Biology subjects

Roberts, K.

Publications and source records attributed to Roberts, K..

4 recordsLinked to original sources

bioRxiv2018

Protection against repeated vaginal SHIV challenges by a combination of VRC01 and an anti-α4β7 antibody

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-4{beta}7 mAb (Rh-4{beta}7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-4{beta}7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-4{beta}7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000TCID50) of SHIVAD8-EO. The combination Rh-4{beta}7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-4{beta}7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to the controls. Interestingly, VRC01-Rh-4{beta}7-treated macaques had less IL-17 producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8- EO envelope in the VRC01-Rh-4{beta}7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-4{beta}7 delayed infection, altered anti-viral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-4{beta}7 on SIV/HIV infection and anti-viral immune responses is warranted and may lead to novel preventive and therapeutic strategies.\n\nShort summaryA combination of VRC01 and Rh-4{beta}7 significantly delayed SHIV acquisition, protected CD4 counts, decreased gut viral load and modified the immune response to the virus.

immunology↗

bioRxiv2018

Changes in temperature alter susceptibility to a virus following a host shift

Host shifts - where a pathogen jumps between different host species - are an important source of emerging infectious disease. With ongoing climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, whilst the mean viral load did not, such that as temperature increased the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species susceptibility across temperatures and proxies for thermal optima; critical thermal maximum and minimum or basal metabolic rate. These results suggest that whilst the rank order of species susceptibilities can remain the same with changes in temperature, the likelihood of host shifts into a given species may increase or decrease.\n\nAuthor SummaryEmerging infectious diseases are often the result of a host shift, where a pathogen jumps from one host species into another. Understanding the factors underlying host shifts is a major goal for infectious disease researchers. This effort has been further complicated by the fact that host-parasite interactions are now taking place in a period of unprecedented global climatic warming. Here, we ask how host shifts are affected by temperature by carrying out experimental infections using an RNA virus across a wide range of related species, at three different temperatures. We find that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. This has important consequences for our understanding of host shift events in a changing climate, and suggests that temperature changes may affect the likelihood of a host shift into certain species.

evolutionary biology↗

bioRxiv2018

Cerox1 and microRNA-488-3p noncoding RNAs jointly regulate mitochondrial complex I catalytic activity

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation (OXPHOS) and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

biochemistry↗

bioRxiv2017

Analysis of Bone Healing with a Novel Bone Wax Substitute Compared to Bone Wax in a Porcine Bone Defect Model

BackgroundBone wax is used in surgery as a hemostatic device for bone. Despite its good functional capacity as a bone hemostat, Bone wax materials often have very poor long-term interactions with bone. This study describes a novel composite of hydroxyapatite (HA) and biodegradable poly-lactic acid (PLA) with wax-like handling properties (OsteoStat). The goal was to compare qualitative and quantitative measures between OsteoStat versus Bone wax.\n\nMethodsThe porcine critical size defect model was chosen in this study. OsteoStat and Bone wax were introduced into separate critical size defects located in the femur and humerus of a single porcine specimen. After a duration of 6 weeks, the defect sites were harvested for clinical, histological, and histomorphometric analysis.\n\nResultsBoth groups had effective hemostatic action when introduced into the defects. Analysis of the histomorphometric data revealed that the amount of new bone was significantly greater at 6 weeks in the OsteoStat group (38.05%) versus the Bone wax group (11.88%), p=0.028. OsteoStat also demonstrated less soft tissue and less test material remaining in the defect sites; however, this was not statistically significant.\n\nConclusionsWe speculate that the incomplete biodegradation of Bone wax as well as its intrinsic inflammatory properties may have retarded osseous regeneration and promoted fibrosis. In contrast, well known biodegradation pathways for PLA combined with the HA component of OsteoStat may have accounted for the positive results of OsteoStat compared to Bone wax. It is important that bone hemostat substances have biocompatible, osteoconductive, hemostatic, as well as good handling properties.

bioengineering↗