Sperm parameters on Iberian red deer: Electroejaculation and post-mortem collection

P. 216-226Artificial reproductive technologies (ART) for cervids have improved, but a need remains for the collection of basic data. We studied two models of sperm collection in Iberian red deer, post-mortem (PM) in a wild population (179 samples) and by electroejaculation (EE) in a farmed population (37 samples), recording: testicular and epididymal weight, testicular diameter, sperm quantity, pH and osmolality and spermatozoa quality (motility by CASA, abnormal forms, cytoplasmic droplets, viability and acrosomal status). We tested the relationship of these parameters with stag age and compared the two models (PM and EE; medians showed). Genitalia parameters were linearly related to stag age (testicular diameter: 31.5–50.5 mm for 2–9 years). Total number of spermatozoa collected were PM: 2.5 × 109 and EE: 3.6 × 109 (P > 0.05), increasing with age only for PM. We found a positive relationship between testicular size and spermatozoa collected for PM. Osmolality and pH were PM: 6.28 and 378 mOsm/kg; EE: 7.63 and 309 mOsm/kg (P < 0.05). The pH increased with age only for EE. Percentage of motile spermatozoa was similar for PM and EE, but motility quality was lower for PM. Abnormal forms, proximal and distal droplets were lower for EE (22%, 1.3%, 1.5% vs. PM: 23%, 4.3%, 83%). Viability was similar (74%) and intact acrosomes were higher for EE (97% vs. 89%). Both PM and EE samples could be used for germplasm banking. This study contributes with new data on red deer spermatology and for the development of ART in cervids.S

A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction

BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern european populations

Genome-wide association studies have successfully identified 20 colorectal cancer susceptibility loci. Amongst these, four of the signals are defined by tagging single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4 and BMP2, respectively). By investigating these four SNPs in an initial cohort of Spanish origin, we found substantial evidence that minor allele frequencies (MAFs) may be different in northern and southern European populations. Therefore, we genotyped three additional southern European cohorts comprising a total of 2028 cases and 4273 controls. The meta-analysis results show that only one of the association signals (rs961253) is effectively replicated in the southern European populations, despite adequate power to detect all four. The other three SNPs (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and linkage disequilibrium patterns between northern and southern European cohorts. We hypothesize that this lack of replication could be the result of differential tagging of the functional variant in both sets of populations. Were this true, it would have complex consequences in both our ability to understand the nature of the real causative variants, as well as for further study designs

Single Nucleotide Polymorphisms in the Wnt and BMP Pathways and Colorectal Cancer Risk in a Spanish Cohort

BACKGROUND: Colorectal cancer (CRC) is considered a complex disease, and thus the majority of the genetic susceptibility is thought to lie in the form of low-penetrance variants following a polygenic model of inheritance. Candidate-gene studies have so far been one of the basic approaches taken to identify these susceptibility variants. The consistent involvement of some signaling routes in carcinogenesis provided support for pathway-based studies as a natural strategy to select genes that could potentially harbour new susceptibility loci. METHODOLOGY/PRINCIPAL FINDINGS: We selected two main carcinogenesis-related pathways: Wnt and BMP, in order to screen the implicated genes for new risk variants. We then conducted a case-control association study in 933 CRC cases and 969 controls based on coding and regulatory SNPs. We also included rs4444235 and rs9929218, which did not fulfill our selection criteria but belonged to two genes in the BMP pathway and had consistently been linked to CRC in previous studies. Neither allelic, nor genotypic or haplotypic analyses showed any signs of association between the 37 screened variants and CRC risk. Adjustments for sex and age, and stratified analysis between sporadic and control groups did not yield any positive results either. CONCLUSIONS/SIGNIFICANCE: Despite the relevance of both pathways in the pathogenesis of the disease, and the fact that this is indeed the first study that considers these pathways as a candidate-gene selection approach, our study does not present any evidence of the presence of low-penetrance variants for the selected markers in any of the considered genes in our cohort

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Form Factor Improvement of Smart-Pixels for Vision Sensors through 3-D Vertically- Integrated Technologies

While conventional CMOS active pixel sensors embed only the circuitry required for photo-detection, pixel addressing and voltage buffering, smart pixels incorporate also circuitry for data processing, data storage and control of data interchange. This additional circuitry enables data processing be realized concurrently with the acquisition of images which is instrumental to reduce the number of data needed to carry to information contained into images. This way, more efficient vision systems can be built at the cost of larger pixel pitch. Vertically-integrated 3D technologies enable to keep the advnatges of smart pixels while improving the form factor of smart pixels.Peer reviewe

The effect of the cysteine proteinase from Micrococcus sp. INIA 528 on the ripening process of Manchego cheese

The effect of adding 0.5, 1.0, and 2.0 AU l-1 of the cysteine proteinase from Micrococcus sp. INIA 528 to pasteurized ewe's milk on the acceleration of Manchego cheese ripening was investigated. Whey dry matter and protein content were higher for experimental cheeses than for control cheese. Residual α(s)-casein was significantly lower in experimental cheeses than in control cheese from day 30 and residual β-casein from day 15. Hydrophobic peptides, hydrophilic peptides, their ratio and N soluble in phosphotungstic acid were significantly higher in experimental cheeses than in control cheese from day 15. Experimental cheeses showed a less firm texture with lower values for fracturability, elasticity and hardness from day 30 due to their more pronounced proteolysis. Flavor quality was improved by cysteine proteinase addition to milk, and no differences between bitterness scores of experimental and control cheeses were recorded. Flavor intensity was enhanced by enzyme addition to milk from day 15. Manchego cheese made from milk with 2.0 AU l-1 cysteine proteinase would reach in 36 days the flavor intensity of 60-day control cheese. The effect of adding 0.5, 1.0, and 2.0 AU l-1 of the cysteine proteinase from Micrococcus sp. INIA 528 to pasteurized ewe's milk on the acceleration of Manchego cheese ripening was investigated. Whey dry matter and protein content were higher for experimental cheeses than for control cheese. Residual αs-casein was significantly lower in experimental cheeses than in control cheese from day 30 and residual β-casein from day 15. Hydrophobic peptides, hydrophilic peptides, their ratio and N soluble in phosphotungstic acid were significantly higher in experimental cheeses than in control cheese from day 15. Experimental cheeses showed a less firm texture with lower values for fracturability, elasticity, and hardness from day 30 due to their more pronounced proteolysis. Flavor quality was improved by cysteine proteinase addition to milk, and no differences between bitterness scores of experimental and control cheeses were recorded. Flavor intensity was enhanced by enzyme addition to milk from day 15. Manchego cheese made from milk with 2.0 AU l-1 cysteine proteinase would reach in 36 days the favor intensity of 60-day control cheese