Behavioral and phylogenetic correlates of limb length proportions in extant apes and monkeys: Implications for interpreting hominin fossils.

The body proportions of extant animals help inform inferences about the behaviors of their extinct relatives, but relationships between body proportions, behavior, and phylogeny in extant primates remain unclear. Advances in behavioral data, molecular phylogenies, and multivariate analytical tools make it an opportune time to perform comprehensive comparative analyses of primate traditional limb length proportions (e.g., intermembral, humerofemoral, brachial, and crural indices), body size-adjusted long bone proportions, and principal components. In this study we used a mix of newly-collected and published data to investigate whether and how the limb length proportions of a diverse sample of primates, including monkeys, apes, and modern humans, are influenced by behavior and phylogeny. We reconfirm that the intermembral index, followed by the first principal component of traditional limb length proportions, is the single most effective variable distinguishing hominoids and other anthropoids. Combined limb length proportions and positional behaviors are strongly correlated in extant anthropoid groups, but phylogeny is a better predictor of limb length proportion variation than of behavior. We confirm convergences between members of the Atelidae and extant apes (especially Pan), members of the Hylobatidae and Pongo, and a potential divergence of Presbytis limb proportions from some other cercopithecoids, which correlate with adaptations for forelimb-dominated behaviors in some colobines. Collectively, these results substantiate hypotheses indicating that extinct hominins and other hominoid taxa can be distinguished by analyzing combinations of their limb length proportions at different taxonomic levels. From these results, we hypothesize that fossil skeletons characterized by notably disparate limb length proportions are unlikely to have exhibited similar behavioral patterns.

Imaging of lymphatic dysplasia in Noonan syndrome: Case studies and historical atlas.

To determine the historical use and utility of various lymphatic imaging modalities in Noonan syndrome (NS) patients, we performed a comprehensive literature review by collecting the published medical imaging of NS lymphatic dysplasias. We correlated imaging findings with clinical phenotypes and treatment. Our analysis of lymphatic imaging modalities provides an algorithmic approach to imaging and patient care across the spectrum of NS developmental defects. A total of 54 NS cases have been published since 1975. Using the observations reported in 15 reviewed publications, an association was made between disruptions in central lymphatic flow and poor clinical presentations/outcomes in NS patients.

A Chaplain's Comprehensive Spiritual Assessment And Military Mission.

Commanders expect their Chaplains to care for their Soldiers and their Families. Given the number of Soldiers and their Families, this responsibility can be daunting. Between 2007 and 2012, a comprehensive spiritual assessment was developed and used within the 98th Training Division, which was able to identify issues before they became debilitating problems. Approved by the Commanding Generals, this spiritual assessment was essential for Chaplains to find the Soldiers and their Families who needed care.

Review: Modelling the pathology and behaviour of frontotemporal dementia.

Frontotemporal dementia (FTD) encompasses a collection of clinically and pathologically diverse neurological disorders. Clinical features of behavioural and language dysfunction are associated with neurodegeneration, predominantly of frontal and temporal cortices. Over the past decade, there have been significant advances in the understanding of the genetic aetiology and neuropathology of FTD which have led to the creation of various disease models to investigate the molecular pathways that contribute to disease pathogenesis. The generation of in vivo models of FTD involves either targeting genes with known disease-causative mutations such as GRN and C9orf72 or genes encoding proteins that form the inclusions that characterize the disease pathologically, such as TDP-43 and FUS. This review provides a comprehensive summary of the different in vivo model systems used to understand pathomechanisms in FTD, with a focus on disease models which reproduce aspects of the wide-ranging behavioural phenotypes seen in people with FTD. We discuss the emerging disease pathways that have emerged from these in vivo models and how this has shaped our understanding of disease mechanisms underpinning FTD. We also discuss the challenges of modelling the complex clinical symptoms shown by people with FTD, the confounding overlap with features of motor neuron disease, and the drive to make models more disease-relevant. In summary, in vivo models can replicate many pathological and behavioural aspects of clinical FTD, but robust and thorough investigations utilizing shared features and variability between disease models will improve the disease-relevance of findings and thus better inform therapeutic development.

No calcitonin change in a person taking dulaglutide diagnosed with pre-existing medullary thyroid cancer.

BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon-like peptide-1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma, or in people with multiple endocrine neoplasia type 2. However, there are substantial differences between rodent and human responses to glucagon-like peptide-1 receptor agonists. This report presents the case of a woman with pre-existing medullary thyroid carcinoma who exhibited no significant changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for 6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes-5 clinical study (NCT00734474). CASE REPORT: Elevated serum calcitonin was noted in a 56-year-old woman with Type 2 diabetes mellitus at the 6-month discontinuation visit in a study of long-term dulaglutide therapy. Retroactive assessment of serum collected before study treatment yielded an elevated calcitonin level. At 3 months post-study, calcitonin level remained elevated; ultrasonography revealed multiple bilateral thyroid nodules. Eventually, medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive for a germline RET proto-oncogene mutation. CONCLUSION: The tumour was not considered stimulated by dulaglutide therapy because calcitonin remained stable throughout.

Mechanism of resistance to mesotrione in an Amaranthus tuberculatus population from Nebraska, USA.

Amaranthus tuberculatus is a troublesome weed in corn and soybean production systems in Midwestern USA, due in part to its ability to evolve multiple resistance to key herbicides including 4-hydroxyphenylpyruvate dioxygenase (HPPD). Here we have investigated the mechanism of resistance to mesotrione, an important chemical for managing broadleaf weeds in corn, in a multiple herbicide resistant population (NEB) from Nebraska. NEB showed a 2.4-fold and 45-fold resistance increase to mesotrione compared to a standard sensitive population (SEN) in pre-emergence and post-emergence dose-response pot tests, respectively. Sequencing of the whole HPPD gene from 12 each of sensitive and resistant plants did not detect any target-site mutations that could be associated with post-emergence resistance to mesotrione in NEB. Resistance was not due to HPPD gene duplication or over-expression before or after herbicide treatment, as revealed by qPCR. Additionally, no difference in mesotrione uptake was detected between NEB and SEN. In contrast, higher levels of mesotrione metabolism via 4-hydroxylation of the dione ring were observed in NEB compared to the sensitive population. Overall, the NEB population was characterised by lower levels of parent mesotrione exported to other parts of the plant, either as a consequence of metabolism in the treated leaves and/or impaired translocation of the herbicide. This study demonstrates another case of non-target-site based resistance to an important class of herbicides in an A. tuberculatus population. The knowledge generated here will help design strategies for managing multiple herbicide resistance in this problematic weed species.

Nutrient and mineral composition during shoot growth in seven species of Phyllostachys and Pseudosasa bamboo consumed by giant panda.

During the annual period of bamboo shoot growth in spring, free-ranging giant pandas feed almost exclusively on the shoots while ignoring the leaves and full- height culm. Little is known about the nutritional changes that occur during bamboo shoot growth, if nutritional changes differ among species, or how these changes might influence forage selection. Our objective was to examine the nutrient and mineral composition during three phases of shoot growth (<60, 90-150 and >180 cm) for seven species of bamboo (Phyllostachys (P.) aurea, P. aureosulcata, P. bissetii, P. glauca, P. nuda, P. rubromarginata, Pseudosasa japonica) fed to captive giant pandas at the Memphis Zoo. Total dietary fiber content of bamboo shoots increased (p < 0.0001) from an overall species average of 61% dry matter (DM) at < 60 cm to 75% DM at shoot heights > 180 cm, while crude protein, fat and ash exhibited significant declines (p < 0.05). Phyllostachys nuda had the overall greatest (p = 0.007) crude protein (21% DM) and fat (4% DM) content, and lowest overall total fibre (61% DM) content compared to the other species examined. In contrast, Pseudosasa japonica had the overall lowest crude protein and fat, and relatively higher fibre content (9%, 3% and 74% respectively). Concentrations of Zn and Fe were highest in shoots <60 cm (10-50 µg/g DM) and decreased (p < 0.05) during growth in all species examined. Concentrations of Ca, Cu, Mn, Na and K varied among species and were largely unaffected by growth stage. Due to their higher concentrations of nutrients and lower fibre content in comparison to culm and leaf, bamboo shoots should be a major component of captive giant panda diets when available.

Nutrition and health in amphibian husbandry.

Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas.

Transcutaneous electrical nerve stimulation and conditioned pain modulation influence the perception of pain in humans.

