OBJECTIVESSARS-CoV-2 testing has been critical in monitoring and containing the COVID-19 pandemic, but there is a dearth of studies on how individuals' adherence to testing varies according to their ...working conditions. This study aimed to investigate the association between the type of employment contract and COVID-19 testing among wage workers in South Korea.STUDY DESIGNWe used a nationally representative sample of employees aged 20-65 years collected from March 24 to 31, 2022. To focus on individual responses when the test was recommended, our sample consisted of 1266 participants who had experienced symptoms of COVID-19 or had been exposed to a confirmed case in the household.METHODSWe used multivariate logistic regression to estimate the association between the odds of receiving a PCR test and the type of employment contract while controlling for other potential covariates.RESULTSThe percentage of participants who had a SARS-CoV-2 PCR test was 77.8%. After adjusting for all potential covariates, daily workers (OR = 0.35, 95% CI 0.18 to 0.70, P = 0.003) and part-time workers (OR = 0.58, 95% CI 0.39 to 0.86, P = 0.007) had significantly lower odds of being tested relative to standard workers. Other temporary or atypical workers showed no significant differences from standard workers.CONCLUSIONOur findings suggested that individuals in the most vulnerable job positions, with less job security and working hours, exhibited a decreased inclination to undergo COVID-19 testing. More effective job retention and income support policies are required to improve compliance.
Abstract Induced pluripotent stem cells (iPSCs) hold great promise as a cell source for regenerative medicine yet its culture, maintenance of pluripotency and induction of differentiation remain ...challenging. Conversely, graphene (G) and graphene oxide (GO) have captured tremendous interests in the fields of materials science, physics, chemistry and nanotechnology. Here we report on that G and GO can support the mouse iPSCs culture and allow for spontaneous differentiation. Intriguingly, G and GO surfaces led to distinct cell proliferation and differentiation characteristics. In comparison with the glass surface, iPSCs cultured on the G surface exhibited similar degrees of cell adhesion and proliferation while iPSCs on the GO surface adhered and proliferated at a faster rate. Moreover, G favorably maintained the iPSCs in the undifferentiated state while GO expedited the differentiation. The iPSCs cultured on both G and GO surfaces spontaneously differentiated into ectodermal and mesodermal lineages without significant disparity, but G suppressed the iPSCs differentiation towards the endodermal lineage whereas GO augmented the endodermal differentiation. These data collectively demonstrated that the different surface properties of G and GO governed the iPSCs behavior and implicate the potentials of graphene-based materials as a platform for iPSCs culture and diverse applications.
BACKGROUND AND PURPOSE Transient receptor potential ion channel vanilloid 3 (TRPV3) is expressed in skin keratinocytes and plays an important role in thermal and chemical nociceptions in the ...periphery. The presence of TRPV3 inhibitors would improve our understanding of TRPV3 function and help to develop receptor‐specific analgesics. However, little is known about physiological substances that specifically inhibit TRPV3 activity. Here, we investigated whether 17(R)‐resolvin D1 (17R‐RvD1), a naturally occurring pro‐resolving lipid specifically affects TRPV3 activity.
EXPERIMENTAL APPROACH We examined the effect of 17R‐RvD1 on sensory TRP channels using Ca2+ imaging and whole cell electrophysiology experiments in a HEK cell heterologous expression system, cultured sensory neurons and keratinocytes. We also examined changes in sensory TRP agonist‐specific acute licking/flicking or flinching behaviours and mechanical and thermal pain behaviours using Hargreaves, Randall‐Selitto and von Frey assay systems in the absence and presence of inflammation.
KEY RESULTS We showed that 17R‐RvD1 specifically suppresses TRPV3‐mediated activity at nanomolar and micromolar concentrations. The voltage‐dependence of TRPV3 activation by camphor was shifted rightwards by 17R‐RvD1, which indicates its inhibitory mechanism is as a result of a shift in voltage‐dependence. Consistently, TRPV3‐specific acute pain behaviours were attenuated by locally injected 17R‐RvD1. Moreover, the administration of 17R‐RvD1 significantly reversed the thermal hypersensitivity that occurs during an inflammatory response. Knockdown of epidermal TRPV3 blunted these antinociceptive effects of 17R‐RvD1.
CONCLUSIONS AND IMPLICATIONS 17R‐RvD1 is a novel natural inhibitory substance specific for TRPV3. The results of our behavioural studies suggest that 17R‐RvD1 has acute analgesic potential via TRPV3‐specific mechanisms.
Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this ...process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.
Abstract
The role of the cosmic web in shaping galaxy properties is investigated in the Galaxy And Mass Assembly (GAMA) spectroscopic survey in the redshift range 0.03 ≤ z ≤ 0.25. The stellar mass, ...u − r dust corrected colour and specific star formation rate (sSFR) of galaxies are analysed as a function of their distances to the 3D cosmic web features, such as nodes, filaments and walls, as reconstructed by DisPerSE. Significant mass and type/colour gradients are found for the whole population, with more massive and/or passive galaxies being located closer to the filament and wall than their less massive and/or star-forming counterparts. Mass segregation persists among the star-forming population alone. The red fraction of galaxies increases when closing in on nodes, and on filaments regardless of the distance to nodes. Similarly, the star-forming population reddens (or lowers its sSFR) at fixed mass when closing in on filament, implying that some quenching takes place. These trends are also found in the state-of-the-art hydrodynamical simulation Horizon-AGN. These results suggest that on top of stellar mass and large-scale density, the traceless component of the tides from the anisotropic large-scale environment also shapes galactic properties. An extension of excursion theory accounting for filamentary tides provides a qualitative explanation in terms of anisotropic assembly bias: at a given mass, the accretion rate varies with the orientation and distance to filaments. It also explains the absence of type/colour gradients in the data on smaller, non-linear scales.
Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship ...between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.
Human tumors are stiff and data suggest that the extracellular matrix stiffening is consistent with experimental mammary tumor models in which stiffness drives tumor invasion and metastasis.
Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial ...vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.
Coronary computed tomographic angiography (coronary CT) is a non-invasive test for diagnosis of cardiac function. Coronary calcium scores determined by coronary CT are associated with cardiovascular ...risk factors. However, no studies have investigated the association between coronary calcium scores and cardiovascular complications after liver transplantation (LT). We therefore evaluated the utility of preoperative coronary calcium scores for predicting early postoperative cardiovascular complications in LT recipients.
Between 2010 and 2012, 443 LT recipients were analysed retrospectively. Preoperative cardiovascular assessments, including coronary CT, were performed. A coronary calcium score >400 was defined as a positive finding. Predictive factors of early postoperative cardiovascular complications were evaluated by univariate and multivariate analyses. Major cardiovascular complications occurring during a period of 1 month after LT were noted.
Of the 443 patients, 38 (8.6%) experienced one or more cardiovascular complications. Positive coronary CT findings were seen in 11 (2.5%) patients. In the multivariate analysis, a coronary calcium score >400 {odds ratio (OR)=4.62 95% confidence interval (CI): 1.14–18.72, P=0.032} and female sex OR=2.76 (1.37–5.57), P=0.005 were predictive of cardiovascular complications.
A preoperative coronary calcium score of >400 predicted cardiovascular complications occurring 1 month after LT, suggesting that preoperative evaluation of coronary calcium scores could help predict early postoperative cardiovascular complications in LT recipients.
Bronchopulmonary dysplasia (BPD) is potentially one of the most devastating conditions in premature infants with longstanding consequences involving multiple organ systems including adverse effects ...on pulmonary function and neurodevelopmental outcome. Here we review recent studies in the field to summarize the progress made in understanding in the pathophysiology, prognosis, prevention, and treatment of BPD in the last decade. The work reviewed includes the progress in understanding its pathobiology, genomic studies, ventilatory strategies, outcomes, and therapeutic interventions. We expect that this review will help guide clinicians to treat premature infants at risk for BPD better and lead researchers to initiate further studies in the field.
Claudins (CLDNs) are a family of integral membrane proteins central to the formation of tight junctions, structures that are involved in paracellular transport and cellular growth and ...differentiation, and are critical for the maintenance of cellular polarity. Recent studies have provided evidence that CLDNs are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs). However, little is known about how CLDN expression is involved in cancer progression. In this study, we show that CLDN1 has a causal role in the epithelial-mesenchymal transition (EMT) in human liver cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the induction of malignant progression by CLDN1. Overexpression of CLDN1 induced expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby led to repression of E-cadherin, β-catenin expression, enhanced expression of N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in normal liver cells and HCC cells. In line with these findings, inhibition of either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a reversal of N-cadherin and E-cadherin expression patterns, and restored normal motility. Collectively, these results indicate that CLDN1 is necessary for the induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1-ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the malignant phenotype. The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC.
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