The effects of orbital precession on tropical precipitation: Mechanisms controlling precipitation changes over land and ocean

The tropical precipitation response to precessional forcing is investigated using idealized precession experiments from the Geophysical Fluid Dynamics Laboratory Coupled Model version 2.1 and mid-Holocene experiments from ten general circulation models participating in the Paleoclimate Modeling Intercomparison Project Phase III. Both sets of experiments show a seasonal land-ocean asymmetry in the tropical precipitation response: precipitation increases over land and decreases over ocean in the season with increased insolation and the opposite is true in the season with decreased insolation. This response is examined using a framework that describes how changes in net top-of-atmosphere radiation affect the atmosphere and surface energy balances. Over land, surface energy storage is small and changes in precipitation are balanced by changes in moist static energy flux divergence. Over ocean, surface energy storage is large, moist static energy flux divergence is small, and changes in precipitation are ultimately driven by changes in circulation and atmospheric stability

Extreme low-lying carotid bifurcations

A 52-year-old male with no past medical history was referred to the transient ischaemic attack (TIA) clinic following an event at home. The transient symptoms were of an inability to move his left arm and leg for a period of approximately 15 minutes. The patient denied any numbness of the face, headaches or blurring of vision. A careful history revealed two previous transient attacks of blurred vision approximately 1–2 years prior to this presentation. He had no other co-morbidities or associated syndromes. Given this history, suggestive of TIA(s) in the right anterior circulation, an ultrasound examination of the carotid vessels was performed to include or exclude an atherosclerotic source of embolus. The ultrasound scan demonstrated an extremely short common carotid artery (CCA) of just 2.5 cm on the right, with apparently normal flows and velocities in both the external and internal carotids (ECA and ICA) but poor views of the bifurcation. Similarly, the flows and velocities in the left ICA and ECA were also normal, with the carotid bulb lying low in the base of the neck, so further imaging with a magnetic resonance angiogram (MRA) was performed (Panel A) to clarify the anatomic and ultrasound findings. This confirmed extremely low-lying bilateral carotid bifurcations (highlighted in Panel A). The short, right-side CCA bifurcates at the level of C7/T1 (Panel B) and the left carotid bifurcation is at the level of C6/C7 (Panel C)

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint

Admixture Mapping of Quantitative Trait Loci for BMI in African Americans: Evidence for Loci on Chromosomes 3q, 5q, and 15q

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93743/1/oby_1443_sm_2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93743/2/oby_1443_sm_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93743/3/oby.2009.24.pd

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10-9). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin