The complete mitochondrial genome of Epomophorus gambianus (Chiroptera: Pteropodidae) and its phylogenetic analysis

The Gambian epauletted fruit bat, Epomophorus gambianus, is widely distributed across sub-Saharan Africa. Its assembled and annotated mitochondrial genome (GenBank accession no. KT963027) is 16,702 bases in length, containing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two non-coding regions: the control region (D-loop) and the origin of light-strand replication (OL). The average base composition is 32.2% A; 27.6% C; 14% G; and 26.1% T. The mitogenome presented a structural composition greatly conserved between members of the Pteropodidae family

A broader role for AmyR in Aspergillus niger: regulation of the utilisation of d-glucose or d-galactose containing oligo- and polysaccharides

AmyR is commonly considered a regulator of starch degradation whose activity is induced by the presence of maltose, the disaccharide building block of starch. In this study, we demonstrate that the role of AmyR extends beyond starch degradation. Enzyme activity assays, genes expression analysis and growth profiling on d-glucose- and d-galactose-containing oligo- and polysaccharides showed that AmyR regulates the expression of some of the Aspergillus niger genes encoding α- and β-glucosidases, α- and β- galactosidases, as well as genes encoding α-amlyases and glucoamylases. In addition, we provide evidence that d-glucose or a metabolic product thereof may be the inducer of the AmyR system in A. niger and not maltose, as is commonly assumed

The P2X(7) receptor tracer [C-11]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study

Purpose: The novel PET tracer [11C]SMW139 binds with high affinity to the P2X7 receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [11C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify in vivo neuroinflammation in RRMS. / Methods: Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [11C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion. / Results: The optimal model for describing [11C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k4 fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (VT) and binding potential (BPND) in RRMS compared with HC in normal appearing brain regions. BPND in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased VT was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional VT and BPND values. / Conclusions: This first in-man study demonstrated that uptake of [11C]SMW139 can be quantified with PET using BPND as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Adjustable Gastric Banding Conversion to One Anastomosis Gastric Bypass: Data Analysis of a Multicenter Database

Introduction: One anastomosis gastric bypass (OAGB) has been proposed as a rescue technique for laparoscopic adjustable gastric banding (LAGB) poor responders. Aim: We sought to analyze, complications, mortality, and medium-term weight loss results after LAGB conversion to OAGB. Methods: Data analysis of an international multicenter database. Results: One hundred eighty-nine LAGB-to-OAGB operations were retrospectively analyzed. Eighty-seven (46.0%) were converted in one stage. Patients operated on in two stages had a higher preoperative body mass index (BMI) (37.9 vs. 41.3 kg/m2, p = 0.0007) and were more likely to have encountered technical complications, such as slippage or erosions (36% vs. 78%, p < 0.0001). Postoperative complications occurred in 4.8% of the patients (4.6% and 4.9% in the one-stage and the two-stage group, respectively). Leak rate, bleeding episodes, and mortality were 2.6%, 0.5%, and 0.5%, respectively. The final BMI was 30.2 at a mean follow-up of 31.4 months. Follow-up at 1, 3, and 5 years was 100%, 88%, and 70%, respectively. Conclusion: Conversion from LAGB to OAGB is safe and effective. The one-stage approach appears to be the preferred option in non-complicate cases, while the two-step approach is mostly done for more complicated cases.info:eu-repo/semantics/publishedVersio

The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.

While aggregation-prone proteins are known to accelerate aging and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that MOAG-4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation-prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age-related protein toxicity

Dendritic cell vaccination and immune monitoring

We exploited dendritic cells (DC) to vaccinate melanoma patients. We recently demonstrated a statistical significant correlation between favorable clinical outcome and the presence of vaccine-related tumor antigen-specific T cells in delayed type hypersensitivity (DTH) skin biopsies. However, favorable clinical outcome is only observed in a minority of the treated patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof of principle trials the fate, interactions and effectiveness of the injected DC

The Gambian Epauletted Fruit Bat Shows Increased Genetic Divergence in the Ethiopian Highlands and in an Area of Rapid Urbanisation

The Gambian epauletted fruit bat (Epomophorus gambianus) is an abundant species that roosts in both urban and rural settings. The possible role of E. gambianus as a reservoir host of zoonotic diseases underlines the need to better understand the species movement patterns. So far, neither observational nor phylogenetic studies have identified the dispersal range or behavior of this species. Comparative analyses of mitochondrial and nuclear markers from 20 localities across the known distribution of E. gambianus showed population panmixia, except for the populations in Ethiopia and southern Ghana (Accra and Ve‐Golokwati). The Ethiopian population may be ancestral and is highly divergent to the species across the rest of its range, possibly reflecting isolation of an ancient colonization along an east–west axis. Mitochondrial haplotypes in the Accra population display a strong signature of a past bottleneck event; evidence of either an ancient or recent bottleneck using microsatellite data, however, was not detected. Demographic analyses identified population expansion in most of the colonies, except in the female line of descent in the Accra population. The molecular analyses of the colonies from Ethiopia and southern Ghana show gender dispersal bias, with the mitochondrial DNA fixation values over ten times those of the nuclear markers. These findings indicate free mixing of the species across great distances, which should inform future epidemiological studies

Phylogeography and demographic history of Epomophorus gambianus: contrasting nuclear and mitochondrial DNA

The Gambian epauletted fruit bat (Epomophorus gambianus) is an abundant species that roosts in both urban and rural settings. The possible role of E. gambianus as a reservoir host of zoonotic diseases underlines the need to better understand the species movement patterns. So far, neither observational nor phylogenetic studies have identified the dispersal range or behavior of this species. Comparative analyses of mitochondrial and nuclear markers from 20 localities across the known distribution of E. gambianus showed population panmixia, except for the populations in Ethiopia and southern Ghana (Accra and Ve‐Golokwati). The Ethiopian population may be ancestral and is highly divergent to the species across the rest of its range, possibly reflecting isolation of an ancient colonization along an east–west axis. Mitochondrial haplotypes in the Accra population display a strong signature of a past bottleneck event; evidence of either an ancient or recent bottleneck using microsatellite data, however, was not detected. Demographic analyses identified population expansion in most of the colonies, except in the female line of descent in the Accra population. The molecular analyses of the colonies from Ethiopia and southern Ghana show gender dispersal bias, with the mitochondrial DNA fixation values over ten times those of the nuclear markers. These findings indicate free mixing of the species across great distances, which should inform future epidemiological studies