How Do Communities Use a Participatory Public Health Approach to Build Resilience? The Los Angeles County Community Disaster Resilience Project.

Community resilience is a key concept in the National Health Security Strategy that emphasizes development of multi-sector partnerships and equity through community engagement. Here, we describe the advancement of CR principles through community participatory methods in the Los Angeles County Community Disaster Resilience (LACCDR) initiative. LACCDR, an initiative led by the Los Angeles County Department of Public Health with academic partners, randomized 16 community coalitions to implement either an Enhanced Standard Preparedness or Community Resilience approach over 24 months. Facilitated by a public health nurse or community educator, coalitions comprised government agencies, community-focused organizations and community members. We used thematic analysis of data from focus groups (n = 5) and interviews (n = 6 coalition members; n = 16 facilitators) to compare coalitions' strategies for operationalizing community resilience levers of change (engagement, partnership, self-sufficiency, education). We find that strategies that included bidirectional learning helped coalitions understand and adopt resilience principles. Strategies that operationalized community resilience levers in mutually reinforcing ways (e.g., disseminating information while strengthening partnerships) also secured commitment to resilience principles. We review additional challenges and successes in achieving cross-sector collaboration and engaging at-risk groups in the resilience versus preparedness coalitions. The LACCDR example can inform strategies for uptake and implementation of community resilience and uptake of the resilience concept and methods

Genome sequence of a gammaherpesvirus from a common bottlenose dolphin (Tursiops truncatus)

A herpesvirus genome was sequenced directly from a biopsy specimen of a rectal lesion from a female common bottlenose dolphin. This genome sequence comprises a unique region (161,235 bp) flanked by multiple copies of a terminal repeat (4,431 bp) and contains 72 putative genes. The virus was named common bottlenose dolphin gammaherpesvirus 1

H3K56me3 is a novel, conserved heterochromatic mark that largely but not completely overlaps with H3K9me3 in both regulation and localization.

Histone lysine (K) methylation has been shown to play a fundamental role in modulating chromatin architecture and regulation of gene expression. Here we report on the identification of histone H3K56, located at the pivotal, nucleosome DNA entry/exit point, as a novel methylation site that is evolutionary conserved. We identify trimethylation of H3K56 (H3K56me3) as a modification that is present during all cell cycle phases, with the exception of S-phase, where it is underrepresented on chromatin. H3K56me3 is a novel heterochromatin mark, since it is enriched at pericentromeres but not telomeres and is thereby similar, but not identical, to the localization of H3K9me3 and H4K20me3. Possibly due to H3 sequence similarities, Suv39h enzymes, responsible for trimethylation of H3K9, also affect methylation of H3K56. Similarly, we demonstrate that trimethylation of H3K56 is removed by members of the JMJD2 family of demethylases that also target H3K9me3. Furthermore, we identify and characterize mouse mJmjd2E and its human homolog hKDM4L as novel, functionally active enzymes that catalyze the removal of two methyl groups from trimethylated H3K9 and K56. H3K56me3 is also found in C. elegans, where it co-localizes with H3K9me3 in most, but not all, tissues. Taken together, our findings raise interesting questions regarding how methylation of H3K9 and H3K56 is regulated in different organisms and their functional roles in heterochromatin formation and/or maintenance

Equitable Access to Mental Health and Substance Use Care: An Urgent Need

Due to the deepening mental health and substance use crisis in the U.S., there's an urgent need for equitable access to care that is timely, clinically effective, and adequately reimbursed by insurers. This need encompasses psychiatrists, psychologists, social workers, other counselors, and treatment facilities as well as mental health and substance use care delivered by primary care providers.Multiple studies, including analyses of insurance claims and surveys of employers and providers, have demonstrated that in-network health insurance coverage for treatment of mental health and substance use conditions remains inadequate and not "on par" with access to in-network health insurance coverage for physical health treatment.This patient-experience survey conducted by NORC (Survey) explored key topics such as: 1) how often mental health or substance use care is needed but not received; 2) how difficult it is to find in-network providers accepting new patients; 3) how often and why patients use out-ofnetwork providers for mental health or substance use care versus physical health care; 4) how often patients feel that mental health or substance use care from PCPs and other physical health providers is insufficient; 5) how often services are denied; and more

Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies.

