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Pathological ocular angiogenesis has long been associated with myeloid cell activation. However, the precise cellular and molecular mechanisms governing the intricate crosstalk between the immune system and vascular changes during ocular neovascularization formation remain elusive. In this study, we demonstrated that the absence of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells led to a substantial accumulation of microglia and macrophage subsets during the neovascularization process. Our single-cell RNA sequencing data analysis revealed a remarkable increase in the expression of the secreted phosphoprotein 1 (Spp1) gene within these microglia and macrophages, identifying subsets of Spp1-expressing microglia and macrophages during neovascularization formation in angiogenesis mouse models. Notably, the number of Spp1-expressing microglia and macrophages exhibited further elevation during neovascularization in mice lacking myeloid SOCS3. Moreover, our investigation unveiled the Spp1 gene as a direct transcriptional target gene of signal transducer and activator of transcription 3. Importantly, pharmaceutical activation of SOCS3 or blocking of SPP1 resulted in a significant reduction in pathological neovascularization. In conclusion, our study highlights the pivotal role of the SOCS3/STAT3/SPP1 axis in the regulation of pathological retinal angiogenesis.
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Macrófagos , Microglia , Osteopontina , Neovascularização Retiniana , Proteína 3 Supressora da Sinalização de Citocinas , Animais , Camundongos , Angiogênese , Modelos Animais de Doenças , Regulação da Expressão Gênica , Macrófagos/metabolismo , Camundongos Knockout , Microglia/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Osteopontina/metabolismo , Osteopontina/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/etiologia , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genéticaRESUMO
Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.
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Proteína ADAM17 , Proteínas Proto-Oncogênicas c-fos , Neovascularização Retiniana , Animais , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Retiniana/genética , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Camundongos , Humanos , Retinopatia da Prematuridade/metabolismo , Retinopatia da Prematuridade/patologia , Retinopatia da Prematuridade/genética , Camundongos Endogâmicos C57BL , Transcrição Gênica , Regulação da Expressão Gênica , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/patologia , Modelos Animais de Doenças , AngiogêneseRESUMO
Electron transport through noncovalent interaction is of fundamental and practical importance in nanomaterials and nanodevices. Recent single-molecule studies employing single-molecule junctions have revealed unique electron transport properties through noncovalent interactions, especially those through a π-π interaction. However, the relationship between the junction structure and electron transport remains elusive due to the insufficient knowledge of geometric structures. In this article, we employ surface-enhanced Raman scattering (SERS) synchronized with current-voltage (I-V) measurements to characterize the junction structure, together with the transport properties, of a single dimer and monomer junction of naphthalenethiol, the former of which was formed by the intermolecular π-π interaction. The correlation analysis of the vibrational energy and electrical conductance enables identifying the intermolecular and molecule-electrode interactions in these molecular junctions and, consequently, addressing the transport properties exclusively associated with the π-π interaction. In addition, the analysis achieved discrimination of the interaction between the NT molecule and the Au electrode of the junction, i.e., Au-π interactions through-π coupling and though-space coupling. The power density spectra support the noncovalent character at the interfaces in the molecular junctions. These results demonstrate that the simultaneous SERS and I-V technique provides a unique means for the structural and electrical investigation of noncovalent interactions.
