Seed systems smallholder farmers use

Seed can be an important entry point for promoting productivity, nutrition and resilience among smallholder farmers. While investments have primarily focused on strengthening the formal sector, this article documents the degree to which the informal sector remains the core for seed acquisition, especially in Africa. Conclusions drawn from a uniquely comprehensive data set, 9660 observations across six countries and covering 40 crops, show that farmers access 90.2 % of their seed from informal systems with 50.9 % of that deriving from local markets. Further, 55 % of seed is paid for by cash, indicating that smallholders are already making important investments in this arena. Targeted interventions are proposed for rendering formal and informal seed sector more smallholder-responsive and for scaling up positive impacts

A Dose-Dependent Relationship between Exposure to a Street-Based Drug Scene and Health-Related Harms among People Who Use Injection Drugs

While the community impacts of drug-related street disorder have been well described, lesser attention has been given to the potential health and social implications of drug scene exposure on street-involved people who use illicit drugs. Therefore, we sought to assess the impacts of exposure to a street-based drug scene among injection drug users (IDU) in a Canadian setting. Data were derived from a prospective cohort study known as the Vancouver Injection Drug Users Study. Four categories of drug scene exposure were defined based on the numbers of hours spent on the street each day. Three generalized estimating equation (GEE) logistic regression models were constructed to identify factors associated with varying levels of drug scene exposure (2–6, 6–15, over 15 hours) during the period of December 2005 to March 2009. Among our sample of 1,486 IDU, at baseline, a total of 314 (21%) fit the criteria for high drug scene exposure (>15 hours per day). In multivariate GEE analysis, factors significantly and independently associated with high exposure included: unstable housing (adjusted odds ratio [AOR] = 9.50; 95% confidence interval [CI], 6.36–14.20); daily crack use (AOR = 2.70; 95% CI, 2.07–3.52); encounters with police (AOR = 2.11; 95% CI, 1.62–2.75); and being a victim of violence (AOR = 1.49; 95 % CI, 1.14–1.95). Regular employment (AOR = 0.50; 95% CI, 0.38–0.65), and engagement with addiction treatment (AOR = 0.58; 95% CI, 0.45–0.75) were negatively associated with high exposure. Our findings indicate that drug scene exposure is associated with markers of vulnerability and higher intensity addiction. Intensity of drug scene exposure was associated with indicators of vulnerability to harm in a dose-dependent fashion. These findings highlight opportunities for policy interventions to address exposure to street disorder in the areas of employment, housing, and addiction treatment

The genetic basis of DOORS syndrome: an exome-sequencing study.

Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals

Methylation screening of the TGFBI promoter in human lung and prostate cancer by methylation-specific PCR

<p>Abstract</p> <p>Background</p> <p>Hypermethylation of the <it>TGFBI </it>promoter has been shown to correlate with decreased expression of this gene in human tumor cell lines. In this study, we optimized a methylation-specific polymerase chain reaction (MSP) method and investigated the methylation status of the <it>TGFBI </it>promoter in human lung and prostate cancer specimens.</p> <p>Methods</p> <p>Methylation-specific primers were designed based on the methylation profiles of the <it>TGFBI </it>promoter in human tumor cell lines, and MSP conditions were optimized for accurate and efficient amplification. Genomic DNA was isolated from lung tumors and prostatectomy tissues of prostate cancer patients, bisulfite-converted, and analyzed by MSP.</p> <p>Results</p> <p>Among 50 lung cancer samples, 44.0% (22/50) harbored methylated CpG sites in the <it>TGFBI </it>promoter. An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the <it>TGFBI </it>promoter was associated with a metastatic phenotype, with 42.9% (6/14) of metastatic lung cancer samples demonstrating dense methylation vs. only 5.6% (2/36) of primary lung cancer samples (<it>p </it>< 0.05). Similar to these lung cancer results, 82.0% (41/50) of prostate cancer samples harbored methylated CpG sites in the <it>TGFBI </it>promoter, and dense methylation of the promoter was present in 38.9% (7/18) of prostate cancer samples with the feature of locoregional invasiveness vs. only 19.4% (6/31) of prostate cancer samples without locoregional invasiveness (<it>p </it>< 0.05). Furthermore, promoter hypermethylation correlated with highly reduced expression of the <it>TGFBI </it>gene in human lung and prostate tumor cell lines.</p> <p>Conclusion</p> <p>We successfully optimized a MSP method for the precise and efficient screening of <it>TGFBI </it>promoter methylation status. Dense methylation of the <it>TGFBI </it>promoter correlated with the extent of <it>TGFBI </it>gene silencing in tumor cell lines and was related to invasiveness of prostate tumors and metastatic status of lung cancer tumors. Thus, <it>TGFBI </it>promoter methylation can be used as a potential prognostic marker for invasiveness and metastasis in prostate and lung cancer patients, respectively.</p

