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Long-term societal prosperity depends on addressing the world's energy and environmental problems, and photocatalysis has emerged as a viable remedy. Improving the efficiency of photocatalytic processes is fundamentally achieved by optimizing the effective utilization of solar energy and enhancing the efficient separation of photogenerated charges. It has been demonstrated that the fabrication of III-V semiconductor-based photocatalysts is effective in increasing solar light absorption, long-term stability, large-scale production and promoting charge transfer. This focused review explores on the current developments in III-V semiconductor materials for solar-powered photocatalytic systems. The review explores on various subjects, including the advancement of III-V semiconductors, photocatalytic mechanisms, and their uses in H2 conversion, CO2 reduction, environmental remediation, and photocatalytic oxidation and reduction reactions. In order to design heterostructures, the review delves into basic concepts including solar light absorption and effective charge separation. It also highlights significant advancements in green energy systems for water splitting, emphasizing the significance of establishing eco-friendly systems for CO2 reduction and hydrogen production. The main purpose is to produce hydrogen through sustainable and ecologically friendly energy conversion. The review intends to foster the development of greener and more sustainable energy source by encouraging researchers and developers to focus on practical applications and advancements in solar-powered photocatalysis.
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The Rickettsia species transmitted by ticks are mostly classified within the spotted fever group rickettsiae (SFGR), which causes tick-borne rickettsiosis. Although efforts have been made to investigate their prevalence in the Republic of Korea (ROK), research has been limited to certain areas. Furthermore, the pooling method for ticks does not fully reflect the exact infection rate. Therefore, we aimed to perform molecular identification of SFGR in ticks to elucidate the current prevalence of tick-borne rickettsiosis in the ROK. The SFGR of ticks was identified using polymerase chain reaction targeting the 17 kDa antigen, ompA, and gltA, followed by sequencing for species identification and phylogenetic analysis. In total, 302 ticks belonging to four species (Haemaphysalis flava, H. longicornis, Ixodes nipponensis, and Amblyomma testudinarium) were collected between April and November 2022. The overall SFGR infection rate was 26.8% (81/302 patients). Both adult and nymphal ticks and the SFGR infection rate increased during April-May, reaching their peaks in June, followed by a marked decline in August and July, respectively. Phylogenetic analysis revealed three species (R. monacensis, R. heilongjiangensis, and Candidatus R. jingxinensis) of SFGR. Thus, our results emphasize the importance of tick surveys for the prevention and management of tick-borne rickettsiosis.
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The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca2+ concentration and maintains Ca2+ homeostasis1,2. It also mediates diverse cellular processes not associated with Ca2+ balance3-5. The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes6. We determined structures of CaSR in complex with G proteins from three different subfamilies: Gq, Gi and Gs. We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Gα subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1-ICL3), an extended transmembrane helix 3 and an ordered C-terminal region. G-protein binding expands the transmembrane dimer interface, which is further stabilized by phospholipid. The restraint imposed by the receptor dimer, in combination with ICL2, enables G-protein activation by facilitating conformational transition of Gα. We identified a single Gα residue that determines Gq and Gs versus Gi selectivity. The length and flexibility of ICL2 allows CaSR to bind all three Gα subtypes, thereby conferring capacity for promiscuous G-protein coupling.
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Proteínas Heterotriméricas de Ligação ao GTP , Receptores de Detecção de Cálcio , Humanos , Cálcio/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/química , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Modelos Moleculares , Ligação Proteica , Multimerização Proteica , Receptores de Detecção de Cálcio/metabolismo , Receptores de Detecção de Cálcio/química , Proteínas Heterotriméricas de Ligação ao GTP/química , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Sítios de Ligação , Estrutura Secundária de Proteína , Especificidade por SubstratoRESUMO
BACKGROUND: Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via transient receptor potential melastatin 8 (TRPM8) agonism have shown potential in itch management. However, animal studies on itch have limitations, as animals cannot communicate subjective events and their fur-coated skin differs from that of humans. Human studies offer more direct and reliable information. OBJECTIVES: To investigate the effects of a specific TRPM8 agonist gel (cryosim-1) on itch induced by various pruritogens in human skin. METHODS: Calcium imaging experiments determined the binding of cryosim-1 and histamine to their respective receptors. Thirty healthy volunteers underwent skin prick tests with pruritogens and a control vehicle. Itch and pain intensity were measured using a numerical rating scale (NRS) across 10â min. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated at a later date, and skin moisture, transepidermal water loss and mechanical sensitivity were measured. RESULTS: The in vitro study confirmed that histamine is not a TRPM8 agonist and cryosim-1 does not act as an agonist or antagonist on the human histamine 1 receptor. The TRPM8 agonist gel significantly reduced the itch intensity for all pruritogens compared with the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced. CONCLUSIONS: The specific TRPM8 agonist gel effectively suppressed human skin itch induced by various pruritogens. These versatile actions suggest that cooling agents may be promising treatments for multiple forms of itch stimuli.