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Cellulose is the most abundant biomass on Earth, and many microorganisms depend on it as a source of energy. It consists mainly of crystalline and amorphous regions, and natural degradation of the crystalline part is highly dependent on the degree of processivity of the degrading enzymes (i.e., the extent of continuous hydrolysis without detachment from the substrate cellulose). Here, we report high-speed atomic force microscopic (HS-AFM) observations of the movement of four types of cellulases derived from the cellulolytic bacteria Cellulomonas fimi on various insoluble cellulose substrates. The HS-AFM images clearly demonstrated that two of them (CfCel6B and CfCel48A) slide on crystalline cellulose. The direction of processive movement of CfCel6B is from the nonreducing to the reducing end of the substrate, which is opposite that of processive cellulase Cel7A of the fungus Trichoderma reesei (TrCel7A), whose movement was first observed by this technique, while CfCel48A moves in the same direction as TrCel7A. When CfCel6B and TrCel7A were mixed on the same substrate, "traffic accidents" were observed, in which the two cellulases blocked each other's progress. The processivity of CfCel6B was similar to those of fungal family 7 cellulases but considerably higher than those of fungal family 6 cellulases. The results indicate that bacteria utilize family 6 cellulases as high-processivity enzymes for efficient degradation of crystalline cellulose, whereas family 7 enzymes have the same function in fungi. This is consistent with the idea of convergent evolution of processive cellulases in fungi and bacteria to achieve similar functionality using different protein foldings.
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Proteínas de Bactérias/química , Celulases/química , Cellulomonas/enzimologia , Proteínas Fúngicas/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biocatálise , Evolução Biológica , Celulases/genética , Celulases/metabolismo , Cellulomonas/química , Cellulomonas/genética , Cellulomonas/metabolismo , Celulose/química , Celulose/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Cinética , Microscopia de Força AtômicaRESUMO
Single-molecule measurements of biomaterials bring novel insights into cellular events. For almost all of these events, post-translational modifications (PTMs), which alter the properties of proteins through their chemical modifications, constitute essential regulatory mechanisms. However, suitable single-molecule methodology to study PTMs is very limited. Here we show single-molecule detection of peptide phosphorylation, an archetypal PTM, based on electrical measurements. We found that the phosphate group stably bridges a nanogap between metal electrodes and exhibited high electrical conductance, which enables specific single-molecule detection of peptide phosphorylation. The present methodology paves the way to single-molecule studies of PTMs, such as single-molecule kinetics for enzymatic modification of proteins as shown here.
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Peptídeos , Fosfatos , Materiais Biocompatíveis , Peptídeos/metabolismo , Fosfatos/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas/metabolismoRESUMO
OBJECTIVES: We assessed the impact of water, hygiene and sanitation (WASH), maternal, new-born and child health (MNCH), nutrition and early childhood development (ECD) on diarrhoea and microbial quality of water in a resource-constrained rural setting in Kenya. METHODS: Through a controlled intervention study, we tested faecal and water samples collected from both the intervention and control sites before and after the interventions using microbiological, immunological and molecular assays to determine the prevalence of diarrhoeagenic agents and microbial quality of water. Data from the hospital registers were used to estimate all-cause diarrhoea prevalence. RESULTS: After the interventions, we observed a 58.2% (95% CI: 39.4-75.3) decline in all-cause diarrhoea in the intervention site versus a 22.2% (95% CI: 5.9-49.4) reduction of the same in the control site. Besides rotavirus and pathogenic Escherichia coli, the rate of isolation of other diarrhoea-causing bacteria declined substantially in the intervention site. The microbial quality of community and household water improved considerably in both the intervention (81.9%; 95% CI: 74.5%-87.8%) and control (72.5%; 95% CI: 64.2%-80.5%) sites with the relative improvements in the intervention site being slightly larger. CONCLUSIONS: The integrated WASH, MNCH, nutrition and ECD interventions resulted in notable decline in all-cause diarrhoea and improvements in water quality in the rural resource-limited population in Kenya. This indicates a direct public health impact of the interventions and provides early evidence for public health policy makers to support the sustained implementation of these interventions.
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Higiene , Saneamento , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/prevenção & controle , Humanos , Lactente , Quênia/epidemiologia , Saneamento/métodos , Qualidade da ÁguaRESUMO
Arabinogalactan proteins (AGPs) are plant proteoglycans with functions in growth and development. However, these functions are largely unexplored, mainly because of the complexity of the sugar moieties. These carbohydrate sequences are generally analyzed with the aid of glycoside hydrolases. The exo-ß-1,3-galactanase is a glycoside hydrolase from the basidiomycete Phanerochaete chrysosporium (Pc1,3Gal43A), which specifically cleaves AGPs. However, its structure is not known in relation to its mechanism bypassing side chains. In this study, we solved the apo and liganded structures of Pc1,3Gal43A, which reveal a glycoside hydrolase family 43 subfamily 24 (GH43_sub24) catalytic domain together with a carbohydrate-binding module family 35 (CBM35) binding domain. GH43_sub24 is known to lack the catalytic base Asp conserved among other GH43 subfamilies. Our structure in combination with kinetic analyses reveals that the tautomerized imidic acid group of Gln263 serves as the catalytic base residue instead. Pc1,3Gal43A has three subsites that continue from the bottom of the catalytic pocket to the solvent. Subsite -1 contains a space that can accommodate the C-6 methylol of Gal, enabling the enzyme to bypass the ß-1,6-linked galactan side chains of AGPs. Furthermore, the galactan-binding domain in CBM35 has a different ligand interaction mechanism from other sugar-binding CBM35s, including those that bind galactomannan. Specifically, we noted a Gly â Trp substitution, which affects pyranose stacking, and an Asp â Asn substitution in the binding pocket, which recognizes ß-linked rather than α-linked Gal residues. These findings should facilitate further structural analysis of AGPs and may also be helpful in engineering designer enzymes for efficient biomass utilization.
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Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Galactanos/metabolismo , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Mananas/metabolismo , Phanerochaete/enzimologia , Sequência de Aminoácidos , Domínio Catalítico , Cristalografia por Raios X , Galactose/análogos & derivados , Homologia de Sequência , Especificidade por SubstratoRESUMO
Cellobiohydrolases directly convert crystalline cellulose into cellobiose and are of biotechnological interest to achieve efficient biomass utilization. As a result, much research in the field has focused on identifying cellobiohydrolases that are very fast. Cellobiohydrolase A from the bacterium Cellulomonas fimi (CfCel6B) and cellobiohydrolase II from the fungus Trichoderma reesei (TrCel6A) have similar catalytic domains (CDs) and show similar hydrolytic activity. However, TrCel6A and CfCel6B have different cellulose-binding domains (CBDs) and linkers: TrCel6A has a glycosylated peptide linker, whereas CfCel6B's linker consists of three fibronectin type 3 domains. We previously found that TrCel6A's linker plays an important role in increasing the binding rate constant to crystalline cellulose. However, it was not clear whether CfCel6B's linker has similar function. Here we analyze kinetic parameters of CfCel6B using single-molecule fluorescence imaging to compare CfCel6B and TrCel6A. We find that CBD is important for initial binding of CfCel6B, but the contribution of the linker to the binding rate constant or to the dissociation rate constant is minor. The crystal structure of the CfCel6B CD showed longer loops at the entrance and exit of the substrate-binding tunnel compared with TrCel6A CD, which results in higher processivity. Furthermore, CfCel6B CD showed not only fast surface diffusion but also slow processive movement, which is not observed in TrCel6A CD. Combined with the results of a phylogenetic tree analysis, we propose that bacterial cellobiohydrolases are designed to degrade crystalline cellulose using high-affinity CBD and high-processivity CD.
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Proteínas de Bactérias/química , Cellulomonas/enzimologia , Celulose 1,4-beta-Celobiosidase/química , Proteínas Fúngicas/química , Hypocreales/enzimologia , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Domínio Catalítico , Cellulomonas/química , Cellulomonas/metabolismo , Celulose/metabolismo , Celulose 1,4-beta-Celobiosidase/metabolismo , Cristalografia por Raios X , Proteínas Fúngicas/metabolismo , Hypocreales/química , Hypocreales/metabolismo , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Domínios Proteicos , Especificidade por SubstratoRESUMO
Water splitting is an essential process for converting light energy into easily storable energy in the form of hydrogen. As environmentally preferable catalysts, Cu-based materials have attracted attention as water-splitting catalysts. To enhance the efficiency of water splitting, a reaction process should be developed. Single-molecule junctions (SMJs) are attractive structures for developing these reactions because the molecule electronic state is significantly modulated, and characteristic electromagnetic effects can be expected. Here, water splitting is induced at Cu-based SMJ and the produced hydrogen is characterized at a single-molecule scale by employing electron transport measurements. After visible light irradiation, the conductance states originate from Cu/hydrogen molecule/Cu junctions, while before irradiation, only Cu/water molecule/Cu junctions were observed. The vibration spectra obtained from inelastic electron tunneling spectroscopy combined with the first-principles calculations reveal that the water molecule trapped between the Cu electrodes is decomposed and that hydrogen is produced. Time-dependent and wavelength-dependent measurements show that localized-surface plasmon decomposes the water molecule in the vicinity of the junction. These findings indicate the potential ability of Cu-based materials for photocatalysis.
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Lynch syndrome is a hereditary disease characterized by an increased risk of colorectal and other cancers. Germline variants in the mismatch repair (MMR) genes are responsible for this disease. Previously, we screened the MMR genes in colorectal cancer patients who fulfilled modified Amsterdam II criteria, and multiplex ligation-dependent probe amplification (MPLA) identified 11 structural variants (SVs) of MLH1 and MSH2 in 17 patients. In this study, we have tested the efficacy of long read-sequencing coupled with target enrichment for the determination of SVs and their breakpoints. DNA was captured by array probes designed to hybridize with target regions including four MMR genes and then sequenced using MinION, a nanopore sequencing platform. Approximately, 1000-fold coverage was obtained in the target regions compared with other regions. Application of this system to four test cases among the 17 patients correctly mapped the breakpoints. In addition, we newly found a deletion across an 84 kb region of MSH2 in a case without the pathogenic single nucleotide variants. These data suggest that long read-sequencing combined with hybridization-based enrichment is an efficient method to identify both SVs and their breakpoints. This strategy might replace MLPA for the screening of SVs in hereditary diseases.
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Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos/normas , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Programas de Rastreamento , Proteína 1 Homóloga a MutL/ultraestrutura , Proteína 2 Homóloga a MutS/ultraestrutura , Sequenciamento por Nanoporos , Polimorfismo de Nucleotídeo Único/genética , Conformação ProteicaRESUMO
Key clinical symptoms observed among individuals with psychiatric disorders include difficulty falling asleep or maintaining sleep, poor sleep quality and nightmares. Those suffering from sleep disorders often present with symptoms of discontent with regard to sleep quality, timing and quantity, and these symptoms have an adverse impact on function and quality of life. A minimally invasive technique would be preferable in patients with psychiatric disorders, who tend to be sensitive to environmental change. Accordingly, we evaluated the performance of Zmachine Insight Plus, an ambulatory electroencephalography sleep monitor, in patients with psychiatric disorders. One hundred and three patients undergoing polysomnography were enrolled in this study. Zmachine Insight Plus was performed simultaneously with polysomnography. Total sleep time, sleep efficiency, wake after sleep onset, rapid eye movement (REM) sleep, light sleep (stages N1 and N2) and deep sleep (stage N3) were assessed. Total sleep time, sleep efficiency, wake after sleep onset, REM sleep duration and non-REM sleep duration of Zmachine Insight Plus showed a significant correlation with those of polysomnography. Lower sleep efficiency and increased frequency of waking after sleep onset, the arousal index and the apnea-hypopnea index on polysomnography were significantly associated with the difference in sleep parameters between the two methods. Among patients with psychiatric disorders who are sensitive to environmental change, Zmachine Insight Plus would be a useful technique to objectively evaluate sleep quality.
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Eletroencefalografia , Transtornos Mentais/complicações , Monitorização Ambulatorial , Polissonografia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/diagnóstico , Sono , Feminino , Humanos , Masculino , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Qualidade de Vida , Transtornos do Sono-Vigília/fisiopatologiaRESUMO
Although many xylanases have been studied, many of the characteristics of xylanases toward branches in xylan remain unclear. In this study, the substrate specificity of a GH11 xylanase from Streptomyces olivaceoviridis E-86 (SoXyn11B) was elucidated based on its three-dimensional structure. Subsite mapping suggests that SoXyn11B has seven subsites (four subsites on the - side and three subsites on the + side), and it is one longer than the GH10 xylanase from S. olivaceoviridis (SoXyn10A). SoXyn11B has no affinity for the subsites at either end of the scissile glycosidic bond, and the sugar-binding energy at subsite - 2 was the highest, followed by subsite + 2. These properties were very similar to those of SoXyn10A. In contrast, SoXyn11B produced different branched oligosaccharides from bagasse compared with those of SoXyn10A. These branched oligosaccharides were identified as O-ß-D-xylopyranosyl-(1â4)-[O-α-L-arabinofuranosyl-(1â3)]-O-ß-D-xylopyranosyl-(1â4)-ß-D-xylopyranosyl-(1â4)-ß-D-xylopyranose (Ara3Xyl4) and O-ß-D-xylopyranosyl-(1â4)-[O-4-O-methyl-α-D-glucuronopyranosyl-(lâ2)]-ß-D-xylopyranosyl-(1â4)-ß-D-xylopyranosyl-(1â4)-ß-D-xylopyranose (MeGlcA3Xyl4) by nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) and confirmed by crystal structure analysis of SoXyn11B in complex with these branched xylooligosaccharides. SoXyn11B has a ß-jerryroll fold structure, and the catalytic cleft is located on the inner ß-sheet of the fold. The ligand-binding structures revealed seven subsites of SoXyn11B. The 2- and 3-hydroxy groups of xylose at the subsites + 3, + 2, and - 3 face outwards, and an arabinose or a glucuronic acid side chain can be linked to these positions. These subsite structures appear to cause the limited substrate specificity of SoXyn11B for branched xylooligosaccharides. KEY POINTS: ⢠Crystal structure of family 11 ß-xylanase from Streptomyces olivaceoviridis was determined. ⢠Topology of substrate-binding cleft of family 11 ß-xylanase from Streptomyces olivaceoviridis was characterized. ⢠Mode of action of family 11 ß-xylanase from Streptomyces olivaceoviridis for substitutions in xylan was elucidated.
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Endo-1,4-beta-Xilanases , Streptomyces , Endo-1,4-beta-Xilanases/metabolismo , Oligossacarídeos , Streptomyces/metabolismo , Especificidade por Substrato , XilanosRESUMO
Information about the inulosucrase of nonlactic acid bacteria is scarce. We found a gene encoding inulosucrase (inuBK) in the genome of the Gram-positive bacterium Alkalihalobacillus krulwichiae JCM 11691. The inuBK open reading frame encoded a protein comprising 456 amino acids. We expressed His-tagged InuBK in culture medium using a Brevibacillus system. The optimal pH and temperature of purified InuBK were 7.0-9.0 and 50-55 °C, respectively. The findings of high-performance anion-exchange chromatography, nuclear magnetic resonance spectroscopy, and high-performance size-exclusion chromatography with multiangle laser light scattering showed that the polysaccharide produced by InuBK was an inulin with a molecular weight of 3806, a polydispersity index (PI) of 1.047, and fructosyl chain lengths with 3-27 degrees of polymerization. The size of InuBK was smaller than commercial inulins, and the PI of the inulin that it produced was lower.
