Biology subjects

Potter, B.

Publications and source records attributed to Potter, B..

6 recordsLinked to original sources

bioRxiv2026

Neurometabolic correlates of accelerated aging and neurocognitive late effects in long-term survivors of pediatric hodgkin lymphoma and acute lymphoblastic leukemia

Adult survivors of pediatric cancers are at elevated risk for neurocognitive late effects, but how these effects relate to metabolic perturbations in the brain remains unclear. To address this knowledge gap, the present study explored associations between neurometabolite levels and neurocognitive function in adult survivors of Hodgkin lymphoma (HL) and acute lymphocytic leukemia (ALL). Data were collected from a single-center observational study conducted at St. Jude Childrens Research Hospital (SJCRH) between October 2022 and November 2024. Adult survivors of HL (N=11 [5 females]; [≥]5 years post-diagnosis; mean [SD] current age 34 [9.5] years) and ALL (N=24 [16 females]; [≥]5 years post-diagnosis; current age 40 [12.6] years) and community controls (N=35 [17 females]; current age 40 [11] years) completed standardized neurocognitive tests of memory, attention, executive function, and processing speed. Participants also underwent proton magnetic resonance spectroscopy (1H MRS) to quantify neurometabolite levels in the left dorsolateral prefrontal cortex (dlPFC), left hippocampus, and left cerebellum. Analyses used regression models to examine differences in the slope of the relationship between neurometabolite and neurocognitive function or between neurometabolite and age. When comparing HL survivors vs controls, significant interactions were identified for group x age on the ratio of myo-inositol to N-Acetyl aspartic acid (mI/NAA; p=0.007) and group x Gamma-Aminobutyric Acid (GABA) on processing speed (p=0.04) in the left dlPFC. When comparing ALL survivors vs controls, significant interactions were identified for group x myo-inositol on verbal fluency in the left hippocampus (p=0.01) and group x GABA on cognitive flexibility in the left cerebellum (p=0.01). These preliminary findings suggest that neuroinflammation may be a mechanistic underpinning of age-associated neurocognitive impairment in pediatric cancer survivors.

neuroscience↗

bioRxiv2025

The global phylogeography of rapidly expanding multidrug resistant Ural lineage 4.2 Mycobacterium tuberculosis

Multidrug resistant tuberculosis (MDR-TB) is a leading global health challenge. Recent studies identified a reproductively fit Ural lineage 4.2 MDR M. tuberculosis (Mtb) variant circulating within the Republic of Moldova. We searched a large publicly available dataset of [~]200,000 Mtb whole genome sequences and identified a clade of 1604 drug-resistant Mtb sequences harboring conserved resistance-conferring mutations that are closely related to the MDR Mtb variant circulating in Moldova. We identified the Russian Federation as the most likely country of origin for this clade, and we inferred several independent migration events from Russia and Moldova to other former Soviet Republics and several European countries. Using local branching index, we found that this clade is expanding more rapidly than comparable clades of lineage 4.2. This evolutionarily successful strains presence beyond Moldova poses a threat to MDR-TB control, and enhanced surveillance is necessary to reduce the risk of MDR-TB epidemics in the region. FundingThe authors report funding from the National Institutes of Health (R01AI180209, P01AI159402)

microbiology↗

bioRxiv2020

Helicobacter pylori diversification during chronic infection within a single host generates sub-populations with distinct phenotypes

Helicobacter pylori chronically infects the stomach of approximately half of the worlds population. Manifestation of clinical diseases associated with H. pylori infection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related to H. pylori pathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 2,232 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4 substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A dendrogram based on genetic similarity, clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple sub-niches within the stomach during chronic infection. Author SummaryHelicobacter pylori, one of the most common bacterial pathogens colonizing humans, is the main agent responsible for stomach ulcers and cancer. Certain strain types are associated with increased risk of disease, however many factors contributing to disease outcome remain unknown. Prior work has documented genetic diversity among bacterial populations within single individuals, but the impact of this diversity for continued bacterial infection or disease progression remains understudied. In our analysis we examined both genetic and functional features of many stomach isolates from a single individual infected over six years. During these six years the subject shifted from having excess acid production and a duodenal ulcer to lower acid production from gastric atrophy. The 39 isolates form sub-populations based on gene sequence changes that accumulated in the different isolates. In addition to having distinguishing genetic features, these sub-populations also have differences in several bacterial properties, including cell shape, ability to activate immune responses, and colonization in a mouse model of infection. This apparent functional specialization suggests that the bacterial sub-populations may have adapted to distinct sub-niches within the stomach during chronic infection.