Managing itching and the effects of histamine can be difficult for people with allergies. Cooling the skin or applying menthol provides some relief from itch, but the way they work is not fully understood. Cooling agents interact with a protein called TRPM8 (also known as the 'cold and menthol receptor') and have shown potential for the management of itch. However, much of the research has been done on animals and has limitations when compared with human studies. Antihistamine medications can help with histamine-induced itching, but they may not work for other causes of itch. This study investigated the effects of a specific TRPM8 agonist (a chemical that activates a receptor to produce a biologic response) gel called cryosim-1 on itch in human skin. To do this, we conducted tests on 30 healthy people using five different substances that cause itching. Participants rated the itch intensity and pain using a scale and we measured various aspects of their skin. The results showed that all substances caused significant itching compared to a control substance, but itchiness gradually decreased over time. Histamine and compound 48/80 also caused pain. However, when participants applied the TRPM8 activator gel before exposure, they experienced less itching and lower itch intensity versus the gel without the activator. There were no significant differences in pain between the TRPM8 activator and the gel without it. In summary, our findings showed that activating TRPM8 receptors with a specific substance effectively relieved itching caused by various irritants on human skin. This suggests its potential as a treatment for itch-related conditions. Further research is needed to understand its mechanisms better and evaluate its effectiveness in real-life situations.
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Histamina , Prurido , Canais de Cátion TRPM , Humanos , Prurido/tratamento farmacológico , Prurido/induzido quimicamente , Canais de Cátion TRPM/agonistas , Canais de Cátion TRPM/antagonistas & inibidores , Adulto , Masculino , Histamina/administração & dosagem , Histamina/efeitos adversos , Feminino , Adulto Jovem , Géis , Pessoa de Meia-Idade , Antipruriginosos/administração & dosagem , Antipruriginosos/farmacologia , Antipruriginosos/efeitos adversos , Método Duplo-Cego , Administração CutâneaRESUMO
Itching is an unpleasant sensation that provokes the desire to scratch. In general, itching is caused by dermatologic diseases, but it can also be caused by systemic diseases. Since itching hampers patients' quality of life, it is important to understand the appropriate treatment and pathophysiology of pruritus caused by systemic diseases to improve the quality of life. Mechanisms are being studied through animal or human studies, and various treatments are being tested through clinical trials. We report current trends of two major systemic diseases: chronic kidney disease and cholestatic liver disease. This review summarizes the causes and pathophysiology of systemic diseases with pruritus and appropriate treatments. This article will contribute to patients' quality of life. Further research will help understand the mechanisms and develop new strategies in the future.
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Colestase , Insuficiência Renal Crônica , Animais , Humanos , Qualidade de Vida , Prurido/terapia , Prurido/tratamento farmacológico , Colestase/complicações , Colestase/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , SensaçãoRESUMO
As interest in skin increases, the cosmetic market is also growing. It is difficult to choose between the numerous types of basic cosmetics on the market. This article aims to provide advice and guidance on which products to recommend according to a patient's skin condition. Appropriate application of a moisturizer attempts not only to improve the dryness, but also improve the skin's natural barrier function to protect the skin from internal and external irritants to keep the skin healthy. Moisturizers consist of various ingredients, including occlusive agents, emollients, humectants, lipid mixture, emulsifiers, and preservatives. Pathophysiology of dry skin is also discussed to provide readers with the background they need to choose the right moisturizer for themselves. As moisturizers play an important role as adjuvant in the treatment of common skin diseases, such as atopic dermatitis, contact dermatitis, psoriasis, acne and rosacea, which type of moisturizer is appropriate for each disease was also dealt with. Basic cosmetics, especially moisturizers, should be recommended in consideration of the ingredients, effectiveness and safety of each product, and the skin condition of each patient.
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Dermatite Atópica , Dermatopatias , Administração Tópica , Emolientes/uso terapêutico , Humanos , Pele , Dermatopatias/tratamento farmacológicoRESUMO
Darier disease is an autosomal dominant disorder with dark crusty patches and is classified as hereditary acantholytic dermatosis. Keratotic papules and crust are often present on the scalp, forehead, chest, back, upper arms, elbows, groin, and behind the ears, predominantly in seborrheic areas. A 48-year-old male patient presented skin lesions with pruritus on the trunk and both upper and lower extremities. He first noticed the lesion 15 years before. On physical examination, there were multiple erythematous papules with crust on the trunk and red-brown colored keratotic plaque on both extremities. The suspected histopathological diagnosis was psoriasis vulgaris. The patient's skin lesions and pruritus were significantly improved after the psoriasis treatment. While continuing psoriasis treatment, the patient showed sudden worsening of the skin lesions on the scalp, abdomen, and fingernails (V-shaped nicks) with pruritus. Punch biopsy was performed on the abdominal lesion again and the final diagnosis was Darier disease. The patient was then treated using alitretinoin while maintaining the use of guselkumab for psoriasis. There are only a few cases that we found in which patients with Darier disease also had psoriasis. We report this rare case of Darier disease with psoriasis and propose that an additional biopsy might be necessary for accurate diagnosis and proper treatment.
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Doença de Darier , Psoríase , Biópsia , Doença de Darier/complicações , Doença de Darier/diagnóstico , Doença de Darier/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prurido , Psoríase/complicações , Psoríase/tratamento farmacológico , Pele/patologiaRESUMO
The human extracellular calcium-sensing (CaS) receptor controls plasma Ca2+ levels and contributes to nutrient-dependent maintenance and metabolism of diverse organs. Allosteric modulation of the CaS receptor corrects disorders of calcium homeostasis. Here, we report the cryogenic-electron microscopy reconstructions of a near-full-length CaS receptor in the absence and presence of allosteric modulators. Activation of the homodimeric CaS receptor requires a break in the transmembrane 6 (TM6) helix of each subunit, which facilitates the formation of a TM6-mediated homodimer interface and expansion of homodimer interactions. This transformation in TM6 occurs without a positive allosteric modulator. Two modulators with opposite functional roles bind to overlapping sites within the transmembrane domain through common interactions, acting to stabilize distinct rotamer conformations of key residues on the TM6 helix. The positive modulator reinforces TM6 distortion and maximizes subunit contact to enhance receptor activity, while the negative modulator strengthens an intact TM6 to dampen receptor function. In both active and inactive states, the receptor displays symmetrical transmembrane conformations that are consistent with its homodimeric assembly.
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Cálcio/metabolismo , Regulação da Expressão Gênica/fisiologia , Homeostase/fisiologia , Receptores de Detecção de Cálcio/metabolismo , Microscopia Crioeletrônica , Células HEK293 , Humanos , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Receptores de Detecção de Cálcio/genética , Transdução de SinaisRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The human GABAB receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2-6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions. GABAB1 recognizes orthosteric ligands7,8, while GABAB2 couples with G proteins9-14. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail15. Although the VFT heterodimer structure has been resolved16, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABAB receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.
