O uso da laserterapia em dose específica modula o processo inflamatório pulmonar em um modelo experimental de sepse em ratos

This study aimed to determine the effectiveness of LLLT in decreasing the lung inflammatory process in septic rats. A total of 32 male Wistar rats were divided into four groups (n=8): control group (CG), sepsis 24h (S24), sepsis and LLLT with 30 J/cm² (S24L30); sepsis and LLLT with 65 J/cm² (S24L65). The irradiation was performed immediately after surgery in the anterior region of the trachea and ventral regions of the chest, bilaterally, just below the ribs. Histological analysis of lung tissue was performed and the number of inflammatory cells was quantified. The S24 group showed an increase of inflammatory cells compared to the CG (pEl objetivo del estudio es determinar la eficacia de la LLLT en la disminución del proceso inflamatorio pulmonar en ratones sépticos. Se utilizaron 32 ratones machos Wistar divididos en cuatro grupos (n=8): control (CG); sepsis 24h (S24); sepsis y tratamiento con LLLT 30 J/cm2 (S24L30); sepsis y tratamiento con LLLT 65 J/cm2 (S24L65). Se realizó la irradiación inmediatamente después de la cirugía en la región anterior de la tráquea y en las regiones ventrales del tórax, bilateralmente, debajo de las costillas. Se realizó un análisis histológico del tejido pulmonar y se cuantificó el número de células inflamatorias. El grupo S24 presentó un aumento de células inflamatorias en comparación al CG (pO objetivo do estudo foi determinar a eficácia da LLLT na diminuição do processo inflamatório pulmonar em ratos sépticos. Foram utilizados 32 ratos machos Wistar divididos em quatro grupos (n=8): controle (CG); sepse 24h (S24); sepse e tratamento com LLLT 30 J/cm² (S24L30); sepse e tratamento com LLLT 65 J/cm² (S24L65). A irradiação foi realizada imediatamente após a cirurgia na região anterior de traqueia e nas regiões ventrais do tórax, bilateralmente, logo abaixo das costelas. Foi realizada análise histológica do tecido pulmonar e o número de células inflamatórias foi quantificado. O grupo S24 apresentou um aumento de células inflamatórias comparado ao CG (

Dosage-dependent deregulation of an AGAMOUS-LIKE gene cluster contributes to interspecific incompatibility.

Postzygotic lethality of interspecies hybrids can result from differences in gene expression, copy number, or coding sequence and can be overcome by altering parental genome dosage. In crosses between Arabidopsis thaliana and A. arenosa, embryo arrest is associated with endosperm hyperproliferation and delayed development similar to paternal-excess interploidy crosses and polycomb-repressive complex (PRC) mutants. Failure is accompanied by parent-specific loss of gene silencing including the dysregulation of three genes suppressed by PRC. Increasing the maternal genome dosage rescues seed development and gene silencing. A gene set upregulated in the failing seed transcriptome encoded putative AGAMOUS-LIKE MADS domain transcription factors (AGL) that were expressed in normal early endosperm and were shown to interact in a previous yeast 2-hybrid analysis. Suppression of these AGL's expression upon cellularization required PRC. Preceding seed failure, expression of the PRC member FIS2 decreased concomitant with overexpression of the AGL cluster. Inactivating two members, AGL62 and AGL90, attenuated the postzygotic barrier between A. thaliana and A. arenosa. We present a model where dosage-sensitive loss of PRC function results in a dysregulated AGL network, which is detrimental for early seed development

A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation

During normal megakaryocyte development, in response to thrombopoetin, mature cells enter a senescence-like state in which they shed platelets; this state, characterized by cell cycle arrest, is defective in malignant megakaryocytes

Generation of a Novel Regulatory NK Cell Subset from Peripheral Blood CD34+ Progenitors Promoted by Membrane-Bound IL-15

BACKGROUND: NK cells have been long time considered as cytotoxic lymphocytes competent in killing virus-infected cells and tumors. However, NK cells may also play essential immuno-regulatory functions. In this context, the real existence of a defined NK subset with negative regulatory properties has been hypothesized but never clearly demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we show the in vitro generation from human peripheral blood haematopoietic progenitors (PB-HP), of a novel subset of non-cytolytic NK cells displaying a mature phenotype and remarkable immuno-regulatory functions (NK-ireg). The main functional hallmark of these NK-ireg cells is represented by the surface expression/release of HLA-G, a major immunosuppressive molecule. In addition, NK-ireg cells secrete two powerful immuno-regulatory factors: IL-10 and IL-21. Through these factors, NK-ireg cells act as effectors of the down-regulation of the immune response: reconverting mature myeloid DC (mDC) into immature/tolerogenic DC, blocking cytolytic functions on conventional NK cells and inducing HLA-G membrane expression on PB-derived monocytes. The generation of "NK-ireg" cells is obtained, by default, in culture conditions favouring cell-to-cell contacts, and it is strictly dependent on reciprocal trans-presentation of membrane-bound IL-15 forms constitutively and selectively expressed by human CD34(+) PB-HP. Finally, a small subset of NKp46(+) HLA-G(+) IL-10(+) is detected within freshly isolated decidual NK cells, suggesting that these cells could represent an in vivo counterpart of the NK-ireg cells. CONCLUSIONS/SIGNIFICANCE: In conclusion, NK-ireg cells represent a novel truly differentiated non-cytolytic NK subset with a self-sustainable phenotype (CD56(+) CD16(+) NKp30(+) NKp44(+) NKp46(+) CD94(+) CD69(+) CCR7(+)) generated from specific pSTAT6(+) GATA3(+) precursors. NK-ireg cells could be employed to develop new immuno-suppressive strategies in autoimmune diseases, transplant rejection or graft versus host diseases. In addition, NK-ireg cells can be easily derived from peripheral blood of the patients and could constitute an autologous biotherapic tool to be used combined or in alternative to other immuno-regulatory cells

高梁市国民健康保険成羽病院

Flavocytochrome c(3) from Shewanella frigidimarina WO is a tetrahaem periplasmic protein of 64 kDa with fumarate reductase activity. This work reports the first example of NMR techniques applied to the assignment of the thermodynamic order of oxidation of the four individual haems for such large protein, expanding its applicability to a wide range of proteins. NMR data from partially and fully oxidised samples of fcc(3) and a mutated protein with an axial ligand of haem IV replaced by alanine were compared with calculated chemical shifts, allowing the structural assignment of the signals and the unequivocal determination of the order of oxidation of the haems. As oxidation progresses the fcc(3) haem domain is polarised, with haems I and II much more oxidised than haems III and IV, haem IV being the most reduced. Thus, during catalysis as an electron is taken by the flavin adenosine dinucleotide from haem IV, haem III is eager to re-reduce haem IV, allowing the transfer of two electrons to the active site

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Late quaternary sea-ice and sedimentary redox conditions in the eastern Bering Sea – Implications for ventilation of the mid-depth North Pacific and an Atlantic-Pacific seesaw mechanism

On glacial-interglacial and millennial timescales, sea ice is an important player in the circulation and primary productivity of high latitude oceans, affecting regional and global biogeochemical cycling. In the modern North Pacific, brine rejection during sea-ice freezing in the Sea of Okhotsk drives the formation of North Pacific Intermediate Water (NPIW) that ventilates the North Pacific Ocean at 300 m to 1000 m water depth. Glacial intervals of the late Quaternary, however, experienced a deepening of glacial NPIW to at least 2000 m, with the strongest ventilation observed during cold stadial conditions of the last deglaciation. However, the origin of the shifts in NPIW ventilation is poorly understood. Numerical simulations suggest an atmospheric teleconnection between the North Atlantic and the North Pacific, in response to a slowdown or shutdown of the Atlantic meridional overturning circulation. This leads to a build-up of salinity in the North Pacific surface ocean, triggering deep ventilation. Alternatively, increased sea-ice formation in the North Pacific and its marginal seas may have caused strengthened overturning in response to enhanced brine rejection. Here we use a multi-proxy approach to explore sea-ice dynamics, sedimentary redox chemistry, and benthic ecology at Integrated Ocean Drilling Program Site U1343 in the eastern Bering Sea across the last 40 ka. Our results suggest that brine rejection from enhanced sea-ice formation during early Heinrich Stadial 1 locally weakened the halocline, aiding in the initiation of deep overturning. Additionally, deglacial sea-ice retreat likely contributed to increased primary productivity and expansion of mid-depth hypoxia at Site U1343 during interstadials, confirming a vital role of sea ice in the deglacial North Pacific carbon cycle

Rede social e religião : como o público interage com os youtubers critãos

Orientadora: Valquíria Michela John.Monografia (graduação) - Universidade Federal do Paraná, Setor de Artes, Comunicação e Design, Curso de Graduação em Comunicação Social, habilitação em Jornalismo.Inclui referênciasInfluenciadores digitais estão presentes em diversos sites de redes sociais. Neste Trabalho de Conclusão de Curso - TCC, discutimos a atuação dos formadores de opinião do Youtube que produzem conteúdo cristão. Esses influenciadores digitais têm conquistado o público com temas específicos, estabelecido laços a partir da identificação e transformado processos de produção e de negócios na comunicação. Para compreender esse fenômeno sobre a relação entre a internet e a religião, pesquisamos a plataforma do Youtube como site de rede social e a conversação entre produtores de conteúdo cristãos e o público. Neste TCC, analisamos como ocorre a interação nos vídeos da influenciadora digital Fabiola Melo, uma evangélica que tem mais de 1,5 milhão de seguidores no Youtube. Foi realizado inicialmente um levantamento quantitativo, identificando quantos vídeos foram produzidos por ano e quantas visualizações e comentários foram obtidos nos vídeos do primeiro semestre de 2018. A partir desse mapeamento, foram selecionados dois vídeos que têm os comentários analisados, de acordo com a categoria em que estão inseridos. Com essa pesquisa, podemos ter um vislumbre de como os vídeos digitais têm contribuído para a comunicação de nicho. Notamos há a relação entre os conceitos de rede, segmentação da audiência, sites de rede sociais e conversação em rede com a evolução do conteúdo religioso na internet. Observamos que o engajamento acontece através das relações de identificação, apoio e conversação