Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms.

Cardiac dysfunction is a prominent cause of mortality in myotonic dystrophy I (DM1), a disease where expanded CUG repeats bind and disable the muscleblind-like family of splice regulators. Deletion of muscleblind-like 1 (Mbnl1(ΔE2/ΔE2)) in 129 sv mice results in QRS, QTc widening, bundle block and STc narrowing at 2-4 months of age. With time, cardiac function deteriorates further and at 6 months, decreased R wave amplitudes, sinus node dysfunction, cardiac hypertrophy, interstitial fibrosis, multi-focal myocardial fiber death and calcification manifest. Sudden death, where no end point illness is overt, is observed at a median age of 6.5 and 4.8 months in ~67% and ~86% of male and female Mbnl1(ΔE2/ΔE2) mice, respectively. Mbnl1 depletion results in the persistence of embryonic splice isoforms in a network of cardiac RNAs, some of which have been previously implicated in DM1, regulating sodium and calcium currents, Scn5a, Junctin, Junctate, Atp2a1, Atp11a, Cacna1s, Ryr2, intra and inter cellular transport, Clta, Stx2, Tjp1, cell survival, Capn3, Sirt2, Csda, sarcomere and cytoskeleton organization and function, Trim55, Mapt, Pdlim3, Pdlim5, Sorbs1, Sorbs2, Fhod1, Spag9 and structural components of the sarcomere, Myom1, Tnnt2, Zasp. Thus this study supports a key role for Mbnl1 loss in the initiation of DM1 cardiac disease

Racial differences in neurocognitive outcomes post-stroke: The impact of healthcare variables

AbstractObjectives:The present study examined differences in neurocognitive outcomes among non-Hispanic Black and White stroke survivors using the NIH Toolbox-Cognition Battery (NIHTB-CB), and investigated the roles of healthcare variables in explaining racial differences in neurocognitive outcomes post-stroke.Methods:One-hundred seventy adults (91 Black; 79 White), who participated in a multisite study were included (age:M=56.4;SD=12.6; education:M=13.7;SD=2.5; 50% male; years post-stroke: 1–18; stroke type: 72% ischemic, 28% hemorrhagic). Neurocognitive function was assessed with the NIHTB-CB, using demographically corrected norms. Participants completed measures of socio-demographic characteristics, health literacy, and healthcare use and access. Stroke severity was assessed with the Modified Rankin Scale.Results:An independent samplesttest indicated Blacks showed more neurocognitive impairment (NIHTB-CB Fluid Composite T-score:M=37.63;SD=11.67) than Whites (Fluid T-score:M=42.59,SD=11.54;p=.006). This difference remained significant after adjusting for reading level (NIHTB-CB Oral Reading), and when stratified by stroke severity. Blacks also scored lower on health literacy, reported differences in insurance type, and reported decreased confidence in the doctors treating them. Multivariable models adjusting for reading level and injury severity showed that health literacy and insurance type were statistically significant predictors of the Fluid cognitive composite (p&lt;.001 andp=.02, respectively) and significantly mediated racial differences on neurocognitive impairment.Conclusions:We replicated prior work showing that Blacks are at increased risk for poorer neurocognitive outcomes post-stroke than Whites. Health literacy and insurance type might be important modifiable factors influencing these differences. (JINS, 2017,23, 640–652)</jats:p

Brucella abortus Infection of Placental Trophoblasts Triggers Endoplasmic Reticulum Stress-Mediated Cell Death and Fetal Loss via Type IV Secretion System-Dependent Activation of CHOP.

Subversion of endoplasmic reticulum (ER) function is a feature shared by multiple intracellular bacteria and viruses, and in many cases this disruption of cellular function activates pathways of the unfolded protein response (UPR). In the case of infection with Brucella abortus, the etiologic agent of brucellosis, the unfolded protein response in the infected placenta contributes to placentitis and abortion, leading to pathogen transmission. Here we show that B. abortus infection of pregnant mice led to death of infected placental trophoblasts in a manner that depended on the VirB type IV secretion system (T4SS) and its effector VceC. The trophoblast death program required the ER stress-induced transcription factor CHOP. While NOD1/NOD2 expression in macrophages contributed to ER stress-induced inflammation, these receptors did not play a role in trophoblast death. Both placentitis and abortion were independent of apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain (ASC). These studies show that B. abortus uses its T4SS to induce cell-type-specific responses to ER stress in trophoblasts that trigger placental inflammation and abortion. Our results suggest further that in B. abortus the T4SS and its effectors are under selection as bacterial transmission factors.IMPORTANCE Brucella abortus infects the placenta of pregnant cows, where it replicates to high levels and triggers abortion of the calf. The aborted material is highly infectious and transmits infection to both cows and humans, but very little is known about how B. abortus causes abortion. By studying this infection in pregnant mice, we discovered that B. abortus kills trophoblasts, which are important cells for maintaining pregnancy. This killing required an injected bacterial protein (VceC) that triggered an endoplasmic reticulum (ER) stress response in the trophoblast. By inhibiting ER stress or infecting mice that lack CHOP, a protein induced by ER stress, we could prevent death of trophoblasts, reduce inflammation, and increase the viability of the pups. Our results suggest that B. abortus injects VceC into placental trophoblasts to promote its transmission by abortion

Imprints in silica grains induced during an open-channel flow experiment:Determination of microtextural signatures during aqueous transport

