Biology subjects

Sherman, B.

Publications and source records attributed to Sherman, B..

4 recordsLinked to original sources

bioRxiv2024

OzWheat: a genome-to-phenome platform to resolve complex traits for wheat pre-breeding and research.

For over a century, Australian wheat breeders have successfully adapted wheat to a broad range of climatic conditions and crop management practices. The OzWheat genome-to-phenome (G2P) platform was established to capture this breeding history and explore traits, genes, and their interactions with the environment to enable ongoing research and deliver targets for wheat improvement. A panel of 285 cultivars and landraces were chosen through knowledge of breeding pedigrees to represent both global diversity and the historic flow of genetic variation over more than 100 years of selective breeding in Australia. Genetic characterisation of the panel included identification of genome-wide sequence variants and gene expression profiling across environments. Important traits for adaptation (flowering time and plant height) were assayed in controlled environments and at multiple field sites and years, with genome-wide association analyses (GWAS) using linear mixed models detecting both known and novel loci. Here, we report establishment of the OzWheat G2P platform as a powerful tool to integrate wheat genomes and phenomes and demonstrate its use to identify candidate genes and understand gene by environment interactions. This provides the wheat research and breeding community a new resource to support future cultivar development.

genomics↗

bioRxiv2020

Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75NTR) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals. Author SummaryThere are no effective treatments to halt the progression of most neurodegenerative diseases including HIV-associated neurodegeneration. Neurotrophins have the potential to provide strong neuroprotection but it has been difficult to develop usable interventions. A new drug, LM11A-31, that targets the p75 neurotrophin receptor has been developed that provides potent neuroprotection, is orally bioavailable and has the potential to prevent disease progression. The current studies were designed to evaluate the effects of the compound in an animal model of active HIV infection in preparation for a human clinical trial. Treatment of chronically infected animals with LM11A-31 normalized deficits in T maze performance, novel object recognition and open field behavior with no measurable adverse effects. Potential adverse effects associated with natural neurotrophins such as changes in sensory perception and increased systemic viral burden were not observed. A decrease in CSF FIV titers and a slight improvement in the CD4:CD8 ratio suggested that LM11A-31 may have beneficial effects beyond the anticipated neuroprotective effects. These findings are similar to beneficial effects seen in other animal models of neurodegeneration and CNS injury and support the use of LM11A-31 as an adjunctive neuroprotective agent for the treatment of HIV infected individuals.

neuroscience↗

bioRxiv2018

Proviral sequencing suggests the majority of the HIV reservoir is expressed over time but significant decay is obscured by clonal expansion

After initiating antiretroviral therapy (ART), a rapid decline in plasma viremia is followed by reservoir stabilization. Viral outgrowth assay suggests the reservoir continues to decline slowly, but variation over time and among individuals complicates our understanding of selective pressures during ART. We used full-length sequencing to study more than 800 HIV proviruses of two subjects on ART at four time points over nine years to investigate the selection pressures influencing the dynamics of the reservoir. We found that intact as well as defective proviruses capable of significant protein expression decrease over time. Moreover, proviruses lacking genetic elements to promote viral protein expression, yet containing strong splice donor sequences increase relative to other defectives over time, especially among clones. Our work suggests that HIV expression occurs to a significant extent during ART and results in HIV clearance, but this is obscured by clones generated by donor splice site-enhanced clonal expansion.

immunology↗

bioRxiv2017

Endogenous Oxytocin, Vasopressin and Aggression in Domestic Dogs

Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP) - neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species - and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs) for the measurement of free (unbound) and total (free + bound) OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

animal behavior and cognition↗