First characterization of congenital myasthenic syndrome type 5 in North Africa

Molecular Biology Reports - Congenital myasthenic syndromes (CMS) are associated with defects in the structure and the function of neuromuscular junctions. These rare disorders can result from...     

The Highly Conserved Layer-3 Component of the HIV-1 gp120 Inner Domain Is Critical for CD4-Required Conformational Transitions

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, we report that a highly conserved element of the gp120 inner domain, layer 3, plays a pivot-like role in these allosteric changes. In the unliganded state, layer 3 modulates the association of gp120 with the Env trimer, probably by influencing the relationship of the gp120 inner and outer domains. Importantly, layer 3 governs the efficiency of the initial gp120 interaction with CD4, a function that can also be fulfilled by filling the Phe43 cavity. This work defines the functional importance of layer 3 and completes a picture detailing the role of the gp120 inner domain in CD4-induced conformational transitions in the HIV-1 Env trimer.     

A germline mutation in BLOC1S3/reduced pigmentation causes a novel variant of Hermansky-Pudlak syndrome (HPS8)

Hermansky-Pudlak syndrome (HPS) is genetically heterogeneous, and mutations in seven genes have been reported to cause HPS. Autozygosity mapping studies were undertaken in a large consanguineous family with HPS. Affected individuals displayed features of incomplete oculocutaneous albinism and platelet dysfunction. Skin biopsy demonstrated abnormal aggregates of melanosomes within basal epidermal keratinocytes. A homozygous germline frameshift mutation in BLOC1S3 (p.Gln150ArgfsX75) was identified in all affected individuals. BLOC1S3 mutations have not been previously described in patients with HPS, but BLOC1S3 encodes a subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Mutations in other BLOC-1 subunits have been associated with an HPS phenotype in humans and/or mouse, and a nonsense mutation in the murine orthologue of BLOC1S3 causes the reduced pigmentation (rp) model of HPS. Interestingly, eye pigment formation is reported to be normal in rp, but we found visual defects (nystagmus, iris transilluminancy, foveal hypoplasia, reduced visual acuity, and evidence of optic pathway misrouting) in affected individuals. These findings define a novel form of human HPS (HPS8) and extend genotype-phenotype correlations in HPS.     

Infectivity-deficient vesicular stomatitis virus produced in the presence of interferon has a functional virion core

Interferon induces two antiviral actions against vesicular stomatitis virus by (i) inhibiting viral protein synthesis which leads to a reduction in virion production, and (ii) producing progeny which are deficient in infectivity (VSVIF). At low or physiological concentrations of interferon, while the virion production was decreased by less than 10-fold, the virion infectivity yield was suppressed more than 1000-fold. The VSVIF was found to be deficient (quantitatively) in envelop glycoprotein G and protein M. Tryptic peptide mapping indicated that there was no detectable structural abnormality in the G, M, and N proteins of VSVIF. The virion cores, lacking only the envelop G protein, isolated from VSVIF and control VSV have essentially identical specific infectivity. This indicated that the virion proteins L, N, NS, and M, as well as viral RNA that make up the virion core, must be functionally normal, and the observed deficiency in G protein was likely to be the cause of the functional deficiency of the virion. Low concentrations of DEAE-dextran, which is known to partially overcome the virion's dependence on the G protein for adsorption to the cell during infection, were found to enhance the infectivity of VSVIF more than the control virion. These results together indicated that the loss of infectivity in the VSVIF was due to the deficiency of the surface glycoprotein G.     

Regulation of LHCII aggregation by different thylakoid membrane lipids

In the present study the influence of the lipid environment on the organization of the main light-harvesting complex of photosystem II (LHCII) was investigated by 77K fluorescence spectroscopy. Measurements were carried out with a lipid-depleted and highly aggregated LHCII which was supplemented with the different thylakoid membrane lipids. The results show that the thylakoid lipids are able to modulate the spectroscopic properties of the LHCII aggregates and that the extent of the lipid effect depends on both the lipid species and the lipid concentration. Addition of the neutral galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) seems to induce a modification of the disorganized structures of the lipid-depleted LHCII and to support the aggregated state of the complex. In contrast, we found that the anionic lipids sulfoquinovosyldiacylglycerol (SQDG) and phosphatidylglycerol (PG) exert a strong disaggregating effect on the isolated LHCII. LHCII disaggregation was partly suppressed under a high proton concentration and in the presence of cations. The strongest suppression was visible at the lowest pH value (pH 5) and the highest Mg(2+) concentration (40 mM) used in the present study. This suggests that the negative charge of the anionic lipids in conjunction with negatively charged domains of the LHCII proteins is responsible for the disaggregation. Additional measurements by photon correlation spectroscopy and sucrose gradient centrifugation, which were used to gain information about the size and molecular mass of the LHCII aggregates, confirmed the results of the fluorescence spectroscopy. LHCII treated with MGDG and DGDG formed an increased number of aggregates with large particle sizes in the micromm-range, whereas the incubation with anionic lipids led to much smaller LHCII particles (around 40 nm in the case of PG) with a homogeneous distribution.     

Estimation of aboveground biomass in conserved areas of Stipa tenacissima L. stands in the high steppes of western Algeria by mean of the Landsat 8 imagery‐based vegetation indices

The main aim of this paper was to evaluate the use of OLI spectral data as a tool to assess the steppe vegetation in a conservation context. The field sampling was conducted for two specific areas of treatment (a) an exclosure area and (b) a free grazing area. After testing several vegetation indices (VIs), the optimal results were obtained for the Normalised Difference Vegetation Index (NDVI)‐based aboveground biomass model with r² = 0.61 and r² = 0.72 for total and perennial biomass, respectively. No difference between observed and predicted total and perennial biomass was found (p = 0.700 and p = 0.306, respectively). The comparison between the two treatments using the field sampling revealed a significant difference on total plant cover (p = 0.016) and total biomass (p = 0.005), with a plant cover of 50.6% and a biomass of 325.771 kg dry matter per hectare (kg DM ha^?1) on average in grazed area and 66.9%, 1,407.869 kg DM ha^?1 in exclosure. Finally, a concordance is noted between the results obtained by the NDVI‐based biomass model and the field sampling‐based biomass.