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Microscopia Crioeletrônica , Receptores de GABA-B/química , Receptores de GABA-B/ultraestrutura , Cálcio/metabolismo , Etanolaminas/química , Etanolaminas/metabolismo , Humanos , Ligantes , Modelos Moleculares , Fosforilcolina/química , Fosforilcolina/metabolismo , Domínios Proteicos , Multimerização Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Receptores de GABA-B/metabolismo , Relação Estrutura-AtividadeRESUMO
Inhibiting high-voltage-activated calcium channels (HVACCs; CaV1/CaV2) is therapeutic for myriad cardiovascular and neurological diseases. For particular applications, genetically-encoded HVACC blockers may enable channel inhibition with greater tissue-specificity and versatility than is achievable with small molecules. Here, we engineered a genetically-encoded HVACC inhibitor by first isolating an immunized llama nanobody (nb.F3) that binds auxiliary HVACC CaVß subunits. Nb.F3 by itself is functionally inert, providing a convenient vehicle to target active moieties to CaVß-associated channels. Nb.F3 fused to the catalytic HECT domain of Nedd4L (CaV-aßlator), an E3 ubiquitin ligase, ablated currents from diverse HVACCs reconstituted in HEK293 cells, and from endogenous CaV1/CaV2 channels in mammalian cardiomyocytes, dorsal root ganglion neurons, and pancreatic ß cells. In cardiomyocytes, CaV-aßlator redistributed CaV1.2 channels from dyads to Rab-7-positive late endosomes. This work introduces CaV-aßlator as a potent genetically-encoded HVACC inhibitor, and describes a general approach that can be broadly adapted to generate versatile modulators for macro-molecular membrane protein complexes.
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Produtos Biológicos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Anticorpos de Domínio Único/farmacologia , Animais , Produtos Biológicos/isolamento & purificação , Bloqueadores dos Canais de Cálcio/isolamento & purificação , Camelídeos Americanos , Células HEK293 , Humanos , Ligação ProteicaRESUMO
Metabotropic GABAB receptors mediate a significant fraction of inhibitory neurotransmission in the brain. Native GABAB receptor complexes contain the principal subunits GABAB1 and GABAB2, which form an obligate heterodimer, and auxiliary subunits, known as potassium channel tetramerization domain-containing proteins (KCTDs). KCTDs interact with GABAB receptors and modify the kinetics of GABAB receptor signaling. Little is known about the molecular mechanism governing the direct association and functional coupling of GABAB receptors with these auxiliary proteins. Here, we describe the high-resolution structure of the KCTD16 oligomerization domain in complex with part of the GABAB2 receptor. A single GABAB2 C-terminal peptide is bound to the interior of an open pentamer formed by the oligomerization domain of five KCTD16 subunits. Mutation of specific amino acids identified in the structure of the GABAB2-KCTD16 interface disrupted both the biochemical association and functional modulation of GABAB receptors and G protein-activated inwardly rectifying K+ channel (GIRK) channels. These interfacial residues are conserved among KCTDs, suggesting a common mode of KCTD interaction with GABAB receptors. Defining the binding interface of GABAB receptor and KCTD reveals a potential regulatory site for modulating GABAB-receptor function in the brain.
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Peptídeos e Proteínas de Sinalização Intracelular , Proteínas do Tecido Nervoso , Receptores de GABA-B , Sítios de Ligação/genética , Cristalografia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Modelos Moleculares , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Ligação Proteica/genética , Receptores de GABA-B/química , Receptores de GABA-B/genética , Receptores de GABA-B/metabolismo , Transdução de Sinais/genéticaRESUMO
SUMMARY: The purpose of this research was to enable anyone to learn the sectional anatomy of the head anywhere, anytime by presenting software to browse sectioned images on a Google Android mobile device. Among the 2,343 sectioned images at 0.1 mm intervals, 234 sectioned images at 1 mm intervals were chosen. The corresponding 234 segmented images containing 236 head structures were selected. The software of the mobile version was programmed and debugged in the Java programming language. The folders of the sectioned images and segmented images and the txt file of the segmentation data were arranged in the source code of the software. The software was distributed free of charge at the homepage (neuroanatomy.kr) and Google Play Store. After installing the software, the sectioned images and corresponding segmented images could be browsed by touching and swiping the screen. In the medical category of the Google Play Store, the software earned a good reputation. The software of the Android mobile version was usable regardless of the time and place. The software is under the authors' non-commercial policy. Other investigators may modify the mobile software to browse their own images. The mobile version of the software will aid medical students and doctors in learning sectional anatomy.
RESUMEN: El propósito de esta investigación fue permitir que toda persona aprendiera la anatomía de secciones de la cabeza, en cualquier lugar y en cualquier momento, a través de un software para examinar imágenes seccionadas en un dispositivo móvil Android de Google. De las 2.343 imágenes seccionadas a intervalos de 0,1 mm, se seleccionaron 234 imágenes seccionadas a intervalos de 1 mm. Se seleccionaron las 234 imágenes segmentadas que contenían 236 estructuras de cabeza. El software de la versión móvil fue programado y depurado en el lenguaje de programación Java. Las carpetas de las imágenes seccionadas y las imágenes segmentadas y el archivo .txt de los datos de segmentación se organizaron en el código fuente del software. El software se distribuyó gratuitamente en la página principal (neuroanatomy.kr) y Google Play Store. Después de instalar el software, las imágenes seccionadas y las imágenes segmentadas correspondientes se pueden navegar tocando y deslizando la pantalla. En la categoría médica de Google Play Store, el software obtuvo buena recepción. El software de la versión móvil de Android fue utilizado independientemente de la hora y el lugar. El software está bajo la política no comercial de los autores. Otros investigadores pueden modificar el software móvil para navegar por sus propias imágenes. La versión móvil del software ayudará a los estudiantes de medicina y los médicos en el aprendizaje de la anatomía seccional.
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Humanos , Educação Médica/métodos , Aplicativos Móveis , Smartphone , Cabeça/anatomia & histologia , Anatomia Transversal , Projetos Ser Humano Visível , Cabeça/diagnóstico por imagem , Anatomia/educação , AprendizagemRESUMO
INTRODUCTION: Scientific collaboration is an important mechanism that enables the integration of the least developed countries into research activities. In the present study, we use the order of author signatures and addresses for correspondence in scientific publications as variables to analyze the interactions between countries of very high (VHHD), high (HHD), medium (MHD), and low human development (LHD). METHODOLOGY: We identified all documents published between 2011 and 2015 in journals included in the Science Citation Index-Expanded categories' of Tropical Medicine, Infectious Diseases, Parasitology, and Pediatrics. We then classified the countries participating in the publications according to their Human Development Index (HDI), analyzing the international collaboration; positioning and influence of some countries over others in cooperative networks; their leadership; and the impact of the work based on the HDI and the type of collaboration. RESULTS: We observed a high degree of international collaboration in all the areas analyzed, in the case of both LHD and MHD countries. We identified numerous cooperative links between VHHD countries and MHD/LHD countries, reflecting the fact that cooperative links are an important mechanism for integrating research activities into the latter. The countries with large emerging economies, such as Brazil and China stand out due to the dominance they exert in the collaborations established with the United States, the UK, and other European countries. The analysis of the leadership role of the countries, measured by the frequency of lead authorships, shows limited participation by MHD/LHD countries. This reduced participation among less developed countries is further accentuated by their limited presence in the addresses for correspondence. We observed significant statistical differences in the degree of citation according to the HDI of the participating countries. CONCLUSIONS: The order of signatures and the address for correspondence in scientific publications are bibliographic characteristics that facilitate a precise, in-depth analysis of cooperative practices and their associations with concepts like dominance or leadership. This is useful to monitor the existing balance in research participation in health research publications.
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Autoria , Países Desenvolvidos , Países em Desenvolvimento , Cooperação Internacional , Editoração , Humanos , Liderança , Influência dos Pares , Predomínio SocialRESUMO
Orchidaceous plants have symbiotic relationships with endophytic fungi, including mycorrhizal fungi, which play important roles in the seed germination and growth of the host plants. In this study, endophytic fungal communities isolated from the roots of Cephalanthera longibracteata collected from three different sites in Korea were analyzed, and it was determined whether fungal communities were preferentially correlated with the sites. The fungal isolates were identified by sequence analysis of the internal transcribed spacer regions of rDNA. In total, 30 species of endophytic fungi, including two species of mycorrhizal fungi belonging to the genus Tulasnella, were identified. Leptodontidium orchidicola showed the highest frequency and was isolated from all root samples. Species diversity and richness were not significantly different among sites. However, the community structure of the endophytic fungi significantly differed among sites, suggesting that the site characteristics affected the community composition of the endophytic fungi colonizing the roots of C. longibracteata. Our findings will aid in developing methods involving the use of symbiotic fungi for orchid conservation and restoration in native habitats.
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BACKGROUND: Although researchers have worked in collaboration since the origins of modern science and the publication of the first scientific journals in the eighteenth century, this phenomenon has acquired exceptional importance in the last several decades. Since the mid-twentieth century, new knowledge has been generated from within an ever-growing network of investigators, working cooperatively in research groups across countries and institutions. Cooperation is a crucial determinant of academic success. OBJECTIVE: The aim of the present paper is to analyze the evolution of scientific collaboration at the micro level, with regard to the scientific production generated on psoriasis research. METHODS: A bibliographic search in the Medline database containing the MeSH terms "psoriasis" or "psoriatic arthritis" was carried out. The search results were limited to articles, reviews and letters. After identifying the co-authorships of documents on psoriasis indexed in the Medline database (1942-2013), various bibliometric indicators were obtained, including the average number of authors per document and degree of multi-authorship over time. In addition, we performed a network analysis to study the evolution of certain features of the co-authorship network as a whole: average degree, size of the largest component, clustering coefficient, density and average distance. We also analyzed the evolution of the giant component to characterize the changing research patterns in the field, and we calculated social network indicators for the nodes, namely betweenness and closeness. RESULTS: The main active research clusters in the area were identified, along with their authors of reference. Our analysis of 28,670 documents sheds light on different aspects related to the evolution of scientific collaboration in the field, including the progressive increase in the mean number of co-authors (which stood at 5.17 in the 2004-2013 decade), and the rise in multi-authored papers signed by many different authors (in the same decade, 25.77% of the documents had between 6 and 9 co-authors, and 10.28% had 10 or more). With regard to the network indicators, the average degree gradually increased up to 10.97 in the study period. The percentage of authors pertaining to the largest component also rose to 73.02% of the authors. The clustering coefficient, on the other hand, remained stable throughout the entire 70-year period, with values hovering around 0.9. Finally, the average distance peaked in the decades 1974-1983 (8.29) and 1984-2003 (8.12) then fell over the next two decades, down to 5.25 in 2004-2013. The construction of the co-authorship network (threshold of collaboration ≥ 10 co-authored works) revealed a giant component of 161 researchers, containing 6 highly cohesive sub-components. CONCLUSIONS: Our study reveals the existence of a growing research community in which collaboration is increasingly important. We can highlight an essential feature associated with scientific collaboration: multi-authored papers, with growing numbers of collaborators contributing to them, are becoming more and more common, therefore the formation of research groups of increasing depth (specialization) and breadth (multidisciplinarity) is now a cornerstone of research success.
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Bibliometria , Pesquisa Biomédica , Comportamento Cooperativo , Psoríase/terapia , Pesquisadores/ética , Autoria , Humanos , Disseminação de Informação , MEDLINE , Publicações Periódicas como Assunto/ética , Pesquisadores/psicologia , Rede Social , Recursos HumanosRESUMO
Several Fusarium species produce the polyketide mycotoxin zearalenone (ZEA), a causative agent of hyperestrogenic syndrome in animals that is often found in F. graminearum-infected cereals in temperate regions. The ZEA biosynthetic cluster genes PKS4, PKS13, ZEB1 andâ ZEB2 encode a reducing polyketide synthase, a non-reducing polyketide synthase, an isoamyl alcohol oxidase and a transcription factor respectively. In this study, the production of two isoforms (ZEB2L and ZEB2S) from the ZEB2 gene in F. graminearum via an alternative promoter was characterized. ZEB2L contains a basic leucine zipper (bZIP) DNA-binding domain at the N-terminus, whereas ZEB2S is an N-terminally truncated form of ZEB2L that lacks the bZIP domain. Interestingly, ZEA triggers the induction of both ZEB2L and ZEB2S transcription. ZEB2L and ZEB2S interact with each other to form a heterodimer that regulates ZEA production by reducing the binding affinity of ZEB2L for the ZEB2L gene promoter. Our study provides insight into the autoregulation of ZEB2 expression by alternative promoter usage and a feedback loop during ZEA production; this regulatory mechanism is similar to that observed in higher eukaryotes.
