Large-N spacetime reduction and the sign and silver-blaze problems of dense QCD

We study the spacetime-reduced (Eguchi-Kawai) version of large-N QCD with nonzero chemical potential. We explore a method to suppress the sign fluctuations of the Dirac determinant in the hadronic phase; the method employs a re-summation of gauge configurations that are related to each other by center transformations. We numerically test this method in two dimensions, and find that it successfully solves the silver-blaze problem. We analyze the system further, and measure its free energy F, the average phase theta of its Dirac determinant, and its chiral condensate . We show that F and are independent of mu in the hadronic phase but that, as chiral perturbation theory predicts, the quenched chiral condensate drops from its mu=0 value when mu~(pion mass)/2. Finally, we find that the distribution of theta qualitatively agrees with further, more recent, predictions from chiral perturbation theory.Comment: 43 pages, 17 figure

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria

BACKGROUND: Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. METHODOLOGY AND SIGNIFICANT FINDINGS: Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. CONCLUSION: This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs

Immunity of an Alternative Host Can Be Overcome by Higher Densities of Its Parasitoids Palmistichus elaeisis and Trichospilus diatraeae

Interactions of the parasitoids Palmistichus elaeisis Delvare & LaSalle and Trichospilus diatraeae Cherian & Margabandhu (Hymenoptera: Eulophidae) with its alternative host Anticarsia gemmatalis (Hübner) (Lepidoptera: Noctuidae) affect the success or failure of the mass production of these parasitoids for use in integrated pest management programs. The aim of this study was to evaluate changes in the cellular defense and encapsulation ability of A. gemmatalis pupae against P. elaeisis or T. diatraeae in adult parasitoid densities of 1, 3, 5, 7, 9, 11 or 13 parasitoids/pupae. We evaluated the total quantity of circulating hemocytes and the encapsulation rate versus density. Increasing parasitoid density reduced the total number of hemocytes in the hemolymph and the encapsulation rate by parasitized pupae. Furthermore, densities of P. elaeisis above 5 parasitoids/pupae caused higher reduction in total hemocyte numbers. The encapsulation rate fell with increasing parasitoid density. However, parasitic invasion by both species induced generally similar responses. The reduction in defensive capacity of A. gemmatalis is related to the adjustment of the density of these parasitoids to their development in this host. Thus, the role of the density of P. elaeisis or T. diatraeae by pupa is induced suppression of cellular defense and encapsulation of the host, even without them possesses a co-evolutionary history. Furthermore, these findings can predict the success of P. elaeisis and T. diatraeae in the control of insect pests through the use of immunology as a tool for evaluation of natural enemies

Factors that could explain the increasing prevalence of type 2 diabetes among adults in a Canadian province: a critical review and analysis

Abstract: Background: The prevalence of diabetes has increased since the last decade in New Brunswick. Identifying factors contributing to the increase in diabetes prevalence will help inform an action plan to manage the condition. The objective was to describe factors that could explain the increasing prevalence of type 2 diabetes in New Brunswick since 2001. Methods: A critical literature review was conducted to identify factors potentially responsible for an increase in prevalence of diabetes. Data from various sources were obtained to draw a repeated cross-sectional (2001–2014) description of these factors concurrently with changes in the prevalence of type 2 diabetes in New Brunswick. Linear regressions, Poisson regressions and Cochran Armitage analysis were used to describe relationships between these factors and time. Results: Factors identified in the review were summarized in five categories: individual-level risk factors, environmental risk factors, evolution of the disease, detection effect and global changes. The prevalence of type 2 diabetes has increased by 120% between 2001 and 2014. The prevalence of obesity, hypertension, prediabetes, alcohol consumption, immigration and urbanization increased during the study period and the consumption of fruits and vegetables decreased which could represent potential factors of the increasing prevalence of type 2 diabetes. Physical activity, smoking, socioeconomic status and education did not present trends that could explain the increasing prevalence of type 2 diabetes. During the study period, the mortality rate and the conversion rate from prediabetes to diabetes decreased and the incidence rate increased. Suggestion of a detection effect was also present as the number of people tested increased while the HbA1c and the age at detection decreased. Period and birth cohort effect were also noted through a rise in the prevalence of type 2 diabetes across all age groups, but greater increases were observed among the younger cohorts. Conclusions: This study presents a comprehensive overview of factors potentially responsible for population level changes in prevalence of type 2 diabetes. Recent increases in type 2 diabetes in New Brunswick may be attributable to a combination of some individual-level and environmental risk factors, the detection effect, the evolution of the disease and global changes

Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

BACKGROUND:DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. METHODS:Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation. RESULTS:Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. CONCLUSIONS:Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes

A Dynamic View of Domain-Motif Interactions

Many protein-protein interactions are mediated by domain-motif interaction, where a domain in one protein binds a short linear motif in its interacting partner. Such interactions are often involved in key cellular processes, necessitating their tight regulation. A common strategy of the cell to control protein function and interaction is by post-translational modifications of specific residues, especially phosphorylation. Indeed, there are motifs, such as SH2-binding motifs, in which motif phosphorylation is required for the domain-motif interaction. On the contrary, there are other examples where motif phosphorylation prevents the domain-motif interaction. Here we present a large-scale integrative analysis of experimental human data of domain-motif interactions and phosphorylation events, demonstrating an intriguing coupling between the two. We report such coupling for SH3, PDZ, SH2 and WW domains, where residue phosphorylation within or next to the motif is implied to be associated with switching on or off domain binding. For domains that require motif phosphorylation for binding, such as SH2 domains, we found coupled phosphorylation events other than the ones required for domain binding. Furthermore, we show that phosphorylation might function as a double switch, concurrently enabling interaction of the motif with one domain and disabling interaction with another domain. Evolutionary analysis shows that co-evolution of the motif and the proximal residues capable of phosphorylation predominates over other evolutionary scenarios, in which the motif appeared before the potentially phosphorylated residue, or vice versa. Our findings provide strengthening evidence for coupled interaction-regulation units, defined by a domain-binding motif and a phosphorylated residue

Cardiovascular disease and the role of oral bacteria

In terms of the pathogenesis of cardiovascular disease (CVD) the focus has traditionally been on dyslipidemia. Over the decades our understanding of the pathogenesis of CVD has increased, and infections, including those caused by oral bacteria, are more likely involved in CVD progression than previously thought. While many studies have now shown an association between periodontal disease and CVD, the mechanisms underpinning this relationship remain unclear. This review gives a brief overview of the host-bacterial interactions in periodontal disease and virulence factors of oral bacteria before discussing the proposed mechanisms by which oral bacterial may facilitate the progression of CVD