Publications by authors named "S Peter Howard"

1,376 Publications

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Gravity-Driven Microfluidic Siphons: Fluidic Characterization and Application to Quantitative Immunoassays.

ACS Sens 2021 Dec 2. Epub 2021 Dec 2.

Reading School of Pharmacy, University of Reading, Whiteknights Campus, Reading, RG6 6AD United Kingdom.

A range of biosensing techniques including immunoassays are routinely used for quantitation of analytes in biological samples and available in a range of formats, from centralized lab testing (e.g., microplate enzyme-linked immunosorbent assay (ELISA)) to automated point-of-care (POC) and lateral flow immunochromatographic tests. High analytical performance is intrinsically linked to the use of a sequence of reagent and washing steps, yet this is extremely challenging to deliver at the POC without a high level of fluidic control involving, e.g., automation, fluidic pumping, or manual fluid handling/pipetting. Here we introduce a microfluidic siphon concept that conceptualizes a multistep ″dipstick″ for quantitative, enzymatically amplified immunoassays using a strip of microporous or microbored material. We demonstrated that gravity-driven siphon flow can be realized in single-bore glass capillaries, a multibored microcapillary film, and a glass fiber porous membrane. In contrast to other POC devices proposed to date, the operation of the siphon is only dependent on the hydrostatic liquid pressure (gravity) and not capillary forces, and the unique stepwise approach to the delivery of the sample and immunoassay reagents results in zero dead volume in the device, no reagent overlap or carryover, and full start/stop fluid control. We demonstrated applications of a 10-bore microfluidic siphon as a portable ELISA system without compromised quantitative capabilities in two global diagnostic applications: (1) a four-plex sandwich ELISA for rapid smartphone dengue serotype identification by serotype-specific dengue virus NS1 antigen detection, relevant for acute dengue fever diagnosis, and (2) quantitation of anti-SARS-CoV-2 IgG and IgM titers in spiked serum samples. Diagnostic siphons provide the opportunity for high-performance immunoassay testing outside sophisticated laboratories, meeting the rapidly changing global clinical and public health needs.
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http://dx.doi.org/10.1021/acssensors.1c01524DOI Listing
December 2021

A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer.

Genes Dev 2021 Dec 24;35(23-24):1642-1656. Epub 2021 Nov 24.

Simpson Querrey Center for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

Mutations in the chromatin regulator cause the human neurodevelopmental disorder Chung-Jansen syndrome, while alterations in expression are linked to cancer. Precisely how PHIP functions in these contexts is not fully understood. Here we demonstrate that PHIP is a chromatin-associated CRL4 ubiquitin ligase substrate receptor and is required for CRL4 recruitment to chromatin. PHIP binds to chromatin through a trivalent reader domain consisting of a H3K4-methyl binding Tudor domain and two bromodomains (BD1 and BD2). Using semisynthetic nucleosomes with defined histone post-translational modifications, we characterize PHIPs BD1 and BD2 as respective readers of H3K14ac and H4K12ac, and identify human disease-associated mutations in each domain and the intervening linker region that likely disrupt chromatin binding. These findings provide new insight into the biological function of this enigmatic chromatin protein and set the stage for the identification of both upstream chromatin modifiers and downstream targets of PHIP in human disease.
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http://dx.doi.org/10.1101/gad.348766.121DOI Listing
December 2021

Individual differences in emotion regulation and cardiovascular responding to stress.

Emotion 2021 Nov 22. Epub 2021 Nov 22.

SASHLab.

Instructed use of reappraisal to regulate stress in the laboratory is typically associated with a more adaptive cardiovascular response to stress, indexed by either (a) lower cardiovascular reactivity (CVR; e.g., lower blood pressure) or (b) a challenge-oriented response profile (i.e., greater cardiac output paired with lower total peripheral resistance). In contrast, instructed use of suppression is associated with exaggerated CVR (e.g., greater heart rate, blood pressure). Despite this, few studies have examined if the use of these strategies are related to cardiovascular responding during stress. The current study examined the relationship between cardiovascular responses to acute stress and individual differences in emotion regulation style: trait reappraisal, suppression, and emotion regulation difficulties. Forty-eight participants (25 women, 23 men) completed a standardized laboratory stress paradigm incorporating a 20-minute acclimatization period, a 10-minute baseline, and two 5-minute speech tasks separated by a 10-minute intertask rest period. The emotional valence of the speech task was examined as a potential moderating factor; participants spoke about a block of negative-emotion words and a block of neutral-emotion words. Cardiovascular parameters were measured using the Finometer Pro. Greater habitual use of suppression was associated with exaggerated blood pressure responding to both tasks. However, only in response to the negative-emotion task was greater use of reappraisal associated with a challenge-oriented cardiovascular response. The findings suggest that individual differences in emotion regulation translate to differing patterns of CVR to stress, but the emotional valence of the stressor may play a role. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/emo0001037DOI Listing
November 2021

Executive Function and Self-Regulation: Bi-Directional Longitudinal Associations and Prediction of Early Academic Skills.

Front Psychol 2021 27;12:733328. Epub 2021 Oct 27.

Early Start, University of Wollongong, Wollongong, NSW, Australia.

Despite a tendency to study executive function (EF) and self-regulation (SR) separately, parallel lines of research suggest considerable overlap between the two abilities. Specifically, both show similar developmental trajectories (i.e., develop rapidly in the early years), predict a broad range of overlapping outcomes across the lifespan (e.g., academic success, mental and physical health, and social competence), and have overlapping neural substrates (e.g., prefrontal cortex). While theoretical frameworks diverge in how they reconcile EF and SR - ranging from treating the two as functionally synonymous, to viewing them as related yet distinct abilities - there is no consensus and limited empirical evidence on the nature of their relationship and how this extends developmentally. The current study examined bi-directional longitudinal associations between early EF and SR, and their longitudinal associations with subsequent early academic skills, in a sample of 199 3- to 5-year-old pre-school children. The adopted measures permitted EF and SR to be modelled as composite indices for these analyses, thereby decreasing task-specific components of these associations. Early academic skills were captured by a standardized direct assessment. Bi-directional associations between EF and SR were found, with both accounting for unique variance in early academic skills 7 and 19months later. The current results provide important evidence to distinguish between EF and SR abilities, yet also for their reciprocal influence and across early development.
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http://dx.doi.org/10.3389/fpsyg.2021.733328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579059PMC
October 2021
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