The aim of this work is to identify and characterize microtextural signatures in silica glass grains (used as analogous to quartz) that are produced during aqueous transport at different flow velocities, with variable sediment concentrations, transport distances, and time intervals. To achieve this, an open-channel flow experiment was conducted with a mixture of sand and silica glass microspheres in varying conditions-velocity (from 0.67 to 1.4 m/s), duration (1 or 10 minutes), distance (0 to 2.5 m) and sediment concentration (60 or 80%). Experimental conditions were used to replicate natural phenomena such as river superficial velocity or coastal swash processes. Before the experiment the microsphere surfaces were imaged and clear of any microtextural imprint. Increasing velocity, distance, and sediment concentration exhibited a strong correlation with higher numbers of surfaces abundantly covered with microtextures of mechanical origin (i.e., craters, abrasion marks, and v-shaped percussion marks). SEM microphotographs of silica were analyzed and classified to provide examples of the specific microtextures produced during the open-channel flow experiment. The purpose of the experiment was to characterize surface microscopic signatures in quartz grains replicating hydrodynamic conditions of coastal and fluvial environments. The results demonstrated a strong correlation between higher velocities (and higher sediment concentrations) and a larger presence of microtextural mechanical imprints in the grains analyzed, thus demonstrating a clear relation between microtextural imprints and water flow modes. These results have important implications for future microtextural works analyzing grain imprints and their relation to sediment transport types. An example demonstrated here is that the higher presence of v-marks could be used as an indicator of supercritical flow conditions.OAIID:RECH_ACHV_DSTSH_NO:T201739753RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080988CITE_RATE:2.358FILENAME:2017_PCosta_et_al_JSR_proofs.pdfDEPT_NM:건설환경공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/112e346c-4bbf-4c27-93db-2904a43392d2/linkY

The impact of the 18F(a,p)21Ne reaction on asymptotic giant branch nucleosynthesis

We present detailed models of low and intermediate-mass asymptotic giant branch (AGB) stars with and without the 18F(a,p)21Ne reaction included in the nuclear network, where the rate for this reaction has been recently experimentally evaluated for the first time. The lower and recommended measured rates for this reaction produce negligible changes to the stellar yields, whereas the upper limit of the rate affects the production of 19F and 21Ne. The stellar yields increase by ~50% to up to a factor of 4.5 for 19F, and by factors of ~2 to 9.6 for 21Ne. While the 18}F(a,p)21Ne reaction competes with 18O production, the extra protons released are captured by 18O to facilitate the 18O(p,a)15N(a,g)19F chain. The higher abundances of 19F obtained using the upper limit of the rate helps to match the [F/O] ratios observed in AGB stars, but only for large C/O ratios. Extra-mixing processes are proposed to help to solve this problem. Some evidence that the 18F(a,p)21Ne rate might be closer to its upper limit is provided by the fact that the higher calculated 21Ne/22Ne ratios in the He intershell provide an explanation for the Ne isotopic composition of silicon-carbide grains from AGB stars. This needs to be confirmed by future experiments of the 18F(a,p)21Ne reaction rate. The availability of accurate fluorine yields from AGB stars will be fundamental for interpreting observations of this element in carbon-enhanced metal-poor stars.Comment: 9 pages, accepted for publication in Ap

Composição química e atividade inibidora de acetilcolinesterase de óleos voláteis de Myrceugenia myrcioides(Cambess.) O. Berg and Eugenia riedeliana O. Berg, Myrtaceae

The chemical composition of volatile oils from two Myrtaceae species, Myrceugenia myrcioidesand Eugenia riedeliana, both native from the Brazilian Atlantic Rain Forest, was analyzed by GC-MS. Acetylcholinesterase inhibitory activity was colorimetrically evaluated for these oils. For M. myrcioides, monoterpene hydrocarbons represented the major class in the volatile oil, with &#945;-pinene as the most abundant component and a weak inhibitory activity was observed, whilst for E. riedeliana sesquiterpenes were found in higher amounts, being valerianol the major compound, and this oil presented a strong acetylcholinesterase inhibition.A composição química dos óleos voláteis de duas espécies de Myrtaceae, Myrceugenia myrcioidese Eugenia riedeliana, ambas nativas da Mata Atlântica, foi analisada por CG-EM. A atividade inibidora de acetilcolinesterase foi determinada colorimetricamente para estes óleos. Em M. myrcioides, hidrocarbonetos monoterpênicos representaram a classe majoritária de compostos presentes no óleo volátil, sendo &#945;-pineno o componente mais abundante e a atividade inibidora de acetilcolinesterase foi baixa, enquanto para E. riedelianaos sesquiterpenos foram observados em maiores concentrações, sendo o valerianol o componente majoritário, e este óleo apresentou uma forte atividade inibidora da enzima.BIOTA/FAPESPCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Anticholinesterase activity evaluation of alkaloids and coumarin from stems of Conchocarpus fontanesianus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conchocarpus fontanesianus (A. St.-Hill.) Kallunki & Pirani, Rutaceae, popularly known as pitaguara, is a native and endemic tree from Sao Paulo and Rio de Janeiro States, Brazil. Based in the information that anticholinesterasic derivatives could act as new prototypes to treatment of Alzheimer disease, this work describes the fractionation guided by evaluation of the anticholinesterase activity of the ethanolic stems extract from C. fontanesianus. This procedure afforded the alkaloids dictamnine (1), gamma-fagarine (2), skimianine (3), and 2-phenyl-1-methyl-4-quinolone (4), as well as the coumarin marmesin (5).222374380Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

The Prevalence of Latent Mycobacterium Tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey Among Urban Adults in Mwanza, Tanzania.

One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10(B) 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test. LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies

Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.

Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture