Elevated hypertension risk for African-origin populations in biracial societies : Modeling the Epidemiologic Transition Study.

OBJECTIVES: Blood pressures in persons of African descent exceed those of other racial/ethnic groups in the United States. Whether this trait is attributable to the genetic factors in African-origin populations, or a result of inadequately measured environmental exposures, such as racial discrimination, is not known. To study this question, we conducted a multisite comparative study of communities in the African diaspora, drawn from metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. METHODS: At each site, 500 participants between the age of 25 and 49 years, with approximately equal sex balance, were enrolled for a longitudinal study of energy expenditure and weight gain. In this study, we describe the patterns of blood pressure and hypertension observed at baseline among the sites. RESULTS: Mean SBP and DBP were very similar in the United States and South Africa in both men and women, although among women, the prevalence of hypertension was higher in the United States (24 vs. 17%, respectively). After adjustment for multiple covariates, relative to participants in the United States, SBP was significantly higher among the South Africans by 9.7 mmHg (P < 0.05) and significantly lower for each of the other sites: for example, Jamaica: -7.9 mmHg (P = 0.06), Ghana: -12.8 mmHg (P < 0.01) and Seychelles: -11.1 mmHg (P = 0.01). CONCLUSION: These data are consistent with prior findings of a blood pressure gradient in societies of the African diaspora and confirm that African-origin populations with lower social status in multiracial societies, such as the United States and South Africa, experience more hypertension than anticipated based on anthropometric and measurable socioeconomic risk factors

Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans

Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin-O-acyl transferase-null (GOAT/) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis in vitro was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational acylation of ghrelin is important to neurogenesis and memory in mice. To determine relevance in humans, we analyzed circulating AG:UAG in Parkinson disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients, and controls. Notably, plasma AG:UAG was only reduced in PDD. Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT+ cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice

New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory, identifying factors that regulate AHN may be important for ameliorating age‐related cognitive decline. Calorie restriction (CR) has been shown to enhance AHN and improve memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, has also been shown to promote aspects of AHN. The 5:2 diet is a popular form of IF; however, its effects on AHN are not well characterised. To address this, we quantified AHN in adolescent and adult wild‐type and ghrelin‐receptor‐deficient mice following 6 weeks on a 5:2 diet. We report an age‐related decline in neurogenic processes. However, the 5:2 diet does not increase AHN nor enhance memory performance, suggesting that this specific form of IF is ineffective in promoting brain plasticity to support learning

Determination of |Vcb| using the semileptonic decay \bar{B}^0 --> D^{*+}e^-\bar{\nu}

We present a measurement of the Cabibbo-Kobayashi-Maskawa (CKM) matrix element |Vcb| using a 10.2 fb^{-1} data sample recorded at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e^+e^- storage ring. By extrapolating the differential decay width of the \bar{B}^0 --> D^{*+}e^-\bar{\nu} decay to the kinematic limit at which the D^{*+} is at rest with respect to the \bar{B}^0, we extract the product of |Vcb| with the normalization of the decay form factor F(1), |Vcb |F(1)= (3.54+/-0.19+/-0.18)x10^{-2}, where the first error is statistical and the second is systematic. A value of |Vcb| = (3.88+/-0.21+/-0.20+/-0.19)x10^{-2} is obtained using a theoretical calculation of F(1), where the third error is due to the theoretical uncertainty in the value of F(1). The branching fraction B(\bar{B}^0 --> D^{*+}e^-\bar{\nu}) is measured to be (4.59+/-0.23+/-0.40)x10^{-2}.Comment: 20 pages, 6 figures, elsart.cls, submitted to PL

Autism associated with tetrasomy 15: A further report

Association of autism with tetrasomy of chromosome 15 has recently been described in six males. In this report, we describe the occurrence of autism in a girl with tetrasomy of chromosome 15. The patient showed hyperactivity, hand-flapping, short-stature, eye abnormalities, and hypotonia, which have been reported in males with tetrasomy of chromosome 15. This suggests that autism may be associated in both sexes with a distinct syndrome characterized by tetrasomy of chromosome 15, mental retardation and characteristic physical features. L'association d'autisme avec une tétrasomie du chromosome 15 a été décrite récemment chez six garçons. Dans cet article, nous décrivons la survenue d'un autisme chez une fille avec une tétrasomie du chromosome 15. La patiente présentait une hyperactivité, un battement des mains, une petite taille, des anormalités des yeux et une hypotonie qui ont été rapportées chez des garçons avec tétrasomie du chromosome 15. Ceci suggère que l'autisme peut être associé dans les deux sexes avec un syndrome distinct caractérisé par une tétrasomie du chromosome 15, un retard mental et des traits physiques caractéristiques. Kürzlich wurde eine Assoziation einer Tetrasomie des Chromosoms 15 mit Autismus bei 6 männlichen Individuen beschrieben. In dem vorliegenden Fallbericht wird das Vorkommen eines Autismus bei einem Mädchen mit einer Tetrasomie des Chromosoms 15 dargestellt. Die Patientin zeigte Hyperaktivität, Handstereotypien, ophthalmologische Auffälligkeiten und Hypotonie. Diese Auffälligkeiten sind auch bei den männlichen Individuen mit einer Tetrasomie 15 beschrieben worden. Diese Befunde legen nahe, daß bei beiden Geschlechtern Autismus mit einem eigenständigen Syndrom im Falle des Vorliegens einer Tetrasomie 15 einhergeht, dessen wesentliche Merkmale geistige Behinderung und charakteristische Auffälligkeiten sind.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41756/1/787_2005_Article_BF02098582.pd

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants

Geological history of the Winchcombe meteorite - A new cm Chrondrite fall

Introduction: The Mighei-like (CM) carbonaceous chondrites are the largest class of hydrated meteorites, representing collisionally derived fragments of water-rich asteroids [1,2]. Most (>95%) are breccias, whose clasts sample a range of aqueous alteration extents [3]. They can therefore act as “snapshots” recording the progression of fluidrock interaction on the CM parent body. Conversely, analysis of the material between clasts (termed cataclastic matrix) provides an opportunity to study the post-hydration history of the CM parent body, specifically its fragmentation and re-accretion. Here, we investigate both aspects of the CM chondrites’ geological history through study of the newly recovered fall: Winchcombe [4, 5]. Methods: Sixteen polished sections with a total area of 190 mm2 were generated for this work. They were studied under scanning electron microscopy (SEM) using backscattered electron (BSE) imaging, energy dispersive X-ray spectroscopy (EDX) and electron microprobe analysis (EMPA). These sections sample the two largest masses (the main mass [320 g] and the agricultural field stone [152 g]) recovered from the Winchcombe strewn field [4]. Results: Winchcombe is a breccia, composed of lithological clasts held within a cataclastic matrix. We identified eight distinct lithologies. Their aqueous alteration extents vary between intensely altered CM2.0 and moderately altered CM2.6 [6]. Although no lithology dominates, three rock types represent >70% of the studied area. Several lithologies contain abundant tochilinite-cronstedtite intergrowths (TCIs). Type-II forms with zoned textures are most common, typically they have Fe-rich rims (“FeO”/SiO2 wt.%: 1-5) and Mg-rich cores (“FeO”/SiO2 wt.%: < 1), however, forms with hollow cores or cores containing a mix of phyllosilicate and calcite or phyllosilciates and anhydrous silicate are also found. The cataclastic matrix represents ~15% of the studied area. It has a coarse, heterogenous texture and includes abundant subangular fragments. Fragments include the full range of CM chondrite components (e.g. Fe-sulphides, whole chondrules with or without fine-grained rims, olivine and pyroxene grains, serpentine, carbonate grains, TCI clusters, as well as coherent blocks of fine-grained matrix). The cataclastic matrix is, therefore, a complex mix of components, with both heavily altered and mildly altered phases found in close association. Another striking feature is the apparent low abundance (< 3 area%) of identifiable whole chondrules. Discussion and conclusions: Our data suggest that both anhydrous silicates and carbonates (T1a calcites) act as precursor phases for type-II TCI formation. Cross-cutting relationships allow the sequence of mineralization to be reconstructed. Initially, inward dissolution by Fe-rich and S-rich fluids forms rims composed of intermixed tochilinite and cronstedtite. In the intermediate stages of type-II TCI formation, further dissolution continues without concurrent precipitation, resulting in the formation of hollow structures. These voids were later infilled, most often by Mg-rich phyllosilicates. As alteration advanced, early-formed secondary phases became unstable and were either dissolved (e.g. T1a calcites) or chemically altered (e.g. TCI rims). The presence of numerous lithological clasts with variable aqueous alteration extents and abrupt boundaries found in close juxtaposition indicates that the cataclastic matrix formed by the deposition of fines, alongside larger fragments (the clasts), on or near the surface of the parent asteroid. Furthermore, the composition of the cataclastic matrix is consistent with formation by fragmentation and mixing of debris derived from the entire clast population. The cataclastic matrix is, therefore, interpreted as an impact-derived fallback breccia. Analysis of grain size and texture suggests that disruption of the original parent asteroid responded by intergranular fracture at grain sizes <100 μm, while larger phases, such as whole chondrules, splintered apart. Re-accretion formed a poorly lithified rubble-pile body. During atmospheric entry, the meteoroid broke apart with new fractures preferentially cutting through the weaker cataclastic matrix and thereby separating the Winchcombe meteoroid into its component- lithological clasts. Thus, the strength of the cataclastic matrix imparts a significant control on the survival of CM chondrite meteoroids. References: [1] McSween, 1979. GCA, 43:1761-1770. [2] Suttle et al. 2021. GCA, 299:219-256. [3] Bischoff, et al. 2017, 80th MetSoc. (Abstr.#6089), [4] Meteoritical Bulletin Database, Winchcombe entry (available at: https://www.lpi.usra.edu/meteor/metbull.php?code=74388). [5] Daly et al., (this meeting). [6] Rubin et al. 2007,GCA, 71:2361-2382