X-ray diffraction study of feline leukemia virus fusion peptide and lipid polymorphism

AbstractThe structural effects of the fusion peptide of feline leukemia virus (FeLV) on the lipid polymorphism of N-methylated dioleoylphosphatidylethanolamine were studied using a temperature ramp with sequential X-ray diffraction. This peptide, the hydrophobic amino-terminus of p15E, has been proven to be fusogenic and to promote the formation of highly curved, intermediate structures on the lamellar liquid-crystal to inverse hexagonal phase transition pathway. The FeLV peptide produces marked effects on the thermotropic mesomorphic behaviour of MeDOPE, a phospholipid with an intermediate spontaneous radius of curvature. The peptide is shown to reduce the lamellar repeat distance of the membrane prior to the onset of an inverted cubic phase. This suggests that membrane thinning may play a role in peptide-induced membrane fusion and strengthens the link between the fusion pathway and inverted cubic phase formation. The results of this study are interpreted in relation to models of the membrane fusion mechanism

Interaction of substance P with phospholipid bilayers: A neutron diffraction study

AbstractNeutron diffraction has been used to study the membrane-bound structure of substance P (SP), a member of the tachykinin family of neuropeptides. The depth of penetration of its C-terminus in zwitterionic and anionic phospholipid bilayers was probed by specific deuteration of leucine 10, the penultimate amino acid residue. The results show that the interaction of SP with bilayers, composed of either dioleoylphosphatidylcholine (DOPC), or a 50:50 mixture of DOPC and the anionic phospholipid dioleoylphosphatidylglycerol (DOPG), takes place at two locations. One requires insertion of the peptide into the hydrophobic region of the bilayer, the other is much more peripheral. The penetration of the peptide into the hydrophobic region of the bilayer is reflected in a marked difference in the water distribution profiles. SP is seen to insert into DOPC bilayers, but a larger proportion of the peptide is found at the surface when compared to the anionic bilayers. The positions of the two label populations show only minor differences between the two types of bilayer

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The effect of fusion inhibitors on the phase behaviour of N-methylated dioleoylphosphatidylethanolamine

AbstractThe effects of two fusion inhibitors on the lipid polymorphism of N-methylated dioleoylphosphatidylethanolamine were studied using temperature-resolved, small-angle X-ray diffraction. The inhibitory role of the tri-peptide carbobenzoxy-d-phenylalanine-l-phenylalanine-glycine and the lipid 1-lauroyl-2-hydroxy-sn-glycero-3-phosphocholine in the fusion pathway was studied, using the non-lamellar phase behaviour of the lipid as a model. We used p15EK, the N-terminal region of gp41 from feline leukaemia virus as promoter of membrane fusion, and measured the structural parameters of each observed lipid phase as a function of temperature. The fusion inhibitors were found to impede the expression of negative curvature of lipid monolayers even in the presence of fusion peptide. The results of this study are interpreted in relation to models of the membrane fusion mechanism

Fluxo de biomassa em capim-tanzânia pastejado por ovinos sob três períodos de descanso Biomass flow in tanzaniagrass pasture under three resting periods grazed by sheep

Avaliou-se o fluxo de biomassa em Panicum maximum cv. Tanzânia pastejado por ovinos com três períodos de descanso (PD), definidos pela expansão de 1,5; 2,5 e 3,5 novas folhas por perfilho, em um delineamento inteiramente casualizado, com duas repetições (piquetes). Estimaram-se as taxas de alongamento de lâmina foliar total (TAlF), de senescência de lâminas foliares remanescentes do pastejo anterior (TSFA), de senescência das novas folhas formadas no PD (TSFP) e de senescência total (TSFT=TSFA+TSFP), a taxa de alongamento das hastes (TAlH), a razão entre as TAlF das folhas 1 e 2 (razão TAlF1/TAlF2), a densidade populacional de perfilhos (DPP), o filocrono e as taxas de crescimento (TCC) e de acúmulo (TAC) da cultura. A razão TAlF1/2 não foi afetada pelos PD, mas reduziu ao longo dos ciclos na pastagem sob PD 3,5. A TAlF não foi afetada pelos PD. A TAlH, a TSFA e a TSFT na pastagem sob PD 1,5 foram menores que nas demais. Houve TSFP somente na pastagem sob PD 3,5. O filocrono da pastagem sob PD 1,5 foi superior ao observado nas demais. A densidade populacional de perfilhos (DPP) da pastagem sob o PD 2,5 foi similar à verificada na pastagem sob PD 1,5 e superior à verificada sob PD 3,5. Houve redução na DPP ao longo dos ciclos na pastagem sob PD 3,5. As taxas de crescimento (TCC) e de acúmulo (TAC) foram superiores na pastagem sob PD 2,5. O prolongamento do PD elevou as TAlH e TSFT e reduziu a DPP e a TAC. Portanto, o PD do capim-tanzânia pastejado por ovinos não deve exceder o tempo necessário à expansão de 2,5 novas folhas por perfilho.<br>The biomass flow in Panicum maximum cv. Tanzânia pasture grazed by sheep under three resting periods (PD), defined by the expansion of 1.5; 2.5 and 3.5 new leaves per tiller (1.5F; 2.5F and 3.5F, respectively) was evaluated in a randomized completely design with two replicates (paddocks). It was determined the leaf elongation rate (TAlF), the residual leaf senescence rate (TSFA), the post-grazing leaf senescence rate (TSFP) and the total leaf senescence rate (TSFT), the stem elongation rate (TAlH), the TAlF of leaves 1 and 2 ratio (TALF1/2), the tiller population density (DPP), the phylochron and the crop growth (TCC) and accumulation (TAC) rates. The TAlF1/2 ratio was not affected by the PD, however, it decreased over the cycles at the 3.5F PD pasture. The TAlF was not affected by the PD. The TAlH was inferior at the 1.5F PD pasture, as well as the TSFA and the TSFT. There was TSFP only at the 3.5F PD pasture. The phylochron of the 1.5F PD pasture was superior to the others. The DPP of the 2.5F PD pasture was similar to that of the 1.5F PD pasture, and it was superior to the 3.5F PD pasture. There was reduction of the DPP following the cycles at the 3.5F PD pasture. The TCC and the TAC of the 2.5F PD pasture were superior than the others. The extension of the PD raised the TAlH and the TSFT and reduced the DPP and the TAC. As a conclusion, the resting period should not exceed the time necessary to the expansion of 2.5 leaves on the tiller for tanzaniagrass pastures grazed by sheep