Identifying Context-Specific Categories for Visualizing Livability of Cities—a Case Study of Malmö

Livability is a concept being applied to cities, even though it is vague. Worldwide, there are several livable city ranking schemes in use, which compare the livability of cities by making use of standardized indicator sets. The research presented here recognizes, as a point of departure, that each city is unique, implying that comparisons of cities by standardized categories only does not adequately reflect the reality of each city. A qualitative approach to identify context-specific categories of livability is proposed and employed to the case of Malmo ̈ in Sweden. Through interviews, nine context-specific categories were identified and visualized. The findings of the study demonstrate that a qualitative approach enables a more in-depth description of livability categories because it can capture and illustrate relationships among the categories. An explicit awareness of such relationships may provide a more holistic perspective to city officials and planners as they aim to improve the livability of their cities. The study concludes that a qualitative approach in identifying context-specific categories can complement existing assessment schemes and allow a better grasp of livability challenges to cities

Claudin-6は、腸型胃がんの亜群において独立した予後因子であるとともにがん促進遺伝子として機能する

Background We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. Methods Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated. Results CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren’s intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part. Conclusions: This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients

Elevation of Bombina variegata peptide 8 in mice with collagen-induced arthritis

<p>Abstract</p> <p>Background</p> <p><it>Bombina variegate </it>peptide 8 (Bv8) is a small protein secreted by frog skin. Recently it has been shown to contribute to tumor angiogenesis in mouse model. The purpose of this study was to investigate Bv8 in mice with type II collagen-induced arthritis (CIA).</p> <p>Methods</p> <p>We induced CIA in male DBA/1J mice. The severity of arthritis was evaluated based on an arthritis score. RNA was extracted from the joint, and examined for Bv8 mRNA expression by RT-PCR and real-time RT-PCR. Synovial tissue and bone marrow were immunohistochemically examined using anti-Bv8 antibody.</p> <p>Results</p> <p>The level of Bv8 mRNA expression in the joint was below the detection limit in the control group, but was elevated in the CIA group, and was correlated with the arthritis score. In addition, an increase in Bv8-positive cells was observed in the synovium and bone marrow in the CIA group.</p> <p>Conclusion</p> <p>Bv8 was elevated in the synovium and bone marrow of CIA mice, suggesting that Bv8 plays an important role in the pathogenesis of arthritis.</p

Identifying Context-Specific Categories for Visualizing Livability of Cities—a Case Study of Malmö

Livability is a concept being applied to cities, even though it is vague. Worldwide, there are several livable city ranking schemes in use, which compare the livability of cities by making use of standardized indicator sets. The research presented here recognizes, as a point of departure, that each city is unique, implying that comparisons of cities by standardized categories only does not adequately reflect the reality of each city. A qualitative approach to identify context-specific categories of livability is proposed and employed to the case of Malmo ̈ in Sweden. Through interviews, nine context-specific categories were identified and visualized. The findings of the study demonstrate that a qualitative approach enables a more in-depth description of livability categories because it can capture and illustrate relationships among the categories. An explicit awareness of such relationships may provide a more holistic perspective to city officials and planners as they aim to improve the livability of their cities. The study concludes that a qualitative approach in identifying context-specific categories can complement existing assessment schemes and allow a better grasp of livability challenges to cities

Immunolocalization of Voltage-Gated Potassium Channel Kv3.4 Subunit in the Cochlea

Immunohistochemical localization of voltage-gated potassium channel Kv3.4 subunit was studied in the guinea-pig cochlea. Kv3.4-like immunoreactivity was present in the type I and suprastrial fibrocytes of the spiral ligament and the basal cells of the stria vascularis. Immunostaining was also found in the type II-IV fibrocytes of the spiral ligament and the connective tissue cells of the spiral limbus. In the organ of Corti, Kv3.4-like immunoreactivity was found in the sensory cells and the neighboring supporting cells. The root cells and interdental cells were positively immunostained. Immunoreactivity was also found in the endothelial cells of the blood vessels in the cochlear modiolus. These results suggest that Kv3.4 may participate in the potassium ion recycling mechanism in the cochlea

KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression

KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Correlation Between Preparation Parameters And Properties Of Molybdenum Back Contact Layer For Cigs Thin Film Solar Cells

Molybdenum (Mo) thin film back contact layers for thin film CuIn(1-x)GaxSe2 (CIGS) solar cells were deposited onto soda lime glass substrates using a direct current (DC) planar magnetron sputtering deposition technique. Requirements for the Mo thin film as a back contact layer for CIGS solar cells are various. Sheet resistance, contact resistance to the CIGS absorber, optical reflectance, surface morphology, and adhesion to the glass substrate are the most important properties that the Mo thin film back contact layer must satisfy. Experiments were carried out under various combinations of sputtering power and working gas pressure, for it is well known that mechanical, morphological, optical, and electrical property of a sputter-deposited Mo thin film are dependent on these process parameters. Various properties of each Mo film were measured and discussed. Sheet resistances were measured using a four-point probe equipment and minimum value of 0.25 Ω/sq was obtained for the 0.6 µm-thick Mo film. Average surface roughnesses of each Mo film ranged from 15 to 26 Å were measured by Dektak profilometer which was also employed to measure film thicknesses. Resistivities were calculated from the sheet resistance and film thickness of each film. Minimum resistivity of 11.9 µΩ∙cm was obtained with the Mo thin film deposited at 0.1 mTorr and 250 W. A residual stress analysis was conducted with a bending beam technique with very thin glass strips, and maximum tensile stress of 358 MPa was obtained; however, films did not exhibit a compressive stress. Adhesive strengths were examined for all films with a Scotch-tape test, and all films showed a good adhesion to the glass substrate. iv Sputter-deposited Mo thin films are commonly employed as a back contact layer for CIGS and CuInSe2 (CIS)-based solar cells; however, there are several difficulties in fabricating a qualified back contact layer. Generally, Mo thin films deposited at higher sputtering power and lower working gas pressure tend to exhibit lower resistivity; however, such films have a poor adhesion to the glass substrate. On the other hand, films deposited at lower power and higher gas pressure tend to have a higher resistivity, whereas the films exhibit an excellent adhesion to the glass substrate. Therefore, it has been a practice to employ multi-layered Mo thin film back contact layers to achieve the properties of good adhesion to the glass substrate and low resistivity simultaneously. However, multi layer processes have a lower throughput and higher fabricating cost, and requires more elaborated equipment compared to single layer processes, which are not desirable from the industrial point of view. As can be seen, above mentioned process parameters and the corresponding Mo thin film properties are at the two extreme ends of the spectrum. Hence experiments were conducted to find out the mechanisms which influence the properties of Mo thin films by changing the two process parameters of working gas pressure and sputtering power individually. The relationships between process parameters and above mentioned properties were studied and explained. It was found that by selecting the process parameters properly, less resistive, appropriatesurfaced, and highly adhesive single layer Mo thin films for CIGS solar cells can be achieved