Embryonic Mutant Huntingtin Aggregate Formation in Mouse Models of Huntington’s Disease

The role of aggregate formation in the pathophysiology of Huntington’s disease (HD) remains uncertain. However, the temporal appearance of aggregates tends to correlate with the onset of symptoms and the numbers of neuropil aggregates correlate with the progression of clinical disease. Using highly sensitive immunohistochemical methods we have detected the appearance of diffuse aggregates during embryonic development in the R6/2 and YAC128 mouse models of HD. These are initially seen in developing axonal tracts and appear to spread throughout the cerebrum in the early neonate

Abundance and local-scale processes contribute to multi-phyla gradients in global marine diversity

Among themost enduring ecological challenges is an integrated theory explaining the latitudinal biodiversity gradient, including discrepancies observed at different spatial scales. Analysis of Reef Life Survey data for 4127 marine species at 2406 coral and rocky sites worldwide confirms that the total ecoregion richness peaks in low latitudes, near +15 degrees N and -15 degrees S. However, although richness at survey sites is maximal near the equator for vertebrates, it peaks at high latitudes for large mobile invertebrates. Site richness for different groups is dependent on abundance, which is in turn correlated with temperature for fishes and nutrients for macroinvertebrates. We suggest that temperature-mediated fish predation and herbivory have constrained mobile macroinvertebrate diversity at the site scale across the tropics. Conversely, at the ecoregion scale, richness responds positively to coral reef area, highlighting potentially huge global biodiversity losses with coral decline. Improved conservation outcomes require management frameworks, informed by hierarchical monitoring, that cover differing site- and regional-scale processes across diverse taxa, including attention to invertebrate species, which appear disproportionately threatened by warming seas

Barium isotopes reveal role of ocean circulation on barium cycling in the Atlantic

We diagnose the relative influences of local-scale biogeochemical cycling and regional-scale ocean circulation on Atlantic barium cycling by analysing four new depth profiles of dissolved Ba concentrations and isotope compositions from the South and tropical North Atlantic. These new profiles exhibit systematic vertical, zonal and meridional variations that reflect the influence of both local-scale barite cycling and large-scale ocean circulation. Epipelagic decoupling of dissolved Ba and Si reported previously in the tropics is also found to be associated with significant Ba isotope heterogeneity. As such, we contend that this decoupling originates from the depth segregation of opal and barite formation but is exacerbated by weak vertical mixing. Zonal influence from isotopically-‘heavy’ water masses in the western North Atlantic evidence the advective inflow of Ba-depleted Upper Labrador Sea Water, which is not seen in the eastern basin or the South Atlantic. Meridional variations in Atlantic Ba isotope systematics below 2000 m appear entirely controlled by conservative mixing. Using an inverse isotopic mixing model, we calculate the Ba isotope composition of the Ba-poor northern end-member as +0.45 ‰ and the Ba-rich southern end-member +0.26 ‰, relative to NIST SRM 3104a. The near-conservative behaviour of Ba below 2000 m indicates that Ba isotopes can serve as an independent tracer of the provenance of northern- versus southern-sourced water masses in the deep Atlantic Ocean. This finding may prove useful in palaeoceanographic studies, should appropriate sedimentary archives be identified, and offers new insights into the processes that cycle Ba in seawater

The Effects of Previous Error and Success in Alzheimer’s Disease and Mild Cognitive Impairment

This work investigated in Alzheimer’s disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment

Vitamin D and subsequent all-age and premature mortality: a systematic review

<br>Background: All-cause mortality in the population < 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.</br> <br>Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.</br> <br>Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).</br> <br>Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.</br&gt

Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

BACKGROUND: Several clinical trials have demonstrated the efficacy of fluconazole as empiric antifungal therapy in cancer patients with fever and neutropenia. Our objective was to assess the frequency and resource utilization associated with treatment failure in cancer patients given empiric fluconazole antifungal therapy in routine inpatient care. METHODS: We performed a retrospective cohort study of cancer patients treated with oral or intravenous fluconazole between 7/97 and 6/01 in a tertiary care hospital. The final study cohort included cancer patients with neutropenia (an absolute neutrophil count below 500 cells/mm(3)) and fever (a temperature above 38°C or 100.4°F), who were receiving at least 96 hours of parenteral antibacterial therapy prior to initiating fluconazole. Patients' responses to empiric therapy were assessed by reviewing patient charts. RESULTS: Among 103 cancer admissions with fever and neutropenia, treatment failure after initiating empiric fluconazole antifungal therapy occurred in 41% (95% confidence interval (CI) 31% – 50%) of admissions. Patients with a diagnosis of hematological malignancy had increased risk of treatment failure (OR = 4.6, 95% CI 1.5 – 14.8). When treatment failure occurred the mean adjusted increases in length of stay and total costs were 7.4 days (95% CI 3.3 – 11.5) and $18,925 (95% CI 3,289 – 34,563), respectively. CONCLUSION: Treatment failure occurred in more than one-third of neutropenic cancer patients on fluconazole as empiric antifungal treatment for fever in routine clinical treatment. The increase in costs when treatment failure occurs is substantial

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

Long-term effects of chronic light pollution on seasonal functions of European blackbirds (turdus merula)

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems