Exosomes surf on filopodia to enter cells at endocytic hot spots,traffic within endosomes,and are targeted to the ER

Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.     

Identification of gravid mosquitoes from changes in spectral and polarimetric backscatter cross sections

Improving the survey of mosquito populations is of the utmost importance to further enhance mitigation techniques that protect human populations from mosquito‐borne diseases. While mosquito populations are generally studied using physical traps, stand‐off optical sensors allow to study insect ecosystems with potentially better spatial and temporal resolution. This can be greatly beneficial to eco‐epidemiological models and various mosquito control programs. In this contribution, we demonstrate that the gravidity of female mosquitoes can be identified from changes in their spectral and polarimetric backscatter cross sections. Among other predictive variables, the wing beat frequency and the depolarization ratio of the mosquito body allows for the identification of gravid females with a precision and recall of 86% and 87%, respectively. Since female mosquitoes need a blood meal to become gravid, statistics on gravidity is of prime importance as only females that have been gravid might carry infectious diseases. In addition, it allows to detect possible breeding habitat, predict a potential increase in the mosquito population and provide a better overall understanding of the ecosystem dynamics. As a result, targeted and localized mitigation techniques can be used, reducing the cost and improving the efficiency of mosquito population control.     

Basal rate of metabolism and temperature regulation in Sorex coronatus and S. minutus (Soricidae: Mammalia)

1. The basal rate of metabolism (BMR), body temperature and thermal conductance of Sorex minutus and Sorex coronatus were studied. Special attention was given to measuring BMR in resting and postabsorptive shrews. 2. Both species exhibit a high BMR, respectively 339 and 289% of the value expected on the basis of body mass. 3. The thermal conductance of both species is similar to the predicted value and their body temperature averages 38.6 and 37.6 degrees C respectively. 4. Available data suggest that a very high BMR may be a common feature within the genus Sorex.     

Notch1 control of oligodendrocyte differentiation in the spinal cord

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.     

Prion proteins and infertility: insight from mouse models

A wealth of evidence points to an abnormal form of the prion protein called PrP(Sc) as the transmissible agent responsible for prion diseases. However, the physiological function of its normal conformer, the cellular prion protein (PrP(C)), is still unknown. Recently, a homologue of PrP(C) was discovered and denoted Doppel (Dpl). In contrast to PrP, mice deficient for Dpl suffer from an important pathological phenotype: male sterility. This phenotype shifts the attention from the brain, where most of the investigations on Dpl have been performed, to testis, raising hope to resolve the long lasting search of PrP(C) function.     

Basal rate of metabolism and temperature regulation in Goeldi's monkey (Callimico goeldii)

Basal rate of metabolism (BMR) and temperature regulation are described for Goeldi's monkey (Callimico goeldii), a threatened New World primate species of the family Callitrichidae. Measurements were conducted on sleeping individuals during the night, using a special nestbox designed to serve as a respirometry chamber, such that test animals remained undisturbed in their customary surroundings. Oxygen consumption was measured at ambient temperatures between 17.5 and 32 degrees C for 10 individuals with an average body mass of 557 g. Average BMR was 278+/-41 ml O(2) h(-1), which is lower than the value predicted on the basis of body mass. Individual differences in BMR were significant even when body mass was accounted for. Body temperature was measured in five individuals below thermoneutrality and averaged 36+/-0.3 degrees C. The corresponding thermal conductance averaged 29.3+/-2.2 ml O(2) h(-1) degrees C(-1), which is similar to the expected value. The metabolic and thermoregulatory patterns observed in C. goeldii resemble those of the closely related marmosets and tamarins. Low BMR is presumably associated with limited access to energy resources and may be directly linked with phylogenetic dwarfing in the family Callitrichidae.     

Partitioning and inactivation of viruses by the caprylic acid precipitation followed by a terminal pasteurization in the manufacturing process of horse immunoglobulins

Caprylic acid (octanoic acid), has been used for over 50 years as a stabilizer of human albumin during pasteurization. In addition caprylic acid is of great interest, by providing the advantage of purifying mammalian immunoglobulins and clearing viruses infectivity in a single step. Exploiting these two properties, we sequentially used the caprylic acid precipitation and the pasteurization to purify horse hyperimmune globulins used in the manufacturing of Sérocytol. To evaluate the effectiveness of the process for the removal/inactivation of viruses, spiking studies were carried out for each dedicated step. Bovine viral diarrhoea virus (BVDV), pseudorabies virus (PRV), encephalomyocarditis virus (EMCV) and minute virus of mice (MVM) were used for the virological validation. Our data show that the treatment with caprylic acid 5% (v/v) can effectively be used as well to purify or to ensure viral safety of immunoglobulins. Caprylic acid precipitation was very efficient in removing and/or inactivating enveloped viruses (PRV, BVDV) and moderately efficient against non-enveloped viruses (MVM, ECMV). However the combination with the pasteurization ensured an efficient protection against both enveloped and non-enveloped viruses. So that viruses surviving to the caprylic acid precipitation will be neutralized by pasteurization. Significant log reduction were achieved > or =9 log(10) for enveloped viruses and 4 log(10) for non-enveloped viruses, providing the evidence of a margin of viral safety achieved by our manufacturing process. Its a simple and non-expensive manufacturing process of immunoglobulins easily validated that we have adapted to a large production scale with a programmable operating system.     

Role of elastin anisotropy in structural strain energy functions of arterial tissue

The vascular wall exhibits nonlinear anisotropic mechanical properties. The identification of a strain energy function (SEF) is the preferred method to describe its complex nonlinear elastic properties. Earlier constituent-based SEF models, where elastin is modeled as an isotropic material, failed in describing accurately the tissue response to inflation–extension loading. We hypothesized that these shortcomings are partly due to unaccounted anisotropic properties of elastin. We performed inflation–extension tests on common carotid of rabbits before and after enzymatic degradation of elastin and applied constituent-based SEFs, with both an isotropic and an anisotropic elastin part, on the experimental data. We used transmission electron microscopy (TEM) and serial block-face scanning electron microscopy (SBFSEM) to provide direct structural evidence of the assumed anisotropy. In intact arteries, the SEF including anisotropic elastin with one family of fibers in the circumferential direction fitted better the inflation–extension data than the isotropic SEF. This was supported by TEM and SBFSEM imaging, which showed interlamellar elastin fibers in the circumferential direction. In elastin-degraded arteries, both SEFs succeeded equally well in predicting anisotropic wall behavior. In elastase-treated arteries fitted with the anisotropic SEF for elastin, collagen engaged later than in intact arteries. We conclude that constituent-based models with an anisotropic elastin part characterize more accurately the mechanical properties of the arterial wall when compared to models with simply an isotropic elastin. Microstructural imaging based on electron microscopy techniques provided evidence for elastin anisotropy. Finally, the model suggests a later and less abrupt collagen engagement after elastase treatment.     

Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem

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