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Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial–mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.

The aim was to examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the US general population. Respondents in the National Comorbidity Survey Replication with common 12-month DSM-IV mood, anxiety, substance, impulse control and childhood disorders were asked about perceived need for treatment, structural barriers and attitudinal/evaluative barriers to initiation and continuation of treatment. Low perceived need was reported by 44.8% of respondents with a disorder who did not seek treatment. Desire to handle the problem on one's own was the most common reason among respondents with perceived need both for not seeking treatment (72.6%) and for dropping out of treatment (42.2%). Attitudinal/evaluative factors were much more important than structural barriers both to initiating (97.4% v. 22.2%) and to continuing (81.9% v. 31.8%) of treatment. Reasons for not seeking treatment varied with illness severity. Low perceived need was a more common reason for not seeking treatment among individuals with mild (57.0%) than moderate (39.3%) or severe (25.9%) disorders, whereas structural and attitudinal/evaluative barriers were more common among respondents with more severe conditions. Low perceived need and attitudinal/evaluative barriers are the major barriers to treatment seeking and staying in treatment among individuals with common mental disorders. Efforts to increase treatment seeking and reduce treatment drop-out need to take these barriers into consideration as well as to recognize that barriers differ as a function of sociodemographic and clinical characteristics.

On the basis of first-principles calculations, we show that the M-type hexaferrite BaFe12O19 exhibits frustrated antiferroelectricity associated with its trigonal bipyramidal Fe3+ sites. The ferroelectric state of BaFe12O19 , reachable by applying an external electric field to the antiferroelectric state, can be made stable at room temperature by appropriate element substitution or strain engineering. Thus, M-type hexaferrite, as a new type of multiferoic with coexistence of antiferroelectricity and ferrimagnetism, provides a basis for studying the phenomenon of frustrated antiferroelectricity and realizing multiple-state memory devices.

All 61 known species of scombrids and billfishes were assessed under International Union for Conservation of Nature Red List Categories and Criteria, providing for the first time a comprehensive risk assessment of each species’ global population and conservation status. These fishes are among the most valuable global fishery resource, and high fishing pressure has led to the overexploitation of some populations, most notably those which are longest-lived; 11% of tunas and billfishes were listed in Red List threatened categories, including the most highly valued tunas: Southern Bluefin Tuna (Thunnus maccoyii), Atlantic Bluefin Tuna (Thunnus thynnus), and Bigeye Tuna (Thunnus obesus). Sustainability of most populations and recovery of overfished populations is possible with effective fisheries management, although some species’ populations show no sign of recovery after prolonged management.

Understanding how flowering phenology responds to warming and cooling (i.e., symmetric or asymmetric response) is needed to predict the response of flowering phenology to future climate change that will happen with the occurrence of warm and cold years superimposed upon a long-term trend. A three-year reciprocal translocation experiment was performed along an elevation gradient from 3200 m to 3800 m in the Tibetan Plateau for six alpine plants. Transplanting to lower elevation (warming) advanced the first flowering date (FFD) and transplanting to higher elevation (cooling) had the opposite effect. The FFD of early spring flowering plants (ESF) was four times less sensitive to warming than to cooling (by −2.1 d/°C and 8.4 d/°C, respectively), while midsummer flowering plants (MSF) were about twice as sensitive to warming than to cooling (−8.0 d/°C and 4.9 d/°C, respectively). Compared with pooled warming and cooling data, warming alone significantly underpredicted 3.1 d/°C for ESF and overestimated 1.7 d/°C for MSF. These results suggest that future empirical and experimental studies should consider nonlinear temperature responses that can cause such warming-cooling asymmetries as well as differing life strategies (ESF vs. MSF) among plant species.