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Action Mechanism of Inhibin α-Subunit on the Development of Sertoli Cells and First Wave of Spermatogenesis in Mice

Inhibin is an important marker of Sertoli cell (SC) activity in animals with impaired spermatogenesis. However, the precise relationship between inhibin and SC activity is unknown. To investigate this relationship, we partially silenced both the transcription and translation of the gene for the α-subunit of inhibin, Inha, using recombinant pshRNA vectors developed with RNAi-Ready pSIREN-RetroQ-ZsGreen Vector (Clontech Laboratories, Mountain View, Calif). We found that Inha silencing suppresses the cell-cycle regulators Cyclin D1 and Cyclin E and up-regulates the cell-cycle inhibitor P21 (as detected by Western blot analysis), thereby increasing the number of SCs in the G1 phase of the cell cycle and decreasing the amount in the S-phase of the cell cycle (as detected by flow cytometry). Inha silencing also suppressed Pdgfa, Igf1, and Kitl mRNA levels and up-regulated Tgfbrs, Inhba, Inhbb, Cyp11a1, Dhh, and Tjp1 mRNA levels (as indicated by real-time polymerase chain reaction [PCR] analysis). These findings indicate that Inha has the potential to influence the availability of the ligand inhibin and its antagonist activin in the SC in an autocrine manner and inhibit the progression of SC from G1 to S. It may also participate in the development of the blood–testis barrier, Leydig cells, and spermatogenesis through its effect on Dhh, Tjp1, Kitl, and Pdgfa. Real-time PCR and Western blot analyses of Inha, Inhba, and Inhbb mRNA and Inha levels over time show that Inha plays an important role in the formation of round spermatid during the first wave of spermatogenesis in mice

Unconventional Transcriptional Response to Environmental Enrichment in a Mouse Model of Rett Syndrome

Background: Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2) and one of the leading causes of mental retardation in females. RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait. We studied the effects of environmental enrichment (EE) on the phenotypic manifestations of a RTT mouse model that lacks MeCP2 (Mecp2 2/y). Principal Findings: We found that EE delayed and attenuated some neurological alterations presented by Mecp2 2/y mice and prevented the development of motor discoordination and anxiety-related abnormalities. To define the molecular correlate of this beneficial effect of EE, we analyzed the expression of several synaptic marker genes whose expression is increased by EE in several mouse models. Conclusions/Significance: We found that EE induced downregulation of several synaptic markers, suggesting that th

Interpreting Meta-Analyses of Genome-Wide Association Studies

Meta-analysis is an increasingly popular tool for combining multiple genome-wide association studies in a single analysis to identify associations with small effect sizes. The effect sizes between studies in a meta-analysis may differ and these differences, or heterogeneity, can be caused by many factors. If heterogeneity is observed in the results of a meta-analysis, interpreting the cause of heterogeneity is important because the correct interpretation can lead to a better understanding of the disease and a more effective design of a replication study. However, interpreting heterogeneous results is difficult. The standard approach of examining the association p-values of the studies does not effectively predict if the effect exists in each study. In this paper, we propose a framework facilitating the interpretation of the results of a meta-analysis. Our framework is based on a new statistic representing the posterior probability that the effect exists in each study, which is estimated utilizing cross-study information. Simulations and application to the real data show that our framework can effectively segregate the studies predicted to have an effect, the studies predicted to not have an effect, and the ambiguous studies that are underpowered. In addition to helping interpretation, the new framework also allows us to develop a new association testing procedure taking into account the existence of effect

Skeletal muscle specific genes networks in cattle

While physiological differences across skeletal muscles have been described, the differential gene expression underlying them and the discovery of how they interact to perform specific biological processes are largely to be elucidated. The purpose of the present study was, firstly, to profile by cDNA microarrays the differential gene expression between two skeletal muscle types, Psoas major (PM) and Flexor digitorum (FD), in beef cattle and then to interpret the results in the context of a bovine gene coexpression network, detecting possible changes in connectivity across the skeletal muscle system. Eighty four genes were differentially expressed (DE) between muscles. Approximately 54% encoded metabolic enzymes and structural-contractile proteins. DE genes were involved in similar processes and functions, but the proportion of genes in each category varied within each muscle. A correlation matrix was obtained for 61 out of the 84 DE genes from a gene coexpression network. Different groups of coexpression were observed, the largest one having 28 metabolic and contractile genes, up-regulated in PM, and mainly encoding fast-glycolytic fibre structural components and glycolytic enzymes. In FD, genes related to cell support seemed to constitute its identity feature and did not positively correlate to the rest of DE genes in FD. Moreover, changes in connectivity for some DE genes were observed in the different gene ontologies. Our results confirm the existence of a muscle dependent transcription and coexpression pattern and suggest the necessity of integrating different muscle types to perform comprehensive networks for the transcriptional landscape of bovine skeletal muscle