Some consequences for social behavior of perinatal asphyxia and c-section delivery of full term male rats

The process of birth (parturition) has a critical impact on normal human development. Any deviations from the typical parturition process are defined clinically as birth complications, and have been linked to the development of neurological deficits. Two relatively common types of consequences from birth complications are perinatal asphyxia and Caesarean Section delivery (C-section); however, C-section is becoming more common as a matter of choice (elective C-section delivery) rather than as a consequence of some birth complication (Barber et al., 2011; Martin et al., 2012). The two consequences of birth complications differ: perinatal asphyxia involves extended periods of oxygen deprivation during delivery, whereas elective C-section deprives the fetus of the typical conditions associated with a vaginal delivery. Animal research reveals that both perinatal asphyxia and C-section lead to increased expression of dopamine in the mesolimbic dopaminergic pathway. Since this dopaminergic pathway is important for learning, attention, working memory, motivation, movement and mood there is evidence that such increases in dopamine expression result in deficits in these functions. Because the mesolimbic dopaminergic system innervates the hypothalamus, previous research suggested that the complication of perinatal asphyxia results in an increased sensitivity to stress via alterations in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Such alterations may be apparent in the development of sensitivity to stressful situations. One test of sensitivity to stressful situations for rodents is to present a resident adult male with an adult male intruder. This social situation can be marked by investigatory and aggressive behaviors on the part of the resident male. The hypothesis for this thesis is that perinatal asphyxia and C-section delivery of male rats will result in differences in adult investigatory and aggressive social behaviors in this stress test. This study compares the social behavior of 55 day old, postpubertal male rats exposed to asphyxia and C-section at birth, with that of vaginally delivered rats. The social behaviors also were examined in relation to neuroanatomical and neurochemical alterations in dopamine transmission, specifically in the nucleus accumbens

Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling

Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcription, replication and repair. Post-translational modifications (PTMs) of the histone proteins within nucleosomes regulate these DNA processes. Histone H3(T118) is a site of phosphorylation [H3(T118ph)] and is implicated in regulation of transcription and DNA repair. We prepared H3(T118ph) by expressed protein ligation and determined its influence on nucleosome dynamics. We find H3(T118ph) reduces DNA–histone binding by 2 kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) increases the rate of hMSH2–hMSH6 nucleosome disassembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions

Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Background: Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.Results: Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.Conclusions: Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA

Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes

Lens epithelium-derived growth factor (LEDGF/p75) tethers lentiviral preintegration complexes (PICs) to chromatin and is essential for effective HIV-1 replication. LEDGF/p75 interactions with lentiviral integrases are well characterized, but the structural basis for how LEDGF/p75 engages chromatin is unknown. We demonstrate that cellular LEDGF/p75 is tightly bound to mononucleosomes (MNs). Our proteomic experiments indicate that this interaction is direct and not mediated by other cellular factors. We determined the solution structure of LEDGF PWWP and monitored binding to the histone H3 tail containing trimethylated Lys36 (H3K36me3) and DNA by NMR. Results reveal two distinct functional interfaces of LEDGF PWWP: a well-defined hydrophobic cavity, which selectively interacts with the H3K36me3 peptide and adjacent basic surface, which non-specifically binds DNA. LEDGF PWWP exhibits nanomolar binding affinity to purified native MNs, but displays markedly lower affinities for the isolated H3K36me3 peptide and DNA. Furthermore, we show that LEDGF PWWP preferentially and tightly binds to in vitro reconstituted MNs containing a tri-methyl-lysine analogue at position 36 of H3 and not to their unmodified counterparts. We conclude that cooperative binding of the hydrophobic cavity and basic surface to the cognate histone peptide and DNA wrapped in MNs is essential for high-affinity binding to chromatin

Evolution of predator dispersal in relation to spatio-temporal prey dynamics : how not to get stuck in the wrong place!

Peer reviewedPublisher PD

Vulnerable Road User Mobility Assistance Platform (VRU-MAP)

69A3551747125This report documents the development of a prototype Vulnerable Road User Mobility Assistance Platform (VRU-MAP), a novel effort to conceptualize and develop a navigation solution directed toward the needs of people with disabilities (PWD). PWD represent about 15% of the world\u2019s population and disproportionately face barriers to transportation, which represents a critical component to daily life, relative to people without disabilities. One barrier to transportation is the lack of dedicated walking navigation solutions. While smartphones and other GPS implementations have made walking directions from location to location nearly universally obtainable, these tools generally do not provide routing that takes into account an individual user\u2019s capabilities and needs. This VRU-MAP application, which is currently implemented in a functional prototype, uses novel coding based on combining existing open-source maps (OpenStreetMap), publicly available environmental information (e.g., weather, elevation, etc.) and crowd-sourced hazard information with a user\u2019s self-reported personal capabilities and needs. This combination of persistent and real-time information allows for the generation of personalized navigation directions, which are then presented in a turn-by-turn manner to users. Real-world testing demonstrated substantial promise in the functional prototype, while at the same time illustrating areas for future improvement and refinement including expanding capabilities, improving interface design, and improving routing component integration. Next steps include identifying additional partners to develop the prototype into a deployable application, including partnering with disability experts to ensure that final design and implementation are both useful and acceptable to the broadest possible range of users, including integrating with and being accessible by current assistive technologies such as screen readers

Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1