Post-translational processing of the glycoproteins of lymphocytic choriomeningitis virus.

Intracellular events in the synthesis, glycosylation, and transport of the lymphocytic choriomeningitis virus (LCMV) glycoproteins have been examined. We have shown by N-glycanase digestion that LCMV strain Arm-4 bears five oligosaccharides on GP-1 and two on GP-2. By pulse-chase labeling experiments in the presence of drugs which inhibit N-linked oligosaccharide addition and processing we demonstrate that addition of high mannose precursor oligosaccharides is necessary for transport and cleavage of the viral GP-C glycoprotein. Moreover, in the presence of tunicamycin which inhibits en bloc addition of these mannose-rich side chains, virus budding was substantially decreased and infectious virions were reduced by more than 1000-fold in the supernatant medium. Incubation in the presence of castantospermine, which permits addition of oligomannosyl-rich chains but blocks further processing, restored transport and cleavage of GP-C and maturation of virions. Finally, by temperature block experiments we have determined that maturation of GP-C oligosaccharides to an endoglycosidase H resistant form precedes cleavage to GP-1 and GP-2. The latter process is most likely to occur in the Golgi or post-Golgi compartment

Wild psychometrics: Evidence for 'general' cognitive performance in wild New Zealand robins, Petroica longipes

In human psychometric testing, individuals' scores in tests of diverse cognitive processes are positively correlated, with a ‘general intelligence’ factor (g) typically accounting for at least 40% of total variance. Individual differences in cognitive ability have been extensively studied in humans, yet they have received far less attention in nonhuman animals. In particular, the development of a test battery suitable for quantifying individual cognitive performance in birds remains in its infancy. Additionally, implementing this approach in the wild, where the ecological significance of cognition can also be explored, presents considerable logistical challenges for most species. We developed a cognitive test battery for wild New Zealand North Island robins. Our battery comprised six tasks based on established measures of avian cognitive performance: a motor task, colour and shape discrimination, reversal learning, spatial memory and inhibitory control. Robins varied greatly in their ability to solve these tasks and we found weakly positive, nonsignificant correlations between most tasks. A principal components analysis of task performances yielded two factors with eigenvalues >1. The first component extracted explained over 34% of the variance in cognitive performance and all six tasks loaded positively on this first component. We show, using randomization tests, that these results are robust. Our results thus suggest that a general cognitive factor, analogous to human g, underpins cognitive performance in wild North Island robins tested in their natural habitat.This research was funded by a Fast-Start grant from the Marsden Fund of the Royal Society of New Zealand (VUW1304) and a Rutherford Foundation New Zealand Postdoctoral Fellowship to R.C.S.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.anbehav.2015.08.00

Incidence and significance of elevated platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios among hospitalised HIV-positive adult patients

There is increasing interest in the peripheral blood platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation. We audited records of unselected hospitalised HIV-positive adults to identify the frequency of elevated PLR and NLR, potential associations with specific diagnoses, and outcome. Of 259 patients audited, their median age was 47 years (interquartile range = 41–54); 188 (73%) were men. An elevated PLR occurred in 87 patients (33.6%); 67 (25.9%) had an elevated NLR; 200 (77%) had an elevated C-reactive protein (CRP). Elevated PLR and NLR was associated with a variety of infectious, inflammatory, and malignant conditions similar to conditions described in the general non-HIV-infected adult population. Additionally, elevated PLR and NLR occurred both in patients in receipt of antiretroviral therapy (with undetectable viral loads), as well as in those with newly-diagnosed and poorly-controlled infection. Fourteen patients with infectious and inflammatory conditions had an elevated PLR and normal CRP, with/without elevated NLR. There was no association between elevated PLR or NLR and ICU admission, p = 0.1001 and p = 0.605, respectively. Elevated NLR, but not PLR was associated with death, p = 0.0405 and p = 1.000, respectively: two-tailed Fisher’s exact test. The single site nature of the audit and relatively small number of patients limits these observations

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Incidence and significance of an elevated red blood cell distribution width among hospitalised HIV-infected adult patients

We audited the records of unselected hospitalised HIV-positive adults admitted to a University-affiliated inner London hospital to identify the frequency of elevated red blood cell distribution width (RDW), and potential associations with specific diagnoses, and with outcome. Of 259 patients audited, 188 (73%) were men. Patients' median age was 47 years (interquartile range = 41-54). An elevated RDW was seen in 50 patients (19%); 200 (77%) had an elevated C-reactive protein (CRP), and 77 (30%) had a low haemoglobin. Only five patients had an elevated RDW without an elevated CRP and/or low haemoglobin. An elevated RDW was associated with a wide range of infectious, inflammatory, and malignant conditions similar to observed associations reported in the general non-HIV infected adult population. Additionally an elevated RDW occurred both in patients with well-controlled HIV infection and in receipt of antiretroviral therapy, as well as in those with newly diagnosed and poorly-controlled infection. Five (10%) of 50 patients with an elevated RDW needed intensive care unit (ICU) admission and two (4%) died. Two (0.95%) of 209 patients with a normal RDW needed ICU admission and four (1.9%) died. The findings of this audit are limited by the relatively small number of patients and the single site nature of the audit

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

The association between levels of alcohol consumption and mental health problems and academic performance among young university students