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Bacillaceae/enzimologia , Hexosiltransferases/metabolismo , Bacillaceae/genética , Cromatografia Líquida de Alta Pressão/métodos , Clonagem Molecular , Meios de Cultura , Genes Bacterianos , Hexosiltransferases/genética , Hexosiltransferases/isolamento & purificação , Inulina/biossíntese , Espectroscopia de Ressonância Magnética/métodos , Peso Molecular , Filogenia , TemperaturaRESUMO
We describe an autopsy case of neuronal intermediate filament inclusion disease (NIFID), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused-in-sarcoma (FUS) inclusions (FTLD-FUS). A 57-year-old man developed dysarthria and dysphagia. One year and five months later, he was admitted to a hospital, and pseudobulbar palsy and right upper motor neuron signs were observed on examination. Needle electromyography revealed no active or chronic denervation. His neurological symptoms gradually deteriorated, and behavioral alterations occurred. He died of hemoperitoneum secondary to rupture of a ureteric tumor. The total duration of the disease was six years and 10 months. Neuropathologically, the frontal cortex, including the motor cortex, and the pyramidal tract were severely affected, whereas the lower motor neurons in the spinal cord and brainstem were mildly damaged. The striatum and substantia nigra were also severely damaged. Hyaline conglomerate inclusions, neuronal cytoplasmic inclusions with a distinct eosinophilic core (so-called cherry spot), Pick body-like inclusions, and eosinophilic round inclusions were observed in the remaining neurons. Immunohistochemical examination revealed that these inclusions were immunoreactive for FUS. HC inclusions were also immunoreactive for α-internexin and phosphorylated neurofilament protein. FUS-immunoreactive NCIs were abundant in the basal ganglia but not in the hippocampus, in contrast to previously reported NIFID cases. Furthermore, Bunina bodies identified by immunohistochemistry for cystatin C were also observed in the lower motor neurons. Bunina bodies may be present in NIFID. This case confirms the pathological heterogeneity of NIFID and supports the notion of the difference between amyotrophic lateral sclerosis and NIFID.
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Esclerose Lateral Amiotrófica , Infecções por Citomegalovirus , Doença dos Neurônios Motores , Autopsia , Humanos , Filamentos Intermediários , Masculino , Pessoa de Meia-Idade , Neurônios Motores , Proteína FUS de Ligação a RNARESUMO
BACKGROUND: This study aimed to determine the present oral health status of the rural Kenyan elderly population and to investigate whether oral health status is associated with the perceived general health. METHODS: A total of 131 individuals aged 65 years and over in Mbita Constituency, Homa Bay County in Kenya were randomly selected and visited at home. The home visit study, which was conducted from 2014 to 2016, included oral examination by a dentist and administration of a self-reporting questionnaire. The number of teeth present and functional tooth unit (FTU) points were calculated using the dental chart. Perceived general health, subjective masticatory ability, and self-reported periodontal symptoms were collected using a questionnaire sheet. Fisher's exact test and nonparametric test were used to determine the difference in percentage and means. The odds ratio of good general health based on the participants' masticatory satisfaction was calculated by logistic analysis. RESULTS: Satisfactory mastication was dependent on the number of teeth present, FTU points, and self-reported "gum bleeding" and "tooth mobility". Furthermore, satisfactory mastication was associated with perceived general health status independent of sex and age. The adjusted odds ratio of good perceived general health was 2.29 (95% confidence interval 1.05-4.99) for participants who had the subjective masticatory ability. CONCLUSION: Among the Kenyan elderly population, satisfactory mastication was related to the number of teeth present, FTU points, and self-reported periodontal symptoms. Furthermore, satisfactory mastication was associated with perceived general health status independently.
