Caveolin-1 Down-Regulation Reduces VEGF-A Secretion Induced by IGF-1 in ARPE-19 Cells

The insulin-like growth factor 1 (IGF-1) stimulates expression and secretion of vascular endothelial growth factor-A (VEGF-A), the main actor in ocular neovascularization, by RPE cells. Activity of IGF-1 is regulated by interaction between its receptor and Caveolin-1 (Cav-1), the main component of caveolae. The aim of this study was to investigate whether modulation of Cav-1 expression affects synthesis and secretion of VEGF-A. ARPE-19 cells were transfected with small interfering RNA for Cav-1 (si-Cav-1) and with control siRNA (si-CTR) and stimulated with IGF-1. We found that down-regulation of Cav-1 did not affect activation of IGF-1R but regulated in an opposite manner the phosphorylation of Akt and Erk1/2. Moreover, we found that IGF-1 increased mRNA levels of VEGF-A in both si-CTR and in si-Cav-1 ARPE-19 cells and that Cav-1 silencing significantly reduced basal and IGF-1-stimulated VEGF-A release. Then we investigated the response of the microvascular endothelial cell line HMEC-1 to secretory products of ARPE-19 cells by evaluating wound healing closure, finding that conditioned media from si-Cav-1-ARPE-19 cells reduced endothelial cell migration rate. These data demonstrate that Cav-1 regulates secretion of VEGF-A, and that the depletion of Cav-1 reduces IGF-1 induced VEGF-A secretion in ARPE-19 cells and the migratory potential of their secretory products.

miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner

Apoptotic cell death of cardiomyocytes is a characteristic hallmark of ischemia–reperfusion (I/R) injury. The master hypoxamiR, microRNA-210 (miR-210), is considered the primary driver of the cellular response to hypoxic stress. However, to date, no consensus has emerged with regards to the polarity of the miR-210-elicited cellular response, as miR-210 has been shown to exacerbate as well as attenuate hypoxia-driven apoptotic cell death. Herein, in AC-16 cardiomyocytes subjected to hypoxia-reoxygenation (H-R) stress, we unravel novel facets of miR-210 biology and resolve the biological response mediated by miR-210 into the hypoxia and reoxygenation temporal components. Using transient overexpression and decoy/inhibition vectors to modulate miR-210 expression, we elucidated a Janus role miR-210 in the cellular response to H-R stress, wherein miR-210 mitigated the hypoxia-induced apoptotic cell death but exacerbated apoptotic cell death during cellular reoxygenation. We further delineated the underlying cellular mechanisms that confer this diametrically opposite effect of miR-210 on apoptotic cell death. Our exhaustive biochemical assays cogently demonstrate that miR-210 attenuates the hypoxia-driven intrinsic apoptosis pathway, while significantly augmenting the reoxygenation-induced caspase-8-mediated extrinsic apoptosis pathway. Our study is the first to unveil this Janus role of miR-210 and to substantiate the cellular mechanisms that underlie this functional duality.

Evolution of 14-3-3 Proteins in Angiosperm Plants: Recurring Gene Duplication and Loss

14-3-3 proteins are key regulatory factors in plants and are involved in a broad range of physiological processes. We addressed the evolutionary history of 14-3-3s from 46 angiosperm species, including basal angiosperm Amborella and major lineage of monocotyledons and eudicotyledons. Orthologs of Arabidopsis isoforms were detected. There were several rounds of duplication events in the evolutionary history of the 14-3-3 protein family in plants. At least four subfamilies (iota, epsilon, kappa, and psi) formed as a result of ancient duplication in a common ancestor of angiosperm plants. Recent duplication events followed by gene loss in plant lineage, among others Brassicaceae, Fabaceae, and Poaceae, further shaped the high diversity of 14-3-3 isoforms in plants. Coexpression data showed that 14-3-3 proteins formed different functional groups in different species. In some species, evolutionarily related groups of 14-3-3 proteins had coexpressed together under certain physiological conditions, whereas in other species, closely related isoforms expressed in the opposite manner. A possible explanation is that gene duplication and loss is accompanied by functional plasticity of 14-3-3 proteins.