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Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fusarium/genética , Fusarium/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zearalenona/biossíntese , Grão Comestível/química , Retroalimentação Fisiológica , Proteínas Fúngicas/química , Fusarium/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica , Homeostase , Zíper de Leucina , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Isoformas de Proteínas , Multimerização Proteica , Fatores de Transcrição/química , Transcrição Gênica , Técnicas do Sistema de Duplo-Híbrido , Zearalenona/farmacologiaRESUMO
Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located.
Assuntos
Citocromo P-450 CYP1A1/genética , Proteínas Recombinantes/genética , Sequência de Aminoácidos , Animais , Benzo(a)pireno/metabolismo , Células CHO , Clonagem Molecular , Cricetulus , Citocromo P-450 CYP1A1/metabolismo , Escherichia coli/genética , Heme/química , Humanos , Hidroxilação , Microssomos/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fases de Leitura Aberta , Oxazinas/metabolismo , Polimorfismo Genético , Conformação Proteica , Proteínas Recombinantes/metabolismo , Alinhamento de SequênciaRESUMO
The fractional flow reserve (FFR) is a widely used clinical index to evaluate the functional severity of coronary stenosis. A computer simulation method based on patients' computed tomography (CT) data is a plausible non-invasive approach for computing the FFR. This method can provide a detailed solution for the stenosed coronary hemodynamics by coupling computational fluid dynamics (CFD) with the lumped parameter model (LPM) of the cardiovascular system. In this work, we have implemented a simple computational method to compute the FFR. As this method uses only coronary arteries for the CFD model and includes only the LPM of the coronary vascular system, it provides simpler boundary conditions for the coronary geometry and is computationally more efficient than existing approaches. To test the efficacy of this method, we simulated a three-dimensional straight vessel using CFD coupled with the LPM. The computed results were compared with those of the LPM. To validate this method in terms of clinically realistic geometry, a patient-specific model of stenosed coronary arteries was constructed from CT images, and the computed FFR was compared with clinically measured results. We evaluated the effect of a model aorta on the computed FFR and compared this with a model without the aorta. Computationally, the model without the aorta was more efficient than that with the aorta, reducing the CPU time required for computing a cardiac cycle to 43.4%.
Assuntos
Velocidade do Fluxo Sanguíneo , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Pressão Sanguínea , Simulação por Computador , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Radiografia , Reprodutibilidade dos Testes , Reologia/métodos , Sensibilidade e Especificidade , Resistência ao Cisalhamento , Resistência VascularRESUMO
BACKGROUND: Although catheter ablation is an effective rhythm control strategy for atrial fibrillation (AF), empirically-based ablation has a substantial recurrence rate. The purposes of this study were to develop a computational platform for patient-specific virtual AF ablation and to compare the anti-fibrillatory effects of 5 different virtual ablation protocols with empirically chosen clinical ablations. METHODS: We included 20 patients with AF (65% male, 60.1 ± 10.5 years old, 80% persistent AF [PeAF]) who had undergone empirically-based catheter ablation: circumferential pulmonary vein isolation (CPVI) for paroxysmal AF (PAF) and additional posterior box lesion (L1) and anterior line (L2) for PeAF. Using patient-specific three-dimensional left atrial (LA) geometry, we generated a finite element model and tested the AF termination rate after 5 different virtual ablations: CPVI alone, CPVI + L1, CPVI + L1,2, CPVI with complex fractionated atrial electrogram (CFAE) ablation, and CFAE ablation alone. RESULTS: 1. Virtual CPVI + L1,2 ablation showed the highest AF termination rate in overall patients (55%) and PeAF patients (n = 16, 62.5%). 2. The virtual AF maintenance duration was shortest in the case of virtual CPVI + L1,2 ablation in overall patients (2.19 ± 1.28 vs. 2.91 ± 1.04 s, p = 0.009) and in patients with PeAF (2.05 ± 1.23 vs. 2.93 ± 10.2 s, p = 0.004) compared with other protocols. CONCLUSION: Virtual AF ablation using personalized in-silico model of LA is feasible. Virtual ablation with CPVI + L1,2 shows the highest antifibrillatory effect, concordant with the empirical ablation protocol in patients with PeAF.