| 1. |
- Aamodt, K., et al.
(author)
-
The ALICE experiment at the CERN LHC
- 2008
-
In: Journal of Instrumentation. - 1748-0221. ; 3:S08002
-
Research review (peer-reviewed)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
|
|
| 2. |
- Rana, Brinda K., et al.
(author)
-
Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24 : influence on heritable autonomic traits in twin pairs
- 2009
-
In: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 331:2, s. 419-428
-
Journal article (peer-reviewed)abstract
- Nicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine α and four β subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by α3, α5, and β4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion. Genes encoding these subunits (CHRNA3, CHRNA5, and CHRNB4) are clustered on human chromosome 15q24. Because variation in this cluster may alter autonomic regulation of BP, we sequenced ∼15 kilobase pairs in 15q24 containing their coding and 5′- and 3′-untranslated regions in 80 individuals. We identified 63 variants: 25 in coding regions of CHRNA3, CHRNA5, and CHRNB4 and 48 noncoding single-nucleotide polymorphisms (SNPs). Haplotype frequencies varied across ethnic populations. We assessed the contribution of six SNPs in the putative catestatin binding region of CHRNA3 and CHRNB4 to autonomic traits. In twins, catestatin and BP were heritable. CHRNA3 SNPs and haplotypes containing K95K (G285A) associated with circulating plasma catestatin, epinephrine levels, as well as systolic BP, suggesting altered coupling of the nAChRs to BP. Studies of chromaffin cells in vitro reveal that nicotinic agonist stimulation releases catecholamines and CHGA, a process augmented by overexpression of CHRNA3 and blocked by catestatin. These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins.
|
|
| 3. |
- Rao, Fangwen, et al.
(author)
-
Catecholamine release-inhibitory peptide catestatin (chromogranin A352-372) : Naturally occurring amino acid variant Gly364Ser causes profound changes in human autonomic activity and alters risk for hypertension
- 2007
-
In: Circulation. - 0009-7322 .- 1524-4539. ; 115:17, s. 2271-2281
-
Journal article (peer-reviewed)abstract
- BACKGROUND - Chromogranin A, coreleased with catecholamines by exocytosis, is cleaved to the catecholamine release-inhibitory fragment catestatin. We identified a natural nonsynonymous variant of catestatin, Gly364Ser, that alters human autonomic function and blood pressure. METHODS AND RESULTS - Gly364Ser heterozygotes and controls underwent physiological and biochemical phenotyping, including catecholamine production, chromogranin A precursor, and its catestatin product. Case-control studies replicated effects of the gene on blood pressure in the population. Gly364Ser displayed diminished inhibition of catecholamine secretion from cultured neurons. Gly/Ser heterozygotes displayed increased baroreceptor slope during upward deflections (by ≈47%) and downward deflections (by ≈44%), increased cardiac parasympathetic index (by ≈2.4-fold), and decreased cardiac sympathetic index (by ≈26%). Renal norepinephrine excretion was diminished by ≈26% and epinephrine excretion by ≈34% in Gly/Ser heterozygotes. The coalescent dated emergence of the variant to ≈70 000 years ago. Gly364Ser was in linkage disequilibrium with 1 major Chromogranin A promoter haplotype, although promoter haplotypes did not predict autonomic phenotypes. The 364Ser variant was associated with lower diastolic blood pressure in 2 independent/confirmatory groups of patients with hypertension; genotype groups differed by ≈5 to 6 mm Hg, and the polymorphism accounted for ≈1.8% of population diastolic blood pressure variance, although a significant gene-by-sex interaction existed, with an enhanced effect in men. CONCLUSIONS - The catestatin Gly364Ser variant causes profound changes in human autonomic activity, both parasympathetic and sympathetic, and seems to reduce risk of developing hypertension, especially in men. A model for catestatin action in the baroreceptor center of the nucleus of the tractus solitarius accounts for these actions.
|
|
| 4. |
- Ahsan, Amimul, et al.
(author)
-
Modeling the impacts of best management practices (BMPs) on pollution reduction in the Yarra River catchment, Australia
- 2023
-
In: Applied water science. - : Springer. - 2190-5487 .- 2190-5495. ; 13
-
Journal article (peer-reviewed)abstract
- Pollution of a watershed by different land uses and agricultural practices is becoming a major challenging factor that results in deterioration of water quality affecting human health and ecosystems. Sustainable use of available water resources warrants reduction of Non-Point Source (NPS) pollutants from receiving water bodies through best management practices (BMPs). A hydrologic model such as the Soil and Water Assessment Tool (SWAT) can be used for analyzing the impacts of various BMPs and implementing of different management plans for water quality improvement, which will help decision makers to determine the best combination of BMPs to maximize benefits. The objective of this study is to assess the potential reductions of sediments and nutrient loads by utilizing different BMPs on the Yarra River watershed using the SWAT model. The watershed is subdivided into 51 sub-watersheds where seven different BMPs were implemented. A SWAT model was developed and calibrated against a baseline period of 1998–2008. For calibration and validation of the model simulations for both the monthly and annual nutrients and sediments were assessed by using the Nash–Sutcliffe efficiency (NSE) statistical index. The values of the NSE were found more than 0.50 which indicates satisfactory model predictions. By utilizing different BMPs, the highest pollution reduction with minimal costs can be done by 32% targeted mixed-crop area. Furthermore, the combined effect of five BMPs imparts most sediments and nutrient reductions in the watershed. Overall, the selection of a BMP or combinations of BMPs should be set based on the goals set in a BMP application project.
|
|
| 5. |
- Chen, Yuqing, et al.
