Impact of global structure on diffusive exploration of organelle networks

We investigate diffusive search on planar networks, motivated by tubular organelle networks in cell biology that contain molecules searching for reaction partners and binding sites. Exact calculation of the diffusive mean first-passage time on a spatial network is used to characterize the typical search time as a function of network connectivity. We find that global structural properties --- the total edge length and number of loops --- are sufficient to largely determine network exploration times for a variety of both synthetic planar networks and organelle morphologies extracted from living cells. For synthetic networks on a lattice, we predict the search time dependence on these global structural parameters by connecting with percolation theory, providing a bridge from irregular real-world networks to a simpler physical model. The dependence of search time on global network structural properties suggests that network architecture can be designed for efficient search without controlling the precise arrangement of connections. Specifically, increasing the number of loops substantially decreases search times, pointing to a potential physical mechanism for regulating reaction rates within organelle network structures.Comment: 13 pages, 4 figures. Accepted for publication in Scientific Report

Examining Minority Youth Swimmers’ versus Non-Swimmers’ Perceptions of Swimming Involvement

Drowning is one of the leading causes of death in youth, especially among minority populations (Gilchrest & Parker, 2014). According to the World Health Organization (2014), every hour of every day approximately 42 people lose their lives to drowning. Additionally, African-Americans are 14 times more likely to drown in a pool than other racial or ethnic group members (Waller & Norwood, 2011). The purpose of this study was to examine survey results between swimming and non-swimming minority youth participants. Forty African American students between the ages of 5-17 from an after-school program completed the Swimming Involvement Survey. Results indicated that swimmers, independent of group or gender, would like to swim more than they currently do. These results can help structure more effective swimming programs targeting minority youth

“I would love to see these big institutions… throwing their weight around”: qualitative findings regarding health and social sector collaborations to address community-level socioeconomic adversity

BackgroundHealth and social sector organizations are increasingly working together to mitigate socioeconomic adversity within their communities. We sought to learn about the motivations, experiences, and perspectives of organizations engaged in these collaborations.MethodsWe conducted semi-structured, 60-minute interviews with 34 leaders from 25 health and social sector organizations between January-April 2021. Interviews explored motivations, benefits and challenges, and ways in which health sector organizations can most effectively address community-level socioeconomic adversity. Interviews were audio recorded and transcribed; themes were coded using Dedoose software.ResultsPartnerships were primarily motivated by mission-driven organizations and key health sector leaders who were interested in addressing root causes of poor health; policies such as certificate of need laws and value-based care incentives that aligned community-level investments with health sector organizations' financial interests facilitated these efforts. While partnerships were mostly regarded as mutually beneficial ways to increase impact (for the health sector) and resource access (for the social sector), social sector organizations voiced frustrations regarding the outsized expectations, unsustained interest, and lack of partnership from their health sector collaborators. Despite these frustrations, both health and social sector interviewees supported the health sector's continued involvement in community-level socioeconomic initiatives and expansion of policy and systems efforts.ConclusionsCross-sector, community-level socioeconomic initiatives were mutually beneficial, but social sector organizations experienced more frustrations. Policy and organizational changes within the health sector can further mobilize and sustain support for these efforts

Deriving a Provisional Tolerable Intake for Intravenous Exposure to Silver Nanoparticles Released from Medical Devices

Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL05) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 μg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general

Interoceptive and exteroceptive attention have opposite effects on subsequent somatosensory perceptual decision making

Evidence suggests that interoceptive and exteroceptive attention might have different perceptual effects. However, the effects of these different types of body-focused attention have never been directly compared. The current research investigated how interoceptive and exteroceptive attention affect subsequent performance on the somatic signal detection task (SSDT). In Experiment 1, 37 participants completed the SSDT under usual testing conditions and after performing an interoceptive heartbeat perception task. This task led to a more liberal response criterion, leading to increased touch reports in the presence and absence of a target vibration. This finding is consistent with suggestions that attending internally contributes to physical symptom reporting in patients with medically unexplained symptoms (MUS). In Experiment 2, 40 participants completed the SSDT before and after an exteroceptive grating orientation task. This task led to a more stringent response criterion, leading to decreased touch reports in the presence and absence of the target, possibly via a reduction in sensory noise. This work demonstrates that internal and external body-focused attention can have opposite effects on subsequent somatic perceptual decision making and suggests that attentional training could be useful for patients reporting MUS. </jats:p

Demyelination and axonal preservation in a transgenic mouse model of Pelizaeus-Merzbacher disease

It is widely thought that demyelination contributes to the degeneration of axons and, in combination with acute inflammatory injury, is responsible for progressive axonal loss and persistent clinical disability in inflammatory demyelinating disease. In this study we sought to characterize the relationship between demyelination, inflammation and axonal transport changes using a Plp1-transgenic mouse model of Pelizaeus-Merzbacher disease. In the optic pathway of this non-immune mediated model of demyelination, myelin loss progresses from the optic nerve head towards the brain, over a period of months. Axonal transport is functionally perturbed at sites associated with local inflammation and 'damaged' myelin. Surprisingly, where demyelination is complete, naked axons appear well preserved despite a significant reduction of axonal transport. Our results suggest that neuroinflammation and/or oligodendrocyte dysfunction are more deleterious for axonal health than demyelination per se, at least in the short ter

Complete Genome Sequence of Pelosinus fermentans JBW45, a Member of a Remarkably Competitive Group of Negativicutes in the Firmicutes Phylum.

The genome of Pelosinus fermentans JBW45, isolated from a chromium-contaminated site in Hanford, Washington, USA, has been completed with PacBio sequencing. Nine copies of the rRNA gene operon and multiple transposase genes with identical sequences resulted in breaks in the original draft genome and may suggest genomic instability of JBW45

Clinical Implications in Vaginal Orgasm Response

Previous research has shown that counselors feel uncomfortable addressing clients’ sexual concerns due to a lack of education on topics related to human sexuality. Various studies have attempted to identify the characteristics of vaginal orgasm, including whether women and other people with vaginas (PWV) can achieve different kinds of orgasms. The current study examines responses to participants surveyed across the United States on their orgasm response and compares responses of participants who achieved orgasm through masturbation and those who achieved orgasm through sex with a partner to determine whether PWV experience one kind of orgasm during masturbation and experience a different kind of orgasm during sex with a partner. Results from the current study suggest that there are two distinct orgasm experiences achieved by PWV which differ in physiological and psychological response. Counselors and counselor educators can use results from this study to help expand their knowledge on sexual response to feel more confident in their practice

DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial.

Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the 'predicted sensitive' group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2- patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care