cGAS goes viral: A conserved immune defense system from bacteria to humans.

To survive, all organisms need the ability to accurately recognize and neutralize pathogens. As a result, many of the fundamental strategies that our innate immune system uses to fight infection have deep evolutionary roots. The innate immune sensor cyclic-GMP-AMP synthase (cGAS), an enzyme that plays a critical role in our bodies by sensing and signaling in response to microbial infection, is broadly conserved and has functional homologs in many vertebrates, invertebrates, and even bacteria.

Evaluation of age-banded dosing of oral paracetamol in hospitalised children: a retrospective analysis using clinical data in a tertiary paediatric hospital.

Objective: To evaluate age-banded dosing in paediatric inpatients by determining the proportion of patients whose dose would fall outside the therapeutic range (by weight).

Design: A retrospective observational study. Weight and height measurements and details of hospital admissions were matched from the electronic patient record of a single, tertiary paediatric hospital.

Ubiquitin-like conjugation by bacterial cGAS enhances anti-phage defence.

cGAS is an evolutionarily conserved enzyme that has a pivotal role in immune defence against infection. In vertebrate animals, cGAS is activated by DNA to produce cyclic GMP-AMP (cGAMP), which leads to the expression of antimicrobial genes. In bacteria, cyclic dinucleotide (CDN)-based anti-phage signalling systems (CBASS) have been discovered.

The Impact of COVID-19 on Patient Experience Within a Midwest Hospital System: A Case Study.

Patient-centered communication and patient-provider relationships directly affect patient outcomes. The purpose of this study was to compare inpatient perception of provider/nurse communication in both COVID versus non-COVID diagnoses groups. A qualitative retrospective study was conducted by performing a priori analysis on Hospital Consumer Assessment of Healthcare Providers and Systems surveys from 4 different hospitals for both COVID and non-COVID diagnoses.

Repetitive transcranial magnetic stimulation for the treatment of postpartum depression.

Background: Postpartum depression (PPD) is a common and gravely disabling health concern. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depression and may be a valuable tool in the treatment of PPD. The treatment effect of rTMS is rapid, generally well tolerated, without systemic effects, and without medication exposure to a fetus and/or breastfed infant.

Gender, videogames and navigation in virtual space.

Spatial abilities associated with success in educational and occupational fields of Science, Technology, Engineering, and Mathematics (STEM) have been repeatedly shown to be gendered, with males demonstrating measurably better spatial abilities than females. Less is known about why this is, or about how experience with spatial systems (videogames, for example) affects these abilities. We conducted two experiments with 82 participants with varying degrees of videogame experience on measures of mental rotation, spatial learning, and spatial memory.

Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1.

Understanding the relationship between protein sequence and structure well enough to design new proteins with desired functions is a longstanding goal in protein science. Here, we show that recurring tertiary structural motifs (TERMs) in the PDB provide rich information for protein-peptide interaction prediction and design. TERM statistics can be used to predict peptide binding energies for Bcl-2 family proteins as accurately as widely used structure-based tools.

"The Entrepreneurial Gamer": Regendering the Order of Play.

The designation "gamer" is structurally bound to networked economies of digital play that are rewarded fiscally, socially, and publically, an order of play that is proving difficult to overturn. That girls and women have enjoyed at best marginal positions within video game cultures is by now well recognized, yet at the very same time is too easily dismissed in light of persuasively documented increases in the numbers of women who play. This article traces a large-scale transformation of ludic engagement from participation to spectatorship that parallels the professionalizing and commodifying of traditionally embodied sports, games, and play to demonstrate how new and emerging economies of gameplay, far from opening up the playing field, threaten a further entrenchment of gendered relations.

Peptide design by optimization on a data-parameterized protein interaction landscape.

Many applications in protein engineering require optimizing multiple protein properties simultaneously, such as binding one target but not others or binding a target while maintaining stability. Such multistate design problems require navigating a high-dimensional space to find proteins with desired characteristics. A model that relates protein sequence to functional attributes can guide design to solutions that would be hard to discover via screening.

Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells.

Bcl-2 family proteins regulate apoptosis, and aberrant interactions of overexpressed antiapoptotic family members such as Mcl-1 promote cell transformation, cancer survival, and resistance to chemotherapy. Discovering potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is thus a high priority for cancer research. An attractive strategy for disabling Mcl-1 involves using designer peptides to competitively engage its binding groove, mimicking the structural mechanism of action of native sensitizer BH3-only proteins.

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1.

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding.

Reducing childhood obesity through U.S. federal policy: a microsimulation analysis.