BACKGROUND: Research in animal models suggests that transcutaneous electrical nerve stimulation (TENS) and conditioned pain modulation (CPM) produce analgesia via two different supraspinal pathways. No known studies have examined whether TENS and CPM applied simultaneously in human subjects will enhance the analgesic effect of either treatment alone. The purpose of the current study was to investigate whether the simultaneous application of TENS and CPM will enhance the analgesic effect of that produced by either treatment alone. METHODS: Sixty healthy adults were randomly allocated into two groups: (1) CPM plus active TENS; (2) CPM plus placebo TENS. Pain threshold for heat (HPT) and pressure (PPT) were recorded from subject's left forearm at baseline, during CPM, during active or placebo TENS, and during CPM plus active or placebo TENS. CPM was induced by placing the subjects' contralateral arm in a hot water bath (46.5 °C) for 2 min. TENS (100 µs, 100 Hz) was applied to the forearm for 20 min at a strong but comfortable intensity. RESULTS: Active TENS alone increased PPT (but not HPT) more than placebo TENS alone (p = 0.011). Combining CPM and active TENS did not significantly increase PPT (p = 0.232) or HPT (p = 0.423) beyond CPM plus placebo TENS. There was a significant positive association between PPT during CPM and during active TENS (r(2) = 0.46; p = 0.003). CONCLUSIONS: TENS application increases PPT; however, combining CPM and TENS does not increase the CPM's hypoalgesic response. CPM effect on PPT is associated with the effects of TENS on PPT.

Transportin 1 colocalization with Fused in Sarcoma (FUS) inclusions is not characteristic for amyotrophic lateral sclerosis-FUS confirming disrupted nuclear import of mutant FUS and distinguishing it from frontotemporal lobar degeneration with FUS inclusions.

AIMS: Transportin 1 (TNPO 1) is an abundant component of the Fused in Sarcoma (FUS)-immunopositive inclusions seen in a subgroup of frontotemporal lobar degeneration (FTLD-FUS). TNPO 1 has been shown to bind to the C-terminal nuclear localizing signal (NLS) of FUS and mediate its nuclear import. Amyotrophic lateral sclerosis (ALS)-linked C-terminal mutants disrupt TNPO 1 binding to the NLS and impair nuclear import in cell culture. If this held true for human ALS then we predicted that FUS inclusions in patients with C-terminal FUS mutations would not colocalize with TNPO 1. METHODS: Expression of TNPO 1 and colocalization with FUS was studied in the frontal cortex of FTLD-FUS (n = 3) and brain and spinal cord of ALS-FUS (n = 3), ALS-C9orf72 (n = 3), sporadic ALS (n = 7) and controls (n = 7). Expression levels and detergent solubility of TNPO 1 was measured by Western blot. RESULTS: Aggregates of TNPO 1 were abundant and colocalized with FUS inclusions in the cortex of all FTLD-FUS cases. In contrast, no TNPO 1-positive aggregates or FUS colocalization was evident in two-thirds, ALS-FUS cases and was rare in one ALS-FUS case. Nor were they present in C9orf72 or sporadic ALS. No increase in the levels of TNPO 1 was seen in Western blots of spinal cord tissues from all ALS cases compared with controls. CONCLUSIONS: These findings confirm that C-terminal FUS mutations prevent TNPO 1 binding to the NLS, inhibiting nuclear import and promoting cytoplasmic aggregation. The presence of TNPO 1 in wild-type FUS aggregates in FTLD-FUS distinguishes the two pathologies and implicates different disease mechanisms.

Pregnancy in a woman with proportionate (primordial) dwarfism: a case report and literature review.

Primordial dwarfism is a rare form of severe proportionate dwarfism which poses significant challenges in pregnancy. A 27-year-old with primordial dwarfism (height 97 cm, weight 22 kg) and coexisting morbidities of familial hypercholesterolaemia and hypertension presented to our unit. Early pregnancy was complicated by difficult blood pressure control, sinus tachycardia, biochemical hyperthyroidism and insulin-requiring gestational diabetes. Delivery was indicated at 24 weeks with uncontrollable hypertension, progressive renal impairment and intrauterine growth restriction. A caesarean section was performed under general anaesthesia, resulting in the delivery of a 486 g male infant. This case highlights the difficulties of managing pregnancy in a woman with primordial dwarfism. Her limited capacity to respond to the physiological demands of pregnancy created a life-threatening situation, culminating in profound preterm birth.

Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis.

FUS, EWS, and TAF15 belong to the TET family of structurally similar DNA/RNA-binding proteins. Mutations in the FUS gene have recently been discovered as a cause of familial amyotrophic lateral sclerosis (FALS). Given the structural and functional similarities between the three genes, we screened TAF15 and EWS in 263 and 94 index FALS cases, respectively. No coding variants were found in EWS, while we identified six novel changes in TAF15. Of these, two 24 bp deletions and a R388H missense variant were also found in healthy controls. A D386N substitution was shown not to segregate with the disease in the affected pedigree. A single A31T and two R395Q changes were identified in FALS cases but not in over 1,100 controls. Interestingly, one of the R395Q FALS cases also harbors a TARDBP mutation (G384R). Altogether, these results suggest that additional studies are needed to determine whether mutations in the TAF15 gene represent a cause of FALS.

Nitric oxide is involved in phosphorus deficiency-induced cluster-root development and citrate exudation in white lupin.

*White lupin (Lupinus albus) forms specialized cluster roots characterized by exudation of organic anions under phosphorus (P) deficiency. Here, the role of nitric oxide (NO) in P deficiency-induced cluster-root formation and citrate exudation was evaluated. *White lupin plants were treated with the NO donor sodium nitroprusside (SNP) and scavenger or inhibitor of NO synthase under conditions of P deficiency (0 muM) or P sufficiency (50 muM). *Phosphorus deficiency enhanced NO production in primary and lateral root tips, with a greater increase in cluster roots than in noncluster roots. NO concentrations decreased with cluster root development from the pre-emergent stage, through the juvenile stage, to the mature stage. The P deficiency-induced increase in NO production was inhibited by antagonists of NO synthase and xanthine oxidoreductase, suggesting the involvement of these enzymes in NO production. SNP markedly increased the number of cluster roots. Citrate exudation from different root segments in P-deficient roots was positively correlated with endogenous root NO concentrations. *These findings demonstrate differential patterns of NO production in white lupin, depending on root zone, developmental stage and P nutritional status. NO appears to play a regulatory role in the formation of cluster roots and citrate exudation in white lupin under conditions of P deficiency.

Four novel SPG3A/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype.

Mutation of the atlastin gene (SPG3A) is responsible for approximately 10% of autosomal dominant hereditary spastic paraplegia (AD-HSP) cases. The goal of this study was to identify novel disease causing atlastin mutations. Atlastin nucleotide variations were detected by direct sequencing of all 14 exons in 70 autosomal dominant (AD), 16 single sibship and 14 sporadic spastic paraplegia patients. Six mis-sense mutations (four of which were novel) were identified in six unrelated AD-HSP kindreds in exons 4, 7 and 8 of the atlastin gene. One kindred with a novel mutation showed variability in clinical phenotype and age of onset. Mutations are predicted to decrease GTPase activity, cause morphological abnormalities of the endoplasmic reticulum and prevent maturation of the Golgi complex resulting in impaired vesicle trafficking. Our study significantly adds to the spectrum of mutations and clinical phenotype of SPG3A. We advocate that all spastin mutation negative AD-HSP kindreds should be screened for pathogenic atlastin mutations regardless of age of onset or phenotypic complexity.

Artificial fertilization for amphibian conservation: current knowledge and future considerations.

Amphibian populations in the wild are experiencing massive die-offs that have led to the extinction of an estimated 168 species in the last several decades. To address these declines, zoological institutions are playing an important role in establishing captive assurance colonies to protect species in imminent danger of extinction. Many of the threatened species recently placed into captivity are failing to reproduce before they expire, and maintaining founder populations is becoming a formidable challenge. Assisted reproductive technologies, such as hormone synchronization, gamete storage and artificial fertilization, are valuable tools for addressing reproductive failure of amphibians in captive facilities. Artificial fertilization has been commonly employed for over 60 years in several keystone laboratory species for basic studies in developmental biology and embryology. However, there are few instances of applied studies for the conservation of threatened or endangered amphibian species. In this review, we summarize valuable technological achievements in amphibian artificial fertilization, identify specific processes that need to be considered when developing artificial fertilization techniques for species conservation, and address future concerns that should be priorities for the next decade.

