Cotton is one of the most economically important crop plants worldwide. Its fiber, commonly known as cotton lint, is the principal natural source for the textile industry. Approximately 33 million ha (5% of the world's arable land) is used for cotton planting 1 , with an annual global market value of textile mills of approximately $630.6 billion in 2011 (MarketPublishers; see URLs). Apart from its economic value, cotton is also an excellent model system for studying polyploidization, cell elongation and cell wall biosynthesis 2-5 .The Gossypium genus contains 5 tetraploid (AD 1 to AD 5 , 2n = 4×) and over 45 diploid (2n = 2×) species (where n is the number of chromosomes in the gamete of an individual), which are believed to have originated from a common ancestor approximately 5-10 million years ago 6 . Eight diploid subgenomes, designated as A to G and K, have been found across North America, Africa, Asia and Australia. The haploid genome size of diploid cottons (2n = 2× = 26) varies from about 880 Mb (G. raimondii Ulbrich) in the D genome to 2,500 Mb in the K genome 7,8 . Diploid cotton species share a common chromosome number (n = 13), and high levels of synteny or colinearity are observed among them 9-12 . The tetraploid cotton species (2n = 4× = 52), such as G. hirsutum L. and Gossypium barbadense L., are thought to have formed by an allopolyploidization event that occurred approximately 1-2 million years ago, which involved a D-genome species as the pollen-providing parent and an A-genome species as the maternal parent 13,14 . To gain insights into the cultivated polyploid genomes-how they have evolved and how their subgenomes interact-it is first necessary to have a basic knowledge of the structure of the component genomes. Therefore, we have created a draft sequence of the putative D-genome parent, G. raimondii, using DNA samples prepared from Cotton Microsatellite Database (CMD) 10 (refs. 15,16), a genetic standard originated from a single seed (accession D 5 -3) in 2004 and brought to near homozygosity by six successive generations of self-fertilization. We believe that sequencing of the G. raimondii genome will not only provide a major source of candidate genes important for the genetic improvement of cotton quality and productivity, but it may also serve as a reference for the assembly of the tetraploid G. hirsutum genome. RESULTS Sequencing and assemblyA whole-genome shotgun strategy was used to sequence and assemble the G. raimondii genome. A total of 78.7 Gb of next-generation Illumina paired-end 50-bp, 100-bp and 150-bp reads was generated by sequencing genome shotgun libraries of different fragment lengths (170 bp, 250 bp, 500 bp, 800 bp, 2 kb, 5 kb, 10 kb, 20 kb and 40 kb) that covered 103.6-fold of the 775.2-Mb assembled G. raimondii genome (Supplementary Table 1). The resulting assembly appeared to cover a very large proportion of the euchromatin of the G. raimondii genome. The unassembled genomic regions are likely to contain heterochromatic satellites, large repetitive sequences or ribosoma...

Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P = 0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein–negative colon cancers than among the 276 (87.9%) with CDX2 protein–positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P = 0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P = 0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P = 0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P = 0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.)

Summary The family Euphorbiaceae includes some of the most efficient biomass accumulators. Whole genome sequencing and the development of genetic maps of these species are important components in molecular breeding and genetic improvement. Here we report the draft genome of physic nut (Jatropha curcas L.), a biodiesel plant. The assembled genome has a total length of 320.5 Mbp and contains 27 172 putative protein‐coding genes. We established a linkage map containing 1208 markers and anchored the genome assembly (81.7%) to this map to produce 11 pseudochromosomes. After gene family clustering, 15 268 families were identified, of which 13 887 existed in the castor bean genome. Analysis of the genome highlighted specific expansion and contraction of a number of gene families during the evolution of this species, including the ribosome‐inactivating proteins and oil biosynthesis pathway enzymes. The genomic sequence and linkage map provide a valuable resource not only for fundamental and applied research on physic nut but also for evolutionary and comparative genomics analysis, particularly in the Euphorbiaceae.

The topic of gut microbiota is currently attracting considerable interest as a potential factor in Alzheimer's disease (AD). However, the extent and time course of alterations in the gut microbiota, and their effects on AD pathology remain uncertain. Herein, we compared the fecal microbiomes and fecal short chain fatty acid composition (SCFAs) between wild-type and AD model mice at different ages under strictly controlled specific pathogen free conditions, and also conducted microscopic investigations of intestinal structures. Our results showed that the microbiota composition and diversity were perturbed and the level of SCFAs was reduced in AD mice, predicting alterations in more than 30 metabolic pathways, which may be associated with amyloid deposition and ultrastructural abnormalities in AD mouse intestine. These findings indicate that AD pathology might not only affect brain function directly, but also exacerbate cognitive deficits through reducing the level of SCFAs via alterations of gut microbiota induced by intestinal amyloid deposition. Our data may support a role of gut microbiota, and suggest a novel route for therapeutic intervention in AD.

