Molecular markers associated with a new source of resistance to the cassava mosaic disease

The predominant source of resistance to the cassava mosaic disease (CMD) is known to be polygenic requiring evaluation in multiple environments to characterise resistant genotypes, which makes the detection of genes for resistance using segregation analysis inefficient. Recently, some landraces have been identified which exhibit high levels of resistance to CMD. In this study, molecular markers associated with resistance to CMD in a resistant landrace were identified, using F1 progenies derived from a cross between the CMD resistant landrace TME7 and the susceptible line TMS30555, as a first step in marker assisted breeding for CMD resistance. Bulk segregant analysis (BSA) on the parents, resistant and susceptible DNA pools, using simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers revealed that an SSR marker, SSRY28-180, donated by the resistant parent was linked with resistance to CMD. Marker-trait association detected by regression analysis showed that the marker, accounted for 57.41% of total phenotypic variation for resistance. The analysis furthershowed that another SSR marker, SSRY106-207 and an AFLP marker, E-ACC/M-CTC-225, accounted for 35.59% and 22.5% of the total phenotypic variation for resistance, respectively. The implication of the results in breeding for resistance to CMD is discussed

Flavonoid intake and the risk of age-related cataract in China’s Heilongjiang Province

Background/Objectives: Epidemiological evidence suggests that diets rich in flavonoids may reduce the risk of developing age-related cataract (ARC). Flavonoids are widely distributed in foods of plant origin and the objective of this study was to evaluate retrospectively the association between the intakes of the five flavonoid subclasses and the risk of ARC.  Subjects/Methods: A population-based case-control study (249 cases and 66 controls) was carried out in Heilongjiang province, which is located in the Northeast of China, and where intakes and availability of fresh vegetables and fruits can be limited. Dietary data gathered by food-frequency questionnaire (FFQ) were used to calculate flavonoid intake. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression.  Results: No linear associations between risk of developing ARC and intakes of total dietary flavonoids, anthocyanidins, flavon-3-ol, flavanone, total flavones or total flavonols were found, but quercetin and isorhamnetin intake was inversely associated with ARC risk (OR 11.78, 95% CI: 1.62-85.84, P<0.05, and OR 6.99, 95% CI:1.12-43.44, P<0.05, quartile 4 vs quartile 1, respectively).  Conclusion: As quercetin is contained in many plant foods and isorhamnetin is only contained in very few foods, we concluded that higher quercetin intake may be an important dietary factor in the reduction of risk of age-related cataract

Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration.

The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non‑diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS‑P, n = 9) or slow (PPMS‑NP, n = 10) disease course based on worsening disability and/or MRI‑visible appearance of new T2 lesions over a one‑year‑assessment. Partial least squares‑discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin‑d18:1/14:0 and mono‑hexosylceramide‑d18:1/20:0 were differentially abundant in the plasma of ppMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso‑phosphatidic acid‑18:2 (LPA‑18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA‑18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin‑d18:1/14:0, mono‑hexosylceramide‑d18:1/20:0, and LPA‑18:2 may represent important targets for future studies aimed at understanding disease progression in MS

A quantitative atlas of histone modification signatures from human cancer cells

BACKGROUND: An integral component of cancer biology is the understanding of molecular properties uniquely distinguishing one cancer type from another. One class of such properties is histone post-translational modifications (PTMs). Many histone PTMs are linked to the same diverse nuclear functions implicated in cancer development, including transcriptional activation and epigenetic regulation, which are often indirectly assayed with standard genomic technologies. Thus, there is a need for a comprehensive and quantitative profiling of cancer lines focused on their chromatin modification states. RESULTS: To complement genomic expression profiles of cancer lines, we report the proteomic classification of 24 different lines, the majority of which are cancer cells, by quantifying the abundances of a large panel of single and combinatorial histone H3 and H4 PTMs, and histone variants. Concurrent to the proteomic analysis, we performed transcriptomic analysis on histone modifying enzyme abundances as a proxy for quantifying their activity levels. While the transcriptomic and proteomic results were generally consistent in terms of predicting histone PTM abundance from enzyme abundances, several PTMs were regulated independently of the modifying enzyme expression. In addition, combinatorial PTMs containing H3K27 methylation were especially enriched in breast cell lines. Knockdown of the predominant H3K27 methyltransferase, enhancer of zeste 2 (EZH2), in a mouse mammary xenograft model significantly reduced tumor burden in these animals and demonstrated the predictive utility of proteomic techniques. CONCLUSIONS: Our proteomic and genomic characterizations of the histone modification states provide a resource for future investigations of the epigenetic and non-epigenetic determinants for classifying and analyzing cancer cells

Classifying and scoring of molecules with the NGN: new datasets, significance tests, and generalization

<p>Abstract</p> <p/> <p>This paper demonstrates how a Neural Grammar Network learns to classify and score molecules for a variety of tasks in chemistry and toxicology. In addition to a more detailed analysis on datasets previously studied, we introduce three new datasets (BBB, FXa, and toxicology) to show the generality of the approach. A new experimental methodology is developed and applied to both the new datasets as well as previously studied datasets. This methodology is rigorous and statistically grounded, and ultimately culminates in a Wilcoxon significance test that proves the effectiveness of the system. We further include a complete generalization of the specific technique to arbitrary grammars and datasets using a mathematical abstraction that allows researchers in different domains to apply the method to their own work.</p> <p>Background</p> <p>Our work can be viewed as an alternative to existing methods to solve the quantitative structure-activity relationship (QSAR) problem. To this end, we review a number approaches both from a methodological and also a performance perspective. In addition to these approaches, we also examined a number of chemical properties that can be used by generic classifier systems, such as feed-forward artificial neural networks. In studying these approaches, we identified a set of interesting benchmark problem sets to which many of the above approaches had been applied. These included: ACE, AChE, AR, BBB, BZR, Cox2, DHFR, ER, FXa, GPB, Therm, and Thr. Finally, we developed our own benchmark set by collecting data on toxicology.</p> <p>Results</p> <p>Our results show that our system performs better than, or comparatively to, the existing methods over a broad range of problem types. Our method does not require the expert knowledge that is necessary to apply the other methods to novel problems.</p> <p>Conclusions</p> <p>We conclude that our success is due to the ability of our system to: 1) encode molecules losslessly before presentation to the learning system, and 2) leverage the design of molecular description languages to facilitate the identification of relevant structural attributes of the molecules over different problem domains.</p

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

Doctor, how much weight will I lose? - a new individualized predictive model for weight loss

Bariatric surgery is an effective treatment for weight loss, but the patient’s ability to reach a sustained weight loss depends upon several technical and individual factors. Creating an easy model that adapts bariatric surgery’s weight loss goals for each patient is very important for pre-surgery and follow-up evaluations.info:eu-repo/semantics/publishedVersio

Body Mass Index in Multiple Sclerosis modulates ceramide-induced DNA methylation and disease course.

abstract Background: Multiple Sclerosis (MS) results from genetic predisposition and environmental variables, including elevated Body Mass Index (BMI) in early life. This study addresses the effect ofBMI on the epigenome ofmono- cytesand diseasecourseinMS. Methods: Fifty-four therapy-naive Relapsing Remitting (RR)MS patientswith high and normal BMI received clin- ical andMRI evaluation. Blood samples were immunophenotyped, and processed for unbiased plasma lipidomic profiling and genome-wide DNA methylation analysis of circulating monocytes. The main findings at baseline were validated in an independent cohort of 91 therapy-naïve RRMS patients. Disease course was evaluated by a two-year longitudinal follow up and mechanistic hypotheses tested in human cell cultures and in animal models ofMS. Findings: Higher monocytic counts and plasma ceramides, and hypermethylation of genes involved in negative regulation ofcell proliferationwere detected in the high BMI group ofMSpatients compared to normal BMI. Cer- amide treatment of monocytic cell cultures increased proliferation in a dose-dependent manner and was prevented by DNA methylation inhibitors. The high BMI group ofMS patients showed a negative correlation be- tween monocytic counts and brain volume. Those subjects at a two-year follow-up showed increased T1 lesion load, increased disease activity, and worsened clinical disability. Lastly, the relationship between body weight, monocytic infiltration, DNA methylation and disease course was validated in mouse models ofMS. Interpretation: High BMI negatively impacts disease course in Multiple Sclerosis by modulating monocyte cell number through ceramide-induced DNA methylation of anti-proliferative genes

Balancing carrots and sticks: incentives for sustainable hilsa fishery management in Bangladesh

Mihir Kanti Majumder, Md Mokammel Hossain, Atiq Rahman, Belayet Hussei