Teaching Students with Developmental Disabilities Daily Living Skills Using Point-of-View Modeling Plus Video Prompting with Error Correction

A primary goal of instruction for students with developmental disabilities is to enhance their future quality of life by promoting skill acquisition which will enable them to live, function, and participate in the community. One instructional method that can help students with developmental disabilities improve independence in performing daily living skills is video prompting. This study investigated the effectiveness of a video prompting plus error correction procedure on skill acquisition when teaching daily living skills to four adolescents with mild and moderate developmental disabilities. A multiple baseline across participants design demonstrated that all four participants rapidly acquired dish washing skills upon introduction of the intervention. Future research should further explore the efficacy of error correction procedures used with video prompting and the impact that these procedures have on student learning and skill retention

Prevalence of the E321G MYH1 variant for immune-mediated myositis and nonexertional rhabdomyolysis in performance subgroups of American Quarter Horses.

BackgroundImmune-mediated myositis (IMM) in American Quarter Horses (QHs) causes acute muscle atrophy and lymphocytic infiltration of myofibers. Recently, an E321G mutation in a highly conserved region of the myosin heavy chain 1 (MYH1) gene was associated with susceptibility to IMM and nonexertional rhabdomyolysis.ObjectivesTo estimate prevalence of the E321G MYH1 variant in the QH breed and performance subgroups.AnimalsThree-hundred seven elite performance QHs and 146 random registered QH controls.MethodsProspective genetic survey. Elite QHs from barrel racing, cutting, halter, racing, reining, Western Pleasure, and working cow disciplines and randomly selected registered QHs were genotyped for the E321G MYH1 variant and allele frequencies were calculated.ResultsThe E321G MYH1 variant allele frequency was 0.034 ± 0.011 in the general QH population (6.8% of individuals in the breed) and the highest among the reining (0.135 ± 0.040; 24.3% of reiners), working cow (0.085 ± 0.031), and halter (0.080 ± 0.027) performance subgroups. The E321G MYH1 variant was present in cutting (0.044 ± 0.022) and Western Pleasure (0.021 ± 0.015) QHs at lower frequency and was not observed in barrel racing or racing QHs.Conclusions and clinical importanceKnowing that reining and working cow QHs have the highest prevalence of the E321G MYH1 variant and that the variant is more prevalent than the alleles for hereditary equine regional dermal asthenia and hyperkalemic periodic paralysis in the general QH population will guide the use of genetic testing for diagnostic and breeding purposes

Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight

Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei

Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis

Background: Both type 1 (PSSM1) and type 2 polysaccharide storage myopathy (PSSM2) are characterised by aggregates of abnormal polysaccharide in skeletal muscle. Whereas the genetic basis for PSSM1 is known (R309H GYS1), the cause of PSSM2 in Quarter Horses (PSSM2-QH) is unknown and glycogen concentrations not defined. Objectives: To characterise the histopathological and biochemical features of PSSM2-QH and determine if an associated monogenic variant exists in genes known to cause glycogenosis. Study design: Retrospective case control. Methods: Sixty-four PSSM2-QH, 30 PSSM1-QH and 185 control-QH were identified from a biopsy repository and clinical data, histopathology scores (0–3), glycogen concentrations and selected glycolytic enzyme activities compared. Coding sequences of 12 genes associated with muscle glycogenoses were identified from whole genome sequences and compared between seven PSSM2-QH and five control-QH. Results: Exertional rhabdomyolysis in PSSM2-QH occurred predominantly in barrel racing and working cow/roping performance types and improved with regular exercise and a low starch/fat-supplemented diet. Histopathological scores, including the amount of amylase-resistant polysaccharide (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, control-QH 0 ± 0, p \u3c 0.001), and glycogen concentrations (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, control-QH 80 ± 27 mmol/kg, p \u3c 0.0001) were intermediate in PSSM2-QH with significant differences among groups. In PSSM2-QH, abnormal polysaccharide had a less filamentous ultrastructure than PSSM1-QH and phosphorylase and phosphofructokinase activities were normal. Seventeen of 30 PSSM2-QH with available pedigrees descended from one of three stallions within four generations. Of the 29 predicted high or moderate impact genetic variants identified in candidate genes, none were present in only PSSM2-QH and absent in control-QH

Utility of photochemical traits as diagnostics of thermal tolerance amongst great barrier reef corals

© 2018 Nitschke, Gardner, Goyen, Fujise, Camp, Ralph and Suggett. Light availability is considered a key factor regulating the thermal sensitivity of reef building corals, where excessive excitation of photosystem II (PSII) further exacerbates pressure on photochemical pathways already compromised by heat stress. Coral symbionts acclimate to changes in light availability (photoacclimation) by continually fine-tuning the photochemical operating efficiency of PSII. However, how this process adjusts throughout the warmest months in naturally heat-tolerant or sensitive species is unknown, and whether this influences the capacity to tolerate transient heat stress is untested. We therefore examined the PSII photophysiology of 10 coral species (with known thermal tolerances) from shallow reef environments at Heron Island (Great Barrier Reef, Australia), in spring (October-November, 2015) vs. summer (February-March, 2016). Corals were maintained in flow-through aquaria and rapid light curve (RLC) protocols using pulse amplitude modulated (PAM) fluorometry captured changes in the PSII photoacclimation strategy, characterized as the minimum saturating irradiance (Ek), and the extent of photochemical ([1-C], operating efficiency) vs. non-photochemical ([1-Q]) energy dissipation. Values of Ek across species were > 2-fold higher in all coral species in spring, consistent with a climate of higher overall light exposure (i.e., higher PAR from lower cloud cover, rainfall and wind speed) compared with summer. Summer decreases in Ek were combined with a shift toward preferential photochemical quenching in all species. All coral species were subsequently subjected to thermal stress assays. An equivalent temperature-ramping profile of 1°C increase per day and then maintenance at 32°C was applied in each season. Despite the significant seasonal photoacclimation, the species hierarchy of thermal tolerance [maximum quantum yields of PSII (Fv/Fm), monitored at dawn and dusk] did not shift between seasons, except for Pocillopora damicornis (faster declines in summer) and Stylophora pistillata (total mortality in spring). Furthermore, the strategy for dealing with light energy (i.e., preferential photochemical vs. non-photochemical quenching) was unchanged for thermally tolerant species across seasons, whereas thermally sensitive species switched between preferential [1-Q] and [1-C] from spring to summer. We discuss how such traits can potentially be used as a diagnostic of thermal tolerance under non-stressed conditions

B4: Bedrock Geology of Mt. Washington, Presidential Range, NH

Guidebook for field trips in Western Maine and Northern New Hampshire: New England Intercollegiate Geological Conference, p. 177-196

Genomic Characterization of Patient-Derived Xenograft Models Established from Fine Needle Aspirate Biopsies of a Primary Pancreatic Ductal Adenocarcinoma and from Patient-Matched Metastatic Sites

N-of-1 trials target actionable mutations, yet such approaches do not test genomically-informed therapies in patient tumor models prior to patient treatment. To address this, we developed patient-derived xenograft (PDX) models from fine needle aspiration (FNA) biopsies (FNA-PDX) obtained from primary pancreatic ductal adenocarcinoma (PDAC) at the time of diagnosis. Here, we characterize PDX models established from one primary and two metastatic sites of one patient. We identified an activating KRAS G12R mutation among other mutations in these models. In explant cells derived from these PDX tumor models with a KRAS G12R mutation, treatment with inhibitors of CDKs (including CDK9) reduced phosphorylation of a marker of CDK9 activity (phospho-RNAPII CTD Ser2/5) and reduced viability/growth of explant cells derived from PDAC PDX models. Similarly, a CDK inhibitor reduced phospho-RNAPII CTD Ser2/5, increased apoptosis, and inhibited tumor growth in FNA-PDX and patient-matched metastatic-PDX models. In summary, PDX models can be constructed from FNA biopsies of PDAC which in turn can enable genomic characterization and identification of potential therapies

Succession and determinants of the early life nasopharyngeal microbiota in a South African birth cohort

