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Rising global temperatures can lead to heat waves, which in turn can pose health risks to the community. However, a notable gap remains in highlighting the primary contributing factors that amplify heat-health risk among vulnerable populations. This study aims to evaluate the precedence of heat stress contributing factors in urban and rural vulnerable populations living in hot and humid tropical regions. A comparative cross-sectional study was conducted, involving 108 respondents from urban and rural areas in Klang Valley, Malaysia, using a face-to-face interview and a validated questionnaire. Data was analyzed using the principal component analysis, categorizing factors into exposure, sensitivity, and adaptive capacity indicators. In urban areas, five principal components (PCs) explained 64.3% of variability, with primary factors being sensitivity (health morbidity, medicine intake, increased age), adaptive capacity (outdoor occupation type, lack of ceiling, longer residency duration), and exposure (lower ceiling height, increased building age). In rural, five PCs explained 71.5% of variability, with primary factors being exposure (lack of ceiling, high thermal conductivity roof material, increased building age, shorter residency duration), sensitivity (health morbidity, medicine intake, increased age), and adaptive capacity (female, non-smoking, higher BMI). The order of heat-health vulnerability indicators was sensitivity > adaptive capacity > exposure for urban areas, and exposure > sensitivity > adaptive capacity for rural areas. This study demonstrated a different pattern of leading contributors to heat stress between urban and rural vulnerable populations., (© 2024. The Author(s).)

Nucleus pulposus (NP) cells of the intervertebral disc are essential for synthesizing extracellular matrix that contributes to disc health and mechanical function. NP cells have a unique morphology and molecular expression pattern derived from their notochordal origin, and reside in N-cadherin (CDH2) positive cell clusters in vivo. With disc degeneration, NP cells undergo morphologic and phenotypic changes including loss of CDH2 expression and ability to form cell clusters. Here, we investigate the role of CDH2 positive cell clusters in preserving healthy, biosynthetically active NP cells. Using a laminin-functionalized hydrogel system designed to mimic features of the native NP microenvironment, we demonstrate NP cell phenotype and morphology is preserved only when NP cells form CDH2 positive cell clusters. Knockdown (CRISPRi) or blocking CDH2 expression in vitro and in vivo results in loss of a healthy NP cell. Findings also reveal that degenerate human NP cells that are CDH2 negative can be promoted to re-express CDH2 and healthy, juvenile NP matrix synthesis patterns by promoting cell clustering for controlled microenvironment conditions. This work also identifies CDH2 interactions with β-catenin-regulated signaling as one mechanism by which CDH2-mediated cell interactions can control NP cell phenotype and biosynthesis towards maintenance of healthy intervertebral disc tissues.

SSX genes show extensive nucleotide sequence conservation but little is known of their function. Disruption of SSX1 or SSX2, by chromosome translocation and 'in-frame' fusion to SYT, is a consistent feature of synovial sarcomas. The resulting SYT-SSX1/SSX2 proteins are activators of transcription; transactivation function is located in SYT. Unrearranged SSX1 can repress transcription, and this has been attributed to a putative Krüppel associated box (KRAB) repression domain at the N-terminus. Here we isolated SSX-KRAB domains to specifically measure repression activity, using a previously characterized KOX1-KRAB domain as a control. In our repressor assay SSX1- and SSX2-KRAB domains down-modulated the transactivation of a reporter gene by threefold, compared with 83-fold repression achieved by KOX1-KRAB in the assay. Yeast two-hybrid analysis showed that SSX1-KRAB, unlike KOX1-KRAB, fails to interact with the KRAB co-repressor TIF1beta. These results raise questions about the evolutionary and functional relationship of SSX-KRAB and typical KRAB domains of Krüppel zinc finger genes. We found that full-length SSX1 showed potent (74-fold) repression in our repressor assay, indicating the existence of a repression domain distinct from SSX-KRAB. By assaying deletion constructs of SSX1 we localized repression activity to 33 amino acids at the C-terminus. This novel domain is conserved between SSX family members, and, unlike the KRAB-related domain, is retained on fusion with SYT. This has important implications in understanding the mechanism by which the SYT-SSX fusion protein could contribute to neoplasia.