Calcium cycling protein density and functional importance to automaticity of isolated sinoatrial nodal cells are independent of cell size

Spontaneous, localized, rhythmic ryanodine receptor (RyRs) Ca(2+) releases occur beneath the cell membrane during late diastolic depolarization in cardiac sinoatrial nodal cells (SANCs). These activate the Na(+)/Ca(2+) exchanger (NCX1) to generate inward current and membrane excitation that drives normal spontaneous beating. The morphological background for the proposed functional of RyR and NCX crosstalk, however, has not been demonstrated. Here we show that the average isolated SANC whole cell labeling density of RyRs and SERCA2 is similar to atrial and ventricle myocytes, and is similar among SANCs of all sizes. Labeling of NCX1 is also similar among SANCs of all sizes and exceeds that in atrial and ventricle myocytes. Submembrane colocalization of NCX1 and cardiac RyR (cRyR) in all SANCs exceeds that in the other cell types. Further, the Cx43 negative primary pacemaker area of the intact rabbit sinoatrial node (SAN) exhibits robust positive labeling for cRyR, NCX1, and SERCA2. Functional studies in isolated SANCs show that neither the average action potential (AP) characteristics, nor those of intracellular Ca(2+) releases, nor the spontaneous cycle length vary with cell size. Chelation of intracellular [Ca(2+)], or disabling RyRs or NCX1, markedly attenuates or abolishes spontaneous SANC beating in all SANCs. Thus, there is dense labeling of SERCA2, RyRs, and NCX1 in small-sized SANCs, thought to reside within the SAN center, the site of impulse initiation. Because normal automaticity of these cells requires intact Ca(2+) cycling, interactions of SERCA, RyR2 and NCX molecules are implicated in the initiation of the SAN impulse.     

A Review of Impact of Textile Research on Protective Face Masks

COVID-19, classified as SARS-CoV-2, is causing an ongoing global pandemic. The pandemic has resulted in the loss of lives and has caused economic hardships. Most of the devices used to protect against the transmission of the novel COVID-19 disease are related to textile structures. Hence, the challenge for textile professionals is to design and develop suitable textile structures with multiple functionalities for capturing viruses, passivating them, and, at the same time, having no adverse effects on humans during the complete period of use. In addition to manufacturing efficient, biocompatible, and cost-effective protective face masks, it is also necessary to inform the public about the benefits and risks of protective face mask materials. The purpose of this article is to address the concerns of efficiency and efficacy of face masks by primarily reviewing the literature of research conducted at the Technical University of Liberec. The main focus is on the presentation of problems related to the specification of aims of face mask applications, mechanisms of capture, durability, and modes of sterilization. The recommendations, instead of conclusions, are addressed to the whole textile society because they should be leading players in the design, creation, and proper treatment of face masks due to their familiarity with the complex behavior of textile structures and targeted changes of structural hierarchy starting from polymeric chains (nano-level) and ending in planar textile structures (millimeter level) due to action by mechanical, physical and chemical fields. This becomes extremely critical to saving hundreds of thousands of lives from COVID-19.     

Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

AIM: To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2, miR-27a and miR-146a genes are associated with sporadic colorectal cancer (CRC).METHODS: In order to investigate the effect of these SNPs in CRC, we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis.RESULTS: The genotype and allele frequencies of SNPs were compared between the cases and the controls. None of the performed analysis showed any statistically significant results.CONCLUSION: Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.     

Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse

Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences.     

Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells

Purpose

MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC.

Methods

We examined the expression level of miR-21 in 44 paired samples of tumoral and non-tumoral colon tissues diagnosed for CRC using TaqMan real-time PCR method. Furthermore, we used miR-21 inhibitor (anti-miR-21) to transient knockdown of miR-21 in DLD-1 colon cancer cells and examined the effects of miR-21 silencing on viability, apoptosis, chemosensitivity, cell cycle, and migration of DLD1 cells.

Results

The expression levels of miR-21 were significantly increased in CRC tumor tissue (P?<?0.0001). Significant differences in miR-21 levels were observed also between CRC tissues of patients with CRC in different clinical stages: I vs. II (P?=?0.033) and I vs. IV (P?=?0.021). Kaplan–Meier analysis proved that the miR-21 expression levels are correlated to shorter overall survival of CRC patients (P?=?0.0341). MiR-21 silencing in DLD1 cell line had no effect on the cell viability; however, when combined with chemotherapeutics (5-FU, L-OHP, and SN38), it contributed to the decrease of cell viability. Suppression of miR-21 decreased cell migration ability of DLD-1 cells by nearly 30?% (P?=?0.016).

Conclusion

We have confirmed the overexpression of miR-21 in CRC samples and its correlation with advanced disease and shorter overall survival. These findings could be described in part by the fact that CRC cells with increased expression of miR-21 have higher migration ability.     

Pulmonary Arterial Impedance Analysis by the Use of the Oscillated Assist Flow

Abstract: Pulmonary arterial impedance is an important and interesting characteristic that can be used to evaluate the physiological properties of the pulmonary vessel. However, power spectrum analysis of the pulmonary artery pressure and flow pattern have suggested that peak power in the relatively high frequency range (>10 Hz) is significantly low; thus, we cannot analyze the vessel properties in the high frequency range. In this study, we used the newly developed vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10–50 Hz) for right heart bypass, to evaluate the pulmonary arterial impedance pattern in the high frequency range. Acute animal experiments of the right heart bypass from the right atrium to the pulmonary artery using 6 healthy adult goats were performed. The flow pattern and pressure of the pulmonary artery, electrocardiograms (ECGs), and arterial and right atrial pressures were continuously monitored during the experiments. Spectral analysis of the he-modynamic parameters using the fast Fourier transform (FFT) method was performed to evaluate the spectral properties. The coherence function, transfer function, and phase patterns were calculated to analyze the impedance pattern in the relatively high frequency area. Previously, various investigators had tried to analyze the impedance patterns of the pulmonary artery: however, they could not analyze the impedance patterns over 10 Hz because the spectral patterns of the pulmonary flow do not have high power at high frequencies. These physiological analyses may be useful in designing the optimal pulmonary circulation.     

Islet autoantibody development during follow-up of high-risk children from the general Norwegian population from three months of age: design and early results from the MIDIA study

We describe the design of the MIDIA study and present serial islet autoantibody data from 3 months of age in the 526 first enrolled children from the general population carrying the type 1 diabetes high-risk HLA-DRB1*0401-DQA1*03-DQB1*0302/DRB1*0301-DQA1*05-DQB1*02 genotype. Blood samples were obtained from children at ages 3, 6, 9 and 12 months and annually thereafter to a median age of 12 months. Autoantibodies to insulin, glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured with radiobinding assays. About 25,000 general population newborns were genotyped, and among 526 children with the high-risk HLA genotype, 2104 samples were assayed. Fourteen children were positive in at least two consecutive samples, including 12 who were positive for > or =2 autoantibodies at least once, of which five developed type 1 diabetes at median age 15.3 months. Seven of 14 persistently positive children seroconverted before 9 months, including two before 6 months of age. The estimated cumulative probability of multiple autoantibody positivity at 5 years was 7.3% (95% confidence interval: 3.5-12.4%). Thus, persistent islet autoimmunity is not uncommon in the first year of life in children from the general population carrying the high-risk HLA genotype, and may develop as early as at 6 months of age.