Designing and validating a One Health Research Translation Framework through literature-based case studies in Egypt.

Within One Health, research translation is a dynamic process involving collaboration and communication between the human, animal, and environmental health sectors to create and apply research findings to address health threats at the human-animal-environment interface. Research translation is essential for the creation of evidence-based policies and programs for the prevention and control of infectious diseases and other health threats, and thus is an important component of a robust national capacity to effectively prevent, control, and mitigate biological incidents. However, there is a lack of conceptual guidance and training materials for research translation in a One Health context. To address this need, we developed a novel One Health Research Translation Framework that describes an iterative process for research and policy stakeholders to collaborate to design and implement research applications addressing One Health zoonotic disease challenges. In addition, we developed accompanying training materials to validate the Framework and facilitate capacity building for understanding and applying research translation concepts to zoonotic disease threats. The training materials consist of exercises to map One Health communication pathways and literature-based case studies on research translation to address zoonotic disease concerns. The Framework and training materials were piloted with Egyptian One Health stakeholders at a workshop in Cairo in 2018. The outcomes of the workshop validated the comprehensiveness and applicability of the Framework and training materials, as participants were able to demonstrate a firm understanding of research translation processes and successfully apply research translation and One Health concepts to real-world zoonotic disease scenarios. Overall, the Framework and accompanying training materials address an important gap in capacity building for One Health stakeholders and are valuable tools for strengthening research translation networks that promote development of innovative, evidence-based solutions to One Health zoonotic disease threats.

Analysis of Language Translations of State Governments' Coronavirus Disease 2019 Vaccine Websites.

Introduction: During the coronavirus disease 2019 (COVID-19) vaccination campaign, non-English-communicating individuals have faced inequities in access to resources for vaccine education and uptake. We characterized the language translation status of states' COVID-19 vaccine websites to inform discussion on the sufficiency of translated information and strategies for expanding the availability of multilingual vaccine information. Methods: We identified the primary COVID-19 vaccine website for all 50 states, the District of Columbia, and the federal government ("jurisdictions") and determined the languages into which information about obtaining the vaccine (access) and vaccine safety and efficacy had been translated, as of October 2021. We compared these findings with data from the American Community Survey to determine how many individuals had these online resources available in their primary language. Results: Only 56% of jurisdictions provided professionally translated information about COVID-19 vaccine safety and efficacy, and only 50% provided professionally translated information about how to register for or obtain the COVID-19 vaccine, in at least one language. Consequently, ∼26 million Americans may not have accurate vaccine safety and efficacy information available, and ∼29 million Americans may not have vaccine access information available, from their jurisdiction in their primary language. Furthermore, translated information often was limited in scope and/or number of languages provided. Conclusion: Translation of COVID-19 vaccine information on state government websites currently is insufficient to meet the needs of non-English-communicating populations. This analysis can inform discussions about resource needs and operational considerations for adequate provision of multilingual, critical health information.

Biodefense Policy Analysis-A Systems-based Approach.

Understanding the overall biosecurity and biodefense policy landscape, the relationships between policies and their effects on each other, and the mechanisms for leveraging advances in science and technology to enhance defensive capabilities is crucial for ensuring that policy strategies address long-standing gaps and challenges. To date, policy analyses have been conducted primarily on single issues, which limits analyses of broader effects of policies, particularly after implementation. Here we describe the first-ever systems-based analysis of the US biosecurity and biodefense policy landscape to analyze functional relationships between policies, including examination of the unintended positive or negative consequences of policy actions. This analysis revealed a striking bifurcation of the US policy landscape for countering biological threats, with one grouping of policies focused on prevention of theft, diversion, or deliberate malicious use of biological sciences knowledge, skills, materials, and technologies (ie, biosecurity) and a second grouping on development of capabilities and knowledge to assess, detect, monitor, respond to, and attribute biological threats (ie, biodefense). An analysis of indirect effects demonstrated that policies within groups may result in mutual benefit, but policies in different groups may counteract each other, limiting achievement of the policy objectives in either group. The current policy landscape predominantly focuses on pathogens and toxins, having limited focus on rapidly changing biotechnologies with potential to positively contribute to biodefense capabilities or introduce unknown and/or unacceptable security risk. Based on our analyses, we present actions for implementing biosecurity and biodefense policy in the United States that intends to harness the benefits of science and technology while also minimizing potential risks. This article synthesizes and highlights the major findings and conclusions from the detailed analyses, which can be found in the full report ( http://www.gryphonscientific.com/biosecurity-policy/ ).

Activation of focal adhesion kinase by Salmonella suppresses autophagy via an Akt/mTOR signaling pathway and promotes bacterial survival in macrophages.

