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It has been reported that genetic factors are associated with risk factors and onset of lifestyle-related diseases, but this finding is still the subject of much debate. The aim of the present study was to investigate the correlation of genetic factors, including salivary telomere length and three single nucleotide polymorphisms (SNPs) that may influence lifestyle-related diseases, with lifestyle-related diseases themselves. In one year at a single facility, relative telomere length and SNPs were determined by using monochrome multiplex quantitative polymerase chain reaction and TaqMan SNP Genotyping Assays, respectively, and were compared with lifestyle-related diseases in 120 Japanese individuals near our university. In men and all participants, age was inversely correlated with relative telomere length with respective p values of 0.049 and 0.034. In men, the frequency of hypertension was significantly higher in the short relative telomere length group than in the long group with unadjusted p value of 0.039, and the difference in the frequency of hypertension between the two groups was of borderline statistical significance after adjustment for age (p = 0.057). Furthermore, in men and all participants, the sum of the number of affected lifestyle-related diseases, including hypertension, was significantly higher in the short relative telomere length group than in the long group, with p values of 0.004 and 0.029, respectively. For ADIPOQ rs1501299, men's ankle brachial index was higher in the T/T genotype than in the G/G and G/T genotypes, with p values of 0.001 and 0.000, respectively. For SIRT1 rs7895833, men's body mass index and waist circumference and all participants' brachial-ankle pulse wave velocity were higher in the A/G genotype than in the G/G genotype, with respective p values of 0.048, 0.032 and 0.035. For FOXO3A rs2802292, women's body temperature and all participants' saturation of peripheral oxygen were lower in the G/T genotype than in the T/T genotype, with respective p values of 0.039 and 0.032. However, relative telomere length was not associated with physiological or anthropometric measurements except for height in men (p = 0.016). ADIPOQ rs1501299 in men, but not the other two SNPs, was significantly associated with the sum of the number of affected lifestyle-related diseases (p = 0.013), by genotype. For each SNPs, there was no significant difference in the frequency of hypertension or relative telomere length by genotype. Relative telomere length and the three types of SNPs determined using saliva have been shown to be differentially associated with onset of and measured risk factors for lifestyle-related diseases consisting mainly of cardiovascular diseases and cancer.

A detailed investigation including a low-speed flow study is presented on the development of ultra-light dragonfly mimetic flying robots with a focus on the dragonfly’s remarkable gliding capability. It is revealed that the dragonfly’s corrugated wing structure and cruciform configuration provide superior flying characteristics for fixed wing robots in low Reynolds number flight. It was also found that the dragonfly configuration has additional merit in its compatibility with propellers or high lift devices. This combination with such classic aero-engineering makes possible robots with broader flight envelope than conventional fixed-wing flying robots.

272 isolates of Salmonella Enteritidis (111 isolated from frozen broiler chicken carcasses, 126 from human food and other biological materials involved in food poisoning outbreaks and 35 from different poultry materials) were selected for phage typing. From these, 111 were phage typed, 57.65% being classified as phage type 4, 32.43% as phage type 4a, 3.60% as phage type 6a and 0.90% as phage type 7, whereas 5.40% samples were not phage typeable. The predominance of phage type 4 is in agreement with the results published worldwide, and reinforces the need for studies related to the epidemiological meaning of these findings. Neste trabalho utilizou-se 272 isolados de Salmonella Enteritidis, dos quais 111 foram isolados de carcaças de frango congeladas, 126 de alimentos e material biológico de humanos envolvidos em episódios de toxinfecções alimentares e 35 de diferentes materiais de origem avícola Destas amostras, 111 foram fagotipadas, sendo 57,65% classificadas como fagotipo 4, 32,43% como fagotipo 4a, 3,60% como fagotipo 6a e 0,90% como fagotipo 7, enquanto 5,40% das amostras não foram fagotipáveis A predominância do fagotipo 4 está em concordância com os resultados publicados ao redor do mundo, e reforça a necessidade de estudos relacionados ao significado epidemiológico destes achados.

