Processes on the precipice : seafloor dynamics across the upper Malta-Sicily escarpment

The Malta-Sicily Escarpment (MSE) is a steep, sediment-undersupplied, carbonate escarpment incised by a series of submarine canyons. In this study we present data acquired from the upper MSE during the Eurofleets-funded CUMECS cruise to document a complex seafloor morphology comprising gullies, canyon heads, mass movement scars, channels, contourites and escarpments. The evolution of the upper MSE has been driven by the interaction of fault activity, sedimentary activity related to hemipelagic, pelagic and contouritic sedimentation, and seafloor incision by bottom current activity. Submarine mass movements play a key role in canyon development – they control the extent of lateral and headward extension, facilitate tributary development, remove material from the continental shelf and slope, and feed sediment into the canyons.peer-reviewe

Outer shelf seafloor geomorphology along a carbonate escarpment: The eastern Malta Plateau, Mediterranean Sea

Submarine carbonate escarpments, documented in numerous sites around the world, consist of thick exposures of Mesozoic shallow water carbonate sequences – primarily limestones and dolomites – with reliefs of >1 km and slope gradients of >70°. Whilst most research efforts have focused on the processes that shaped carbonate escarpments into complex and extreme terrains, little attention has been paid to the geomorphology of shelves upslope of carbonate escarpments. In this study we investigate high resolution geophysical, sedimentological and visual data acquired from the eastern Malta Plateau, central Mediterranean Sea, to demonstrate that the outer shelf of a carbonate escarpment is directly influenced by escarpment-forming processes. We document forty eight erosional scars, six long channels and numerous smaller-scale channels, three elongate mounds, and an elongate ridge across the eastern Malta Plateau. By analysing their morphology, seismic character, and sedimentological properties, we infer that the seafloor of the eastern Malta Plateau has been modified by three key processes: (i) Mass movements – in the form of translational slides, spreading and debris flows – that mobilised stratified Plio-Pleistocene hemipelagic mud along the shelf break and that were likely triggered by seismicity and loss of support due to canyon erosion across the upper Malta Escarpment; (ii) NNW-SSE trending sinistral strike-slip deformation in Cenozoic carbonates – resulting from the development of a mega-hinge fault system along the Malta Escarpment since the Late Mesozoic, and SE-NW directed horizontal shortening since the Late Miocene – which gave rise to NW-SE oriented extensional grabens and a NNW-SSE horst; (iii) Flow of bottom currents perpendicular and parallel to the Malta Escarpment, associated with either Modified Atlantic Water flows during sea level lowstands and/or Levantine Intermediate Water flows at present, which was responsible for sediment erosion and deposition in the form of channels and contouritic drifts

The Malta-Sicily Escarpment : mass movement dynamics in a sediment-undersupplied margin

The Malta-Sicily Escarpment (MSE) is a steep carbonate escarpment that appears to have largely remained isolated from inputs of fluvial and littoral sediments since the Messinian Salinity Crisis. Mass movement activity has so far only been inferred from sediment cores at the base of the MSE. In this study we use geophysical and sedimentological data acquired from the upper MSE and outer Malta Plateau to: (i) map and characterise the dominant forms of mass movements, and (ii) determine the nature and origin of these mass movements, and their role in the evolution of the MSE. We document 67 mass movement scars across 370 km2 of seafloor. Slope instability entailed translational slides, spreads and debris flows that mobilised Plio-Pleistocene outer shelf hemipelagic/pelagic sediments or carbonate sequences across the upper continental slope. Slope failure events are caused by loss of support associated with the formation of channels, gullies, canyon heads and fault-related escarpments. Mass movements play a key role in eroding the seafloor and transferring material to the lower MSE. In particular, they control the extent of headward and lateral extension of submarine canyons, facilitate tributary development, remove material from the continental shelf and slope, and feed sediment and drive its transport across the submarine canyon system.peer-reviewe