(author)
-
Naturally occurring human genetic variation in the 3'-untranslated region of the secretory protein chromogranin A is associated with autonomic blood pressure regulation and hypertension in a sex-dependent fashion
- 2008
-
In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 52:18, s. 1468-81
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: We aimed to determine whether the common variation at the chromogranin A (CHGA) locus increases susceptibility to hypertension. BACKGROUND: CHGA regulates catecholamine storage and release. Previously we systematically identified genetic variants across CHGA. METHODS: We carried out dense genotyping across the CHGA locus in >1,000 individuals with the most extreme blood pressures (BPs) in the population, as well as twin pairs with autonomic phenotypes. We also characterized the function of a trait-associated 3'-untranslated region (3'-UTR) variant with transfected CHGA 3'-UTR/luciferase reporter plasmids. RESULTS: CHGA was overexpressed in patients with hypertension, especially hypertensive men, and CHGA predicted catecholamines. In individuals with extreme BPs, CHGA genetic variants predicted BP, especially in men, with a peak association occurring in the 3'-UTR at C+87T, accounting for up to approximately 12/ approximately 9 mm Hg. The C+87T genotype predicted CHGA secretion in vivo, with the +87T allele (associated with lower BP) also diminishing plasma CHGA by approximately 10%. The C+87T 3'-UTR variant also predicted the BP response to environmental (cold) stress; the same allele (+87T) that diminished basal BP in the population also decreased the systolic BP response to stress by approximately 12 mm Hg, and the response was smaller in women (by approximately 6 mm Hg). In a chromaffin cell-transfected CHGA 3'-UTR/luciferase reporter plasmid, the +87T allele associated with lower BP also decreased reporter expression by approximately 30%. In cultured chromaffin cells, reducing endogenous CHGA expression by small interfering ribonucleic acid caused approximately two-thirds depletion of catecholamine storage vesicles. CONCLUSIONS: Common variant C+87T in the CHGA 3'-UTR is a functional polymorphism causally associated with hypertension especially in men of the population, and we propose steps ("intermediate phenotypes") whereby in a sex-dependent fashion this genetic variant influences the ultimate disease trait. These observations suggest new molecular strategies to probe the pathophysiology, risk, and rational treatment of hypertension.
|
|
| 6. |
- Das, Sushil K., et al.
(author)
-
Calibration, validation and uncertainty analysis of a SWAT water quality model
- 2024
-
In: Applied water science. - : Springer Nature. - 2190-5487 .- 2190-5495. ; 14:4
-
Journal article (peer-reviewed)abstract
- Sediment and nutrient pollution in water bodies is threatening human health and the ecosystem, due to rapid land use changes and improper agricultural practices. The impact of the nonpoint source pollution needs to be evaluated for the sustainable use of water resources. An ideal tool like the soil and water assessment tool (SWAT) can assess the impact of pollutant loads on the drainage area, which could be beneficial for developing a water quality management model. This study aims to evaluate the SWAT model’s multi-objective and multivariable calibration, validation, and uncertainty analysis at three different sites of the Yarra River drainage area in Victoria, Australia. The drainage area is split into 51 subdrainage areas in the SWAT model. The model is calibrated and validated for streamflow from 1990 to 2008 and sediment and nutrients from 1998 to 2008. The results show that most of the monthly and annual calibration and validation for streamflow, nutrients, and sediment at the three selected sites are found with Nash–Sutcliffe efficiency values greater than 0.50. Furthermore, the uncertainty analysis of the model shows satisfactory results where the p-factor value is reliable by considering 95% prediction uncertainty and the d-factor value is close to zero. The model's results indicate that the model performs well in the river's watershed, which helps construct a water quality management model. Finally, the model application in the cost-effective management of water quality might reduce pollution in water bodies due to land use and agricultural activities, which would be beneficial to water management managers.
|
|
| 7. |
- Muntjewerff, Elke M., et al.
