Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs.

Cation-chloride-cotransporters (CCCs) catalyze transport of Cl- with K+ and/or Na+across cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the Mus musculus K+-Cl- cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K+ and Cl- ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family

Does the Policy-Making Process Affect Farmer Compliance? A Three-State Case Study of Nutrient Management Regulations

A series of fishkills in 1997 in the Chesapeake Bay were linked to Pfiesteria piscicida, a rare toxic microorganism, and to nutrient pollution from agricultural sources. Manure from poultry production on the Delmarva Peninsula was regarded as the primary source of the excess nutrients. These fishkills served as a focusing event for policy-makers in Maryland, Virginia, and Delaware to update their scientific guidance on phosphorus management, promulgate agricultural regulations, and depart from decades of relying on voluntary technical and financial assistance to improve farm-related water quality problems. This dissertation conducts a comparative case study of these three states to determine if 1) the policy-making process in each state affects compliance by farmers and 2) if the laws improved farmer nutrient management behavior. Data sources include information gathered from interviews with 60 corn farmers on the Peninsula that use broiler chicken manure as fertilizer; interviews with over 60 policy stakeholders; and reviews of primary and secondary documents. Analytical methods include: political analysis of the main stages of the policy development process; policy analysis of the effectiveness of plan-based regulations; statistical tests to determine significant differences between states regarding farmer responses to Likert Opinion Statements and questions about their nutrient management practices; logit regression analysis to determine factors influential to low manure application rates; and a review of compliance data collected by the state regulatory agencies. Answers to both research questions are, overall, "yes," though this answer depends on which dataset of compliance and which metric of improved nutrient management behavior is reviewed; there are "no" answers as well. Results of this dissertation highlight the serious difficulty of regulating dispersed nonpoint source agricultural nutrient pollution through nutrient management plans. Several findings arise, including: plan-based agricultural regulations are in reality voluntary; plans prepared by private and public sector planners result in non-uniform standards; gaining "buy-in" from rather than "alienating" the regulated community likely results in better overall outcomes; regulations that account for on-the-ground realities of farming and state regulatory capacity likely achieve better overall outcomes; and focusing events that turn out to be weak can undermine the justification for new regulatory policies

Endangered by Sprawl: How Runaway Development Threatens America's Wildlife

Estimates the growth of land consumption in metropolitan areas over the next 25 years, investigates locally implemented strategies to protect natural lands from overdevelopment, and offers "smart growth" as an option for reducing suburban sprawl

Catch the Wave: Incorporating QSEN Competencies in a Transition into Practice Program

https://digitalcommons.psjhealth.org/other_pubs/1056/thumbnail.jp

Using the Virtual Reality-Cognitive Rehabilitation Approach to Improve Contextual Processing in Children with Autism

Background. This pilot study investigated the efficacy of a novel virtual reality-cognitive rehabilitation (VR-CR) intervention to improve contextual processing of objects in children with autism. Previous research supports that children with autism show deficits in contextual processing, as well as deficits in its elementary components: abstraction and cognitive flexibility. Methods. Four children with autism participated in a multiple-baseline, single-subject study. The children were taught how to see objects in context by reinforcing attention to pivotal contextual information. Results. All children demonstrated statistically significant improvements in contextual processing and cognitive flexibility. Mixed results were found on the control test and changes in context-related behaviours. Conclusions. Larger-scale studies are warranted to determine the effectiveness and usability in comprehensive educational programs

Sam\u27s Story

We are exploring presenting mental health topics in video games through the eyes of an axolotl named Sam. Sam goes about his day to day life facing many difficult challenges regarding their mental health. This is an educational game to inform about different mental health symptoms and what they may look like

Totally geodesic hyperbolic 3-manifolds in hyperbolic link complements of tori in S4S^4

In this paper we prove that certain hyperbolic link complements of $2$-tori in $S^4$ do not contain closed embedded totally geodesic hyperbolic $3$-manifolds.Comment: 18 pages. arXiv admin note: text overlap with arXiv:2005.1125

Coordination with Humans via Strategy Matching

Human and robot partners increasingly need to work together to perform tasks as a team. Robots designed for such collaboration must reason about how their task-completion strategies interplay with the behavior and skills of their human team members as they coordinate on achieving joint goals. Our goal in this work is to develop a computational framework for robot adaptation to human partners in human-robot team collaborations. We first present an algorithm for autonomously recognizing available task-completion strategies by observing human-human teams performing a collaborative task. By transforming team actions into low dimensional representations using hidden Markov models, we can identify strategies without prior knowledge. Robot policies are learned on each of the identified strategies to construct a Mixture-of-Experts model that adapts to the task strategies of unseen human partners. We evaluate our model on a collaborative cooking task using an Overcooked simulator. Results of an online user study with 125 participants demonstrate that our framework improves the task performance and collaborative fluency of human-agent teams, as compared to state of the art reinforcement learning methods.Comment: 2022 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2022

Vaginal Microbiota and the Use of Probiotics

The human vagina is inhabited by a range of microbes from a pool of over 50 species. Lactobacilli are the most common, particularly in healthy women. The microbiota can change composition rapidly, for reasons that are not fully clear. This can lead to infection or to a state in which organisms with pathogenic potential coexist with other commensals. The most common urogenital infection in premenopausal women is bacterial vaginosis (BV), a condition characterized by a depletion of lactobacilli population and the presence of Gram-negative anaerobes, or in some cases Gram-positive cocci, and aerobic pathogens. Treatment of BV traditionally involves the antibiotics metronidazole or clindamycin, however, the recurrence rate remains high, and this treatment is not designed to restore the lactobacilli. In vitro studies have shown that Lactobacillus strains can disrupt BV and yeast biofilms and inhibit the growth of urogenital pathogens. The use of probiotics to populate the vagina and prevent or treat infection has been considered for some time, but only quite recently have data emerged to show efficacy, including supplementation of antimicrobial treatment to improve cure rates and prevent recurrences