A nucleotide insertion and frameshift cause albumin Kénitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges

Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-59

Pharmacological therapies in post stroke recovery: Recommendations for future clinical trials

Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials. © 2013 Springer-Verlag Berlin Heidelberg

The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity

This work was supported by a grant of the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, Grant Number EXC 1086).Peer reviewedPostprintPostprin

Multidisciplinary estimates of connectivity and population structure suggest the use of multiple units for the conservation and management of meagre, Argyrosomus regius

Information on population structure and connectivity of targeted species is key for proper implementation of spatial conservation measures. We used a combination of genomics, biophysical modelling, and biotelemetry to infer the population structure and connectivity of Atlantic meagre, an important fisheries resource throughout its distribution. Genetic samples from previously identified Atlantic spawning locations (Gironde, Tejo, Guadalquivir, Banc d’Arguin) and two additional regions (Algarve and Senegal) were analysed using genome-wide SNP-genotyping and mitochondrial DNA analyses. Biophysical models were conducted to investigate larval dispersal and connectivity from the known Atlantic spawning locations. Additionally, thirteen fish were double-tagged with biotelemetry transmitters off the Algarve (Portugal) to assess movement patterns and connectivity of adult individuals. This multidisciplinary approach provided a robust overview of meagre population structure and connectivity in the Atlantic. Nuclear SNP-genotyping showed a clear differentiation between the European and African populations, with significant isolation of the few known Atlantic spawning sites. The limited level of connectivity between these subpopulations is potentially driven by adults, capable of wide-ranging movements and connecting sites 500 km apart, as evidenced by tagging studies, whilst larval dispersal inferred by modelling is much more limited (average of 52 km; 95% of connectivity events up to 174 km). Our results show sufficient evidence of population structure, particularly between Africa and Europe but also within Europe, for the meagre to be managed as separate stocks. Additionally, considering the low degree of larvae connectivity, the implementation of marine protected areas in key spawning sites could be crucial towards species sustainability

The Tension on dsDNA Bound to ssDNA/RecA Filaments May Play an Important Role in Driving Efficient and Accurate Homology Recognition and Strand Exchange

It is well known that during homology recognition and strand exchange the double stranded DNA (dsDNA) in DNA/RecA filaments is highly extended, but the functional role of the extension has been unclear. We present an analytical model that calculates the distribution of tension in the extended dsDNA during strand exchange. The model suggests that the binding of additional dsDNA base pairs to the DNA/RecA filament alters the tension in dsDNA that was already bound to the filament, resulting in a non-linear increase in the mechanical energy as a function of the number of bound base pairs. This collective mechanical response may promote homology stringency and underlie unexplained experimental results

Awake fMRI reveals a specialized region in dog temporal cortex for face processing

Recent behavioral evidence suggests that dogs, like humans and monkeys, are capable of visual face recognition. But do dogs also exhibit specialized cortical face regions similar to humans and monkeys? Using functional magnetic resonance imaging (fMRI) in six dogs trained to remain motionless during scanning without restraint or sedation, we found a region in the canine temporal lobe that responded significantly more to movies of human faces than to movies of everyday objects. Next, using a new stimulus set to investigate face selectivity in this predefined candidate dog face area, we found that this region responded similarly to images of human faces and dog faces, yet significantly more to both human and dog faces than to images of objects. Such face selectivity was not found in dog primary visual cortex. Taken together, these findings: 1) provide the first evidence for a face-selective region in the temporal cortex of dogs, which cannot be explained by simple low-level visual feature extraction; 2) reveal that neural machinery dedicated to face processing is not unique to primates; and 3) may help explain dogs’ exquisite sensitivity to human social cues.</jats:p

Epidemiological situation and risk Factors to Infectious Diseases in Dairy Cattle Located in Different Mesoregions of the State of Rio Grande do Sul, Brazil, 2016/2017.

The aim of this study was to describe the epidemiology of infectious bovine rhinotracheitis (IBR), bovine viral diarrhea (BVD), neosporosis (NEO) and leptospirosis (LEP) from the perspective of the impact these diseases have to cause reproductive problems in dairy cattle herds located in different mesoregions of Rio Grande do Sul State. The herds analysed belong to two cooperatives and an association of producers. The seroprevalences of IBR, BVD, NEO and LEP ranged from 54.4 to 60.3%, 30.0 to 42.5%, 21.8 to 35.0% and 15.8 to 27.5%, respectively. The seroprevalences of IBR show a homogeneous distribution of the disease according to the mesoregions. Nevertheless, IBR was associated with estrus recurrence and abortion in herds located in the northeast and northwest mesoregions. BVD was associated with rearing of estrus in herds located in the southeast, southwest, northeast and northwest mesoregions. NEO was associated with cases of abortion in the herds located in the northeast and northwest mesoregions. LEP was associated with miscarriages in herds located in the northwest mesoregion. It was found that the epidemiological character of the disease cases were distinct in the different mesoregions. In this way, the priorities in the control and prevention programs of these diseases are different between the mesoregions, cooperatives and association of producers. Despite that fact, common control procedures were found amongst the disease cases studied; each one of them has its peculiarity in relation to the epidemiology and consequently control and preventio

The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study

<p>Abstract</p> <p>Background</p> <p>By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke.</p> <p>This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response.</p> <p>We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.</p> <p>Results</p> <p>As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01).</p> <p>Conclusions</p> <p>The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.</p