Schistosoma haematobium Infection and CD4+ T-Cell Levels: A Cross-Sectional Study of Young South African Women

Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the association between urogenital S. haematobium infection and CD4 cell counts in 792 female high-school students from randomly selected schools in rural KwaZulu-Natal, South Africa. We also investigated the association between low CD4 cell counts in HIV positive women and the number of excreted schistosome eggs in urine. Sixteen percent were HIV positive and 31% had signs of urogenital schistosomiasis (as determined by genital sandy patches and / or abnormal blood vessels on ectocervix / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV status, participants with and without urogenital schistosomiasis had similar CD4 cell counts. Furthermore, there was no significant difference in prevalence of urogenital schistosomiasis in HIV positive women with low and high CD4 cell counts. There was no significant difference in the number of eggs excreted in urine when comparing HIV positive and HIV negative women. Our findings indicate that urogenital schistosomiasis do not influence the number of circulating CD4 cells.     

Empirical Evidence for Species-Specific Export of Fish Na?veté from a No-Take Marine Protected Area in a Coastal Recreational Hook and Line Fishery

No-take marine protected areas (MPAs) are assumed to enhance fisheries catch via the “spillover” effect, where biomass is exported to adjacent exploited areas. Recent studies in spearfishing fisheries suggest that the spillover of gear-naïve individuals from protected to unprotected sites increases catch rates outside the boundaries of MPAs. Whether this is a widespread phenomenon that also holds for other gear types and species is unknown. In this study, we tested if the distance to a Mediterranean MPA predicted the degree of vulnerability to hook and line in four small-bodied coastal fish species. With the assistance of underwater video recording, we investigated the interaction effect of the distance to the boundary of an MPA and species type relative to the latency time to ingest a natural bait, which was considered as a surrogate of fish naïveté or vulnerability to fishing. Vulnerability to angling increased (i.e., latency time decreased) within and near the boundary of an MPA for an intrinsically highly catchable species (Serranus scriba), while it remained constant for an intrinsically uncatchable control species (Chromis chromis). While all of the individuals of S. scriba observed within the MPA and surrounding areas were in essence captured by angling gear, only one fifth of individuals in the far locations were captured. This supports the potential for the spillover of gear-naïve and consequently more vulnerable fish from no-take MPAs. Two other species initially characterized as intermediately catchable (Coris julis and Diplodus annularis) also had a shorter latency time in the vicinity of an MPA, but for these two cases the trend was not statistically significant. Overall, our results suggest that an MPA-induced naïveté effect may not be universal and may be confined to only intrinsically highly catchable fish species. This fact emphasizes the importance of considering the behavioural dimension when predicting the outcomes of MPAs, otherwise the effective contribution may be smaller than predicted for certain highly catchable species such as S. scriba.     

Molecular Characterization of Two Lysophospholipid:acyl-CoA Acyltransferases Belonging to the MBOAT Family in Nicotiana benthamiana

In the remodeling pathway for the synthesis of phosphatidylcholine (PC), acyl-CoA-dependent lysophosphatidylcholine (lysoPC) acyltransferase (LPCAT) catalyzes the reacylation of lysoPC. A number of genes encoding LPCATs have been cloned and characterized from several plants in recent years. Using Arabidopsis and other plant LPCAT sequences to screen the genome database of Nicotiana benthamiana, we identified two cDNAs encoding the putative tobacco LPCATs (NbLPCAT1 and NbLPCAT2). Both of them were predicted to encode a protein of 463 amino acids with high similarity to LPCATs from other plants. Protein sequence features such as the presence of at least eight putative transmembrane regions, four highly conserved signature motifs and several invariant residues indicate that NbLPCATs belong to the membrane bound O-acyltransferase family. Lysophospholipid acyltransferase activity of NbLPCATs was confirmed by testing lyso-platelet-activating factor (lysoPAF) sensitivity through heterologous expression of each full-length cDNA in a yeast mutant Y02431 (lca1△) disrupted in endogenous LPCAT enzyme activity. Analysis of fatty acid profiles of phospholipids from the NbLPCAT-expressing yeast mutant Y02431 cultures supplemented with polyunsaturated fatty acids suggested more incorporation of linoleic acid (18:2n6, LA) and α-linolenic acid (18:3n3, ALA) into PC compared to yeast mutant harbouring empty vector. In vitro enzymatic assay demonstrated that NbLPCAT1had high lysoPC acyltransferase activity with a clear preference for α-linolenoyl-CoA (18:3), while NbLPCAT2 showed a high lysophosphatidic acid (lysoPA) acyltransferase activity towards α-linolenoyl-CoA and a weak lysoPC acyltransferase activity. Tissue-specific expression analysis showed a ubiquitous expression of NbLPCAT1 and NbLPCAT2 in roots, stems, leaves, flowers and seeds, and a strong expression in developing flowers. This is the first report on the cloning and characterization of lysophospholipid acyltransferases from N. benthamiana.     

