Increased Fear Response to Contextual Cues in Mice Lacking the 5-HT1A Receptor

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A Role for Proapoptotic BID in the DNA-Damage Response

SummaryThe BCL-2 family of apoptotic proteins encompasses key regulators proximal to irreversible cell damage. The BH3-only members of this family act as sentinels, interconnecting specific death signals to the core apoptotic pathway. Our previous data demonstrated a role for BH3-only BID in maintaining myeloid homeostasis and suppressing leukemogenesis. In the absence of Bid, mice accumulate chromosomal aberrations and develop a fatal myeloproliferative disorder resembling chronic myelomonocytic leukemia. Here, we describe a role for BID in preserving genomic integrity that places BID at an early point in the path to determine the fate of a cell. We show that BID plays an unexpected role in the intra-S phase checkpoint downstream of DNA damage distinct from its proapoptotic function. We further demonstrate that this role is mediated through BID phosphorylation by the DNA-damage kinase ATM. These results establish a link between proapoptotic Bid and the DNA-damage response

microRNAs Sculpt Neuronal Communication in a Tight Balance That Is Lost in Neurological Disease

Since the discovery of the first microRNA 25 years ago, microRNAs (miRNAs) have emerged as critical regulators of gene expression within the mammalian brain. miRNAs are small non-coding RNAs that direct the RNA induced silencing complex to complementary sites on mRNA targets, leading to translational repression and/or mRNA degradation. Within the brain, intra- and extracellular signaling events tune the levels and activities of miRNAs to suit the needs of individual neurons under changing cellular contexts. Conversely, miRNAs shape neuronal communication by regulating the synthesis of proteins that mediate synaptic transmission and other forms of neuronal signaling. Several miRNAs have been shown to be critical for brain function regulating, for example, enduring forms of synaptic plasticity and dendritic morphology. Deficits in miRNA biogenesis have been linked to neurological deficits in humans, and widespread changes in miRNA levels occur in epilepsy, traumatic brain injury, and in response to less dramatic brain insults in rodent models. Manipulation of certain miRNAs can also alter the representation and progression of some of these disorders in rodent models. Recently, microdeletions encompassing MIR137HG, the host gene which encodes the miRNA miR-137, have been linked to autism and intellectual disability, and genome wide association studies have linked this locus to schizophrenia. Recent studies have demonstrated that miR-137 regulates several forms of synaptic plasticity as well as signaling cascades thought to be aberrant in schizophrenia. Together, these studies suggest a mechanism by which miRNA dysregulation might contribute to psychiatric disease and highlight the power of miRNAs to influence the human brain by sculpting communication between neurons

The Latino community of Carrboro, Orange County, NC : an action-oriented community diagnosis : a participatory assessment of the Latino community of Carrboro

Carrboro is located adjacent to Chapel Hill, North Carolina and prides itself on being an open and welcoming community. Since 1990 the Latino population of Carrboro has grown 936%, and currently represents 12% of the community. The significant growth of the Latino community of Carrboro has contributed to the town’s diversity and has led to many changes in service delivery. An Action-Oriented Community Diagnosis of the Latino community of Carrboro was conducted by five graduate students from the Department of Health Behavior and Health Education, within the School of Public Health at the University of North Carolina at Chapel Hill. This community diagnosis was conceptualized as part of a larger, county wide assessment being done by the Orange County Health Department for Healthy Carolinians. The purpose of an Action-Oriented Community Diagnosis (AOCD) is to involve community members in identifying their own community’s needs and challenges, as well as its strengths and resources. The information collected through this process can assist the community in conceptualizing methods for dealing with the challenges identified and taking action to confront them. This AOCD process was implemented in three phases. Phase one included the collection of secondary data describing the overall quality of life of Latino residents in Carrboro in terms of physical and mental health, social functioning, economics and growth, crime and safety, housing, recreation, religion, and education. During the second phase, the team conducted interviews and focus groups with community members and service providers to gain firsthand insight into the community and capture the perspective of those who lived and worked there. Between January and April 2003, the students spoke with a total of 47 community members and service providers. In the third phase, the students planned and executed a community forum around the issues related to the major themes that came out of these discussions. The students systematically analyzed all primary data from these interviews. A total of four major themes and four secondary themes emerged from the data. The four major themes – so categorized because of the frequency with which interviewees discussed them – were health, education, employment, and transportation. Secondary themes included community relations, housing, recreation, and youth. Language barriers and documentation issues came up in almost every interview, and were considered overarching themes that affected every facet of life for Carrboro’s Latino population. A committee was formed to help plan the community forum where the interview results would be presented and discussed. The committee was comprised of community members, and service providers within the Latino community of Carrboro. The planning committee assisted in deciding on an appropriate date and location for the event, advised the team on the most important issues to present during the forum, participated in generating publicity about the event, and worked with the team to plan for and facilitate small group discussions at the forum. Being community members and service providers themselves, the planning committee members were essential actors in the AOCD process. Planning committee members named the process ¡Acción Latina! (Latino Action), setting the stage for a results-oriented discussion at the community forum. The community forum took place on Saturday, May 3, 2003. The students presented findings from the four major themes to the assembled group and invited participants to take part in small-group discussions about the issue of their choice. Students and planning committee members facilitated these smaller discussions, with a view to moving participants from identifying common challenges to developing concrete action steps. Participants interested in health issues focused on lack of health insurance among Latinos, the high cost of health care, and the high risk for STDs among Carrboro’s Latinos. They chose to work on strengthening the reach and effectiveness of the highly valued Carrboro Community Health Center, to ensure that information about its affordable and Latino-friendly services are widely disseminated and well-understood. With respect to STD risk, participants decided that a short-term goal should be to provide more information and services through targeted outreach to Latinos and that a long-term goal should be to increase condom use. They developed many specific recommendations to reach these goals. The education group focused primarily on enhancing Latino parents’ opportunities to be involved in their childrens’ education and schools. Participants discussed major barriers to parental involvement such as language issues, not understanding the system, and work schedules. They recommended holding a parent/teacher conference in Spanish during the first week of school which would help bring the parents together with the school system so that the parents could learn what they can do to help their children. The issue of documentation dominated the small group discussion about employment. Specific suggestions included contacting government representatives to advocate for changes to current immigration policies, establishing a volunteer-run student law clinic at the UNC Law School, and holding a workshop or information session on documentation and workers’ rights. Finally, the transportation small group came up with a series of recommendations to improve access to services for Latinos. These suggestions included translating the existing bus schedule into Spanish and encouraging members of the Latino community to join the Transportation Advisory Board and the Extra Territorial Jurisdiction Board. After the individual small group discussions, forum participants reconvened and representatives from each group presented the group’s recommendations and action steps to and accepted responsibility for following up on some of those steps.Master of Public Healt

