A young patient with concurrent splanchnic dynamic vascular compression syndromes

A thirty-year-old lady presented with chronic, postprandial abdominal pain associated with decreased appetite and weight loss. She had a past medical history of ulcerative colitis and past surgical history of Nissen fundoplication, hysterectomy and bilateral oophorectomy for endometriosis. Enhanced computed tomography (CT) of the abdomen/pelvis displayed severe narrowing of the celiac artery (CA) at the level of its ostium (Panel A) with post-stenotic dilatation. In an abdominal vascular ultrasound with respiratory maneuvers we saw a peak systolic velocity (PSV) in the CA during inspiration of 295 cm/s. The PSV was 108 cm/s during expiration for the CA. Peak systolic velocity in the superior mesenteric artery (SMA) was 424 cm/s during inspiration. Magnetic resonance angiogram (MRA, Panel B) showed compression of the SMA with post-stenotic dilatation. No signs of perivascular inflammation or fat stranding were appreciated. Serology studies workup showed only weakly positive anti nuclear antibody (ANA) titer. A mesenteric angiography (Panels C and D) illustrated progression to occlusion of the CA, a dynamic compression of the SMA with kinking mainly during expiration, and post-stenotic dilatation. The pre-operative suspicion for dynamic mesenteric vascular compression syndromes was intra-operatively confirmed with associated scarring along the CA and SMA via the arcuate ligament.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Photoinjector design for the LCLS

The design of the Linac Coherent Light Source assumes that a low-emittance, 1-nC, 10-ps beam will be available for injection into the 15-GeV linac. The proposed rf photocathode injector that will provide a 150-MeV beam with rms normalized emittances of 1 mm in both the transverse and longitudinal dimensions is based on a 1.6-cell S-band rf gun that is equipped with an emittance compensating solenoid. The booster accelerator is positioned at the beam waist coinciding with the first emittance maximum and is provided with an accelerating gradient of ~25 MeV/m, i.e., the "new working point." The uv pulses required for cathode excitation will be generated by tripling the output of a Ti:sapphire laser system consisting of a highly stable cw mode-locked oscillator and two bow-tie amplifiers pumped by a pair of Q-switched Nd:YAG lasers. The large bandwidth of the Ti:sapphire system accommodates the desired temporal pulse shaping. Details of the design and the supporting simulations are presented.Comment: 13 pages (double spaced), 4 figures, contributed to The 23rd International Free Electron Laser Conference, Darmstadt, Germany, 20-24 August 200

Coordinated Expression Domains in Mammalian Genomes

Gene order in eukaryotic genomes is not random. Genes showing similar expression (coexpression) patterns are often clustered along the genome. The goal of this study is to characterize coexpression clustering in mammalian genomes and to investigate the underlying mechanisms.We detect clustering of coexpressed genes across multiple scales, from neighboring genes to chromosomal domains that span tens of megabases and, in some cases, entire chromosomes. Coexpression domains may be positively or negatively correlated with other domains, within and between chromosomes. We find that long-range expression domains are associated with gene density, which in turn is related to physical organization of the chromosomes within the nucleus. We show that gene expression changes between healthy and diseased tissue samples occur in a gene density-dependent manner.We demonstrate that coexpression domains exist across multiple scales. We identify potential mechanisms for short-range as well as long-range coexpression domains. We provide evidence that the three-dimensional architecture of the chromosomes may underlie long-range coexpression domains. Chromosome territory reorganization may play a role in common human diseases such as Alzheimer's disease and psoriasis

Association between Age and the 7 Repeat Allele of the Dopamine D4 Receptor Gene

Longevity is in part (25%) inherited, and genetic studies aim to uncover allelic variants that play an important role in prolonging life span. Results to date confirm only a few gene variants associated with longevity, while others show inconsistent results. However, GWAS studies concentrate on single nucleotide polymorphisms, and there are only a handful of studies investigating variable number of tandem repeat variations related to longevity. Recently, Grady and colleagues (2013) reported a remarkable (66%) accumulation of those carrying the 7 repeat allele of the dopamine D4 receptor gene in a large population of 90-109 years old Californian centenarians, as compared to an ancestry-matched young population. In the present study we demonstrate the same association using continuous age groups in an 18-97 years old Caucasian sample (N = 1801, p = 0.007). We found a continuous pattern of increase from 18-75, however frequency of allele 7 carriers decreased in our oldest age groups. Possible role of gene-environment interaction effects driven by historical events are discussed. In accordance with previous findings, we observed association preferentially in females (p = 0.003). Our results underlie the importance of investigating non-disease related genetic variants as inherited components of longevity, and confirm, that the 7-repeat allele of the dopamine D4 receptor gene is a longevity enabling genetic factor, accumulating in the elderly female population

Transcription and Chromatin Organization of a Housekeeping Gene Cluster Containing an Integrated β-Globin Locus Control Region

The activity of locus control regions (LCR) has been correlated with chromatin decondensation, spreading of active chromatin marks, locus repositioning away from its chromosome territory (CT), increased association with transcription factories, and long-range interactions via chromatin looping. To investigate the relative importance of these events in the regulation of gene expression, we targeted the human β-globin LCR in two opposite orientations to a gene-dense region in the mouse genome containing mostly housekeeping genes. We found that each oppositely oriented LCR influenced gene expression on both sides of the integration site and over a maximum distance of 150 kilobases. A subset of genes was transcriptionally enhanced, some of which in an LCR orientation-dependent manner. The locus resides mostly at the edge of its CT and integration of the LCR in either orientation caused a more frequent positioning of the locus away from its CT. Locus association with transcription factories increased moderately, both for loci at the edge and outside of the CT. These results show that nuclear repositioning is not sufficient to increase transcription of any given gene in this region. We identified long-range interactions between the LCR and two upregulated genes and propose that LCR-gene contacts via chromatin looping determine which genes are transcriptionally enhanced

Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD