Explore the vast range of titles available.

Clinical and experimental observations indicate a role for VEGF secreted by the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC). VEGF in mice is produced as three isoforms, VEGF120, VEGF164, and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces the more soluble isoforms, VEGF120 and VEGF164, but virtually no VEGF188, reflecting the fact that molecules secreted by the RPE must diffuse across Bruch's membrane (BrM) to reach the choriocapillaris. To determine the role of RPE-derived soluble VEGF on the choriocapillaris survival, we used mice that produce only VEGF188. VEGF188/188 mice exhibited normal choriocapillaris development. However, beginning at 7 months of age, we observed a progressive degeneration characterized by choriocapillaris atrophy, RPE and BrM abnormalities, culminating in areas of RPE loss and dramatic choroidal remodeling. Increased photoreceptor apoptosis in aged VEGF188/188 mice led to a decline in visual acuity as detected by electroretinogram (ERG). These changes are reminiscent of geographic atrophy (GA) and point to a role for RPE-derived VEGF in the maintenance of the choriocapillaris.

Pericyte-endothelial cell (EC) interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-beta signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-beta signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-beta signaling was inhibited by systemic expression of soluble endoglin (sEng) and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-beta signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG). Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-beta signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-beta signaling. These results implicate constitutive TGF-beta signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-beta signaling in vasoproliferative and vascular degenerative retinal diseases.

Cardiac hypertrophy is a well-established risk factor for cardiovascular morbidity and mortality. Activation of G(q/11)-mediated signaling is required for pressure overload-induced cardiomyocyte (CM) hypertrophy to develop. We previously showed that among Regulators of G protein Signaling, RGS2 selectively inhibits G(q/11) signaling and its hypertrophic effects in isolated CM. In this study, we generated transgenic mice with CM-specific, conditional RGS2 expression (dTG) to investigate whether RGS2 overexpression can be used to attenuate G(q/11)-mediated signaling and hypertrophy in vivo. Transverse aortic constriction (TAC) induced a comparable rise in ventricular mass and ANF expression and corresponding hemodynamic changes in dTG compared to wild types (WT), regardless of the TAC duration (1-8 wks) and timing of RGS2 expression (from birth or adulthood). Inhibition of endothelin-1-induced G(q/11)-mediated phospholipase C β activity in ventricles and atrial appendages indicated functionality of transgenic RGS2. However, the inhibitory effect of transgenic RGS2 on G(q/11)-mediated PLCβ activation differed between ventricles and atria: (i) in sham-operated dTG mice the magnitude of the inhibitory effect was less pronounced in ventricles than in atria, and (ii) after TAC, negative regulation of G(q/11) signaling was absent in ventricles but fully preserved in atria. Neither difference could be explained by differences in expression levels, including marked RGS2 downregulation after TAC in left ventricle and atrium. Counter-regulatory changes in other G(q/11)-regulating RGS proteins (RGS4, RGS5, RGS6) and random insertion were also excluded as potential causes. Taken together, despite ample evidence for a role of RGS2 in negatively regulating G(q/11) signaling and hypertrophy in CM, CM-specific RGS2 overexpression in transgenic mice in vivo did not lead to attenuate ventricular G(q/11)-mediated signaling and hypertrophy in response to pressure overload. Furthermore, our study suggests chamber-specific differences in the regulation of RGS2 functionality and potential future utility of the new transgenic model in mitigating G(q/11) signaling in the atria in vivo.

Pericyte-endothelial cell (EC) interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-[beta] signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-[beta] signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-[beta] signaling was inhibited by systemic expression of soluble endoglin (sEng) and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-[beta] signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG). Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-[beta] signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-[beta] signaling. These results implicate constitutive TGF-[beta] signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-[beta] signaling in vasoproliferative and vascular degenerative retinal diseases.

This book provides an accessible introduction to the philosophy of educational research. A historical-philosophical journey presents the development of research methods from their origins to the present day. In addition, the book reflects on how research methods have influenced scientific effectiveness. Throughout, the book covers the principal things that need to be known today about the theory and practice of educational research, its epistemological bases, and its development as a discipline within scientific knowledge. The historical events that defined both the methodological evolution and the current situation of contemporary educational research are described to enable its understanding.This book provides an accessible introduction to the philosophy of educational research. A historical-philosophical journey presents the development of research methods from their origins to the present day.. It can also be used as didactic material for classroom discussions on educational research, educational philosophy, and current controversies in education. Its usefulness reaches the social sciences, humanities, and experimental sciences in all areas related to teaching and training. The basis of educational research is exposed, both in its concepts or philosophical visions and methodologies, which ultimately define what education means today.

The improvement of thermal energy storage systems implemented in solar technologies increases not only their performance but also their dispatchability and competitiveness in the energy market. Latent heat thermal energy storage systems are one of those storing methods. Therefore, the need of finding the best materials for each application becomes an appealing research subject. The main goal of this paper is to find suitable and economically viable materials able to work as phase change material (PCM) within the temperature range of 210–270 °C and endure daily loading and unloading processes in a system with Fresnel collector and an organic Rankine cycle (ORC). Twenty-six materials have been tested and characterized in terms of their thermophysical conditions, thermal and cycling stability, and health hazard. Two materials out of the 26 candidates achieved the last stage of the selection process. However, one of the two finalists would require an inert working atmosphere, which would highly increase the cost for the real scale application. This leads to a unique suitable material, solar salt (40 wt % KNO3/60 wt % NaNO3).