Human cells express thousands of different surface proteins that can be used for cell classification, or to distinguish healthy and disease conditions. A method capable of profiling a substantial fraction of the surface proteome simultaneously and inexpensively would enable more accurate and complete classification of cell states. We present a highly multiplexed and quantitative surface proteomic method using genetically barcoded antibodies called phage-antibody next-generation sequencing (PhaNGS). Using 144 preselected antibodies displayed on filamentous phage (Fab-phage) against 44 receptor targets, we assess changes in B cell surface proteins after the development of drug resistance in a patient with acute lymphoblastic leukemia (ALL) and in adaptation to oncogene expression in a Myc-inducible Burkitt lymphoma model. We further show PhaNGS can be applied at the single-cell level. Our results reveal that a common set of proteins including FLT3, NCR3LG1, and ROR1 dominate the response to similar oncogenic perturbations in B cells. Linking high-affinity, selective, genetically encoded binders to NGS enables direct and highly multiplexed protein detection, comparable to RNA-sequencing for mRNA. PhaNGS has the potential to profile a substantial fraction of the surface proteome simultaneously and inexpensively to enable more accurate and complete classification of cell states

Dynamics of a deep-water seagrass population on the Great Barrier Reef: annual occurrence and response to a major dredging program

Global seagrass research efforts have focused on shallow coastal and estuarine seagrass populations where alarming declines have been recorded. Comparatively little is known about the dynamics of deep-water seagrasses despite evidence that they form extensive meadows in some parts of the world. Deep-water seagrasses are subject to similar anthropogenic threats as shallow meadows, particularly along the Great Barrier Reef lagoon where they occur close to major population centres. We examine the dynamics of a deep-water seagrass population in the GBR over an 8 year period during which time a major capital dredging project occurred. Seasonal and inter-annual changes in seagrasses were assessed as well as the impact of dredging. The seagrass population was found to occur annually, generally present between July and December each year. Extensive and persistent turbid plumes from a large dredging program over an 8 month period resulted in a failure of the seagrasses to establish in 2006, however recruitment occurred the following year and the regular annual cycle was re-established. Results show that despite considerable inter annual variability, deep-water seagrasses had a regular annual pattern of occurrence, low resistance to reduced water quality but a capacity for rapid recolonisation on the cessation of impacts

Bovine Spongiform Encephalopathy Infectivity in Greater Kudu (Tragelaphus strepsiceros)

Of all the species exposed naturally to the bovine spongiform encephalopathy (BSE) agent, the greater kudu (Tragelaphus strepsiceros), a nondomesticated bovine from Africa, appears to be the most susceptible to the disease. We present the results of mouse bioassay studies to show that, contrary to findings in cattle with BSE in which the tissue distribution of infectivity is the most limited recorded for any of the transmissible spongiform encephalopathies (TSE), infectivity in greater kudu with BSE is distributed in as wide a range of tissues as occurs in any TSE. BSE agent was also detected in skin, conjunctiva, and salivary gland, tissues in which infectivity has not previously been reported in any naturally occurring TSE. The distribution of infectivity in greater kudu with BSE suggests possible routes for transmission of the disease and highlights the need for further research into the distribution of TSE infectious agents in other host species

O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding.

Alpha-dystroglycan (alpha-DG) is a cell-surface glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains and certain arenaviruses. Receptor binding is thought to be mediated by a posttranslational modification, and defective binding with laminin underlies a subclass of congenital muscular dystrophy. Using mass spectrometry- and nuclear magnetic resonance (NMR)-based structural analyses, we identified a phosphorylated O-mannosyl glycan on the mucin-like domain of recombinant alpha-DG, which was required for laminin binding. We demonstrated that patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as mice with myodystrophy, commonly have defects in a postphosphoryl modification of this phosphorylated O-linked mannose, and that this modification is mediated by the like-acetylglucosaminyltransferase (LARGE) protein. These findings expand our understanding of the mechanisms that underlie congenital muscular dystrophy