Purpose: Mental health problems and harmful alcohol consumption have been found to be high among young university students compared to the general population in Australia. This research aimed to investigate the association between levels of drinking and mental health problems and academic performance among university students aged 18 to 24 years. Methods: This study used a quantitative cross-sectional design using data that were collected in 2014 as part of the Youth Alcohol Project (YAP). Participants were randomly drawn from a cross sectional sample of 6000 undergraduate students. Included in the study were only students who were within the age of 18-24, undergraduate, and internally enrolled at the main campus. A total of 2518 undergraduate students aged 18 to 24 years who were enrolled internally at Curtin University Bentley campus were randomly recruited. Data were collected through an online survey. Students were invited to participate in the study through their student email address. The email invitations coincided with the release of semester results to increase the likelihood of students accessing their emails. A further 628 students were randomly recruited through face to face intercept survey during the campus market days. Data were collected by trained research assistants. Validated instruments were used to collected data on levels of alcohol consumption, mental health, and academic performance. Results: A considerable proportion of participants (44%) reported consuming alcohol at hazardous or harmful levels. Multiple logistic regression analysis showed that students who were consuming alcohol at hazardous levels were 1.2 times more likely to report psychological distress than those with lower levels of alcohol consumption (aOR 1.2, 95% CI: 1.1-1.5). In addition, being late for class (aOR 1.7, 95% CI:1.1-2.4), missing classes (aOR = 2.6, 95% CI: 1.9-2.6), inability to concentrate in class (aOR = 2.6, 95% CI: 1.9-3.4), and inability to complete assignments (aOR = 3.5, 95% CI 2.0-6.0) independently predicted for moderate or hazardous alcohol consumption. Conclusion: The study shows that a considerable proportion of undergraduate students at university consume alcohol at hazardous or harmful levels. In addition, high levels of alcohol consumption are associated with poor academic performance and mental health outcomes among students. The results of the study warrant multi-strategy interventions that focus on policy, organisational, educational, environmental and economic strategies that will help to reduce alcohol related harms among university students

Validity of a novel computerized cognitive battery for mild cognitive impairment

BACKGROUND: The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. METHODS: A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups. RESULTS: Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains. CONCLUSIONS: Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia

Assertive community treatment for elderly people with severe mental illness

Background: Adults aged 65 and older with severe mental illnesses are a growing segment of the Dutch population. Some of them have a range of serious problems and are also difficult to engage. While assertive community treatment is a common model for treating difficult to engage severe mental illnesses patients, no special form of it is available for the elderly. A special assertive community treatment team for the elderly is developed in Rotterdam, the Netherlands and tested for its effectiveness.Methods: We will use a randomized controlled trial design to compare the effects of assertive community treatment for the elderly with those of care as usual. Primary outcome measures will be the number of dropouts, the number of patients engaged in care and patient's psychiatric symptoms, somatic symptoms, and social functioning. Secondary outcome measures are the number of unmet needs, the subjective quality of life and patients' satisfaction. Other secondary outcomes include the number of crisis contacts, rates of voluntary and involuntary admission, and length of stay. Inclusion criteria are aged 65 plus, the presence of a mental disorder, a lack of motivation for treatment and at least four suspected problems with functioning (addiction, somatic problems, daily living activities, housing etc.). If patients meet the inclusion criteria, they will be randomly allocated to either assertive community treatment for the elderly or care as usual. Trained assessors will use mainly observational instruments at the following time points: at baseline, after 9 and 18 months.Discussion: This study will help establish whether assertive community treatment for the elderly produces better results than care as usual in elderly people with severe mental illnesses who are difficult to engage. When assertive community treatment for the elderly proves valuable in these respects, it can be tested and implemented more widely, and mechanisms for its effects investigated

Molecular phylogeny of the subfamily Stevardiinae Gill, 1858 (Characiformes: Characidae): classification and the evolution of reproductive traits

Abstract Background The subfamily Stevardiinae is a diverse and widely distributed clade of freshwater fishes from South and Central America, commonly known as “tetras” (Characidae). The group was named “clade A” when first proposed as a monophyletic unit of Characidae and later designated as a subfamily. Stevardiinae includes 48 genera and around 310 valid species with many species presenting inseminating reproductive strategy. No global hypothesis of relationships is available for this group and currently many genera are listed as incertae sedis or are suspected to be non-monophyletic. Results We present a molecular phylogeny with the largest number of stevardiine species analyzed so far, including 355 samples representing 153 putative species distributed in 32 genera, to test the group’s monophyly and internal relationships. The phylogeny was inferred using DNA sequence data from seven gene fragments (mtDNA: 12S, 16S and COI; nuclear: RAG1, RAG2, MYH6 and PTR). The results support the Stevardiinae as a monophyletic group and a detailed hypothesis of the internal relationships for this subfamily. Conclusions A revised classification based on the molecular phylogeny is proposed that includes seven tribes and also defines monophyletic genera, including a resurrected genus Eretmobrycon, and new definitions for Diapoma, Hemibrycon, Bryconamericus sensu stricto, and Knodus sensu stricto, placing some small genera as junior synonyms. Inseminating species are distributed in several clades suggesting that reproductive strategy is evolutionarily labile in this group of fishes.http://deepblue.lib.umich.edu/bitstream/2027.42/134621/1/12862_2015_Article_403.pd