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1.
Theriogenology ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31787469

RESUMO

Spermiogenesis is a highly organized process of the metamorphosis of round spermatids into spermatozoa in the testes. Autophagy is involved in the physiological process of spermiogenesis and its crucial role in germ-plasm clearance conserved across kingdoms. However, the fate of by-products generated through autophagy during spermiogenesis is still largely unknown. In the present study, we showed that the autophagy enhanced lipid droplets (LDs) formation during spermiogenesis in Chinese soft-shelled turtle, Pelodiscus sinensis. TEM and Oil Red O staining results found that the number and size of LDs within spermatid increased considerably during the process of spermiogenesis. RNA-Seq analysis revealed that autophagy was highly activated via the PI3K pathway during spermatogenesis. Inhibiting autophagy with 3-methyladenine (3-MA) significantly decreased testicular triglycerides (TGs) and fatty acid (FAs) content. In comparison with the control group, the number and size of LD within elongating spermatids was reduced significantly in the 3-MA group. Moreover, DGAT1, a diacylglycerol acyltransferase, which normally localize to the endoplasmic reticulum, was found to co-localize with LDs. Taken together, our results showed that FAs released through the autophagic degradation of germ-plasm was replenished LDs of spermatid, increasing LD number and size, during the process of spermiogenesis. These LDs facilitate long-term sperm storage in the epididymis of Chinese soft-shelled turtle.

2.
Front Pharmacol ; 10: 1306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787894

RESUMO

Objective: Medication adherence is defined as taking medications as advised and prescribed by health care professionals for stated duration. Diabetes mellitus (DM) is one of the most common chronic illnesses in Saudi Arabia. This study aimed to document medication adherence in Saudi patients with type 2 diabetes. Methods: A quantitative cross-sectional study was conducted in Saudi out-patients with type 2 DM in the city of Khobar, Saudi Arabia. The study used the General Medication Adherence Scale (GMAS) to document medication adherence in this population. Data was analyzed through SPSS version 23. Study was ethically approved. Results: Data was collected from 212 patients. Few patients (35.8%) had high adherence to anti diabetic medications. The correlation between HbA1c level and adherence score was negative and significantly strong (ρ = -0.413, p < 0.0001). Most patients (N = 126, 59.4%) modified their medication therapy during month of Ramadan and on Eid occassion. Education level was not a determinant of adherence in this population. Conclusion: This study highlighted that medication adherence is influenced by religious and social factors. Patient counseling is required to improve patient beliefs and increase awareness of adhering to prescribed anti diabetic pharmacotherapy. A pharmacist can play constructive role of a disease educator and patient counselor.

3.
Cureus ; 11(9): e5599, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31700712

RESUMO

Introduction Our study was meant to assess the knowledge, attitude, and barriers towards research in medical students of Pakistan. By assessing the factors, we aim to increase the role of medical students in research, which will eventually help developing countries like Pakistan to achieve self-reliance in health care. Methods Undergraduate and postgraduate students of medicine, dentistry, and pharmacy schools of Dow University of Health Sciences, Karachi, were enrolled from February-March 2018 in a cross-sectional, descriptive study using questionnaires to provide details of the parameters of attitude to the knowledge of and barriers towards research for each individual. All data were coded for each of the parameters. Data analyses were performed by one-way analysis of variance (ANOVA)/Tukey and Student's t-test, Pearson's correlation, and Chi-squared tests. Results A total of 850 questionnaires were received. The overall mean scores of students on attitude, knowledge, and barriers were 69.27 ± 13.44, 70.39 ± 15.67, and 72.46 ± 13.46, respectively; 81.8% of students' scores fell above the middle of the maximum score for knowledge, but 84.5% of attitude scores came in at below the middle of the maximum score. Undergraduate students had a more positive attitude to research than postgraduate students (69.20 ± 11.10 vs 64.23 ± 10.98; p = 0.002). Male students had a better attitude than females (72.97 ± 20.54 vs 67.09 ± 21.56; p = 0.010). Barriers highlighted by students most significantly included a lack of funding support and preference for instruction over research. Conclusion Students showed good knowledge of research, but their attitude was not up to the mark. The barriers highlighted suggest a need for a change in the strategies for research. Attention should be paid to inculcate research as part of the student curriculum and to make available incentives, information, and mentors to solve the problems most students face in the field of research.

4.
Microsc Microanal ; : 1-9, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31753050

RESUMO

The seminiferous tubule (ST) is the location of spermatogenesis, where mature spermatozoa are produced with the assistance of Sertoli cells. The role of extracellular vesicles in the direct communication between Sertoli-germ cells in the ST is still not fully understood. In this study, we reported multivesicular bodies (MVBs) and their source of CD63-enriched exosomes by light and ultrastructure microscopy during the reproductive phases of turtles. Strong CD63 immunopositivity was detected at the basal region in the early and luminal regions of the ST during late spermatogenesis by immunohistochemistry (IHC), immunofluorescence (IF), and western blot (WB) analysis. Labeling of CD63 was detected in the Sertoli cell cytoplasmic processes that surround the developing germ cells during early spermatogenesis and in the lumen of the ST with elongated spermatids during late spermatogenesis. Furthermore, ultrastructure analysis confirmed the existence of numerous MVBs in the Sertoli cell prolongations that surround the round and primary spermatogonia during acrosome biogenesis and with the embedded heads of spermatids in the cytoplasm of Sertoli cells. Additionally, in spermatids, Chrysanthemum flower centers (CFCs) generated isolated membranes involved in MVBs and autophagosome formation, and their fusion to form amphiosomes was also observed. Additionally, autophagy inhibition by 3-methyladenine (after 24 h) increased CD63 protein signals during late spermatogenesis, as detected by IF and WB. Collectively, our study found MVBs and CD63 rich exosomes within the Sertoli cells and their response to autophagy inhibition in the ST during the spermatogenesis in the turtle.

5.
Fish Shellfish Immunol ; 95: 644-649, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704204

RESUMO

Exosomes are secreted from various cells by multivesicular bodies (MVBs) that fuse with the plasma membrane and are involved in the intestinal immune response to maintain intestinal homeostasis. Here, we demonstrate the ultrastructural characteristics of MVBs and their exosomes in immune-related cells of the zebrafish intestine, including goblet cells (GCs), mitochondria-rich cells (MRCs), high endothelial cells (HECs) and lymphocytes. In GCs, MVBs with a low electron density were present under the nucleus. MVBs with exosomes were observed among mucin granules. "Heterogeneous" MVBs were identified within the cytoplasm around mucin granules. MRCs were observed in the intestinal mucosa epithelium, including "open-type" MRCs and "close-type" MRCs. Typical MVBs were identified in these MRCs. MVBs with a variety of exosomes were observed in the HECs of the capillary located in the lamina propria (LP). The HEC basement membrane budded outward to LP cells to form a plurality of basal blebs, later containing a large number of exosomes. MVBs also existed in the LP lymphocytes. A schematic diagram of the ultrastructural distribution of MVBs and their exosomes in the intestinal mucosal immune-related cells was created. Our findings provide cytological evidence for the source and ultrastructural distribution of exosomes within the different intestine cells of zebrafish. Component analysis and immunological functions of exosomes require future study.

6.
Animals (Basel) ; 9(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683774

RESUMO

The ductuli efferentes (DE) form a transit passage for the passage of spermatozoa from the rete testis to the epididymis. After spermiation, various epithelial secretory proteins are transferred via extracellular vesicles (EVs) to the spermatozoa for their maturation and long-term viability. The aim of the present study was to investigate the distribution, classification, and source of multivesicular bodies (MVBs) and their EVs in the epithelia of the efferentes duct in a turtle species, the soft-shelled freshwater turtle Pelodiscus sinensis by using light and transmission electron microscopy. The results showed that CD63 as a classical exosome marker was strongly immunolocalized within the apical and lateral cytoplasm of the ciliated cells (CC) and moderate to weak in the non-ciliated cells (NCC) of DE. The ultrastructure revealed that early endosome was present at the basement membrane and perinuclear cytoplasm of both CC and NCC, whereas MVBs were located over the nucleus in the cytoplasm of NCC and adjacent to the basal bodies of cilia within the CC. Many EVs, as sources of MVBs, were located within the blebs that were attached to the cilia of CC, within the apical blebs from NCC, and the lateral spaces of CC and NCC. There was ultrastructure evidence of EVs associated with spermatozoa in the lumens of DE. Collectively, the present study provides cytological evidence that the DE epithelium secreted EVs to the lumen by (1) apical blebs, (2) ciliary blebs, and (3) from the basolateral region. These EVs were associated with spermatozoa in the DE lumen of this turtle. Characterization and cellular distribution of these EVs in the DE of a turtle may provide a study model to further investigate the transferring of micromolecules via EVs to the spermatozoa.

