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MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from the CD44 + /CD24 −/low sub-population, we have isolated a novel PROCR + /ESA + BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR + /ESA + cells. Coincidently, high upregulation of miR-495 was also found in CD44 + /CD24 −/low BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.

\"The Greater Middle East: Travelogue & Reflections probes into the histories and cultures of different countries in the Greater Middle East through the author's recounting of his travelling experiences in those countries. It explores the historical causes and realistic reasons for the wars in Middle East, North Africa and the Caucasus and shows the author's investigation and understanding of the horizontal exchanges and vertical developments between various human civilizations. Different from the usually-called \"Middle East,\" the author combines the 21 members of the \"Cultural Middle East\" with 10 members of the \"Periphery,\" and collectively refer to these 31 countries as the \"Greater Middle East.\" The focus of this book remained on what the author had parsed from half a century of roaming, observation and reflection throughout the Greater Middle East. In this book, there are descriptions of major changes during these years, and lots of background information and personal impressions. This book can be an introduction book for the common readers, students and scholars interested in this topic\"-- Provided by publisher.

Background Quality of life (QOL) is an important component in assessing people’s health. Environmental quality can influence people’s QOL in the physical health, psychological, social relationships and environment domains. QOL in the four domains, overall QOL and general heath of residents living in the Kowloon Peninsula of Hong Kong were assessed. The association between satisfaction with the neighborhood environment and QOL, and health-related behaviors which mediated the effect were investigated. Methods A sample of 317 residents completed a questionnaire which comprised the WHOQOL-BREF (Hong Kong version) to assess QOL, the International Physical Activity Questionnaire (IPAQ) to study physical activities, and questions on satisfaction with the neighborhood environment, health-related behaviors and socio-demographics. One-way ANOVA and linear regression were used to study the associations between environmental satisfaction and QOL in the four domains, overall QOL and general health, followed by assessing the relationships between environmental satisfaction and the potential health-related behavior mediators with regression tests. Mediation analysis was conducted using multiple linear regressions to study the effects of environmental satisfaction on QOL in the four domains, overall QOL and general health, as well as the potential mediating roles played by various health-related behaviors. A P -value of < 0.05 was considered as statistically significant. Results The residents had a relatively higher physical health mean score of 70.83 ± 12.69, and a lower environmental mean score of 61.98 ± 13.76. Moderate satisfaction with the neighborhood environment had a significant relationship with QOL in the psychological domain (β = 0.170, P  = 0.006), however, this effect was partially mediated by the non-smoking behavior of the residents (β = 0.143, P  = 0.022). Conclusions Our residents had lower QOL in the physical health and psychological domains but similar QOL in the social relationships and environmental domains compared to other countries. Only QOL in the psychological domain could be predicted by the satisfaction with the neighborhood environment, and non-smoking status was a partial mediator of the effect of moderate environmental satisfaction on QOL in the psychological domain. Refrain from smoking seems to be able to lower the influence of neighborhood environment on people’s QOL in the psychological domain to a certain extent.

CMIP5 multimodel ensemble projection of midlatitude storm track changes has been examined. Storm track activity is quantified by temporal variance of meridional wind and sea level pressure (psl), as well as cyclone track statistics. For the Southern Hemisphere (SH), CMIP5 models project clear poleward migration, upward expansion, and intensification of the storm track. For the Northern Hemisphere (NH), the models also project some poleward shift and upward expansion of the storm track in the upper troposphere/lower stratosphere, but mainly weakening of the storm track toward its equatorward flank in the troposphere. Consistent with these, CMIP5 models project significant increase in the frequency of extreme cyclones during the SH cool season, but significant decrease in such events in the NH. Comparisons with CMIP3 projections indicate high degrees of consistency for SH projections, but significant differences are found in the NH. Overall, CMIP5 models project larger decrease in storm track activity in the NH troposphere, especially over North America in winter, where psl variance as well as cyclone frequency and amplitude are all projected to decrease significantly. In terms of climatology, similar to CMIP3, most CMIP5 models simulate storm tracks that are too weak and display equatorward biases in their latitude. These biases have also been related to future projections. In the NH, the strength of a model's climatological storm track is negatively correlated with its projected amplitude change under global warming, while in the SH, models with large equatorward biases in storm track latitude tend to project larger poleward shifts. Key Points CMIP5 ensemble projection of mid‐latitude storm track changes are documented Projections consistent with CMIP3 in SH, but significant differences in the NH Models have biases in climatology which are correlated with future projections

Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.