Autophagy has emerged as an important antimicrobial host defense mechanism that not only orchestrates the systemic immune response, but also functions in a cell autonomous manner to directly eliminate invading pathogens. Pathogenic bacteria such as Salmonella have evolved adaptations to protect themselves from autophagic elimination. Here we show that signaling through the non-receptor tyrosine kinase focal adhesion kinase (FAK) is actively manipulated by the Salmonella SPI-2 system in macrophages to promote intracellular survival. In wild-type macrophages, FAK is recruited to the surface of the Salmonella-containing vacuole (SCV), leading to amplified signaling through the Akt-mTOR axis and inhibition of the autophagic response. In FAK-deficient macrophages, Akt/mTOR signaling is attenuated and autophagic capture of intracellular bacteria is enhanced, resulting in reduced bacterial survival. We further demonstrate that enhanced autophagy in FAK(-/-) macrophages requires the activity of Atg5 and ULK1 in a process that is distinct from LC3-assisted phagocytosis (LAP). In vivo, selective knockout of FAK in macrophages resulted in more rapid clearance of bacteria from tissues after oral infection with S. typhimurium. Clearance was correlated with reduced infiltration of inflammatory cell types into infected tissues and reduced tissue damage. Together, these data demonstrate that FAK is specifically targeted by S. typhimurium as a novel means of suppressing autophagy in macrophages, thereby enhancing their intracellular survival.

Rab4 orchestrates a small GTPase cascade for recruitment of adaptor proteins to early endosomes.

BACKGROUND: Early, sorting endosomes are a major crossroad of membrane traffic, at the intersection of the endocytic and exocytic pathways. The sorting of endosomal cargo for delivery to different subcellular destinations is mediated by a number of distinct coat protein complexes, including adaptor protein 1 (AP-1), AP-3, and Golgi-localized, gamma adaptin ear-containing, Arf-binding (GGAs) protein. Ultrastructural studies suggest that these coats assemble onto tubular subdomains of the endosomal membrane, but the mechanisms of coat recruitment and assembly at this site remain poorly understood. RESULTS: Here we report that the endosomal Rab protein Rab4 orchestrates a GTPase cascade that results in the sequential recruitment of the ADP-ribosylation factor (Arf)-like protein Arl1; the Arf-specific guanine nucleotide exchange factors BIG1 and BIG2; and the class I Arfs, Arf1 and Arf3. Knockdown of Arf1, or inhibition of BIG1 and BIG2 activity with brefeldin A results in the loss of AP-1, AP-3, and GGA-3, but not Arl1, from endosomal membranes and the formation of elongated tubules. In contrast, depletion of Arl1 randomizes the distribution of Rab4 on endosomal membranes, inhibits the formation of tubular subdomains, and blocks recruitment of BIG1 and BIG2, Arfs, and adaptor protein complexes to the endosome. CONCLUSIONS: Together these findings indicate that Arl1 links Rab4-dependent formation of endosomal sorting domains with downstream assembly of adaptor protein complexes that constitute the endosomal sorting machinery.

CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly.

Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). Understanding how CENP-A chromatin is assembled and maintained is central to understanding chromosome segregation mechanisms. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. These factors localize to centromeres in telophase/G1, when new CENP-A chromatin is assembled. The mechanisms that control their targeting are unknown. In this paper, we identify a mechanism for recruiting the Mis18 complex protein M18BP1 to centromeres. We show that depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly. We find that M18BP1 directly binds CENP-C through conserved domains in the CENP-C protein. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly.

Interrelated effects of substance use diagnosis, race, and smoking severity on abstinence initiation in dually dependent male smokers: results of a retrospective chart review.

PURPOSE: : Study goals were 2-fold: 1) to examine differences in demographic and clinical characteristics of smokers who fell into 3 diagnostic groups: alcohol abuse/dependence only (ALC), cocaine abuse/dependence only (COC), and mixed alcohol and cocaine abuse/dependence (ALC + COC); and 2) to determine the degree to which diagnostic grouping predicted short-term abstinence from smoking. METHODS: : Retrospective chart reviews were conducted by using the treatment records of male veterans (N = 175) who participated in a voluntary smoking cessation program during their stay in residential substance dependence treatment. RESULTS: : The ALC group smoked more heavily, had higher levels of nicotine dependence, and reported more emotional problems than the other 2 groups. Short-term abstinence rates were high across the 3 groups (38%, 58%, and 57% for the ALC, COC, and ALC + COC groups, respectively). Lighter smoking at treatment entry, non-white race, and a diagnosis of cocaine abuse/dependence (with or without alcohol abuse/dependence) predicted short-term abstinence in the program. CONCLUSIONS: : Substance misusers motivated to quit smoking can initiate smoking abstinence at relatively high rates with the aid of combined pharmacotherapy and intensive group counseling. White subjects who smoke more heavily and have a diagnosis of alcohol abuse/dependence only have lower success rates for abstinence initiation.