Salmonella Typhimurium has become a widespread cause of salmonellosis among humans and animals worldwide. In Brazil, Salmonella Typhimurium (STM) is one of the most prevalent serovars isolated from food for human consumption. The uncontrolled sale and use of antimicrobials in agriculture and for treating human patients contributes to increase multidrug resistance of this serovar. In the present study, a total of 278 STM isolates from different sources and regions of Brazil over the period 1999 to 2004 were phage typed and analyzed for their antimicrobial resistance profile at Laboratory of Enterobacteria, Oswaldo Cruz Institute, FIOCRUZ. The main STM phage types isolated were DT 193 (64.3%), DT 19 (17.4%) and DT 18 (4%). Others phage types as DT 10 (2%), DT 27 (3.24%), DT 13 (0.36%), DT 22 (0.36%), DT 28 (0.36%), DT 29 (0.36%) and DT 149 (0.36%) were obtained in low percentages. A total of 54% STM strains were resistant to three or more antimicrobial classes, while no resistance to third generation cephalosporin or ciprofloxacin was identified in these strains. Those results show the STM phage types circulating among animals, food for human consumption and humans in Brazil as well as the increasing of multidrug resistance. The surveillance of STM strains based on phage typing and antimicrobial resistance profile are useful for detecting outbreaks, identifying sources of infection and implementing prevention and control measures. Salmonella Typhimurium é considerada uma das principais bactérias causadoras de salmonelose nos animais e no homem em todo o mundo. No Brasil, Salmonella Typhimurium é um dos mais prevalentes sorovares isolados de alimentos para consumo humano. O uso indiscriminado de antibióticos em produtos agrícolas e no tratamento de pacientes humanos tem contribuído para aumentar a multirresistência desse sorovar a diversos antimicrobianos. No presente estudo, 278 cepas de STM foram selecionadas de diferentes fontes e regiões do Brasil, no período de 1999 a 2004 e realizadas a fagotipagem e análise do perfil de resistência antimicrobiana no Laboratório de Enterobactérias, Instituto Oswaldo Cruz, FIOCRUZ. Os principais fagotipos isolados foram DT 193 (64,3%), DT 19 (17,4%) e DT 18 (4%). Os fagotipos DT 10 (2%), DT 27 (3,24%), DT 13 (0,36%), DT 22 (0,36%), DT 28 (0,36%), DT 29 (0,36%) e DT 149 (0,36%) foram isolados em menores percentuais. Um total de 54% das cepas de STM foi resistente a três ou mais classes de antimicrobianos e não foi observada resistência a cefalosporinas de terceira geração ou ciprofloxacina. Esses resultados indicam os principais lisotipos de Salmonella Typhimurium circulantes entre os animais, alimentos de consumo humano e seres humanos no Brasil, bem como o aumento da multirresistência antimicrobiana. O monitoramento de cepas de Salmonella Typhimurium baseado na fagotipagem e no padrão de resistência antimicrobiana são ferramentas úteis para detectar surtos, identificar a fonte de infecção e implementar programas de prevenção e controle de salmonelose.

Das 7058 amostras de Vibrio cholerae isoladas de pacientes com suspeita de síndrome coleriforme, no período de 1991 a 1993, no Estado do Ceará, foram detectadas duas com as características de múltipla resistência aos antimicrobianos (tetraciclina, ampicilina, eritromicina, sulfametoxazol-trimetoprima) e ao composto vibriostático O/129 (2,4-diamino-6,7-diisopropilpteridina). Do ponto de vista bacteriológico uma amostra foi identificada como V. cholerae sorogrupo O:1, biotipo El Tor e sorovar Inaba e a outra, caracterizada como V. cholerae sorogrupo O:22, classificada bioquimicamente no tipo II de Heiberg. Foi demonstrado que apenas na amostra do sorogrupo O:1, a multirresistência era codificada por um plasmídio, transferível por conjugação para Escherichia coli K12 e amostras sensíveis de V. cholerae O1 e não O1, numa freqüência entre 8x10-2 a 5x10-6. O plasmídio responsável pela multirresistência apresentou um peso molecular de 147 Kb, compatível com as descrições em outras partes do mundo.