Release of GABA and activation of GABA(A) in the spinal cord mediates the effects of TENS in rats.

Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non-pharmacological, non-invasive treatment for pain. GABA is a neurotransmitter in the dorsal horn of the spinal cord that mediates analgesia locally, and also through activation of supraspinal sites. TENS reduces hyperalgesia through activation of receptor-mediated pathways at the level of the spinal cord, and supraspinally. The current study tested the hypothesis that either high or low frequency TENS applied to the inflamed knee joint increases GABA in the spinal cord dorsal horn and activates GABA receptors spinally. We utilized microdialysis to sample the extracellular fluid before, during and after TENS and analyzed GABA in dialysates with high performance liquid chromatography. We analyzed the extracellular GABA concentrations in animals with and without knee joint inflammation induced by intra-articular injection of kaolin and carrageenan. We further tested if spinal blockade of GABA receptors prevents the antihyperalgesia produced by TENS in rats with joint inflammation. We show that high frequency TENS increases extracellular GABA concentrations in the spinal cord in animals with and without joint inflammation. The increases in GABA do not occur in response to low frequency TENS, and there are no increases in glycine in response to low or high frequency TENS. However, the reduction in primary hyperalgesia by both high and low frequency TENS is prevented by spinal blockade of GABA(A) receptors with bicuculline. Thus, high frequency TENS increases release of GABA in the deep dorsal horn of the spinal cord, and both high and low frequency TENS reduce primary hyperalgesia by activation of GABA(A) receptors spinally.

Differences between forest type and vertical strata in the diversity and composition of hymenopteran families and mymarid genera in northeastern temperate forests.

Most insects' assemblages differ with forest type and show vertical stratification. We tested for differences in richness, abundance and composition of hymenopteran families and mymarid genera between sugar maple (Acer saccharum) and white pine (Pinus strobus) stands and between canopy and understory in northeastern temperate forests in Canada. We used flight interception traps (modified malaise traps) suspended in the canopy and the understory in a split-split block design, with forest type as the main factor, forest stratum as the first split factor, and collection bottle location as the second split factor. Hymenopteran families and mymarid genera differed in their diversity depending on forest type and stratum. Both family and genera richness were higher in maple than in pine forests, whereas family richness was higher in the canopy and top bottles and generic richness was higher in the understory and bottom bottles. Multivariate analysis separated samples by forest type, vegetation stratum, and bottle location. Family composition showed 77% similarity between forest types and 73% between the canopy and understory. At the lower taxa level, mymarid genera showed only 47% similarity between forest types and 40% between forest strata, indicating vertical stratification and relatively high beta-diversity. Our study suggests that hymenopteran diversity and composition is strongly dependent on forest type and structure, making flying members of this order particularly vulnerable to forest management practices. It also shows that insect assemblage composition (especially at low-taxon levels), rather than relative abundance and richness, is the community attribute most sensitive to forest type and vertical stratification.

High-frequency, but not low-frequency, transcutaneous electrical nerve stimulation reduces aspartate and glutamate release in the spinal cord dorsal horn.

Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non-pharmacological treatment for pain. Studies show that low- and high-frequency TENS utilize opioid, serotonin and/or muscarinic receptors in the spinal cord to reduce hyperalgesia induced by joint inflammation in rats. As there is an increase in glutamate and aspartate levels in the spinal cord after joint inflammation, and opioids reduce glutamate and aspartate release, we hypothesized that TENS reduces release of glutamate and aspartate in animals with joint inflammation by activation of opioid receptors. Using microdialysis and HPLC with fluorescence detection, we examined the release pattern of glutamate and aspartate in the dorsal horn in response to either low-frequency (4 Hz) or high-frequency (100 Hz) TENS. We examined the effects of TENS on glutamate and aspartate release in animals with and without joint inflammation. High-frequency, but not low-frequency, TENS significantly reduced spinal glutamate and aspartate in animals with joint inflammation compared with levels in those without joint inflammation. The reduced release of glutamate and aspartate by high-frequency TENS was prevented by spinal blockade of delta-opioid receptors with naltrindole. Thus, we conclude that high-frequency TENS activates delta-opioid receptors consequently reducing the increased release of glutamate and aspartate in the spinal cord.