Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Algèbres de groupe du groupe additif

TesisEl propósito de la presente investigación fue determinar la eficacia de la aplicación del plan de educación emocional en el incremento de habilidades sociales de los adolescentes de los Planteles de Aplicación "Guamán Poma de Ayala". El tipo de investigación es explicativo. El diseño de investigación es cuasi - experimental. La muestra fue de 60 adolescentes de 15 años matriculados en el cuarto año de educación secundaria de los Planteles de Aplicación "Guamán Poma de Ayala", distribuidos del siguiente modo: grupo control (30 alumnos del 4° años A) y experimental (30 alumnos del 4° año 8). La técnica de recolección de datos fue la encuesta, entrevista semi - estructurada y observación estructurada; el instrumento, fue la Lista de Evaluación de Habilidades Sociales. En el análisis estadístico de los datos se empleó la prueba de Wilcoxon y la U de Mann - Whithey

Metabolic phenotyping for understanding the gut microbiome and host metabolic interplay

There is growing interest in the role of the gut microbiome in human health and disease. This unique complex ecosystem has been implicated in a number of health conditions including intestinal disorders, inflammatory skin diseases and metabolic syndrome. However, there is still much to learn regarding its capacity to affect host health. Many gut microbiome research studies focus on compositional analysis to better understand the causal relationships between microbial communities and disease phenotypes. Yet microbial diversity and complexity is such, that community structure alone does not provide full understanding of microbial function. Metabolic phenotyping is an exciting field in systems biology that provides information on metabolic outputs taking place in the system at a given moment in time. These readouts provide information relating to by-products of endogenous metabolic pathways, exogenous signals arising from diet, drugs and other lifestyle and environmental stimuli, as well as products of microbe-host co-metabolism. Thus, better understanding of the gut microbiome and host metabolic interplay can be gleaned by using such analytical approaches. In this Review, we describe research findings focussed on gut microbiota-host interactions, for functional insight into the impact of microbiome composition on host health. We evaluate different analytical approaches for capturing metabolic activity, and discuss analytical methodological advancements that have made a contribution to the field. This information will aid in developing novel approaches to improve host health in the future, and therapeutic modulation of the microbiome may soon augment conventional clinical strategies

BLAST, Vol. 2

https://digitalcommons.whitworth.edu/blast/1001/thumbnail.jp

Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation

Social isolation presents a risk factor and worsens outcome to cerebrovascular diseases; however, the underlying mechanisms remain underspecified. This study examines the effect of social environment on microglial reactivity after global cerebral ischemia, to test the hypothesis that social isolation leads to greater microglial responses. Adult female and male mice were pair-housed or socially isolated for one week prior to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure, and following either 2 or 24 hours of reperfusion, microglia samples were enriched and analyzed for gene expression. At the 2-hour time point, microglia from both females and males exhibited ischemia-induced inflammation, characterized by the gene expression increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), regardless of the housing conditions. However, at 24 hours post-ischemia, social housing attenuated microglial pro-inflammatory gene expression in a sex-specific manner. At this time point, the ischemia-induced increased expression of IL-1β and IL-6 was attenuated by social interaction in microglia from male mice, while among female mice social attenuation of the inflammatory response was observed in the microglial expression of cell surface protein major histocompatibility complex II (MHC II). A second study examined behavioral and physiological measures 96 hours after ischemic injury. At this time point, female and male mice displayed increased locomotion and exploratory behavior following CA/CPR relative to controls. Regardless of sex, ischemia also elicited neuroinflammation and neurodegeneration, both of which were modulated by the social environment. Hippocampal nitric oxide (iNOS), cortical TNF-α, and counts of Fluoro-Jade C positive stained cells in the CA1 region of the hippocampus, were increased in the isolated CA/CPR group relative to sham controls and the pair-housed CA/CPR groups. Together, these data indicate that female and male mice exhibit similar outcome measures and social modulation at 96 hours post-ischemic injury, nonetheless, that social environment influences microglial reactivity to global cerebral ischemia in a sex-specific manner

Commentary: Anxiety- and Depression-like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

A commentary on: Anxiety- and Depression-like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice by Siopi, E., Denizet, M., Gabellec, M. M., de Chaumont, F., Olivo-Marin, J. C., Guilloux, J. P., et al. (2016). J. Neurosci. 36, 518–531. doi: 10.1523/JNEUROSCI.2817-15.201

Mount Gilead Campground

Prepared by the Fall 1990 Conservation of Historic Building Materials class. This Historic Structure Report contains Historical considerations and information about the Mt. Gilead Campground, physical description of the Arbor, Historical Overview of the site, Prospective Use Rationale and Recommendations for rehabilitation of existing structures, as well as, future property development. The purpose of this report is two-fold - provide a rehabilitation plan for existing structures and a future development plan to expand the use areas of the site.https://scholarworks.gsu.edu/history_heritagepreservation/1018/thumbnail.jp