Das 7058 amostras de Vibrio cholerae isoladas de pacientes com suspeita de síndrome coleriforme, no período de 1991 a 1993, no Estado do Ceará, foram detectadas duas com as características de múltipla resistência aos antimicrobianos (tetraciclina, ampicilina, eritromicina, sulfametoxazol-trimetoprima) e ao composto vibriostático O/129 (2,4-diamino-6,7-diisopropilpteridina). Do ponto de vista bacteriológico uma amostra foi identificada como V. cholerae sorogrupo O:1, biotipo El Tor e sorovar Inaba e a outra, caracterizada como V. cholerae sorogrupo O:22, classificada bioquimicamente no tipo II de Heiberg. Foi demonstrado que apenas na amostra do sorogrupo O:1, a multirresistência era codificada por um plasmídio, transferível por conjugação para Escherichia coli K12 e amostras sensíveis de V. cholerae O1 e não O1, numa freqüência entre 8x10-2 a 5x10-6. O plasmídio responsável pela multirresistência apresentou um peso molecular de 147 Kb, compatível com as descrições em outras partes do mundo. Of 7058 Vibrio cholerae strains recovered from patients suspected of cholera in the State of Ceará between December 1991 and September 1993, two were resistant to antimicrobials (Ampicillin, erythromycin, trimethoprim-sulfamethoxazole, tetracycline) and to vibriostatic agent O/129 (2,4-diamino-6,7-diisopropylpteridine). From the bacteriological standpoint, one strain was identified as V. cholerae serogroup O:1, biotype El Tor, serovar Inaba, and another as V. cholerae serogroup O:22, biochemically classified as Heiberg type II. It was shown that only in the serogroup O:1 strain, multiple resistance was encoded by a plasmid transferrable by conjugation to Escherichia coli K12 and a sensitive strains of V. cholerae O1 and non-O1, with at a frequency between 8x10-2 and 5x10-6. The plasmid, with a molecular weight of 147 Kb, encoded both multiple resistance to antimicrobials and the vibriostatic compound (O/129), compatible with descriptions reported in other parts of world.

Of 7058 Vibrio cholerae strains recovered from patients suspected of cholera in the State of Ceará between December 1991 and September 1993, two were resistant to antimicrobials (Ampicillin, erythromycin, trimethoprim-sulfamethoxazole, tetracycline) and to vibriostatic agent O/129 (2,4-diamino-6,7-diisopropylpteridine). From the bacteriological standpoint, one strain was identified as V. cholerae serogroup O:1, biotype El Tor, serovar Inaba, and another as V. cholerae serogroup O:22, biochemically classified as Heiberg type II. It was shown that only in the serogroup O:1 strain, multiple resistance was encoded by a plasmid transferrable by conjugation to Escherichia coli K12 and a sensitive strains of V. cholerae O1 and non-O1, with at a frequency between 8x10-2 and 5x10-6. The plasmid, with a molecular weight of 147 Kb, encoded both multiple resistance to antimicrobials and the vibriostatic compound (O/129), compatible with descriptions reported in other parts of world.

The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints. Current sequencing technologies can shed light on the stepwise progression of lung adenocarcinoma. Here, the authors characterize tumor progression in lung adenocarcinomas from an early stage using short and long read whole-genome sequencing, bulk and spatial transcriptomics, and epigenomics.

Although most cancer deaths are caused by metastasis, there are no effective therapeutic approaches. This study describes the efficacy of a short synthetic mRNA (s-mRNA) designed by the sequence of non-vesicular extracellular IL1β-mRNA found in the pre-metastatic lung of tumor-bearing mice. The administration of s-mRNA inhibits murine lung metastasis by inducing the innate and adaptive immune systems. s-mRNA binds to ZC3H12D, an RNA-binding protein on natural killer cells and cytotoxic T lymphocytes. The ZC3H12D-s-mRNA complex translocated to the nucleus without being involved in translation. This process induces cytolytic activity and cell death in cancer cells without inducing a cytokine storm, and immune cells retain their antitumor activity. Although the antitumor activity of cytotoxic lymphocytes declines as the disease progresses in cancer patients, s-mRNA induces sustained high killing capacities of natural killer cells and cytotoxic T lymphocytes from colon cancer patients. Therefore, s-mRNA could be a breakthrough solution to prevent metastasis. Extracellular mRNAs are found to play an important role in premetastatic organs. Here this group reports the non-vesicular extracellular IL1β-mRNA complexes binding to ZC3H12D followed by the translocation into nucleus without being translated, thereby killing NK cells/CTLs and inhibiting lung metastasis in a preclinical colon cancer model.