Two ligands of Arp2/3 complex, yeast coronin and GMF, interact and synergize in pruning branched actin networks.

The rapid turnover of branched actin networks underlies key in vivo processes such as lamellipodial extension, endocytosis, phagocytosis, and intracellular transport. However, our understanding of the mechanisms used to dissociate, or 'prune', branched filaments has remained limited. Glia maturation factor (GMF) is a cofilin family protein that binds to Arp2/3 complex and catalyzes branch dissociation.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques.

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure.

Health-related quality of life and mental health in patients with major bone and joint infections.

Aims: It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs.

Women's Relationships With Healthcare and Providers: The Role of Weight Stigma in Healthcare and Weight Bias Internalization.

Background: Weight stigma (devaluation due to body weight) in healthcare is common and influences one's engagement in healthcare, health behaviors, and relationship with providers. Positive patient-provider relationships (PPR) are important for one's healthcare engagement and long-term health.

Purpose: To date, no research has yet investigated whether weight bias internalization (self-stigma due to weight; WBI) moderates the effect of weight stigma on the PPR.

What is the agreement between principles and practice of antibiotic stewardship in the management of diabetic foot infection: an in-hospital quality control study.

: Standardization of diagnostic and treatment concepts in diabetes-related foot infection (DFI) is challenging. In 2019, specific recommendations regarding diagnostic principles and antibiotic therapy (ABT) for DFI, including the one for osteomyelitis (DFO), were introduced in our institution. In this study, we assessed the adherence to these in-house guidelines 2 years after their implementation.

Weight stigma is uniquely tied to maladaptive eating across different racial, ethnic, and gender groups.

Weight stigma, racism, and sexism (social devaluation due to body weight, race or ethnicity, and sex or gender), have been linked to increased maladaptive eating behaviors; however, no research has investigated the unique associations between different forms of stigma and eating concurrently. We analyzed within-group (by race/ethnicity and sex) effects of different forms of stigma on maladaptive eating behaviors to test whether there is some unique relationship between weight stigma and maladaptive eating across identities. Additionally, we explored differences by racial/ethnic group and sex, as well as BMI category, in levels of reported weight stigma, racism, sexism, and maladaptive eating.

Can people empathize with offenders and victims during violent scenes? Behavioral and brain correlates of affective and cognitive empathy considering victim vs. offender perspective using the Bochumer affective and cognitive empathy task (BACET).

Empathy is defined as the capacity to resonate with others' emotions and can be subdivided into affective and cognitive components. Few studies have focused on the role of perspective-taking within this ability. Utilizing the novel Bochumer Affective and Cognitive Empathy Task (BACET), the present study aims to determine the characteristics of specific empathy components, as well as the impact of offender vs.

Characterization of the Cynomolgus Macaque Model of Marburg Virus Disease and Assessment of Timing for Therapeutic Treatment Testing.

Marburg virus (MARV) causes severe disease and high mortality in humans. The objective of this study was to characterize disease manifestations and pathogenesis in cynomolgus macaques exposed to MARV. The results of this natural history study may be used to identify features of MARV disease useful in defining the ideal treatment initiation time for subsequent evaluations of investigational therapeutics using this model.

Bacteriophage infection and killing of intracellular .

As we rapidly approach a post-antibiotic era, bacteriophage (phage) therapy may offer a solution for treating drug-resistant bacteria. is an emerging, multidrug-resistant pathogen that causes disease in people with cystic fibrosis, chronic obstructive pulmonary disease, and other underlying lung diseases. can survive inside host cells, a niche that can limit access to antibiotics.

Constant vigilance: The impact of weight stigma, vigilance, and internalization on maladaptive eating behaviors.

Objective: Weight stigma (social devaluation because of weight) and weight bias internalization (self-stigma due to weight) have been independently implicated in maladaptive eating, which ultimately contributes to poor cardiometabolic health. Additionally, vigilance (being on the lookout for social devaluation) is connected to stress, poor sleep, and depression. Most research considers these factors separately but establishing how these variables interact with one another is essential to understanding their cumulative impact on health behaviors.

Vulnerability and resilience to the harmful health consequences of weight discrimination in Black, Latina, and sexual minority women.

Background And Objective: Because they deviate from societal expectations regarding thinness, women with high body weight or large body size frequently experience social devaluation and discrimination and such experiences can negatively affect health. Yet relatively little is known about experiences of weight discrimination among people impacted by overlapping forms of oppression such as racism, sexism, and heterosexism or how high body weight may intersect with other marginalized identities to contribute to health disparities. Guided by an intersectional lens, the purpose of the current study was to assess Black, Latina, and sexual minority women's experiences with weight discrimination and to identify factors associated with vulnerability or resilience to the harmful health consequences of weight discrimination in these women.