SOME PRODUCTION AND NUTRITION PARAMETERS IN VARIOUS SYSTEMS OF COW KEEPING IN EARLY LACTATION

Analizirani su proizvodni pokazatelji i utrošak hrane po jedinici proizvoda u dvije grupe od po 26 grla muznih krava, holštajn-frizijske pasmine koje su se telile u siječnju 1989. godine. Ispitivanja su vršena na farmi slobodnog sistema držanja, kapaciteta 1000 grla s instaliranom kompjuterskom opremom za rukovođenje procesima proizvodnje. Životinje su praćene od telenja do 35. dana laktacije. Ogledna grupa je od 6. dana laktacije bila u slobodnom sistemu držanja, dok je kontrolna grupa bila tokom čitavog trajanja ogleda u klasičnoj staji na vezu. Željelo se ustanoviti mogućnost uvoda krava u mlječnost u slobodnom sistemu držanja s hranidbom koncentrata preko automatskih hranilica i mužnjom u izmuzištu, sa automatikom za individualno praćenje proizvodnje. Ustanovljeno je da kompjuterski sistem omogućava uvod krava u mlječnost u slobodnom sistemu držanja,bez negativnih posljedica na proizvodnju, te da se ostvaruje utrošak hrane po jedinici proizvoda isti kao u klasičnoj staji na vezu.Production indicators and food consumption per product unit in two groups of 26 Holstein-Frisian dairy cows calved in January 1989 were analyzed. Investigations were carried out on a free system dairy farm, capacity a 1000 head, with a computer installed to follow\u27 the production processes. The cows were followed from calčvng until 35- day of lactation. The trial group was kept free from the 6rh lactation day hile the control group was kept tied in a traditional shed during the trial period. The aim was to establish a possibility of introducing the cows to being milked in a free system and fed on concentrates by means of automatic feeding system and milked in the milking parlour; each animal as followed by the computer system. It as established that the computer system enabled initiations of cows into milking in the free keeping system without negative effects on production and that the food consumption per production unit as the same as when the cows were kept tied in a traditional shed

Vitamin D Deficiency and Exogenous Vitamin D Excess Similarly Increase Diffuse Atherosclerotic Calcification in Apolipoprotein E Knockout Mice

Background: Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice. Methods: Mice were fed atherogenic diets with normal vitamin D content (1.5IU/kg) or without vitamin D. Paricalcitol, or matched vehicle, was administered 3× weekly by intraperitoneal injection. Following 20 weeks of these interventions cardiovascular phenotype was characterized by histological assessment of aortic sinus atheroma, soluble markers, blood pressure and echocardiography. To place the cardiovascular assessments in the context of intervention effects on bone, structural changes at the tibia were assessed by microtomography. Results: Vitamin D deficient diet induced significant reductions in plasma vitamin D (p<0.001), trabecular bone volume (p<0.01) and bone mineral density (p<0.005). These changes were accompanied by an increase in calcification density (number of calcifications per mm2) of von Kossa-stained aortic sinus atheroma (461 versus 200, p<0.01). Paricalcitol administration suppressed parathyroid hormone (p<0.001), elevated plasma calcium phosphate product (p<0.005) and induced an increase in calcification density (472 versus 200, p<0.005) similar to that seen with vitamin D deficiency. Atheroma burden, blood pressure, metabolic profile and measures of left ventricular hypertrophy were unaffected by the interventions. Conclusion: Vitamin D deficiency, as well as excess, increases atherosclerotic calcification. This phenotype is induced before other measures of cardiovascular pathology associated clinically with vitamin D deficiency. Thus, maintenance of an optimal range of vitamin D signalling may be important for prevention of atherosclerotic calcification

Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer

Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17β-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Δ5-androsterone-3β,17β-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites

A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.</p

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies

Genetic Variation in the Vitamin D Pathway in Relation to Risk of Prostate Cancer—Results from the Breast and Prostate Cancer Cohort Consortium

BACKGROUND: Studies suggest that vitamin D status may be associated with prostate cancer risk, although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D (25(OH)D) status. We examined prostate cancer risk in relation to SNPs in four genes shown to predict circulating levels of 25(OH)D. METHODS: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the NCI Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. RESULTS: We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D (per A allele, OR=0.86, 95%CI=0.80–0.93, p-trend=0.0002), but an increased risk for non-aggressive disease (per a allele: OR=1.10, 95%CI=1.04–1.17, p-trend=0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6–8 vs. 0–1 alleles = 0.66, 95% CI = 0.44 – 0.98; p-trend=0.003). CONCLUSIONS: In this large, pooled analysis, genetic variants related to lower 25(OH)D were associated with a decreased risk of aggressive prostate cancer. IMPACT: Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk