Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.R01 EB000262 - NIBIB NIH HHS; R01 HL115553 - NHLBI NIH HHSPublished versio

Creative Collaboration in Higher Education: A Guide for Distance Learning Technologies

A capstone submitted in partial fulfillment of the requirements for the degree of Doctor of Education in the College of Education at Morehead State University by Christopher D. Howes on April 13, 2018

Prioritising Infectious Disease Mapping.

BACKGROUND: Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. METHODOLOGY/PRINCIPAL FINDINGS: Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. CONCLUSIONS/SIGNIFICANCE: A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited

Human Visual Search as a Deep Reinforcement Learning Solution to a POMDP

When people search for a target in a novel image they oftenmake use of eye movements to bring the relatively high acuityfovea to bear on areas of interest. The strategies that controlthese eye movements for visual search have been of substantialscientific interest. In the current article we report a new com-putational model that shows how strategies for visual searchare an emergent consequence of perceptual/motor constraintsand approximately optimal strategies. The model solves a Par-tially Observable Markov Decision Process (POMDP) usingdeep Q-learning to acquire strategies that optimise the trade-off between speed and accuracy. Results are reported for theDistractor-ratio task

Revolutionizing our Understanding of Particle Energization in Space Plasmas Using On-Board Wave-Particle Correlator Instrumentation

The development of on-board wave-particle correlator instrumentation using existing instrumental capabilities makes it possible to probe the collisionless wave-particle interactions governing plasma heating and particle acceleration in the heliosphere at full measurement cadence while circumventing telemetry constraints, enabling us to maximize the scientific return from future missions

Mortality associated with clozapine:what is the evidence?

While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.</p

Water quality measurements in Buzzards Bay by the Buzzards Bay Coalition Baywatchers Program from 1992 to 2018

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Jakuba, R. W., Williams, T., Neill, C., Costa, J. E., McHorney, R., Scott, L., Howes, B. L., Ducklow, H., Erickson, M., & Rasmussen, M. Water quality measurements in Buzzards Bay by the Buzzards Bay Coalition Baywatchers Program from 1992 to 2018. Scientific Data, 8(1), 2021: 76, https://doi.org/10.1038/s41597-021-00856-4.The Buzzards Bay Coalition’s Baywatchers Monitoring Program (Baywatchers) collected summertime water quality information at more than 150 stations around Buzzards Bay, Massachusetts from 1992 to 2018. Baywatchers documents nutrient-related water quality and the effects of nitrogen pollution. The large majority of stations are located in sub-estuaries of the main Bay, although stations in central Buzzards Bay and Vineyard Sound were added beginning in 2007. Measurements include temperature, salinity, Secchi depth and concentrations of dissolved oxygen, ammonium, nitrate + nitrite, total dissolved nitrogen, particulate organic nitrogen, particulate organic carbon, ortho-phosphate, chlorophyll a, pheophytin a, and in lower salinity waters, total phosphorus and dissolved organic carbon. The Baywatchers dataset provides a long-term record of the water quality of Buzzards Bay and its sub-estuaries. The data have been used to identify impaired waters, evaluate discharge permits, support the development of nitrogen total maximum daily loads, develop strategies for reducing nitrogen inputs, and increase public awareness and generate support for management actions to control nutrient pollution and improve water quality.We thank the more than 1,500 volunteer Baywatchers citizen monitors who helped collect this information over 27 years. Since its inception, funding for this program has been provided through grants from the Commonwealth of Massachusetts, the U.S. Environmental Protection Agency, Buzzards Bay municipalities, private foundations, and members of the Buzzards Bay Coalition. Thank you to Paul Lefebvre for producing the station map. Amy Costa of the Center for Coastal Studies kindly provided data for comparison. Brian Howes of the School for Marine Science and Technology, University of Massachusetts, Dartmouth kindly provided the data for West Falmouth Harbor collected through the Falmouth Pond Watchers program. We thank the Marine Biological Laboratory and the Woodwell Climate Research Center for support to C. Neill, R. McHorney and L. Scott

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Adversity in childhood linked to elevated striatal dopamine function in adulthood

Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63 = 2.92; P = 0.005), and unstable family arrangements (T57 = 2.80; P = 0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood