Together, these findings demonstrate that each EE variant causes a unique combination of defects in Kv7 channel function and neuronal expression, and suggest a critical need for both prediction algorithms and experimental interrogations to understand pathophysiology of Kv7-associated EE.Jazmurian playa was an ephemeral lake with a large catchment in southeast Iran, which dried up over the last 10 years as a result of prolonged drought. As the lake was recipient of incoming industrial water with trace metals deposited to the sediment, the dust is the cause of environmental concern of the region and requires evaluation and better management. The aim of this study was to evaluate the environmental and ecological pollution of Jazmurian playa. Hence, 24 collected surface sedimentary samples were analyzed with ICP-OES. The environmental pollution indices including degree of contamination (Cd), geoaccumulation index (Igeo), enrichment factor (EF), pollution load index (PLI) and potential ecological risk (PER) were determined. The study revealed moderately to strongly pollution levels of Pb, Ni and Al, while Dy, Pb, Y, Yb, Sm, Te, U, Cu, Mn, Sc represented moderate pollution. The EF values indicated four sites were highly enriched with Dy, Pb and Ni. The PER results showed high risk for four sites and considerable risk for others. Cluster analysis illustrated interconnection between the contaminants and the sites with major pollution at six sites. Obviously, climate change has considerable complex environmental impacts through transformation of local water and sediment pollution problem.Owing to the involvement of cyclooxygenase-2 (COX-2) in carcinogenesis, COX-2-selective inhibitors are increasingly studied for their potential cytotoxic properties. Moreover, the incorporation of carboranes in structures of established anti-inflammatory drugs can improve the potency and metabolic stability of the inhibitors. Herein, we report the synthesis of carborane-containing derivatives of rofecoxib that display remarkable cytotoxic or cytostatic activity in the micromolar range with excellent selectivity for melanoma and colon cancer cell lines over normal cells. Furthermore, it was shown that the carborane-modified derivatives of rofecoxib showed different modes of action that were dependent on the cell type.Cutaneous melanoma is an aggressive neoplasm and is responsible for the majority of skin cancer deaths. Several miRNAs are involved in melanoma tumor progression. One of them is miR-205, the loss of which contributes to the development of melanoma metastasis. We evaluated whole-genome mRNA expression profiling associated with different miR-205 expression levels in melanoma cells. Differential expression analysis identified 243 differentially expressed transcripts including inositol polyphosphate 5′-phosphatase-like protein-1 (INPPL1) and BTB/POZ Domain-Containing Protein 3 (BTBD3). INPPL1 and BTBD3 were downregulated when melanoma cells expressed miR-205, indicating that these genes are potential miR-205 targets. Additionally, the target prediction algorithm TargetScan revealed that INPPL1 and BTBD3 genes had predicted target sites of miR-205 in their 3’UTRs and functional analysis demonstrated that these genes were directly linked to miR-205. Interestingly, our clinical data showed that INPPL1 was significantly associated with lymph node metastasis-free survival (LNMFS), distant metastasis-free survival (DMFS) and melanoma specific survival (MSS). This study supports INPPL1 as a miR-205 target gene and, therefore, that the involvement of miR-205 in the metastatic dissemination of malignant melanoma is, at least in part, via INPPL1.Overweight in children is strongly associated with parental body mass index (BMI) and overweight. We assessed parental transmitted and non-transmitted genetic contributions to overweight in children from the Danish National Birth Cohort by constructing genetic risk scores (GRSs) from 941 common genetic variants associated with adult BMI and estimating associations of transmitted maternal/paternal and non-transmitted maternal GRS with child overweight. Maternal and paternal BMI (standard deviation (SD) units) had a strong association with childhood overweight [Odds ratio (OR) 2.01 (95% confidence interval (CI) 1.74; 2.34) and 1.64 (95% CI 1.43; 1.89)]. Maternal and paternal transmitted GRSs (SD-units) increased odds for child overweight equally [OR 1.30 (95% CI 1.16; 1.46) and 1.30 (95% CI 1.16; 1.47)]. However, both the parental phenotypic and the GRS associations may depend on maternal BMI, being weaker among mothers with overweight. Maternal non-transmitted GRS was not associated with child overweight [OR 0.98 (95% CI 0.88; 1.10)] suggesting no specific influence of maternal adiposity as such. In conclusion, parental transmitted GRSs, based on adult BMI, contribute to child overweight, but in overweight mothers other genetic and environmental factors may play a greater role.Effect of crop row spacing on the belowground ecosystem, especially at an aggregate scale, remains unexplored. To explore how row spacing influenced nematode community and ecosystem function at the aggregate scale, four row spacings i.e. equidistant-row (ER, 50 cm-inter-row distance, 33 cm-intra-row between plants in each row) and non-equidistant-row including NR1 (100 cm + 50 cm row distance and 22 cm intra-row), NR2 (100 cm + 50 cm inter-row and 25 cm intra-row), and NR3 (60 cm + 40 cm inter-row and 33 cm intra-row) were compared, and four soil aggregate fractions i.e. >2 mm, 1-2 mm, 0.25-1 mm and less then 0.25 mm were separated. Row spacing did not impact C and N, but significantly influenced P. The regulation effect of acid phosphatase on soil available P was aggregate-scale dependent. Nematode faunal analysis indicated that NR3 within 0.25-1 mm was less disturbed or relatively undisturbed environments. Structural equation model showed row spacing pattern directly affected multifunctionality, while aggregate fractions indirectly contributed to multifunctionality mainly by regulating the richness of total nematodes and trophic groups. It was concluded that NR3 had potential to construct more stable food web, and therefore was possibly the suitable planting pattern.Breast cancer is the most lethal cancer in women and displaying a broad range of heterogeneity in terms of clinical, molecular behavior and response to therapy. Increasing evidence demonstrated that immune-related genes were an important source of prognostic information for several types of tumors. In this study, the k-mean clustering was applied to gene expression data from the immune-related genes, two molecular clusters were identified for 1980 breast cancer patients. The prognostic significance of the immune-related genes based classification was confirmed in the log-rank test. These clusters were also associated with immune checkpoints, immune-related features and tumor infiltrating levels. In addition, we used the shrunken centroid algorithm to predict the cluster of a given breast cancer sample, and good predictive results were obtained by this algorithm. These results indicated that the proposed classification method is a promising method, and we hope that this method may improve the treatment stratification of breast cancer in the future.Soil moisture is an important variable for land-climate and hydrological interactions. To investigate emergent large-scale, long-term interactions between soil moisture and other key hydro-climatic variables (precipitation, actual evapotranspiration, runoff, temperature), we analyze monthly values and anomalies of these variables in 1378 hydrological catchments across Europe over the period 1980-2010. The study distinguishes results for the main European climate regions, and tests how sensitive or robust they are to the use of three alternative observational and re-analysis datasets. Robustly across the European climates and datasets, monthly soil moisture anomalies correlate well with runoff anomalies, and extreme soil moisture and runoff values also largely co-occur. For precipitation, evapotranspiration, and temperature, anomaly correlation and extreme value co-occurrence with soil moisture are overall lower than for runoff. The runoff results indicate a possible new approach to assessing variability and change of large-scale soil moisture conditions by use of long-term time series of monitored catchment-integrating stream discharges.We investigated endogenous tissue response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch intended for tendon repair. A sheep tendon injury model characterised by a natural history of consistent failure of healing was chosen to assess the biological potential of woven and aligned electrospun fibres to induce a reparative response. Patches were implanted into 8 female adult English Mule sheep. Significant infiltration of tendon fibroblasts was observed within the electrospun component of the patch but not within the woven component. The cellular infiltrate into the electrospun fibres was accompanied by an extensive network of new blood vessel formation. Tendon fibroblasts were the most abundant scaffold-populating cell type. CD45+, CD4+ and CD14+ cells were also present, with few foreign body giant cells. There were no local or systemic signs of excessive inflammation with normal hematology and serology for inflammatory markers three months after scaffold implantation. In conclusion, we demonstrate that an endogenous healing response can be safely induced in tendon by means of biophysical cues using a woven and electrospun patch.We consider the ground state and the collective excitations of dipolar Bose-Einstein condensates in a bubble trap, i.e., a shell-shaped spherically symmetric confining potential. By means of an appropriate Gaussian ansatz, we determine the ground-state properties in the case where the particles interact by means of both the isotropic and short-range contact and the anisotropic and long-range dipole-dipole potential in the thin-shell limit. Moreover, with the ground state at hand, we employ the sum-rule approach to study the monopole, the two-, the three-dimensional quadrupole as well as the dipole modes. We find situations in which neither the virial nor Kohn’s theorem can be applied. On top of that, we demonstrate the existence of anisotropic particle density profiles, which are absent in the case with repulsive contact interaction only. These significant deviations from what one would typically expect are then traced back to both the anisotropic nature of the dipolar interaction and the novel topology introduced by the bubble trap.For patients with cervical cancer, despite the incidence and mortality rates have been declining in recent years, due to its huge population base, cervical cancer has always been a serious public health problem. Our research placed emphasis on the indices greatly associated with overall area-specific social economic status, making up for the defects of traditional research which only pay attention to the situation of some specific disease or patients’ individual social status. A total of 39160 women identified cervical cancer were concluded in our study from the Surveillance, Epidemiology, and End Results (SEER) 18 Program data between 1980 and 2014. With improving the area-specific social economic factors in recent years, the occurrence and prognosis of cervical cancer showed different variation patterns respectively. Some states like California and Georgia for their better economic status and more healthcare investment by local medical institution, population there showed a lower prevalence, incidence, more timely diagnosis, effective treatment, and better prognosis.