(author)
-
Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides
- 2021
-
In: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 232:2
-
Journal article (peer-reviewed)abstract
- Aim A "leaky" gut barrier has been implicated in the initiation and progression of a multitude of diseases, for example, inflammatory bowel disease (IBD), irritable bowel syndrome and celiac disease. Here we show how pro-hormone Chromogranin A (CgA), produced by the enteroendocrine cells, and Catestatin (CST: hCgA(352-372)), the most abundant CgA-derived proteolytic peptide, affect the gut barrier. Methods Colon tissues from region-specific CST-knockout (CST-KO) mice, CgA-knockout (CgA-KO) and WT mice were analysed by immunohistochemistry, western blot, ultrastructural and flowcytometry studies. FITC-dextran assays were used to measure intestinal barrier function. Mice were supplemented with CST or CgA fragment pancreastatin (PST: CgA(250-301)). The microbial composition of cecum was determined. CgA and CST levels were measured in blood of IBD patients. Results Plasma levels of CST were elevated in IBD patients. CST-KO mice displayed (a) elongated tight, adherens junctions and desmosomes similar to IBD patients, (b) elevated expression of Claudin 2, and (c) gut inflammation. Plasma FITC-dextran measurements showed increased intestinal paracellular permeability in the CST-KO mice. This correlated with a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in various diseases. Supplementation of CST-KO mice with recombinant CST restored paracellular permeability and reversed inflammation, whereas CgA-KO mice supplementation with CST and/or PST in CgA-KO mice showed that intestinal paracellular permeability is regulated by the antagonistic roles of these two peptides: CST reduces and PST increases permeability. Conclusion The pro-hormone CgA regulates the intestinal paracellular permeability. CST is both necessary and sufficient to reduce permeability and primarily acts by antagonizing PST.
|
|
| 8. |
- O'Connor, Daniel T., et al.
(author)
-
Heritability and genome-wide linkage in US and australian twins identify novel genomic regions controlling chromogranin a : implications for secretion and blood pressure
- 2008
-
In: Circulation. - 0009-7322 .- 1524-4539. ; 118:3, s. 247-57
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Chromogranin A (CHGA) triggers catecholamine secretory granule biogenesis, and its catestatin fragment inhibits catecholamine release. We approached catestatin heritability using twin pairs, coupled with genome-wide linkage, in a series of twin and sibling pairs from 2 continents. METHODS AND RESULTS: Hypertensive patients had elevated CHGA coupled with reduction in catestatin, suggesting diminished conversion of precursor to catestatin. Heritability for catestatin in twins was 44% to 60%. Six hundred fifteen nuclear families yielded 870 sib pairs for linkage, with significant logarithm of odds peaks on chromosomes 4p, 4q, and 17q. Because acidification of catecholamine secretory vesicles determines CHGA trafficking and processing to catestatin, we genotyped at positional candidate ATP6N1, bracketed by peak linkage markers on chromosome 17q, encoding a subunit of vesicular H(+)-translocating ATPase. The minor allele diminished CHGA secretion and processing to catestatin. The ATP6N1 variant also influenced blood pressure in 1178 individuals with the most extreme blood pressure values in the population. In chromaffin cells, inhibition of H(+)-ATPase diverted CHGA from regulated to constitutive secretory pathways. CONCLUSIONS: We established heritability of catestatin in twins from 2 continents. Linkage identified 3 regions contributing to catestatin, likely novel determinants of sympathochromaffin exocytosis. At 1 such positional candidate (ATP6N1), variation influenced CHGA secretion and processing to catestatin, confirming the mechanism of a novel trans-QTL for sympathochromaffin activity and blood pressure.
|
|
| 9. |
- Shankar, P. Gowri, et al.
(author)
-
King or royal family? : Testing for species boundaries in the King Cobra, Ophiophagus hannah (Cantor, 1836), using morphology and multilocus DNA analyses
- 2021
-
In: Molecular Phylogenetics and Evolution. - : Elsevier. - 1055-7903 .- 1095-9513. ; 165
-
Journal article (peer-reviewed)abstract
- In widespread species, the diverse ecological conditions in which the populations occur, and the presence of many potential geographical barriers through their range are expected to have created ample opportunities for the evolution of distinct, often cryptic lineages. In this work, we tested for species boundaries in one such widespread species, the king cobra, Ophiophagus hannah (Cantor, 1836), a largely tropical elapid snake distributed across the Oriental realm. Based on extensive geographical sampling across most of the range of the species, we initially tested for candidate species (CS) using Maximum-Likelihood analysis of mitochondrial genes. We then tested the resulting CS using both morphological data and sequences of three single-copy nuclear genes. We used snapclust to determine the optimal number of clusters in the nuclear dataset, and Bayesian Phylogenetics and Phylogeography (BPP) to test for likely species status. We used non-metric multidimensional scaling (nMDS) analysis for discerning morphological separation. We recovered four independently evolving, geographically separated lineages that we consider Confirmed Candidate Species: (1) Western Ghats lineage; (2) Indo-Chinese lineage (3) Indo-Malayan lineage; (4) Luzon Island lineage, in the Philippine Archipelago. We discuss patterns of lineage divergence, particularly in the context of low morphological divergence, and the conservation implications of recognizing several endemic king cobra lineages.
|
|
| 10. |
- Wen, Gen, et al.
(author)
-
An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension
- 2007
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 16:14, s. 1752-1764
-
Journal article (peer-reviewed)abstract
- Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.
|
|
