Biology subjects

Hoffman, K.

Publications and source records attributed to Hoffman, K..

6 recordsLinked to original sources

bioRxiv2026

Perinatal exposures and upper respiratory tract microbiome composition are associated with age at first acute otitis media episode

Acute otitis media (AOM) is the most common bacterial infection of childhood and the leading indication for antibiotic prescriptions and healthcare consultations globally. Colonization of the upper respiratory tract (URT) microbiome by bacterial respiratory pathogens precedes AOM episodes; however, the factors that influence colonization susceptibility and subsequent AOM are not well understood. We hypothesized that perinatal exposures, including mode of delivery, intrapartum antibiotic exposure, and infant feeding influence the composition of the URT microbiome at birth, modifying risk of AOM in infancy. We characterized the URT microbiome in nasopharyngeal swabs collected from 163 infants at birth. Swabs were generally collected within two days of delivery (median [IQR] collection time: 25 [17, 45] hours) and microbiome composition was evaluated with 16S rRNA V4 sequencing. Exposures evaluated included birth mode, intrapartum antibiotic exposures, and feeding type at hospital discharge. AOM episodes were identified through electronic health records data. We built Cox proportional hazards models to determine if perinatal exposures and/or microbiome characteristics at birth were associated with the time to first AOM episode in the first two years of life. URT microbiome diversity and composition were associated with feeding type at hospital discharge, wherein exclusive formula feeding was associated with increased diversity and the presence of Staphylococcus and Haemophilus spp. Increased URT microbiome diversity was associated with younger age at first AOM episode. Our findings suggest that perinatal exposures may influence the composition of the birth URT microbiome, and that this early composition may be related to AOM susceptibility in infancy. ImportanceEar infections are the most common bacterial infection of childhood and the leading indication for healthcare consultation and antibiotic receipt. Previous studies have demonstrated that the microbes that inhabit the upper respiratory tract, known as the microbiome, influence risk of ear infection. This study sought to understand how exposures around the time of birth, including delivery type, maternal antibiotic exposures, and infant feeding, influence the development of the infant microbiome, and in turn, how the microbiome is related to ear infections. An analysis of nasal swabs collected from infants shortly after birth demonstrated that increased microbial diversity is associated with earlier age at first ear infection episode. Overall, this study demonstrates that exposures in early life influence respiratory microbiome development, which contributes to infection susceptibility.

microbiology↗

bioRxiv2025

Astrocytic contribution to sensory hypersensitivity in a mouse model of fragile X syndrome

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a leading cause of autism spectrum disorder (ASD). FXS is caused by mutations in the fragile X messenger ribonucleoprotein gene 1 (FMR1), which result in complete or partial loss of expression of its protein product, fragile X messenger ribonucleoprotein (FMRP). Neuronal impairments in the absence of FMRP have been extensively characterized. However, much less is known about the impact that loss of FMRP has on the physiology and function of astrocytes and the implications for behavior. A common behavior exhibited by both FXS and ASD patients is hypersensitivity to sensory stimuli, but how astrocytes contribute to hypersensitivity in the context of FXS remains unknown. Using mice with astrocyte-specific reduction of Fmr1 (Fmr1 conditional KO (cKO)) and mice with astrocyte-specific expression of Fmr1 (Fmr1 cON), we demonstrated that reduction of astrocytic FMRP is sufficient but not necessary to confer susceptibility to audiogenic seizures, an indication of auditory hypersensitivity. In addition, reduction of astrocytic FMRP impacts neuronal activity, resulting in spontaneous seizures. In contrast, we assessed tactile hypersensitivity using a whisker stimulation paradigm but did not detect significant differences in Fmr1 cKO mice. Our results reveal that astrocytes lacking FMRP contribute to auditory hypersensitivity and spontaneous seizures.

neuroscience↗

bioRxiv2023

Examining intra-host genetic variation of RSV by short read high-throughput sequencing

Every viral infection entails an evolving population of viral genomes. High-throughput sequencing technologies can be used to characterize such populations, but to date there are few published examples of such work. In addition, mixed sequencing data are sometimes used to infer properties of infecting genomes without discriminating between genome-derived reads and reads from the much more abundant, in the case of a typical active viral infection, transcripts. Here we apply capture probe-based short read high-throughput sequencing to nasal wash samples taken from a previously described group of adult hematopoietic cell transplant (HCT) recipients naturally infected with respiratory syncytial virus (RSV). We separately analyzed reads from genomes and transcripts for the levels and distribution of genetic variation by calculating per position Shannon entropies. Our analysis reveals a low level of genetic variation within the RSV infections analyzed here, but with interesting differences between genomes and transcripts in 1) average per sample Shannon entropies; 2) the genomic distribution of variation hotspots; and 3) the genomic distribution of hotspots encoding alternative amino acids. In all, our results suggest the importance of separately analyzing reads from genomes and transcripts when interpreting high-throughput sequencing data for insight into intra-host viral genome replication, expression, and evolution.

genomics↗

bioRxiv2023

Organisms employ a mode-switching strategy for solving the explore-vs-exploit problem

The inescapable link between sensing and movement generates a conflict between producing costly movements for gathering information ("explore") versus using previously acquired information to achieve a goal ("exploit"). Determining the optimal balance between explore and exploit is a computationally intractable problem, necessitating the use of heuristics. We looked to nature to measure and model the solutions used by organisms. Here we show that the electric fish Eigenmannia virescens uses a salience-dependent mode-switching strategy to solve the explore-exploit conflict during a refuge tracking task. The fish produced distinctive non-Gaussian (i.e., non-normal) distributions of movement velocities characterized by sharp peaks for slower, task-oriented "exploit" movements and broad shoulders for faster, "explore" movements. The measures of non-normality increased in relation to increased sensory salience. Data from ten phylogenetically diverse organisms, from amoebae to humans, revealed the same distinctive distribution of movement velocities that were also modulated in relation to sensory salience. We propose a state-uncertainty based mode-switching heuristic that (1) reproduces the distinctive velocity distribution, (2) rationalizes modulation by sensory salience, and (3) outperforms the classic persistent excitation approach while using less energy. This mode-switching heuristic provides insights to purposeful exploratory behaviors in organisms as well as a framework for more efficient state estimation and control of robots.

animal behavior and cognition↗

bioRxiv2020

Cortical 6-9 Hz Oscillation are a Reliable Biomarker of Persistent Pain in Rats

Neural biomarkers of chronic pain offer a potential tool for improving the speed of diagnosis and delivery of treatment for this devastating disease. Here, we tested the hypothesis that pain states are associated with distinct changed in cortical brain waves. We induced neuropathic orofacial pain in female rats by chronic constriction injury of the infraorbital nerve (CCI-ION). In most animals, this resulted in lasting reductions in mechanical sensitivity thresholds, and in lasting increases in facial grimace scores. We recorded electrocortigraphy (ECoG) signals over the neocortex of these rats, before and after CCI-ION, and analyzed these signals with a novel, spectral modelling approach. Consistent with our hypothesis, power in the 6-9 Hz bandwidth of the ECoG was differentially modulated in animals displaying signs of chronic pain. Specifically, development of mechanical hypersensitivity correlated with a decrease in 6-9 Hz power. Furthermore, we show that changes in the power of this oscillation after injury, obtained at the individual animal level, provide a more sensitive marker of pain presence than do traditional between animal comparisons of post-injury oscillatory power. Identification of animals demonstrating chronic-pain behaviors was more accurate when estimates of post-injury oscillatory power were compared against each animals own pre-injury baseline than when compared against post-injury power estimates from animals not developing chronic pain. These results highlight the need for establishing individual-specific, "pain-free" baselines from which oscillation disturbances can be measured and which may constitute a reliable, low-cost approach not only for diagnosing chronic pain, but also for identifying individuals likely to transition from acute to chronic pain.

neuroscience↗

bioRxiv2018

Differential generation of saccade, fixation and image onset event-related potentials in the human mesial temporal lobe

The electrophysiological signatures of encoding and retrieval recorded from mesial temporal lobe (MTL) structures are observed as event related potentials (ERPs) during visual memory tasks. The waveforms of the ERPs associated with the onset of visual stimuli (image-onset) and eye movements (saccades and fixations) provide insights into the mechanisms of their generation. We hypothesized that since eye movements and image-onset (common methods of stimulus presentation when testing memory) provide MTL structures with salient visual information, that perhaps they both engage similar neural mechanisms. To explore this question, we used intracranial electroencephalographic (iEEG) data from the MTLs of 11 patients with medically refractory epilepsy who participated in a visual search task. We sought to characterize electrophysiological responses of MTL structures to saccades, fixations and image onset. We demonstrate that the image-onset response is an evoked/additive response with a low-frequency power increase and post-stimulus phase clustering. In contrast, ERPs following eye movements appeared to arise from phase resetting of higher frequencies than the image onset ERP. Intriguingly, this reset was associated with saccade onset and not saccade termination (fixation), suggesting it is likely the MTL response to a corollary discharge, rather than a response to visual stimulation - in stark contrast to the image onset response. The distinct mechanistic underpinnings of these two ERP may help guide future development of visual memory tasks.

neuroscience↗