Rossby wave packets (RWPs) are Rossby waves for which the amplitude has a local maximum and decays to smaller values at larger distances. This review focuses on upper-tropospheric transient RWPs along the midlatitude jet stream. Their central characteristic is the propagation in the zonal direction as well as the transfer of wave energy from one individual trough or ridge to its downstream neighbor, a process called “downstream development.” These RWPs sometimes act as long-range precursors to extreme weather and presumably have an influence on the predictability of midlatitude weather systems. The paper reviews research progress in this area with an emphasis on developments during the last 15 years. The current state of knowledge is summarized including a discussion of the RWP life cycle as well as Rossby waveguides. Recent progress in the dynamical understanding of RWPs has been based, in part, on the development of diagnostic methods. These methods include algorithms to identify and track RWPs in an automated manner, which can be used to extract the climatological properties of RWPs. RWP dynamics have traditionally been investigated using the eddy kinetic energy framework; alternative approaches based on potential vorticity and wave activity fluxes are discussed and put into perspective with the more traditional approach. The different diagnostics are compared to each other and the strengths and weaknesses of individual methods are highlighted. A recurrent theme is the role of diabatic processes, which can be a source for forecast errors. Finally, the paper points to important open research questions and suggests avenues for future research.

Gain of function of membrane receptor was a good strategy exploited by cancer cells to benefit own growth and survival. Overexpression of HER2 has been found to serve as a target for developing trastuzumab to treat 20–25% of breast cancer. However, little or none of the other membrane receptor was found to be useful as a potential target for breast cancer treatment since then. Here, we showed that amplified signaling of interleukin-17 receptor B (IL-17RB) and its ligand IL-17B promoted tumorigenicity in breast cancer cells and impeded acinus formation in immortalized normal mammary epithelial cells. External signal transmitted through IL-17RB activated nuclear factor-κB to upregulate antiapoptotic factor Bcl-2 and induced etoposide resistance. Elevated expression of IL-17RB had a stronger correlation with poor prognosis than HER2 in breast cancer patients. Interestingly, breast cancer patients with high expression of IL-17RB and HER2 had the shortest survival rate. Depletion of IL-17RB in trastuzumab-resistant breast cancer cells significantly reduced their tumorigenic activity, suggesting that IL-17RB and HER2 have an independent role in breast carcinogenesis. Furthermore, treatment with antibodies specifically against IL-17RB or IL-17B effectively attenuated tumorigenicity of breast cancer cells. These results suggest that the amplified IL-17RB/IL-17B signaling pathways may serve as a therapeutic target for developing treatment to manage IL-17RB-associated breast cancer.

Artificial van der Waals heterostructures with two-dimensional (2D) atomic crystals are promising as an active channel or as a buffer contact layer for next-generation devices. However, genuine 2D heterostructure devices remain limited because of impurity-involved transfer process and metastable and inhomogeneous heterostructure formation. We used laser-induced phase patterning, a polymorph engineering, to fabricate an ohmic heterophase homojunction between semiconducting hexagonal (2H) and metallic monoclinic (1T') molybdenum ditelluride (MoTe2) that is stable up to 300°C and increases the carrier mobility of the MoTe2 transistor by a factor of about 50, while retaining a high on/off current ratio of 106. In situ scanning transmission electron microscopy results combined with theoretical calculations reveal that the Te vacancy triggers the local phase transition in MoTe2, achieving a true 2D device with an ohmic contact.

Cold‐season methane (CH4) emissions may be poorly constrained in wetland models. We examined cold‐season CH4 emissions simulated by 16 models participating in the Global Carbon Project model intercomparison and analyzed temporal and spatial patterns in simulation results using prescribed inundation data for 2000–2020. Estimated annual CH4 emissions from northern (>60°N) wetlands averaged 10.0 ± 5.5 Tg CH4 yr−1. While summer CH4 emissions were well simulated compared to in‐situ flux measurement observations, the models underestimated CH4 during September to May relative to annual total (27 ± 9%, compared to 45% in observations) and substantially in the months with subzero air temperatures (5 ± 5%, compared to 27% in observations). Because of winter warming, nevertheless, the contribution of cold‐season emissions was simulated to increase at 0.4 ± 0.8% decade−1. Different parameterizations of processes, for example, freezing–thawing and snow insulation, caused conspicuous variability among models, implying the necessity of model refinement. Plain Language Summary Wetlands in the northern high latitudes are a major source of methane (CH4) to the atmosphere, mainly during the warm season. Previously, models have assumed that cold‐season CH4 emissions are low, but recent observations suggest high‐latitude wetlands can be substantial sources even in winter. We compared CH4 emissions simulated by 16 state‐of‐the‐art wetland models, participating in a model intercomparison project with a focus on the cold‐season in northern wetlands. The model simulations indicated that nearly one third of annual emissions were simulated to occur from September to May, and CH4 emissions to the atmosphere were not negligible even under freezing air temperatures, although the results differed greatly among the models. However, field studies suggest cold‐season emissions account for an even larger fraction of annual emissions. These results highlight the contribution of cold‐season emissions to the annual CH4 budget, which future climatic warming is expected to affect severely, and they also show that simulations of cold‐season CH4 emissions from wetlands need to be improved. Key Points Cold‐season methane (CH4) emissions simulated by 16 Global Carbon Project‐CH4 wetland models were analyzed Most models underestimate the cold‐season emissions in comparison with observational data Further model improvement by including cold‐season processes is required to reduce the model bias and uncertainty