A genome-wide association study reveals specific transferases as candidate loci for bovine milk oligosaccharides synthesis.

BackgroundHuman milk oligosaccharides (OS) play a key role in brain and gut microbiota development of the neonate, but the underlying biosynthetic steps of OS in the mammary gland are still largely unknown. As bovine milk contains OS with somewhat similar structures and functionalities there is increased interest in further understanding the genetic basis underlying the OS content of milk for eventual extraction and generation of value-added ingredients for infant formulas and nutraceuticals. The present study is the first to report on genetic parameter estimation as well as on a genome wide association study (GWAS) from the largest bovine milk OS dataset analyzed to date.ResultsIn total 15 different bovine milk OS were monitored. Heritabilities ranged from 0 to 0.68 in Danish Holstein and from 0 to 0.92 in Danish Jersey. The GWAS identified in total 1770 SNPs (FDR < 0.10) for five different OS in Danish Holstein and 6913 SNPs (FDR < 0.10) for 11 OS in Danish Jersey. In Danish Holstein, a major overlapping QTL was identified on BTA1 for LNH and LNT explaining 24% of the variation in these OS. The most significant SNPs were associated with B3GNT5, a gene encoding a glycosyltransferase involved in glycan synthesis. In Danish Jersey, a very strong QTL was detected for the OS with composition 2 Hex 1 HexNAc (isomer 1) on BTA11. The most significant SNP had -log10(P-value) of 52.88 (BOVINEHD1100030300) and was assigned to ABO, a gene encoding ABO blood group glycosyltransferases. This SNP has been reported to be a missense mutation and explains 56% of the OS variation. Other candidate genes of interest identified for milk OS were ALG3, B3GALNT2, LOC520336, PIGV, MAN1C1, ST6GALNAC6, GLT6D1, GALNT14, GALNT17, COLGALT2, LFNG and SIGLEC.ConclusionTo our knowledge, this is the first study documenting a solid breeding potential for bovine milk OS and a strong indication of specific candidate genes related to OS synthesis underlying this genetic influence. This new information has the potential to guide breeding strategies to achieve production of milk with higher diversity and concentration of OS and ultimately facilitate large-scale extraction of bovine milk OS

Secure and efficient application monitoring and replication

Memory corruption vulnerabilities remain a grave threat to systems software written in C/C++. Current best practices dictate compiling programs with exploit mitigations such as stack canaries, address space layout randomization, and control-flow integrity. However, adversaries quickly find ways to circumvent such mitigations, sometimes even before these mitigations are widely deployed. In this paper, we focus on an "orthogonal" defense that amplifies the effectiveness of traditional exploit mitigations. The key idea is to create multiple diversified replicas of a vulnerable program and then execute these replicas in lockstep on identical inputs while simultaneously monitoring their behavior. A malicious input that causes the diversified replicas to diverge in their behavior will be detected by the monitor; this allows discovery of previously unknown attacks such as zero-day exploits. So far, such multi-variant execution environments (MVEEs) have been held back by substantial runtime overheads. This paper presents a new design, ReMon, that is non-intrusive, secure, and highly efficient. Whereas previous schemes either monitor every system call or none at all, our system enforces cross-checking only for security critical system calls while supporting more relaxed monitoring policies for system calls that are not security critical. We achieve this by splitting the monitoring and replication logic into an in-process component and a cross-process component. Our evaluation shows that ReMon offers same level of security as conservative MVEEs and run realistic server benchmarks at near-native speeds

The development of affective and cognitive striatal neurobiology and connectivity during adolescence