A Comparison between Multiple Regression Models and CUN-BAE Equation to Predict Body Fat in Adults

Background

Because the accurate measure of body fat (BF) is difficult, several prediction equations have been proposed. The aim of this study was to compare different multiple regression models to predict BF, including the recently reported CUN-BAE equation.

Methods

Multi regression models using body mass index (BMI) and body adiposity index (BAI) as predictors of BF will be compared. These models will be also compared with the CUN-BAE equation. For all the analysis a sample including all the participants and another one including only the overweight and obese subjects will be considered. The BF reference measure was made using Bioelectrical Impedance Analysis.

Results

The simplest models including only BMI or BAI as independent variables showed that BAI is a better predictor of BF. However, adding the variable sex to both models made BMI a better predictor than the BAI. For both the whole group of participants and the group of overweight and obese participants, using simple models (BMI, age and sex as variables) allowed obtaining similar correlations with BF as when the more complex CUN-BAE was used (ρ = 0:87 vs. ρ = 0:86 for the whole sample and ρ = 0:88 vs. ρ = 0:89 for overweight and obese subjects, being the second value the one for CUN-BAE).

Conclusions

There are simpler models than CUN-BAE equation that fits BF as well as CUN-BAE does. Therefore, it could be considered that CUN-BAE overfits. Using a simple linear regression model, the BAI, as the only variable, predicts BF better than BMI. However, when the sex variable is introduced, BMI becomes the indicator of choice to predict BF.     

SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer’s disease

Background

Synaptic degeneration is an early pathogenic event in Alzheimer’s disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples.

Results

We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer’s disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer’s disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer’s disease from controls with area under the curve of 0.901 (P?<?0.0001).

Conclusions

We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials.

     

Altered Mucus Glycosylation in Core 1 O-Glycan-Deficient Mice Affects Microbiota Composition and Intestinal Architecture

A functional mucus layer is a key requirement for gastrointestinal health as it serves as a barrier against bacterial invasion and subsequent inflammation. Recent findings suggest that mucus composition may pose an important selection pressure on the gut microbiota and that altered mucus thickness or properties such as glycosylation lead to intestinal inflammation dependent on bacteria. Here we used TM-IEC C1galt ^-/- mice, which carry an inducible deficiency of core 1-derived O-glycans in intestinal epithelial cells, to investigate the effects of mucus glycosylation on susceptibility to intestinal inflammation, gut microbial ecology and host physiology. We found that TM-IEC C1galt ^-/- mice did not develop spontaneous colitis, but they were more susceptible to dextran sodium sulphate-induced colitis. Furthermore, loss of core 1-derived O-glycans induced inverse shifts in the abundance of the phyla Bacteroidetes and Firmicutes. We also found that mucus glycosylation impacts intestinal architecture as TM-IEC C1galt^-/- mice had an elongated gastrointestinal tract with deeper ileal crypts, a small increase in the number of proliferative epithelial cells and thicker circular muscle layers in both the ileum and colon. Alterations in the length of the gastrointestinal tract were partly dependent on the microbiota. Thus, the mucus layer plays a role in the regulation of gut microbiota composition, balancing intestinal inflammation, and affects gut architecture.     

The E3 Ligase Parkin Maintains Mitochondrial Integrity by Increasing Linear Ubiquitination of NEMO

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Highlights? The stress-protective prosurvival activity of parkin depends on NEMO ? Parkin binds to LUBAC and increases linear ubiquitination of NEMO ? OPA1 is upregulated via parkin/NEMO/NF-κB for maintaining mitochondrial integrity ? TNF-α signaling via NEMO/NF-κB is impaired in parkin-deficient cells