Loss to Follow-Up from HIV Screening to ART Initiation in Rural China.

BackgroundPatients who are newly screened HIV positive by EIA are lost to follow-up due to complicated HIV testing procedures. Because this is the first step in care, it affects the entire continuum of care. This is a particular concern in rural China.Objective(s)To assess the routine HIV testing completeness and treatment initiation rates at 18 county-level general hospitals in rural Guangxi.MethodsWe reviewed original hospital HIV screening records. Investigators also engaged with hospital leaders and key personnel involved in HIV prevention activities to characterize in detail the routine care practices in place at each county.Results699 newly screened HIV-positive patients between January 1 and June 30, 2013 across the 18 hospitals were included in the study. The proportion of confirmatory testing across the 18 hospitals ranged from 14% to 87% (mean of 43%), and the proportion of newly diagnosed individuals successfully initiated antiretroviral treatment across the hospitals ranged from 3% to 67% (mean of 23%). The average interval within hospitals for individuals to receive the Western Blot (WB) and CD4 test results from HIV positive screening (i.e. achieving testing completion) ranged from 14-116 days (mean of 41.7 days) across the hospitals. The shortest interval from receiving a positive EIA screening test result to receiving WB and CD4 testing and counseling was 0 day and the longest was 260 days.ConclusionThe proportion of patients newly screened HIV positive that completed the necessary testing procedures for HIV confirmation and received ART was very low. Interventions are urgently needed to remove barriers so that HIV patients can have timely access to HIV/AIDS treatment and care in rural China

Genome-wide association analysis reveal candidate genes and haplotypes related to root weight in cucumber (Cucumis sativus L.).

BACKGROUND: The plant root system is critical for the absorption of water and nutrients, and have a direct influence on growth and yield. In cucumber, a globally consumed crop, the molecular mechanism of root development remains unclear, and this has implications for developing stress tolerant varieties. This study sought to determine the genetic patterns and related genes of cucumber root weight. A core cucumber germplasms population was used to do the GWAS analysis in three environments. RESULTS: Here, we investigated four root-weight related traits including root fresh weight (RFW), root dry weight (RDW), ratio of root dry weight to root fresh weight (RDFW) and the comprehensive evaluation index, D-value of root weight (DRW) deduced based on the above three traits for the core germplasm of the cucumber global repository. According to the D-value, we identified 21 and 16 accessions with light and heavy-root, respectively. We also found that the East Asian ecotype accessions had significantly heavier root than other three ecotypes. The genome-wide association study (GWAS) for these four traits reveals that 4 of 10 significant loci (gDRW3.1, gDRW3.2, gDRW4.1 and gDRW5.1) were repeatedly detected for at least two traits. Further haplotype and expression analysis for protein-coding genes positioned within these 4 loci between light and heavy-root accessions predicted five candidate genes (i.e., Csa3G132020 and Csa3G132520 both encoding F-box protein PP2-B1 for gDRW3.1, Csa3G629240 encoding a B-cell receptor-associated protein for gDRW3.2, Csa4G499330 encodes a GTP binding protein for gDRW4.1, and Csa5G286040 encodes a proteinase inhibitor for gDRW5.1). CONCLUSIONS: We conducted a systematic analysis of the root genetic basis and characteristics of cucumber core germplasms population. We detected four novel loci, which regulate the root weight in cucumber. Our study provides valuable candidate genes and haplotypes for the improvement of root system in cucumber breeding

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Genome-Wide Association Reveals Pigmentation Genes Play a Role in Skin Aging

Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies (GWAS) of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait (p = 4.1 × 10-9); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (p = 8.8 × 10-13), and rs4268748 near MC1R (p = 1.2 × 10-15). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinate of skin aging

Chemokine (C-C Motif) Ligand 2 (CCL2) in Sera of Patients with Type 1 Diabetes and Diabetic Complications

Chemokine (C-C motif) ligand 2 (CCL2), commonly known as monocyte chemoattractant protein-1 (MCP-1), has been implicated in the pathogenesis of many diseases characterized by monocytic infiltration. However, limited data have been reported on MCP-1 in type 1 diabetes (T1D) and the findings are inconclusive and inconsistent.In this study, MCP-1 was measured in the sera from 2,472 T1D patients and 2,654 healthy controls using a Luminex assay. The rs1024611 SNP in the promoter region of MCP-1 was genotyped for a subset of subjects (1764 T1D patients and 1323 controls) using the TaqMan-assay.Subject age, sex or genotypes of MCP-1 rs1024611SNP did not have a major impact on serum MCP-1 levels in either healthy controls or patients. While hemoglobin A1c levels did not have a major influence on serum MCP-1 levels, the mean serum MCP-1 levels are significantly higher in patients with multiple complications (mean = 242 ng/ml) compared to patients without any complications (mean = 201 ng/ml) (p = 3.5×10(-6)). Furthermore, mean serum MCP-1 is higher in controls (mean = 261 ng/ml) than T1D patients (mean = 208 ng/ml) (p<10(-23)). More importantly, the frequency of subjects with extremely high levels (>99(th) percentile of patients or 955 ng/ml) of serum MCP-1 is significantly lower in the T1D group compared to the control group (odds ratio = 0.11, p<10(-33)).MCP-1 may have a dual role in T1D and its complications. While very high levels of serum MCP-1 may be protective against the development of T1D, complications are associated with higher serum MCP-1 levels within the T1D group

Lung Cancer Occurrence in Never-Smokers: An Analysis of 13 Cohorts and 22 Cancer Registry Studies

Michael Thun and colleagues pooled and analyzed comprehensive data on lung cancer incidence and death rates among never-smokers to examine what factors other than active smoking affect lung cancer risk

NtGNL1 Plays an Essential Role in Pollen Tube Tip Growth and Orientation Likely via Regulation of Post-Golgi Trafficking

Background: Tobacco GNOM LIKE 1 (NtGNL1), a new member of the Big/GBF family, is characterized by a sec 7 domain. Thus, we proposed that NtGNL1 may function in regulating pollen tube growth for vesicle trafficking. Methodology/Principal Findings: To test this hypothesis, we used an RNAi technique to down-regulate NtGNL1 expression and found that pollen tube growth and orientation were clearly inhibited. Cytological observations revealed that both timing and behavior of endocytosis was disrupted, and endosome trafficking to prevacuolar compartments (PVC) or multivesicular bodies (MVB) was altered in pollen tube tips. Moreover, NtGNL1 seemed to partially overlap with Golgi bodies, but clearly colocalized with putative late endosome compartments. We also observed that in such pollen tubes, the Golgi apparatus disassembled and fused with the endoplasmic reticulum, indicating abnormal post-Golgi trafficking. During this process, actin organization was also remodeled. Conclusions/Significance: Thus, we revealed that NtGNL1 is essential for pollen tube growth and orientation and it likel