Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs

Although c-Jun NH 2 -terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-B-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4°C for 4 h followed by reperfusion at 37°C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-B qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-␣ into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation

Genetic Study in Left Ventricular Noncompaction

Background—Left ventricular noncompaction (LVNC) has since been classified as a primary genetic cardiomyopathy, but the genetic basis is not fully evaluated. The aim of the present study was to identify the genetic spectrum using next-generation sequencing and to evaluate genotype–phenotype correlations in LVNC patients. Methods and Results—Using next-generation sequencing, we targeted and sequenced 73 genes related to cardiomyopathy in 102 unrelated LVNC patients. We identified 43 pathogenic variants in 16 genes in 39 patients (38%); 28 were novel variants. Sarcomere gene variants accounted for 63%, and variants in genes associated with channelopathies accounted for 12%. MYH7 and TAZ pathogenic variants were the most common, and rare variant collapsing analysis showed variants in these genes contributed to the risk of LVNC, although patients carrying MYH7 and TAZ pathogenic variants displayed different phenotypes. Patients with pathogenic variants had early age of onset and more severely decreased left ventricular ejection fractions. Survival analysis showed poorer prognosis in patients with pathogenic variants, especially those with multiple variants: All died before their first birthdays. Adverse events were noted in 17 patients, including 13 deaths, 3 heart transplants, and 1 implantable cardioverter-defibrillator insertion. Congestive heart failure at diagnosis and pathogenic variants were independent risk factors for these adverse events. Conclusions—Next-generation sequencing revealed a wide spectrum of genetic variations and a high incidence of pathogenic variants in LVNC patients. These pathogenic variants were independent risk factors for adverse events. Patients harboring pathogenic variants showed poor prognosis and should be followed closely

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Grammar conversion from LTAG to HPSG

We propose an algorithm for the conversion of grammars from an arbitrary FB-LTAG grammar into a strongly equivalent HPSG-style grammar. Our algorithm converts LTAG elementary trees into HPSG feature structures by encoding the tree structures in stacks. A set of pre-determined rules manipulate the stack to emulate substitution and adjunction. We have used our algorithm to obtain HPSG-style grammars from existing LTAG grammars. We apply this algorithm to the XTAG English grammar and report some of our findings

THIN ICE AREA EXTRACTION IN THE SEASONAL SEA ICE ZONES OF THE NORTHERN HEMISPHERE USING ASMR2 DATA

Sea ice has an important role of reflecting the solar radiation back into space. In addition, the heat flux of ice in thin ice areas is strongly affected by the ice thickness difference. Therefore, ice thickness is one of the most important parameters of sea ice. In our previous study, the authors have developed a thin ice area extraction algorithm using passive microwave radiometer AMSR2 for the Sea of Okhotsk. The basic idea of the algorithm is to use the brightness temperature scatter plots of AMSR2 19 GHz polarization on difference (V-H) vs 19 GHz V polarization. The algorithm was also applicable to the Bering Sea, and could extract most of the thin n ice areas. However, two problems have become clear. One was that some of the thin ice areas were not well extracted, and the other was that some of the consolidated ice were mis-extracted as thin ice areas. In this study, the authors have improved the thin ice area extraction algorithm to solve these problems. By adjusting the parameters of the algorithm applied to the brightness temperature scatter plots of AMSR2 19 GHz polarization difference (V-H) vs 19 GHz V polarization, most of the thin ice areas were also well extracted in the Bering Sea. The authors also introduced an equation using the brightness temperatures difference of 89GHz vertical and horizontal polarization to reject the thin ice area misextracted over consolidated ice. By applying the above two methods to AMSR2 data, most of the thin ice areas in the Bering Sea were well extracted. The algorithm was also applied to the Gulf of St. Lawrence with good result. The thin ice area extracted data are planed to be approved by JAXA as a AMSR2 research product

A Formal Proof of Strong Equivalence for a Grammar Conversion from LTAG to HPSG-style

This paper presents a sketch of a formal proof of strong equivalence, where both grammars generate equivalent parse results, between any LTAG (Lexicalized Tree Adjoining Grammar: Schabes, Abeille and Joshi (1988)) G and an HPSG (Head-Driven Phrase Structure Grammar: Pollard and Sag (1994))-style grammar converted from G by a grammar conversion (Yoshinaga and Miyao, 2001). Our proof theoretically justifies some applications of the grammar conversion that exploit the nature of strong equivalence (Yoshinaga et al., 2001b; Yoshinaga et al., 2001a), applications which contribute much to the developments of the two formalism