Adolescence is characterized by heightened reward-drive and sensation seeking behavior. Current neurodevelopmental theories hypothesize that this behavior is driven by the development of the brain’s dopaminergic reward system and a developmental imbalance in the influence of the reward system on behavior relative to in cognitive control systems. The striatum is an ideal target for investigating these hypotheses because it is a central hub of the dopaminergic reward system, receives inputs affective and cognitive control systems, and functions to influence action selection. Current evidence for the development of striatal dopaminergic neurobiology during adolescence has been limited to animal models of adolescence due to limitations on the available techniques to assess striatal dopaminergic neurobiology in vivo in the human adolescent. Studies 1 and 2 of this dissertation assess this limitation by assessing a novel tissue property that has been linked multiple aspects of striatal dopamine neurobiology: tissue iron. We first use two MRI metrics sensitive to tissue iron concentration to investigate age-related differences in striatal tissue iron in a developmental sample spanning from adolescence to adulthood (ages 12 – 30) and then conduct a combined PET/MRI experiment in an adult sample (ages 18 - 30) to evaluate the relationship between striatal tissue iron concentration and indices of dopamine neurobiology. We find age-related increases in striatal tissue iron throughout adolescence and a positive association between an MR metric of tissue iron concentration and a PET metric of dopamine concentration in the aspect of the striatum most strongly associated with reward processing, the ventral striatum. Finally, study 3 assesses the hypothesis that there is a developmental imbalance between the influence of affective reward systems and cognitive control systems of behavior during adolescence by investigating corticostriatal connectivity. Specifically, we identify areas of the striatum that integrate corticostriatal projections for brain areas involved affect and cognitive control and investigate age-related differences in the balance of these inputs. We find that the relative integrity of affective projections, in relation to projections from cognitive control systems, decreases with age and is positively associated with an index of reward-driven behavior

Estimation of genetic parameters and detection of chromosomal regions affecting the major milk proteins and their post translational modifications in Danish Holstein and Danish Jersey cattle

Linkage disequilibrium plot (r 2) of the DGAT region in the Danish Jersey breed. (PNG 342 kb

Does virulence assessment of Vibrio anguillarum using sea bass (Dicentrarchus labrax) larvae correspond with genotypic and phenotypic characterization?

Background: Vibriosis is one of the most ubiquitous fish diseases caused by bacteria belonging to the genus Vibrio such as Vibrio (Listonella) anguillarum. Despite a lot of research efforts, the virulence factors and mechanism of V. anguillarum are still insufficiently known, in part because of the lack of standardized virulence assays. Methodology/Principal Findings: We investigated and compared the virulence of 15 V. anguillarum strains obtained from different hosts or non-host niches using a standardized gnotobiotic bioassay with European sea bass (Dicentrarchus labrax L.) larvae as model hosts. In addition, to assess potential relationships between virulence and genotypic and phenotypic characteristics, the strains were characterized by random amplified polymorphic DNA (RAPD) and repetitive extragenic palindromic PCR (rep-PCR) analyses, as well as by phenotypic analyses using Biolog's Phenotype MicroArray (TM) technology and some virulence factor assays. Conclusions/Significance: Virulence testing revealed ten virulent and five avirulent strains. While some relation could be established between serotype, genotype and phenotype, no relation was found between virulence and genotypic or phenotypic characteristics, illustrating the complexity of V. anguillarum virulence. Moreover, the standardized gnotobiotic system used in this study has proven its strength as a model to assess and compare the virulence of different V. anguillarum strains in vivo. In this way, the bioassay contributes to the study of mechanisms underlying virulence in V. anguillarum

A comparative model and techno-economic analysis of next generation AON Ethernet and TDM PON

A global reference model covering next generation active and passive networks has been developed for techno-economic evaluations, and an extensive techno-economic analysis with a focus on CAPEX has been performed for 10G TDM PON and 1G AON - both capable of delivering 1Gbit/s to end-users. Two major cases have been considered: urban and rural at green field deployment. The results show that AON is less expensive than PON solution in urban case while in rural case 10G TDM PON is more competitive

Ethyl anthracene-9-carboxyl­ate

In the title compound, C17H14O2, the COO group and the anthracene fragment form a dihedral angle of 76.00 (19)°. The torsion angle around the O—Csp 3 bond of the ester group is 108.52 (18)°. The crystal structure is stabilized by C—H⋯O inter­actions and edge-to-face arene inter­actions with C—H⋯(ring centroid) distances in the range 2.75–2.84 Å