Antibody response against saliva antigens of Anopheles gambiae and Aedes aegypti in travellers in tropical Africa

Exposure to vectors of infectious diseases has been associated with antibody responses against salivary antigens of arthropods among people living in endemic areas. This immune response has been proposed as a surrogate marker of exposure to vectors appropriate for evaluating the protective efficacy of antivectorial devices. The existence and potential use of such antibody responses in travellers transiently exposed to Plasmodium or arbovirus vectors in tropical areas has never been investigated. The IgM and IgG antibody responses of 88 French soldiers against the saliva of Anopheles gambiae and Aedes aegypti were evaluated before and after a 5-month journey in tropical Africa. Antibody responses against Anopheles and Aedes saliva increased significantly in 41% and 15% of the individuals, respectively, and appeared to be specific to the mosquito genus. A proteomic and immunoproteomic analysis of anopheles and Aedes saliva allowed for the identification of some antigens that were recognized by most of the exposed individuals. These results suggest that antibody responses to the saliva of mosquitoes could be considered as specific surrogate markers of exposure of travellers to mosquito vectors that transmit arthropod borne infections.     

Differentiating megakaryocytes in myelodysplastic syndromes succumb to mitochondrial derangement without caspase activation

Myelodysplastic syndromes (MDS) constitute a preneoplastic condition in which potentially malignant cancer stem cells continuously die during differentiation. This MDS-associated cell death often involves caspase-3 activation, yet can also occur without caspase activation, for instance in differentiating megakaryocytes (MK). We investigated, the mechanisms through which MK from MDS patients undergo premature cell death. While polyploid, mature MK from healthy subjects or MDS patients manifested caspase-3 activation during terminal differentiation, freshly isolated, immature MK from MDS died without caspase-3 activation. Similarly, purified bone marrow CD34⁺ cells from MDS patients that were driven into MK differentiation in vitro died without caspase-3 activation at an immature stage, before polyploidization. The premature death of MDS MK was accompanied by the mitochondrial release of cytochrome c, Smac/DIABLO and endonuclease G, a caspase-independent death effector, as well loss of the mitochondrial membrane potential and plasma membrane phosphatidylserine exposure before definitive loss of viability. Thus, a stereotyped pattern of mitochondrial alterations accompanies differentiation-associated MK death in MDS. T. Braun and G. Carvalho contributed equally to this paper.     

Biofilm formation by asymptomatic and virulent urinary tract infectious Escherichia coli strains

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. In contrast to uropathogenic E. coli (UPEC) that cause symptomatic urinary tract infection, very little is known about the mechanisms by which these strains colonize the urinary tract. Here, we have investigated the biofilm-forming capacity on abiotic surfaces of groups of ABU strains and UPEC strains in human urine. We found that there is a strong bias; ABU strains were significantly better biofilm formers than UPEC strains. Our data suggest that biofilm formation in urinary tract infectious E. coli seems to be associated with ABU strains and appears to be an important strategy used by these strains for persistence in this high-flow environment.     

Persistence of long-term memory storage requires a late protein synthesis- and BDNF- dependent phase in the hippocampus

Persistence is the most characteristic attribute of long-term memory (LTM). To understand LTM, we must understand how memory traces persist over time despite the short-lived nature and rapid turnover of their molecular substrates. It is widely accepted that LTM formation is dependent upon hippocampal de novo protein synthesis and Brain-Derived Neurotrophic Factor (BDNF) signaling during or early after acquisition. Here we show that 12 hr after acquisition of a one-trial associative learning task, there is a novel protein synthesis and BDNF-dependent phase in the rat hippocampus that is critical for the persistence of LTM storage. Our findings indicate that a delayed stabilization phase is specifically required for maintenance, but not formation, of the memory trace. We propose that memory formation and memory persistence share some of the same molecular mechanisms and that recurrent rounds of consolidation-like events take place in the hippocampus for maintenance of the memory trace.     

Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod- driven motility and cell-cycle progression

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Highlights? Rac1 and the Scar/WAVE complex drive pseudopod-based motility of melanoblasts ? Rac1-depleted melanoblasts move using unique actin-based stubs and not blebs ? Rac1 controls pseudopod frequency but is dispensable for pseudopod formation ? Loss of Rac1 delays melanoblast cell-cycle progression and cytokinesis     

Skeletal ossification and sequence heterochrony in xenarthran evolution

Previous analyses of how mammals vary in their ossification sequences have focused on monotremes, marsupials, and boreoeutherian placentals. Here, we focus on the sequence of cranial and postcranial ossification events during growth in the xenarthran skull and skeleton, including armadillos, anteaters, and sloths. We use two different methods to quantify sequence heterochrony: sequence analysis of variance (ANOVA) and event‐paring/Parsimov. Our results indicate that Parsimov is conservative and does not detect clear heterochronic shifts between xenarthran and boreoeutherian placentals. Sequence‐ANOVA performs better, but both methods exhibit sensitivity to the artifactual accumulation of ties. By controlling for ties and taking into account results that the methods have in common, our analysis suggests that xenarthrans significantly differ from other placentals by a late ossification of the sternum and an early ossification of the phalanges and pubis. We interpret these differences as showing that heterochrony plays a role in the skeletal development of xenarthrans, a change from previous studies that have emphasized the developmental homogeneity of the skeleton across placental mammals.     

Power-law input-output transfer functions explain the contrast-response and tuning properties of neurons in visual cortex

We develop a unified model accounting simultaneously for the contrast invariance of the width of the orientation tuning curves (OT) and for the sigmoidal shape of the contrast response function (CRF) of neurons in the primary visual cortex (V1). We determine analytically the conditions for the structure of the afferent LGN and recurrent V1 inputs that lead to these properties for a hypercolumn composed of rate based neurons with a power-law transfer function. We investigate what are the relative contributions of single neuron and network properties in shaping the OT and the CRF. We test these results with numerical simulations of a network of conductance-based model (CBM) neurons and we demonstrate that they are valid and more robust here than in the rate model. The results indicate that because of the acceleration in the transfer function, described here by a power-law, the orientation tuning curves of V1 neurons are more tuned, and their CRF is steeper than those of their inputs. Last, we show that it is possible to account for the diversity in the measured CRFs by introducing heterogeneities either in single neuron properties or in the input to the neurons. We show how correlations among the parameters that characterize the CRF depend on these sources of heterogeneities. Comparison with experimental data suggests that both sources contribute nearly equally to the diversity of CRF shapes observed in V1 neurons.