IMPORTANCE Oxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit. OBJECTIVE To test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy. DESIGN, SETTING, AND PARTICIPANTS Participants in the NSABP C-07 trial were divided into discovery (n = 848) and validation (n = 881) cohorts based on the order of tissue block submission. A reestimated centroid using 72 genes was used to determine Colorectal Cancer Assigner subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was examined with a locked-down algorithm for subtype classification and statistical analysis plan. Post hoc analysis included examination of the entire cohort with Colorectal Cancer Assigner, Colorectal Cancer Subtype (CCS), and Consensus Molecular Subtype (CMS) methods. INTERVENTIONS Fluorouracil plus leucovorin with or without oxaliplatin. MAIN OUTCOMES AND MEASURES Percent recurrence-free survival. RESULTS Among 1729 patients, 744 (43%) were female and mean (SD) age was 58 (11) years. Although C-07 participants with stage III disease with an enterocyte subtype showed a statistically significant benefit from oxaliplatin in the discovery cohort (hazard ratio, 0.22 [95% CI, 0.09–0.56]; P = .001 [N = 65]), no statistically significant benefit was observed in the validation cohort (hazard ratio, 0.53 [95% CI, 0.22–1.24]; P = .14 [N = 70]). The stemlike subtype was associated with poor prognosis and lack of benefit from oxaliplatin treatment (HR, 0.99 [95% CI, 0.73–1.34]; P = .96 [N = 367]). Examination of the different subtyping methods shows that all 3 methods robustly identified patients with poor prognosis (stemlike, CCS-3, and CMS-4) in both stage II and III. CONCLUSIONS AND RELEVANCE Patients with stemlike tumors may be appropriate for clinical trials testing experimental therapies because stemlike tumors were robustly identified and associated with a poor prognosis regardless of stage or chemotherapy regimen. The clinical utility of using subtyping for the identification of patients for treatment with oxaliplatin requires validation in independent clinical trial cohorts. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00004931

Internet addiction (IA) is an emerging social and mental health issue among youths. Analysis of risk factors, as well as their interactions, is crucial for understanding the development of IA. This study investigated the relationship between recent stressful life events, personality traits, perceived family functioning and IA in 892 college students. Subjects were classified into categories (non‐addicted, mild IA or severe IA) using the Chen Internet Addiction Scale. Stressful life events, personality traits and family functioning were assessed using the Adolescent Self‐Rating Life Events Checklist, the Eysenck Personality Questionnaire, and the Family Adaptability and Cohesion Scale, respectively. The results indicated that compared with non‐addicted subjects, subjects with severe IA (9.98%) had lower family functioning, lower extraversion, higher neuroticism and psychoticism, and more stressful life events, and subjects with mild IA (11.21%) had higher neuroticism and more health and adaptation problems. Neuroticism and health and adaptation problems were potential predictors of IA. An interaction effect between psychoticism and total life stress on IA was also found. These findings highlight the role of personality traits and life stress and their interactions in college students' IA. Further research should explore the mechanisms underlying the interaction effect of psychoticism with life stress on IA. Copyright © 2013 John Wiley & Sons, Ltd.

This study indicates that endogenously released orexins act on the PVT to regulate anxiety levels through mechanisms involving the brain kappa and CRF receptors.

There are two subtypes of multiple sclerosis (MS) in Asians: the opticospinal (OSMS) form that shows a selective involvement of the optic nerve and the spinal cord and the conventional (CMS) form that has disseminated lesions in the central nervous system including the cerebrum, cerebellum and brainstem. Both show distinct human leukocyte antigen (HLA) class II associations. OSMS has similar features to the relapsing form of neuromyelitis optica (NMO) in Western populations. Recently, it was shown that antibodies to aquaporin-4 (AQP4) are specifically detected in NMO patients and in some Japanese patients with OSMS or recurrent optic neuritis or myelitis. To clarify the immunogenetic background of anti-AQP4 antibody production, we studied HLA-DRB1 and -DPB1 gene polymorphisms in anti-AQP4 antibody-positive and -negative patients with idiopathic demyelinating diseases, such as MS, recurrent optic neuritis and recurrent myelitis. The phenotypic frequency of the HLA-DPB1*0501 allele was significantly increased in anti-AQP4 antibody-positive patients (89.5%, odds ratio = 4.8; 95% confidence interval = 1.6-14.3, n = 38, P(corr) = 0.032) compared with controls (64.0%, n = 125) but not in either anti-AQP4 antibody-negative OSMS (75.0%, n = 32) or CMS (69.2%, n = 52) patients. There was no significant correlation between any HLA-DRB1 allele and the existence of anti-AQP4 antibody. These findings suggest that the emergence of anti-AQP4 antibody is reinforced by the presence of the HLA-DPB1*0501 allele in Japanese.