Probiotic BC30 Improves Amino Acid Absorption from Plant Protein Concentrate in Older Women

Weizmannia coagulans GBI-30, 6086 (BC30) has previously been shown to increase protein digestion in an in vitro model of the stomach and small intestine and amino acid appearance in healthy men and women after ingestion of milk protein concentrate. The impact of ingesting BC30 with other protein sources or in other demographics is largely unknown. The purpose of this study was to examine the impact of adding BC30 to a 20-g dose of a blend of rice and pea protein on postprandial changes in blood amino acids concentrations in healthy, older women. Healthy, older females (n = 30, 58.5 ± 5.2 years, 165.4 ± 6.8 cm, 65.6 ± 8.8 kg, 23.7 ± 3.2 kg/m2) completed two separate 14-day supplementation protocols separated by a 3-week washout period. Participants were instructed to ingest a 20-g protein dose of a blend of rice and pea protein concentrates (ProDiem Plant Protein Solutions, Kerry) with (PPCBC30) or without (PPC) the addition of 1 × 109 CFU BC30 (Kerry). Body composition and demographics were assessed upon arrival to the laboratory. Upon ingestion of their final assigned supplemental dose, blood samples were taken at 0 (baseline), 30-, 60-, 90-, 120-, 180-, and 240-min post-consumption and analyzed for amino acid concentrations. Alanine (p = 0.018), tryptophan (p = 0.003), cysteine (p = 0.041), essential amino acids (p = 0.050), and total amino acids (p = 0.039) all exhibited significantly (p ≤ 0.05) greater AUC with PPCBC30 when compared to PPC. In addition, tryptophan (p = 0.003), cysteine (p = 0.021), essential amino acids (p = 0.049), and total amino acids (p = 0.035) displayed significantly greater (p ≤ 0.05) concentration maximum (CMax) values in PPCBC30 when compared to PPC. Finally, time to reach CMax (TMax) was similar between conditions with 80% of all measured amino acids and amino acid combinations achieving CMax at a similar time (~ 60 min). Only phenylalanine TMax was found to be different (p = 0.01) between the two conditions with PPC displaying a greater proportion of TMax values after 30 min. Following qualitative (non-inferential) assessment, 88% of all measured outcomes achieved a higher AUC with PPCBC30 and 100% of all outcomes achieved a higher CMax with PPCBC30. In concert with previous findings in a younger mixed gender cohort with milk protein, the addition of BC30 to a daily 20-g dose of plant protein concentrate in healthy older women improved AUC and CMax values in several individual amino acids and amino acid combinations. Retrospectively registered on April 6, 2022, at ClinicalTrials.gov as NCT05313178

The modification of bottom boundary layer turbulence and mixing by internal waves shoaling on a barrier reef

Author Posting. © American Meteorological Society, 2011. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 41 (2011): 2223–2241, doi:10.1175/2011JPO4344.1.Results are presented from an observational study of stratified, turbulent flow in the bottom boundary layer on the outer southeast Florida shelf. Measurements of momentum and heat fluxes were made using an array of acoustic Doppler velocimeters and fast-response temperature sensors in the bottom 3 m over a rough reef slope. Direct estimates of flux Richardson number Rf confirm previous laboratory, numerical, and observational work, which find mixing efficiency not to be a constant but rather to vary with Frt, Reb, and Rig. These results depart from previous observations in that the highest levels of mixing efficiency occur for Frt < 1, suggesting that efficient mixing can also happen in regions of buoyancy-controlled turbulence. Generally, the authors find that turbulence in the reef bottom boundary layer is highly variable in time and modified by near-bed flow, shear, and stratification driven by shoaling internal waves.Funding was provided by grants from the National Oceanic and Atmospheric Administration’s National Undersea Research Program, National Science Foundation Grants OCE-0622967 and OCE- 0824972 to SGM, and the Singapore Stanford Program. Kristen Davis was supported by a National Defense Science and Engineering Graduate Fellowship and an ARCS Foundation Fellowship