Alpha and theta oscillations are inversely related to progressive levels of meditation depth

Meditation training is proposed to enhance mental well-being by modulating neural activity, particularly alpha and theta brain oscillations, and autonomic activity. Although such enhancement also depends on the quality of meditation, little is known about how these neural and physiological changes relate to meditation quality. One model characterizes meditation quality as five increasing levels of ‘depth’: hindrances, relaxation, concentration, transpersonal qualities and nonduality. We investigated the neural oscillatory (theta, alpha, beta and gamma) and physiological (respiration rate, heart rate and heart rate variability) correlates of the self-reported meditation depth in long-term meditators (LTMs) and meditation-naïve controls (CTLs). To determine the neural and physiological correlates of meditation depth, we modelled the change in the slope of the relationship between self-reported experiential degree at each of the five depth levels and the multiple neural and physiological measures. CTLs reported experiencing more ‘hindrances’ than LTMs, while LTMs reported more ‘transpersonal qualities’ and ‘nonduality’ compared to CTLs, confirming the experiential manipulation of meditation depth. We found that in both groups, theta (4–6 Hz) and alpha (7–13 Hz) oscillations were related to meditation depth in a precisely opposite manner. The theta amplitude positively correlated with ‘hindrances’ and increasingly negatively correlated with increasing meditation depth levels. Alpha amplitude negatively correlated with ‘hindrances’ and increasingly positively with increasing depth levels. The increase in the inverse association between theta and meditation depth occurred over different scalp locations in the two groups—frontal midline in LTMs and frontal lateral in CTLs—possibly reflecting the downregulation of two different aspects of executive processing—monitoring and attention regulation, respectively—during deep meditation. These results suggest a functional dissociation of the two classical neural signatures of meditation training, namely, alpha and theta oscillations. Moreover, while essential for overcoming ‘hindrances’, executive neural processing appears to be downregulated during deeper meditation experiences.

Investigation of LINC00493/SMIM26 Gene Suggests Its Dual Functioning at mRNA and Protein Level

The amount of human long noncoding RNA (lncRNA) genes is comparable to protein-coding; however, only a small number of lncRNAs are functionally annotated. Previously, it was shown that lncRNAs can participate in many key cellular processes, including regulation of gene expression at transcriptional and post-transcriptional levels. The lncRNA genes can contain small open reading frames (sORFs), and recent studies demonstrated that some of the resulting short proteins could play an important biological role. In the present study, we investigate the widely expressed lncRNA LINC00493. We determine the structure of the LINC00493 transcript, its cell localization and influence on cell physiology. Our data demonstrate that LINC00493 has an influence on cell viability in a cell-type-specific manner. Furthermore, it was recently shown that LINC00493 has a sORF that is translated into small protein SMIM26. The results of our knockdown and overexpression experiments suggest that both LINC00493/SMIM26 transcript and protein affect cell viability, but in the opposite manner.

NUAK1 and NUAK2 Fine-Tune TGF-β Signaling

Transforming growth factor-β (TGF-β) signaling plays a key role in governing various cellular processes, extending from cell proliferation and apoptosis to differentiation and migration. Due to this extensive involvement in the regulation of cellular function, aberrant TGF-β signaling is frequently implicated in the formation and progression of tumors. Therefore, a full understanding of the mechanisms of TGF-β signaling and its key components will provide valuable insights into how this intricate signaling cascade can shift towards a detrimental course. In this review, we discuss the interplay between TGF-β signaling and the AMP-activated protein kinase (AMPK)-related NUAK kinase family. We highlight the function and regulation of these kinases with focus on the pivotal role NUAK1 and NUAK2 play in regulating TGF-β signaling. Specifically, TGF-β induces the expression of NUAK1 and NUAK2 that regulates TGF-β signaling output in an opposite manner. Besides the focus on the TGF-β pathway, we also present a broader perspective on the expression and signaling interactions of the NUAK kinases to outline the broader functions of these protein kinases.