In this research report, we consider how to empower K-8 teachers as mathematics instructional leaders to initiate and sustain improvements within their schools, as a practical and sustainable model of enacting change in mathematics education more broadly by developing leadership from within. We share the theoretical framework and findings from a 5-year National Science Foundation project. We utilized a longitudinal mixed methods approach, collecting data on teachers’ knowledge, instructional practices, leadership practices, and self-perception of growth throughout the project, triangulated with focus group data from teachers’ school administrators and project leaders and logs of leadership activities. Findings indicate positive changes in teachers’ knowledge and practices and in their role as instructional leaders in their schools, districts, and the mathematics education community. We conclude by sharing factors that appeared to support teachers’ growth as instructional leaders and implications for practice and research.

Introduction. Extracorporeal shock wave lithotripsy (ESWL) is an effective treatment for urolithiasis. Tamsulosin is capable of causing dilation and facilitating the migration of stones. The aim of this study is to evaluate the efficacy of adjuvant treatment with tamsulosin for improving the stone-free rate after a single session of ESWL in the treatment of kidney stones. Methods. This is a randomized, nonplacebo-controlled study with a sample of 60 adults with a single radiopaque kidney stone of 5–20 mm in diameter. After the ESWL session, the patients were divided into two groups. The control group received standard treatment for analgesia consisting of oral diclofenac (75 mg/12 h) as needed. The tamsulosin group received standard treatment for analgesia plus oral tamsulosin (0.4 mg/day) for eight weeks. In both groups, stone-free status was determined using a CT scan eight weeks after ESWL. The protocol of this study was registered with ClinicalTrials.gov, identifier: NCT04819828. Results. Only 57 patients completed the study (28 tamsulosin and 29 control). Overall, the average stone diameter was 11.42 ± 4.52 mm. The stone-free rate was 50.88% (29 of 57) overall, 53.57% (15 of 28) for the tamsulosin group, and 48.27% (14 of 29) for the control group (p = 0.680). The estimated relative risk in favor of the tamsulosin group to achieve a stone-free status was 1.11 (95% CI 0.67–1.9). The estimated number needed to treat to achieve a single patient with renal stone-free status after eight weeks of ESWL adjuvant treatment with tamsulosin was 19. Conclusion. Our findings suggest that tamsulosin as adjuvant treatment after a single ESWL session is well tolerated and safe, but it does not increase the stone-free rate in patients with a single radiopaque renal stone of 5–20 mm in diameter. Our results may support the use of tamsulosin with ESWL in the case of patients with a single radiopaque renal stone of 11–20 mm in diameter based on an apparent higher stone-free rate and a low rate of complications.

Key messageThe moss Pseudocrossidium replicatum is a desiccation-tolerant species that uses an inducible system to withstand severe abiotic stress in both protonemal and gametophore tissues.Desiccation tolerance (DT) is the ability of cells to recover from an air-dried state. Here, the moss Pseudocrossidium replicatum was identified as a fully desiccation-tolerant (FDT) species. Its gametophores rapidly lost more than 90% of their water content when exposed to a low-humidity atmosphere [23% relative humidity (RH)], but abscisic acid (ABA) pretreatment diminished the final water loss after equilibrium was reached. P. replicatum gametophores maintained good maximum photosystem II (PSII) efficiency (Fv/Fm) for up to two hours during slow dehydration; however, ABA pretreatment induced a faster decrease in the Fv/Fm. ABA also induced a faster recovery of the Fv/Fm after rehydration. Protein synthesis inhibitor treatment before dehydration hampered the recovery of the Fv/Fm when the gametophores were rehydrated after desiccation, suggesting the presence of an inducible protective mechanism that is activated in response to abiotic stress. This observation was also supported by accumulation of soluble sugars in gametophores exposed to ABA or NaCl. Exogenous ABA treatment delayed the germination of P. replicatum spores and induced morphological changes in protonemal cells that resembled brachycytes. Transcriptome analyses revealed the presence of an inducible molecular mechanism in P. replicatum protonemata that was activated in response to dehydration. This study is the first RNA-Seq study of the protonemal tissues of an FDT moss. Our results suggest that P. replicatum is an FDT moss equipped with an inducible molecular response that prepares this species for severe abiotic stress and that ABA plays an important role in this response.

The present article proposes an extension of the concept of adverse childhood experiences (ACEs) to apply to crisis migration – where youth and families are fleeing armed conflicts, natural disasters, community violence, government repression, and other large-scale emergencies. We propose that adverse events occurring prior to, during, and following migration can be classified as crisis-migration-related ACEs, and that the developmental logic underlying ACEs can be extended to the new class of crisis-migration-related ACEs. Specifically, greater numbers, severity, and chronicity of crisis-migration-related ACEs would be expected to predict greater impairments in mental and physical health, poorer interpersonal relationships, and less job stability later on. We propose a research agenda centered around definitional clarity, rigorous measurement development, prospective longitudinal studies to establish predictive validity, and collaborations among researchers, practitioners, and policymakers.