Background: Childhood obesity prevalence remains high in the U.S., especially among racial/ethnic minorities and low-income populations.

Effects of marine overwash for atoll aquifers: environmental and human factors.

Inundation of atoll islands by marine overwash is a serious threat to fresh groundwater, which can be a critical emergency water resource after artificial storage or other water resource infrastructure has been exhausted or destroyed. In contrast to drought, which slowly exhausts water supplies and often can be forecasted in time, overwash can occur with little warning and can ruin both rain catchment storage and groundwater reserves. In this study, a SUTRA-based model is applied to estimate how groundwater contamination by overwash and subsequent recovery of fresh groundwater are influenced by geologic factors (aquifer hydraulic conductivity, dispersivity, and the presence or absence of a reef flat plate), the seasonal timing of the event (wet vs.

Transitions between subclasses of bullying and victimization when entering middle school.

We examined the effects of depressive symptoms, antisocial attitudes, and perspective-taking empathy on patterns of bullying and victimization during the transition from late elementary (4th grade to 5th grade) to middle school (6th grade) among 1,077 students who participated in the Youth Matters (YM) bullying prevention trial. Latent transition analysis was used to establish classes of bullying, victimization, bully-victimization, and uninvolvement. The intervention had a positive impact on children as they moved from elementary to middle school.

Patterns of aggressive behavior and peer victimization from childhood to early adolescence: a latent class analysis.

The developmental period characterized by the transition from childhood and elementary school to early adolescence and middle school has been associated with increases in aggressive behavior and peer victimization. Few longitudinal studies, however, have examined the stability of aggression and victimization during this critical transition. This study uses latent class analysis (LCA) to examine patterns of aggressive behavior and victimization during the transition to middle school among urban, public school students (N = 458; Girls = 53%; Latino/a = 53%; M age at t1 = 10.

Revisioning social work clinical education: recent developments in relation to evidence-based practice.

An evidence-based practice (EBP) movement is underway in social work that promises to change the very nature and methods of clinical education and practice. Growing demands for accountability, increasingly sophisticated clients, heightened threats of malpractice liability, and a host of additional factors arising within and external to the profession have contributed to the growth of EBP. This review examines indices of the growing influence of EBP, reasons for the emergence of EBP, misgivings about and potentially positive features of EBP, and examines one school of social work's efforts to implement an evidence-based clinical practice curriculum.

The influence of diet and water on the stable oxygen and hydrogen isotope composition of Chironomidae (Diptera) with paleoecological implications.

Stable oxygen and hydrogen isotope analyses of fossil aquatic organisms, such as the chitinous head capsules of chironomid larvae (Chironomidae: Diptera), are promising proxies for inferring paleoecological conditions. In order for analyses of stable oxygen (delta(18)O) and hydrogen isotope ratios (delta(2)H) of fossil chironomid head capsules to be used effectively in paleoecological research, it is necessary to understand the factors controlling their stable oxygen and hydrogen composition. We cultured chironomid larvae in two isotopically distinct waters under controlled, replicated laboratory conditions.

Development of a risk and resilience-based out-of-school time program for children and youths.

Out-of-school time (OST) programs offer a unique opportunity to provide educational supports to high-risk children and youths.The authors describe the utility of applying principles of risk and resilience to the development and evaluation of an OST program. Academic outcomes among participants at the Bridge Project, an OST program located in three urban public housing communities, are presented to illustrate a risk and resilience approach to service delivery.

Numerical modeling of atoll island hydrogeology.

We implemented Ayers and Vachers' (1986) inclusive conceptual model for atoll island aquifers in a comprehensive numerical modeling study to evaluate the response of the fresh water lens to selected controlling climatic and geologic variables. Climatic factors include both constant and time-varying recharge rates, with particular attention paid to the effects of El Niño and the associated drought it brings to the western Pacific. Geologic factors include island width; hydraulic conductivity of the uppermost Holocene-age aquifer, which contains the fresh water lens; the depth to the contact with the underlying, and much more conductive, Pleistocene karst aquifer, which transmits tidal signals to the base of the lens; and the presence or absence of a semiconfining reef flat plate on the ocean side.

Effects of a skills-based prevention program on bullying and bully victimization among elementary school children.

We report results from a group-randomized trial of a prevention program aimed at preventing bullying and other aggressive behaviors. Fourth grade classrooms at 28 public elementary schools were assigned to receive selected modules of the Youth Matters prevention curriculum or to a no-treatment control condition. Cross-classified multilevel models were fitted to four waves of data collected over 2 years to test the effect of the intervention on self-reported bullying and bully victimization.