A Mycobacteriophage-Based Vaccine Platform: SARS-CoV-2 Antigen Expression and Display.

The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for displaying antigens of SARS-CoV-2 or other infectious agents. The potential advantages of using mycobacteriophages are that a large and diverse variety of them have been described and genomically characterized, engineering tools are available, and there is the capacity to display up to 700 antigen copies on a single particle approximately 100 nm in size.

A qualitative analysis of people's experiences with weight-based discrimination.

Objective: The aim of this study was to describe people's day-to-day experiences with weight-based discrimination and to distill themes that shed new light on this phenomenon.

Design: A qualitative study was conducted in 2019 using a purposive sampling strategy. A racially and ethnically diverse sample of 32 U.

CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species.

CRISPY-BRED and CRISPY-BRIP: efficient bacteriophage engineering.

Genome engineering of bacteriophages provides opportunities for precise genetic dissection and for numerous phage applications including therapy. However, few methods are available for facile construction of unmarked precise deletions, insertions, gene replacements and point mutations in bacteriophages for most bacterial hosts. Here we describe CRISPY-BRED and CRISPY-BRIP, methods for efficient and precise engineering of phages in Mycobacterium species, with applicability to phages of a variety of other hosts.

Remdesivir (GS-5734) Is Efficacious in Cynomolgus Macaques Infected With Marburg Virus.

Marburg virus (MARV) is a filovirus with documented human case-fatality rates of up to 90%. Here, we evaluated the therapeutic efficacy of remdesivir (GS-5734) in nonhuman primates experimentally infected with MARV. Beginning 4 or 5 days post inoculation, cynomolgus macaques were treated once daily for 12 days with vehicle, 5 mg/kg remdesivir, or a 10-mg/kg loading dose followed by 5 mg/kg remdesivir.

Dual sequence definition increases the data storage capacity of sequence-defined macromolecules.

Sequence-defined macromolecules offer applications in the field of data storage. Challenges include synthesising precise and pure sequences, reading stored information and increasing data storage capacity. Herein, the synthesis of dual sequence-defined oligomers and their application for data storage is demonstrated.

Protein-Mediated and RNA-Based Origins of Replication of Extrachromosomal Mycobacterial Prophages.

Temperate bacteriophages are common and establish lysogens of their bacterial hosts in which the prophage is stably inherited. It is typical for such prophages to be integrated into the bacterial chromosome, but extrachromosomally replicating prophages have been described also, with the best characterized being the phage P1 system. Among the large collection of sequenced mycobacteriophages, more than half are temperate or predicted to be temperate, most of which code for a tyrosine or serine integrase that promotes site-specific prophage integration.

Characterization of Ebola Virus Disease (EVD) in Rhesus Monkeys for Development of EVD Therapeutics.

Recent Ebola virus (EBOV) outbreaks in West Africa and the Democratic Republic of the Congo have highlighted the urgent need for approval of medical countermeasures for treatment and prevention of EBOV disease (EVD). Until recently, when successes were achieved in characterizing the efficacy of multiple experimental EVD therapeutics in humans, the only feasible way to obtain data regarding potential clinical benefits of candidate therapeutics was by conducting well-controlled animal studies. Nonclinical studies are likely to continue to be important tools for screening and development of new candidates with improved pharmacological properties.

αKlotho Regulates Age-Associated Vascular Calcification and Lifespan in Zebrafish.

The hormone αKlotho regulates lifespan in mice, as knockouts die early of what appears to be accelerated aging due to hyperphosphatemia and soft tissue calcification. In contrast, the overexpression of αKlotho increases lifespan. Given the severe mouse phenotype, we generated zebrafish mutants for αklotho as well as its binding partner fibroblast growth factor-23 (fgf23).

Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo.

Filoviridae currently includes five official and one proposed genera. Genus Ebolavirus includes five established and one proposed ebolavirus species for Bombali virus (BOMV), Bundibugyo virus (BDBV), Ebola virus (EBOV), Reston virus (RESTV), Sudan virus (SUDV) and Taï Forest virus (TAFV), and genus Marburgvirus includes a single species for Marburg virus (MARV) and Ravn virus (RAVV). Ebola virus (EBOV) has emerged as a significant public health concern since the 2013-2016 Ebola Virus Disease outbreak in Western Africa.