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Mastigação , Saúde Bucal , Idoso , Nível de Saúde , Humanos , Quênia/epidemiologia , Inquéritos e QuestionáriosRESUMO
Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease characterized by cerebellar ataxia. Many causative genes have been identified to date, the most common etiology being the abnormal expansion of repeat sequences, and the mutation of ion channel genes also play an important role in the development of SCA. Some of them encode calcium and potassium channels. However, due to limited reports about potassium genes in SCA, we screened 192 Japanese individuals with dominantly inherited SCA who had no abnormal repeat expansions of causative genes for potassium channel mutations (KCNC3 for SCA13 and KCND3 for SCA19/SCA22) by target sequencing. As a result, two variants were identified from two patients: c.1973G>A, p.R658Q and c.1018G>A, p.V340M for KCNC3, and no pathogenic variant was identified for KCND3. The newly identified p.V340M exists in the extracellular domain, and p.R658Q exists in the intracellular domain on the C-terminal side, although most of the reported KCNC3 mutations are present at the transmembrane site. Adult-onset and slowly progressive cerebellar ataxia are the main clinical features of SCA13 and SCA19 caused by potassium channel mutations, which was similar in our cases. SCA13 caused by KCNC3 mutations may present with deep sensory loss and cognitive impairment in addition to cerebellar ataxia. In this study, mild deep sensory loss was observed in one case. SCA caused by potassium channel gene mutations is extremely rare, and more cases should be accumulated in the future to elucidate its pathogenesis due to channel dysfunction.
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Disfunção Cognitiva/genética , Mutação , Canais de Potássio/genética , Ataxias Espinocerebelares/genética , Adulto , Povo Asiático , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Testes Genéticos , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/diagnóstico por imagemRESUMO
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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We have investigated the structure and electron transport at dichloroethylene-doped metal atomic junctions at low temperatures (20â K) in ultra-high vacuum, using Fe, Ni, Pd, Cu, Ag, and Au. The metal atomic junctions were fabricated using the mechanically controllable break junction technique. After introducing the dichloroethylene (DCE), the conductance behavior of Fe, Ni, and Pd junctions was considerably changed, whereas little change was observed for Cu, Ag, and Au. For the Pd and Cu junctions, a clear peak was observed in their conductance histograms, showing that the single-molecule junction was selectively formed. To investigate the structure of the metal atomic junctions further, their plateau lengths were analyzed. The length analysis revealed that the Au atomic wire was elongated, and the metal atomic wires were formed for the other transition metals: those that do not normally form metal atomic wires without DCE doping, as DCE adsorption stabilized the metal atomic states. There is a strong interaction between DCE and the metals, where DCE supports the formation of the metal atomic wire for Fe, Ni, and Pd.
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The front cover artwork was provided by the group of Prof. Nishino, Tokyo Institute of Technology. The image depicts the investigation of the structure and electron transport of the Au, Ag, Cu, Ni, Fe, and Pd atomic junctions doped with dichloroethylene. Read the full text of the Article at 10.1002/cphc.201900988.
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There is growing evidence supporting the effectiveness of a comprehensive school health program. However, implementation in developing countries is a challenge. Furthermore, the available information on the association between a comprehensive school health program and students' academic attainment is limited. In Kenya, a project to verify the effects of a comprehensive school health program was carried out in Mbita sub-county, Homa Bay County from September 2012 to August 2017. This study aimed to clarify the improvement of school health during the project years and the association between school health and students' academic attainment. Primary schools in Mbita sub-county were selected as study sites. We assessed 44 schools' scores on a school health checklist developed from the Kenyan Comprehensive School Health Program, the students' mean score on the Kenya Certificate of Primary Education (KCPE), and absenteeism during the project years (2013-16). The mean school health checklist score (n = 44 schools) was 135.6 in 2013, 169.9 in 2014, 158.2 in 2015 and 181.3 in 2016. The difference of the mean score between 2013 and 2016 was significant. In addition, correlation analysis showed a significant association between mean KCPE score in the project years and school health checklist score (Pearson's coefficient was 0.43, p = 0.004). The results of this study suggest improvements of school health by the implementation of the Kenyan Comprehensive School Health Program and students' academic attainment.