7.
Genet Med ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578471

RESUMO

PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. RESULTS: Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. CONCLUSIONS: This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.

8.
Microsc Microanal ; 25(6): 1341-1351, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31656212

RESUMO

The present study was designed to investigate the in vivo biological processes of multivesicular bodies (MVBs) and exosomes in mitochondria-rich cells (MRCs), goblet cells (GCs), and absorptive cells (ACs) in turtle intestines during hibernation. The exosome markers, cluster of differentiation 63 (CD63) and tumor susceptibility gene 101 (TSG101), were positively expressed in intestinal villi during turtle hibernation. The distribution and formation processes of MVBs and exosomes in turtle MRCs, GCs, and ACs were further confirmed by transmission electron microscopy. During hibernation, abundantly secreted early endosomes (ees) were localized in the luminal and basal cytoplasm of the MRCs and ACs, and late endosomes (les) were dispersed with the supranuclear parts of the MRCs and ACs. Many "heterogeneous" MVBs were identified throughout the cytoplasm of the MRCs and ACs. Interestingly, the ees, les, and MVBs were detected in the cytoplasm of the GCs during hibernation; however, they were absent during nonhibernation. Furthermore, the exocytosis pathways of exosomes and autophagic vacuoles were observed in the MRCs, GCs, and ACs during hibernation. In addition, the number of different MVBs with intraluminal vesicles (ILVs) and heterogeneous endosome-MVB-exosome complexes was significantly increased in the MRCs, GCs, and ACs during hibernation. All these findings indicate that intestinal epithelial cells potentially perform a role in the secretion of MVBs and exosomes, which are essential for mucosal immunity, during hibernation.

9.
Animals (Basel) ; 9(10)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554287

RESUMO

Although some studies have been conducted over the past few decades, the existence of mitochondria-rich cells (MRCs) in reptiles is still obscure. This is the first study to uncover the presence of MRCs in the small intestine of Chinese soft-shelled turtles. In this study, we investigated the ultrastructural characteristics of MRCs and the secretion of different ion transport proteins in the small intestine of Pelodiscus sinensis. Transmission electron microscopy revealed that the ultrastructural features of MRCs are clearly different from those of other cells. The cytoplasmic density of MRCs was higher than absorptive epithelial cells (AECs) and goblet cells (GCs). MRCs possessed abundant heterogeneous mitochondria and an extensive tubular system in the cytoplasm, however, the AECs and GCs completely lacked a tubular system. Statistical analysis showed that the diameter and quantification of mitochondria were highly significant in MRCs. Mitochondrial vacuolization and despoiled mitochondria were closely associated with autophagosomes in MRCs. The multivesicular bodies (MVBs) and the exosome secretion pathway were observed in MRCs. Immunohistochemical staining of ion transport proteins indicated positive immunoreactivity of Na+/K+_ATPase (NKA) and Na+/K+/2Cl- cotransporter (NKCC) at the basal region of the mucosal surface. Likewise, the immunofluorescence staining results showed a strong positive localization of NKA, NKCC, and carbonic anhydrase (CA) at the basal and apical region of the mucosal surface of small intestine. Our findings suggest that MRCs provide support and regulate cellular ions for intestinal homeostasis and provide energy for cellular quality control in intestine.

10.
Micron ; 126: 102747, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31505373

RESUMO

Despite the exploration of mitochondria-rich cells (MRCs) in different animal classes, very limited information has been documented about MRCs in reptiles. The present study was designed to investigate the effect of seasonal variation on the cell ultrastructure and ion transport protein activity of MRCs during hibernation and non-hibernation of Chinese soft-shelled turtle's intestine. Transmission electron microscopy revealed that, during hibernation the high-density cytoplasm of MRCs occupied large cross-sectional area and showed heterogeneous abundance of mitochondria and an expanded extensive tubular system as compared to non-hibernation. During hibernation the cytoplasm of MRCs exhibited more mitochondrial vacuolization, autophagosomes, phagophore formation and well-structured endoplasmic reticulum. During hibernation, MRCs connected with absorptive cells through wide interdigitation, and created tight junction and more desmosomes as compared to non-hibernation. Immunohistochemistry and immunofluorescence showed, the strong immunopositive reactions and immunosignaling of Na+/K+-ATPase (NKA) and Na+/K+/2Cl- cotransporter (NKCC) at basolateral region of mucosal surface of intestine during hibernation. However, weak immunopositive reactions and immunosignaling of NKA and NKCC during non-hibernation. The statistical analysis showed that the number and size of MRCs with NKA-associated immunoreactivity were significantly increased during hibernation. NKA and NKCC mRNA expression was significantly increased during hibernation via qPCR. Further confirmed, the intensity of NKA and NKCC proteins was more elevated during hibernation than non-hibernation shown by immunobloting. However, the concentrations of the plasma ions Na+ and Cl- were significantly higher during hibernation; conversely, K+ concentration was significantly higher during non-hibernation. The findings suggest that the potential role of MRCs is affected by seasonal fluctuations, during which intestinal homeostasis and hydromineral balance are essential for turtles.

12.
Curr Opin Cell Biol ; 61: 39-47, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31382142

RESUMO

SOX9 is a pivotal transcription factor in chondrocytes, a lineage essential in skeletogenesis. Its mandatory role in transactivating many cartilage-specific genes is well established, whereas its pioneer role in lineage specification, which along with transactivation defines master transcription factors, remains to be better defined. Abundant, but yet incomplete evidence exists that intricate molecular networks control SOX9 activity during the multi-step chondrogenesis pathway. They include a highly modular genetic regulation, post-transcriptional and post-translational modifications, and varying sets of functional partners. Fully uncovering SOX9 actions and regulation is fundamental to explain mechanisms underlying many diseases that directly or indirectly affect SOX9 activities and to design effective disease treatments. We here review current knowledge, highlight recent discoveries, and propose new research directions to answer remaining questions.

13.
Aging (Albany NY) ; 11(15): 5757-5768, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413207

RESUMO

In this study, we investigated the localization, morphological features and cellular interactions of telocytes in the rat testicular interstitium. Transmission electron microscopy (TEM) and immunohistochemical and immunofluorescence analyses of the rat testicular interstitium showed a distinct layer of telocytes surround the seminiferous tubules along with inner layer of peritubular myoid cells. The majority of the telocytes were made up of a small cell body and moniliform prolongations that contained mitochondria and secretory vesicles. Some other telocytes were observed possessing large cell bodies. Within the testicular interstitium, the telocytes formed a network connecting peritubular myoid cells, Leydig cells as well as blood vessels. Immunohistochemical and double immunofluorescence analyses showed that rat testicular telocytes express CD34 and PDGFRα, but are negative for vimentin and α-SMA. Our findings demonstrate the presence of telocytes in the rat testicular interstitium. These cells interact with peritubular myoid cells, seminiferous tubules, Leydig cells and blood vessels via long telopode extensions, which suggests their vital role in the intercellular communication between different cell types within the rat testis.

14.
VideoGIE ; 4(8): 386-388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31388620

RESUMO

Background and Aims: GI bleeding is a leading cause of morbidity and mortality in the United States, with an estimated 20,000 deaths per year. Some subgroups of patients show refractory recurrent bleeding despite standard endoscopic therapy. The U.S. Food and Drug Administration has recently approved a hemostatic spray for clinical use in nonvariceal bleeding. Despite its efficacy, not all endoscopy units have access to this spray, at times because of cost. Our aim was to determine the safety and efficacy of a plant-based hemostatic particle spray in nonvariceal GI bleeding by use of a cross-platform setup. Method: We present 3 cases in which plant-based particle spray was used for hemostasis with a cross-platform delivery system. Conventional therapies failed in the first 2 cases, and in the third case hemostatic particle spray was used as a primary therapy. Results: Successful immediate hemostasis was achieved in all 3 patients. No immediate adverse events or recurrence of bleeding was noted. Conclusions: Plant-based hemostatic particle spray is safe and effective as a temporizing measure in refractory ulcer and postnecrosectomy cavity bleeding. Further studies are needed to establish the safety and comparative efficacy of plant-based hemostatic powder. The cross-platform system used here for plant-based hemostatic particle spray presents a less-expensive alternative in selected cases.

15.
Theriogenology ; 138: 111-120, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31325741

RESUMO

Multilamellar bodies (MLBs) are produced and secreted by many cell types. In this study, we report the existence and ultrastructure of MLBs that are produced by Leydig cells and identification of telocytes in the testicular interstitium of naked mole rat. This study was performed on both breeder and non-breeder male naked mole rats using light microscopy, transmission electron microscopy, and morphometric approaches. In the testicular interstitium, the most prominent cells were Leydig cells, which contained numerous lipid droplets (LDs) in the cytoplasm. We found that MLBs were associated with the LDs of Leydig cells and were secreted into the extracellular or interstitial environment via exocytosis. After their release from Leydig cells, MLBs localized to the space between Leydig cells near blood vessels and attached to telocytes. We also identified telocytes in the testicular interstitium, and their cellular extensions were distributed throughout the interstitium. MLBs were aligned along the cellular extensions of telocytes, and membrane-to-membrane contact was observed between the cellular extensions of telocytes and MLBs, suggesting that telocytes may play a role in the transport of MLBs within the interstitial space. No ultrastructural differences were found in Leydig cells, telocytes, or MLBs between breeder and non-breeder testes. However, morphometric analysis revealed a significant difference in the number of MLBs between the breeder and non-breeder animals. Furthermore, both selective autophagy of LDs and non-selective autophagy were observed in Leydig cells. Typical features of macrolipophagy were also observed, as a few LDs were entirely enclosed by a limiting membrane. Remarkably, autophagy may be a key factor in the biogenesis of MLBs and steroid hormone production. The appearance of MLBs in the testicular interstitium of naked mole rats could thus be related to lipid storage and trafficking.

16.
Aging (Albany NY) ; 11(13): 4641-4653, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31305258

RESUMO

In this study, we investigated the neural changes and their relationships with interstitial cells (ICs) in the rumen of pre-weaning goats by transmission electron microscopy, western blot and immunofluorescence (antibody: general neuronal marker-Protein Gene Product (PGP9.5)/ IC marker-vimentin). The immunofluorescence results showed that PGP9.5-positive reaction was widely distributed in neuronal soma (NS) and nerve fibre (NF). The NSs were observed in the ganglia of the myenteric plexus (MP) but not in the submucosal plexus. The mean optical density (MOD) of the whole of PGP9.5-positive nerves and the protein expression level of PGP.5 in the rumen wall both decreased significantly with age. However an obvious increase MOD of PGP.5-positive NFs within the rumen epithelium were observed. In the MP, the nerves and ICs were interwoven to form two complex networks that gradually tightened with age. Furthermore, NSs and nerve trunks were surrounded by a ring-boundary layer consisting of several ICs that became physically closer with aging. Moreover, ICs were located nearby NFs within the ML, forming connections between ICs, smooth muscle cells and axons. This study describes the pattern of neural distribution and its association with ICs in the developing rumen which shed light on the postpartum development of ruminants.

17.
Environ Sci Pollut Res Int ; 26(24): 24733-24747, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240660

RESUMO

Global warming and greenhouse gas emissions have become a severe threat to our ecosystem. Prior studies on environment posit that ample exhaustion of fossil fuels for energy is one of the fundamental causes of environmental degradation and naturally replenished energy sources are affordable over fossil fuels. This study set out to examine the role of financial sectors and globalization (in the presence of energy and renewable energy consumption) for a sustainable environment in the panel of Central and Eastern European (CEE) countries in One Belt and One Road initiative perspective. The current study uses annual data of 16 CEE countries covering the period of 1980 to 2016. After confirmation of cross-sectional dependency and co-integration among variables, we applied the Dynamic Seemingly Unrelated Regression and Dumitrescu-Hurlin causality approach for long-run estimations and to check the causal relationship, respectively. The empirical findings of the study certify the existence of an environmental Kuznets curve for the selected panel countries. Globalization is enhancing the environmental quality of the CEE economies. It is important to note that energy consumption and renewable energy consumption have a positive and statistically significant whack on carbon emission. In addition, we do not find a significant link between financial development and carbon emission. Granger casualty test confirms a two-way causal relationship between economic growth and carbon emission, globalization and environmental degradation, globalization and renewable energy consumption, economic growth and renewable energy consumption, and between financial development and energy consumption. Moreover, we found one-way causality from energy consumption (renewable and non-renewable) to carbon emissions. Based on the findings, a number of appropriate policy suggestions are presented in the perspective of Central and Eastern European Countries.