The transcriptional repressor Slug is best known to control epithelial–mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E–cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele ‘T’ for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0·55, 95% confidence interval (CI) 0·34–0·91, P = 0·020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0·28, 95% CI 0·09–0·91, P = 0·033). Allele ‘A’ for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0·62, 95% CI 0·39–1·00, P = 0·048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0·45, 95% CI 0·22–0·93, P = 0·031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation.

Grassland soil organic carbon (SOC) is sensitive to anthropogenic activities. Increased anthropogenic disturbance related to overgrazing has led to widespread alpine grassland degradation on the Tibetan Plateau. The degraded grasslands are considered to have great potential for carbon sequestration after adoption of improved management practices. Here, we calibrated and employed the Century model to investigate the effects of overgrazing and improved managements on the SOC dynamics in alpine meadows. We calibrated the Century model against plant productivity at the Haibei Research Station. SOC stocks for validation were obtained in 2009–2010 from degraded alpine meadows in two communes. We found that Century model can successfully capture grassland SOC changes. Overall, our simulation suggests that degraded alpine meadow SOC significantly increased with the advent of restoration management from 2011 to 2030. Carbon sequestration rates ranged between 0.04 Mg C ha−1 yr−1 in lightly degraded winter grazing grasslands and 2.0 Mg C ha−1 yr−1 in moderately degraded summer grazing grasslands. Our modelling work also predicts that improve management in degraded Tibetan grasslands will contribute to an annual carbon sink of 0.022–0.059 Pg C yr−1. These results imply that restoration of degraded grasslands in the Tibetan Plateau has great potential for soil carbon sequestration to mitigate greenhouse gases.

Blast crisis of chronic myeloid leukemia is associated with poor survival and the accumulation of genomic lesions. Using whole-exome and/or RNA sequencing of patients at chronic phase (CP, n = 49), myeloid blast crisis (MBC, n = 19), and lymphoid blast crisis (LBC, n = 20), we found 25 focal gene deletions and 14 fusions in 24 patients in BC. Deletions predominated in LBC (83% of structural variants). Transcriptional analysis identified the upregulation of genes involved in V(D)J recombination, including RAG1/2 and DNTT in LBC. RAG recombination is a reported mediator of IKZF1 deletion. We investigated the extent of RAG-mediated genomic lesions in BC. Molecular hallmarks of RAG activity; DNTT-mediated nucleotide insertions and a RAG-binding motif at structural variants were exclusively found in patients with high RAG expression. Structural variants in 65% of patients in LBC displayed these hallmarks compared with only 5% in MBC. RAG-mediated events included focal deletion and novel fusion of genes associated with hematologic cancer: IKZF1, RUNX1, CDKN2A/B, and RB1. Importantly, 8/8 patients with elevated DNTT at CP diagnosis progressed to LBC by 12 months, potentially enabling early prediction of LBC. This work confirms the central mutagenic role of RAG in LBC and describes potential clinical utility in CML management.

Benzodiazepines and other omega-receptor agonists are frequently used for sleep and anxiety disorders. We studied the rates, correlates, and safety of individual benzodiazepines and zolpidem use from the records of 3690 patients in a national cohort of Dialysis Morbidity and Mortality Study Wave 2 data. We assessed drug utilization and an association between drug use and all-cause mortality. Overall, 14% of incident dialysis patients used a benzodiazepine or zolpidem. Women, Caucasians, current smokers, and patients with chronic obstructive pulmonary disease were more likely to use these drugs, whereas patients with cerebrovascular disease were less likely to use these drugs. In adjusted analyses, benzodiazepine or zolpidem use was associated with a 15% higher mortality rate. Chronic obstructive pulmonary disease significantly modified this association, suggesting that these patients were at higher risk. No association was found between benzodiazepine use and greater risk for hip fracture. We conclude that benzodiazepine or zolpidem use is common in incident dialysis patients and may be associated with greater mortality. Further studies are needed to elucidate the safety of these drugs in the dialysis population, which may lead to cautious and restrictive utilization of omega-receptor agonists in dialysis patients.