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Biology subjects

Kent, B.

Publications and source records attributed to Kent, B..

5 recordsLinked to original sources

The Two Frontiers Project Field Handbook and OpenTools: Standardizing microbial fieldwork for biobank-scale sequencing and culturomics

From medicines to materials, our planets microbial diversity comprises an enormous wellspring of biotechnological potential. For centuries, microbiologists have developed tools for interrogating microbial function, ranging from microscopy and culturing to, more recently, metagenomics. However, deploying these tools during fieldwork requires substantial forward planning, interdisciplinary technical expertise, and plans for navigating permitting and the ethical implications of bioprospecting. To address these challenges, we built The Two Frontiers Project Handbook and OpenTools Resource, which aggregates our expertise in high-throughput sampling, sequencing, and culturing of microbes from thousands of samples. We provide our full suite of fieldwork methods as well as relevant software and hardware. We lay our standards for team roles and construction, general expedition planning, sample transport, permitting, and numerous other key aspects of executing a successful field campaign. The version-controlled resource is available at https://two-frontiers-project.github.io/ and is open for non-commercial use.

microbiology↗

Young and old adult brains experience opposite effects of acute sleep restriction on the functional connectivity network

Chronic, long-term sleep loss is detrimental to brain health and cognitive ability. However, older adults are affected differently by acute, short-term loss of sleep than young and middle-aged adults. Older adults are more resilient to the effects of acute sleep loss and, depending on the cognitive domain, may be completely unaffected while younger adults suffer. To elucidate the brain network responses to sleep loss underlying these cognitive differences between age groups, we investigated the static and dynamic functional connectivity effects of sleep restriction (sleep limited to 3 hours) and how these effects differ between younger adults (20-30 years) and older adults (65-75 years). We found a functional connectivity subnetwork that was primarily strengthened in younger adults after sleep restriction but weakened in older adults after sleep restriction. Similar crossover interactions were consistently observed in further analyses of functional connectivity degree, modularity, and dynamic functional connectivity state fractional occupancy. Our findings demonstrate that the effect of sleep restriction on older adults is fundamentally different from younger adults. These results most strongly support the compensation theory of aging, which predicts a fundamental shift in the effects of sleep loss, rather than a mere dampening of the sleep benefits experienced by younger adults.

neuroscience↗

Repetitive mild traumatic brain injury causes neuronal damage in the APP/PS1 mouse model of Alzheimer's disease without an enduring impact on amyloid pathology, sleep, or epileptiform activity

Traumatic Brain Injury (TBI) is a known risk factor for Alzheimers disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the development of neuropathology. In this study, we characterized sleep, epileptiform activity, and neuropathology after repetitive mild traumatic brain injury (rmTBI) in a mouse model of Alzheimers disease. We used the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) to deliver rmTBI or sham (control) treatment to 6-month-old APP/PS1 mice (N=19). One month post-injury, we implanted electroencephalogram (EEG) and electromyographic (EMG) electrodes, recorded for 72 hours, and then collected brain tissue and blood plasma. Our assessment of sleep architecture showed that time spent in vigilance state was not affected by the rmTBI one month post-injury; however, power spectra analysis showed a shift towards higher frequencies in the rmTBI group during non-rapid eye movement (NREM) sleep. Epileptiform activity did not differ between sham and rmTBI. Compared to sham controls, the rmTBI group showed higher neurofilament light (NF-L), but not glial-fibrillary acidic protein (GFAP) in blood plasma and no change in A{beta} pathology. These results indicate sustained neurological injury in the APP/PS1 mice one month after rmTBI without affecting amyloid deposition in the brain. Our study suggests that rmTBI can induce neural injury without causing enduring sleep disruption, seizures, and exacerbation of amyloidosis in the APP/PS1 mouse model.

neuroscience↗

NEURONS IN THE POSTRHINAL CORTEX ENCODE NONSPATIAL CONTEXT DURING VISUAL BICONDITIONAL DISCRIMINATION

Spatial context, or the physical surroundings that form the background of an experience, is an essential component of episodic memory. The rodent postrhinal cortex and its primate homolog, the parahippocampal cortex, are thought to preferentially process visuospatial information to represent the spatial features of contexts and scenes. In this study, we addressed open questions about postrhinal function and about how context modulates behavior and cognition. The first question was whether the postrhinal cortex also represents nonspatial contexts. The second question was how representations of context might interact with other cues in the environment. We recorded postrhinal neurons as rats performed a visual nonspatial biconditional discrimination task in which the pattern on the floor determined which object in a pair was correct. Critically, this task design allowed dissociation of location from non-spatial context. We found that postrhinal ensembles and neurons signaled changes in non-spatial context and coded for conjunctions of non-spatial context and objects. Importantly, postrhinal neurons coded for conjunctions of context and objects more often than they coded for conjunctions of location and object. The pattern of findings suggests that postrhinal representations of context may behave like occasion setters by modulating the meaning of other cues in the environment.

neuroscience↗

High resolution annotation of Zebrafish transcriptome using long-read sequencing

With the emergence of zebrafish as an important model organism, a concerted effort has been made to study its transcriptome. This effort is limited, however, by gaps in zebrafish annotation, which are especially pronounced concerning transcripts dynamically expressed during zygotic genome activation (ZGA). To date, short read sequencing has been the principal technology for zebrafish transcriptome annotation. In part because these sequence reads are too short for assembly methods to resolve the full complexity of the transcriptome, the current annotation is rudimentary. By providing direct observation of full-length transcripts, recently refined long-read sequencing platforms can dramatically improve annotation coverage and accuracy. Here, we leveraged the SMRT platform to study transcriptome of zebrafish embryos before and after ZGA. Our analysis revealed additional novelty and complexity in the zebrafish transcriptome, identifying 2748 high confidence novel transcripts that originated from previously unannotated loci and 1835 high confidence new isoforms in previously annotated genes. We validated these findings using a suite of computational approaches including structural prediction, sequence homology and functional conservation analyses, as well as by confirmatory transcript quantification with short-read sequencing data. Our analyses provided insight into new homologs and paralogs of functionally important proteins and non-coding RNAs, isoform switching occurrences and different classes of novel splicing events. Several novel isoforms representing distinct splicing events were validated through PCR experiments, including the discovery and validation of a novel 8 kb transcript spanning multiple miR-430 elements, an important driver of early development. Our study provides a significantly improved zebrafish transcriptome annotation resource.

bioinformatics↗