Assuntos
Energia Renovável/economia , Cimentos de Resina/química , Carbono/química , Estudos Transversais , Desenvolvimento Econômico , Ecossistema , Fontes Geradoras de Energia , Europa (Continente) , Combustíveis Fósseis , Aquecimento Global , Gases de Efeito Estufa , Internacionalidade , Políticas
18.
Artigo em Inglês | MEDLINE | ID: mdl-31163652

RESUMO

Environmental pollution, rapid economic growth, and other social factors have adverse effects on public health, which have consequently increased the burden of health expenditures during the last two decades. This paper provides a comprehensive analysis of carbon dioxide (CO2) emissions and the environment index, as well as economic and non-economic factors such as Gross Domestic Product (GDP) growth, foreign direct investment, population aging, and secondary education impacts on per capita government and private health expenditures in 13 emerging economies for the time period of 1994-2017. We employ robust econometric techniques in this endeavor of panel data analysis to account for the issues of heterogeneity and cross-sectional dependence. This study applies the Lagrange Multiplier (LM) bootstrap approach to investigate the presence of panel cointegration and empirical results underscore the existence of cointegration among variables. For the execution of long-run analysis, we incorporate the two latest estimators, i.e., continuously updated-fully modified (CUP-FM) and continuously updated- bias corrected (CUP-BC). Findings of long-run elasticities have documented that the air-pollution indicators, i.e., CO2 emissions and the environment index, have a positive and significant influence on government health expenditures, while in contrast, both factors negatively influence private health expenditures in emerging economies. We find that economic factors such as GDP growth consistently show a positive impact on both government and private health expenditures, whereas, foreign direct investment exhibits a significant negative and positive impact on government and private health expenditures respectively. Findings of non-economic factors can be used to argue that population aging increases health expenditures while secondary education lowers private health spending in emerging markets. Furthermore, empirical analysis of heterogeneous causality indicates that CO2 emissions, the environment index, GDP growth, foreign direct investment, and secondary education have a unidirectional causal relationship with government and private health expenditures. Population aging has a strong relationship of bidirectional causality with government health expenditures and unidirectional causal relationship with private health expenditures. Findings of this paper put forward key suggestions for policy makers which can be used as valuable instruments for better understanding and aiming to maximize public healthcare and environmental quality gains which are highly connected with sustainable GDP growth and developments in emerging economies.

19.
Nucleic Acids Res ; 47(13): 6917-6931, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31194875

RESUMO

SOX8, SOX9 and SOX10 compose the SOXE transcription factor group. They govern cell fate and differentiation in many lineages, and mutations impairing their activity cause severe diseases, including campomelic dysplasia (SOX9), sex determination disorders (SOX8 and SOX9) and Waardenburg-Shah syndrome (SOX10). However, incomplete knowledge of their modes of action limits disease understanding. We here uncover that the proteins share a bipartite transactivation mechanism, whereby a transactivation domain in the middle of the proteins (TAM) synergizes with a C-terminal one (TAC). TAM comprises amphipathic α-helices predicted to form a protein-binding pocket and overlapping with minimal transactivation motifs (9-aa-TAD) described in many transcription factors. One 9-aa-TAD sequence includes an evolutionarily conserved and functionally required EΦ[D/E]QYΦ motif. SOXF proteins (SOX7, SOX17 and SOX18) contain an identical motif, suggesting evolution from a common ancestor already harboring this motif, whereas TAC and other transactivating SOX proteins feature only remotely related motifs. Missense variants in this SOXE/SOXF-specific motif are rare in control individuals, but have been detected in cancers, supporting its importance in development and physiology. By deepening understanding of mechanisms underlying the central transactivation function of SOXE proteins, these findings should help further decipher molecular networks essential for development and health and dysregulated in diseases.

20.
J Xray Sci Technol ; 27(4): 655-664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205012

RESUMO

 The objective of this study is to analyze small field photon beams acquired with commonly available detectors. Beam profiles of 6 MV photons from the Siemens Primus Linear Accelerator were measured with a micro ion chamber (IC CC01, IBA) and linear diode array (LDA-99SC, IBA). Data was acquired using a water phantom for small fields (0.5×0.5 cm2 to 4×4 cm2) at depth of maximum dose, 5 cm and 10 cm. Profiles were also generated with EGSnrc Monte Carlo code. Measured and simulated profiles were compared in terms of percentage difference of the area under the simulated and measured profiles (PD), ratio of the measured to simulated dose at the point of maximum deviation within the central region of profile (R), full width half maximum (FWHM) and penumbra. For field sizes ≥1×1 cm2, the maximum PD is 3.17 % and 2.87 % for IC and LDA respectively, whereas R is in the range of 0.95-1.05 for IC and 0.99-1.05 for LDA. LDA measured FWHM and penumbra are also in better agreement with the simulated results. This study demonstrated that LDA can be used for acquisition of beam profiles for field size as low as 1×1 cm2.

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