal hoof wall mounted triaxial accelerometer.
In vivo experiment, randomised crossover design.
Differences in sagittal and transverse plane angles between standing and mid-stance of the left front hoof of six horses walking with regular horseshoes, egg bar, toe-wide, medial-wide, lateral-wide and three-degree egg bar shoes on turf, sand and hard ground substrates were assessed with linear mixed models with horseshoe and substrate type as fixed factors (p < 0.05) for each animal.
Hoof angles were significantly affected by horseshoe (p < 0.001), surface (p < 0.001) and the combination (p < 0.001). The sagittal plane angle increased in deformable ground substrates at walk-in mid-stance on turf mean (±standard deviation): 2.6° (±3.8°) and on sand 2.6° (±4.1°) across all shoes. The greatest increase was observed with egg bar shoes turf: 4.37° (±3.82°); sand 4.69° (±3.83°). There was a tendency for the hoof to sink laterally into deformable ground substrates among all shoes turf: 1.11° (±1.49°); sand: 0.93° (±1.93°). Medial-wide shoes increased the lateral sinking turf: 2.00° (±1.63°); sand: 1.79° (±1.58°). Lateral-wide shoes reduced the lateral sinking on turf 0.62° (±1.26°) and induced a marginal medial sinking on sand -0.007° (±2.03°).
The substrate properties were not quantitatively assessed, and observations were limited to front hooves at the walk. A larger sample size would be preferable.
Mid-stance hoof orientation changes with specific combinations of shoes and ground substrates in the walking horse.
DNA retrieved from ancient specimens revealed that Neanderthals, our closest extinct relatives, admixed (mated) with modern human contemporaries. As a consequence, Neanderthal DNA survives scattered ...in the genome of present-day human populations. Patterns of Neanderthal introgressed genomic sequences suggest that Neanderthal alleles had distinct fates in the modern human genetic background. Some Neanderthal alleles facilitated human adaptation to new environments, while others had deleterious consequences. In this review, we discuss the body of work on Neanderthal introgression generated over the past decade. We describe how evolutionary forces shaped the genomic landscape of Neanderthal introgression and highlight the impact of introgressed alleles on human biology and phenotypic variation.
•Credit markets affected high school graduation, which is evidence of their far reaching effects.•Individuals whose education was plausibly affected by bank branching deregulation are 1 percentage ...point more likely to graduate high school.•These results pass a series of robustness tests including dynamic treatment and a placebo test, which falsifies the deregulation dates.
Credit markets affect the real economy in multiple ways. This paper utilizes variation in the timing of bank branching deregulation of 39 states between 1970 and 1994 as an exogenous proxy of credit availability to analyze the link between credit markets and educational outcomes. Using CPS data to estimate reduced form models, results indicate a one percentage point increase in the likelihood of graduating high school after bank branching deregulation. Results also suggest heterogeneity of effects over race. The main findings are robust to placebo tests using false deregulation dates.
Background To assess the predictive performance of two established, short clinical screeners in predicting the future development of post-injury depression and PTSD.
Methods This was a prospective, ...cohort design with a 3-month follow-up. Black adult male trauma patients were enrolled at an urban, Level 1 trauma center. The Penn Richmond Screener and the Posttraumatic Adjustment Scale (PAS) were collected in-hospital. Participants were categorized as depressed using the Quick Inventory of Depressive Symptoms-Self Report and as positive for PTSD using the PTSD Check List – 5 (PCL-5) at 3-months post-discharge. Sensitivity, specificity, PPV and NPV of each screener were calculated. We used receiver operating curve (ROC) analyses to calculate the area under the curve (AUC) with 95% CI to assess predictive performance of each screener.
Results A cohort of 623 hospitalized, injured Black men were enrolled during acute hospitalization. 503 participants (80.6%) were retained at 3-months and formed the analytic sample. Mean age was 36.8 years (SD 15.4), 53.1% of injuries were intentional; median injury severity score was 9. At 3 months, 35.3% had moderate to severe depression, 32.7% had significant PTSD symptoms, and 22.4% met criteria for both depression and PTSD. Penn Richmond Screener: sensitivity 0.68, specificity 0.56, and AUC 0.62 for PTSD, and sensitivity 0.64, specificity 0.63, and AUC 0.64 for depression. PAS: sensitivity 0.59, specificity 0.73, and AUC 0.66 for PTSD, and sensitivity 0.75, specificity 0.49, and AUC 0.62 for depression.
Conclusions This study validated the performance of both screeners within the same population, allowing a direct comparison. Two predictive screeners, developed through different methods and in different countries, showed comparable predictive ability. These findings indicate that risk markers for adverse psychological consequences of traumatic injury share some core similarities across populations and countries.
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