Comparisons of the Uncoupled Effects of CO2 on the CH4/O2 Counterflow Diffusion Flame under High Pressure

A comprehensive numerical investigation of the uncoupled chemical, thermal, and transport effects of CO2 on the temperature of CH4/O2 counterflow diffusion flame under high pressure up to 5 atm was conducted. Three pairs of artificial species were introduced to distinguish the chemical effect, thermal effect, and the transport effect of CO2 on the flame temperature. The numerical results showed that both the chemical effect and the thermal effect of the CO2 dilution in the oxidizer side can decrease the flame temperature significantly, while the transport effect of CO2 can only slightly increase the flame temperature and can even be ignored. The reduction value of the temperature caused by the chemical effect of CO2 grows linearly, while that caused by the thermal effect increases exponentially. The RPchem and RPthermal are defined to explain the temperature reduction percentage due to the chemical effect and the thermal effect of CO2 in the total temperature reduction caused by CO2 dilution, respectively. The RPchem decreases with the increase of the pressure, the strain rate, and the CO2 dilution ratio, while the RPthermal behaves in the opposite manner. In the above conditions, the chemical effect plays a dominant role on the flame temperature reduction.

Enhanced Luminescence of Silver Nano-particles Doped Na2O-BaO-Borate Glasses

Na2O-BaO-Borate glasses were synthesized with silver nano-particles of varying silver concentrations by the method of melt-quenching. Their densities of the glasses and hence molar volumes were computed. The existence of the silver nano-particles was depicted by characteristic band in the absorption spectra of UV- Visible studies known as plasmon band. Further the matrix also showed a small amount of nanostructures of the host which imparts the nonlinear behaviour. They were further visualized by the Scanning and Transmission electron microscopy. Optical band gap and Urbach energies were found. The band gap values change exactly in the opposite manner of density with silver doping. The wide luminescence band in the visible region formed for the excitation of plasmon band may be utilized for the luminescence enhancement of luminescent material like rare earth ions. The very significant result perceived from this is that the glass as such with silver nano-particles showed broad emission in the, green & blue portions of electromagnetic spectrum in the close vicinity of white light with the variation of silver content which can be utilized for the enrichment of the emission of lanthanide ions in the visible section of electro-magnetic spectrum.

Altered Ovarian Inositol Ratios May Account for Pathological Steroidogenesis in PCOS

The presence of abnormal ovarian ratios of myo-inositol (MI) to D-chiro-inositol (DCI) is a recurrent feature in PCOS. Available evidence suggests that MI and DCI may modulate steroid biosynthesis, likely in an opposite manner. Specifically, MI seems to induce estrogen production, while DCI has a role in the synthesis of androgens. Elevated insulin levels, generally associated with PCOS, alter the physiological MI/DCI ratio, increasing MI-to-DCI conversion through activation of a specific epimerase enzyme. DCI directly increases testosterone biosynthesis in thecal cells and reduces its conversion to estradiol by downregulating aromatase enzyme in granulosa cells. This manuscript reviews the literature that supports the connection between altered MI/DCI ratios and pathological steroidogenesis observed in PCOS women. Furthermore, it discusses the application of inositol-based treatment protocols in managing PCOS symptoms and improving the quality of patients’ life.

The correlation between teachers’ humor and class climate: A study targeting primary and secondary school students

This study investigated the relationship between types of humor (aggressive humor and affinity humor) of homeroom teachers, as recognized by their students, and five domains of class climate (mutual respect among the students, discipline, willingness, enjoyment, and resistance). The participants included a total of 500 students – 250 primary school students (fourth to sixth grade) and 250 secondary school students (seventh to ninth grade) in Japan. The students answered questions about their homeroom teacher’s type of humor and the climate of their class using a self-report scale. We labeled five variables of class climate as dependent variables, and two types of teachers’ humor as independent variables, and conducted a hierarchal multiple regression analysis with two steps. Findings showed that aggressive humor had a significant negative correlation to all positive class climates, and a significant positive correlation to negative class climates. Affinity humor indicated a significant correlation in the exact opposite manner to the above findings. Furthermore, the interaction effect of the two types of teachers’ humor was insignificant for every variable of class climate. The findings indicated that an ideal class climate could be created if teachers refrained as much as possible from using aggressive humor and used affinity humor.