microbiology↗

bioRxiv2019

Seasonal influenza circulation patterns and projections for September 2019 to September 2020

This report details current seasonal influenza circulation patterns as of August 2019 and makes projections up to September 2020 to coincide with selection of the 2020 Southern Hemisphere vaccine strain. This is not meant as a comprehensive report, but is instead intended as particular observations that weve made that may be of relevance. Please also note that observed patterns reflect the GISAID database and may not be entirely representative of underlying dynamics. All analyses are based on the nextflu/nextstrain pipeline [1,2] with continual updates posted to nextstrain.org/flu. A/H3N2: A/H3N2 viruses continue to show substantial diversity in HA sequences with a deep split between 3c3.A and 3c2.A1b viruses. The most notable recent developments are the rapid rise of clade A1b/137F - a subclade of A1b/135K - in China and Bangladesh and clade A1b/197R - a subclade of A1b/131K - which dominates the ongoing season in Australia. Our models predict that A1b/137F and A1b/197R will be the dominant clades next year with A1b/197R accounting for most circulation. There is, however, large uncertainty in the true extent of A1b/137F circulation. A/H1N1pdm: The S183P substitution has risen to near fixation. The most successful subclade carrying this mutation is 183P-5 which has essentially replaced competing variants. A variant with substitutions 129D/185I is at 60% prevalence globally, while a second variant with substitution 130N is at 50% in North America and ~10% elsewhere. Substitutions at site 156 to D or K have arisen sporadically and result in loss of recognition by antisera raised against viruses with asparagine at position 156. Despite the large antigenic effect, viruses with mutations at site 156 dont seem to spread. Beyond variants at site 156, little to no antigenic evolution is evident in assays with ferret antisera. B/Vic: Antigenically drifted deletion variants at HA1 sites 162, 163 and 164 are now dominating global circulation and have all but taken over. The double deletion variant V1A.1 had previously been circulating at high frequency in the Americas. However, over the course of 2009, the triple deletion variant V1A.3 has increased in frequency globally and is now dominating in all geographic regions. Importantly, V1A.1 and V1A.3 variants appear antigenically distinct by HI assays with 4-8 fold reductions in log2 titer in both directions. B/Yam: B/Yam has not circulated in large numbers since the Northern Hemisphere season 2017/2018 and displays relatively little amino acid variation in HA or antigenic diversity. Amino acid variants at sites 229 and 232 have begun to circulate and population is now split between 229D/232D, 229N/232D and 229D/232N variants. These variants show little sign of antigenic difference in HI assays.

evolutionary biology↗

bioRxiv2017

Nextstrain: real-time tracking of pathogen evolution

SummaryUnderstanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualisation platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, publicly available for use by health professionals, epidemiologists, virologists and the public alike.\n\nAvailability and implementationAll code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org.

evolutionary biology↗

bioRxiv2017

Genetic characterization of the Zika virus epidemic in the US Virgin Islands

Here we release draft genome sequences of Zika virus (ZIKV) that were sequenced from PCR-positive diagnostic specimens collected by the United States Virgin Islands Department of Health (USVI DoH) as part of their ongoing response to the ZIKV outbreak. We will use these sequences to conduct a genomic epidemiological study of ZIKV transmission in the USVI. We are releasing these genomes in the hope that they are useful for those individuals involved in the public health response to ZIKV and to other groups working to understand Zika virus transmission and evolution.

epidemiology↗