Background: Bacteria colonizing the nasopharynx play a key role as gatekeepers of respiratory health. Yet, dynamics of early life nasopharyngeal (NP) bacterial profiles remain understudied in low- and middle-income countries (LMICs), where children have a high prevalence of risk factors for lower respiratory tract infection. We investigated longitudinal changes in NP bacterial profiles, and associated exposures, among healthy infants from low-income households in South Africa. Methods: We used short fragment (V4 region) 16S rRNA gene amplicon sequencing to characterize NP bacterial profiles from 103 infants in a South African birth cohort, at monthly intervals from birth through the first 12 months of life and six monthly thereafter until 30 months. Results: Corynebacterium and Staphylococcus were dominant colonizers at 1 month of life; however, these were rapidly replaced by Moraxella- or Haemophilus-dominated profiles by 4 months. This succession was almost universal and largely independent of a broad range of exposures. Warm weather (summer), lower gestational age, maternal smoking, no day-care attendance, antibiotic exposure, or low height-for-age z score at 12 months were associated with higher alpha and beta diversity. Summer was also associated with higher relative abundances of Staphylococcus, Streptococcus, Neisseria, or anaerobic gram-negative bacteria, whilst spring and winter were associated with higher relative abundances of Haemophilus or Corynebacterium, respectively. Maternal smoking was associated with higher relative abundances of Porphyromonas. Antibiotic therapy (or isoniazid prophylaxis for tuberculosis) was associated with higher relative abundance of anerobic taxa (Porphyromonas, Fusobacterium, and Prevotella) and with lower relative abundances of health associated-taxa Corynebacterium and Dolosigranulum. HIV-exposure was associated with higher relative abundances of Klebsiella or Veillonella and lower relative abundances of an unclassified genus within the family Lachnospiraceae. Conclusions: In this intensively sampled cohort, there was rapid and predictable replacement of early profiles dominated by health-associated Corynebacterium and Dolosigranulum with those dominated by Moraxella and Haemophilus, independent of exposures. Season and antibiotic exposure were key determinants of NP bacterial profiles. Understudied but highly prevalent exposures prevalent in LMICs, including maternal smoking and HIV-exposure, were associated with NP bacterial profiles

An autosomal recessive variant in \u3ci\u3ePYGM\u3c/i\u3e causes myophosphorylase deficiency in Red Angus composite cattle

Background Between 2020 and 2022, eight calves in a Nebraska herd (composite Simmental, Red Angus, Gelbvieh) displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover. Available sire pedigrees contained a paternal ancestor within 2–4 generations in all affected calves. Pedigrees of the calves’ dams were unavailable, however, the cows were ranch-raised and retained from prior breeding seasons, where bulls used for breeding occasionally had a common ancestor. Therefore, it was hypothesized that a de novo autosomal recessive variant was causative of exercise intolerance in these calves. Results A genome-wide association analysis utilizing SNP data from 6 affected calves and 715 herd mates, followed by whole-genome sequencing of 2 affected calves led to the identification of a variant in the gene PYGM (BTA29:g.42989581G \u3e A). The variant, confirmed to be present in the skeletal muscle transcriptome, was predicted to produce a premature stop codon (p.Arg650*). The protein product of PYGM, myophosphorylase, breaks down glycogen in skeletal muscle. Glycogen concentrations were fluorometrically assayed as glucose residues demonstrating significantly elevated glycogen concentrations in affected calves compared to cattle carrying the variant and to wildtype controls. The absence of the PYGM protein product in skeletal muscle was confirmed by immunohistochemistry and label-free quantitative proteomics analysis; muscle degeneration was confirmed in biopsy and necropsy samples. Elevated skeletal muscle glycogen persisted after harvest, resulting in a high pH and dark-cutting beef, which is negatively perceived by consumers and results in an economic loss to the industry. Carriers of the variant did not exhibit differences in meat quality or any measures of animal well-being. Conclusions Myophosphorylase deficiency poses welfare concerns for affected animals and negatively impacts the final product. The association of the recessive genotype with dark-cutting beef further demonstrates the importance of genetics to not only animal health but to the quality of their product. Although cattle heterozygous for the variant may not immediately affect the beef industry, identifying carriers will enable selection and breeding strategies to prevent the production of affected calves