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Background Maple syrup urine disease (MSUD) is a group of neuro-metabolic disorders with autosomal recessive inheritance. MSUD is genetically caused by disruptive mutations in three genes including the BCKDHA, the BCKDHB, and the DBT. Dysfunction of one of these genes leads to the accumulation of branched-chain amino acids (BCAA) and their branched-chain-keto acids (BCKA) in the body and finally to progressive neurological and developmental disturbance. Methods Here, we applied Sanger sequencing of entire exons of the BCKDHA, the BCKDHB, and the DBT genes for 23 patients were diagnosed with MSUD from Southwest Iran. Detected changes were then subjected for in silico analysis to predict their pathogenesis. Results We found eight single nucleotide substitutions (g.13185C > A, g.16666C > T, g.25206G > A, g.25254C > A in BCKDHA, g.62247A > G, g.62259C > T and g.166525G > A in BCKDHB and g.43331A > G in DBT) and two single nucleotide deletions (g.13212_13212delT and g.27078_27078delC in BCKDHA). According to the designed in silico analyses, we suggest that the g.16666C > T, the g.25206G > A, the g.25254C > A, the g.62247A > G, the g.62259C > T, the g.166525G > A, the g.13212_13212delT, and the g.27078_27078delC are probably damaging. On the other hand, the g.13185C > A and the g.43331A > G changes might be neutral variations. Conclusion All variations somewhat can affect the structure, the function and the stability of gene products. The results obtained from this study could be useful to facilitate clinical diagnosis and screening of MSUD patients and partly for at-risk carriers and prenatal detection in the population of southwest of Iran.

Bridges using rolled steel H-section seem to be economical compared with plate girder bridges due to lower material and fabrication cost in the short-span length. The rolled steel H-section is a compact section and no stiffener is necessary. However, as the maximum available web height of the rolled H-sections is 900 mm, the applicable span-length is 20–25 m. A new composite girder bridge was proposed using rolled steel H-section to extend the span-length. The superstructure consists of continuous rolled steel H-girders composite with the RC slab, and the substructure is RC piers. The girder and the pier are rigidly connected by concrete and reinforcements to resist large negative bending moment at the joints. Experiments were conducted with the partial SRC bridge model, which showed that the proposed structure with a rolled H-girder had high ultimate strength with good ductile property, and attained the full plastic moment. A FE model was established considering material non-linearity and shear transfer between steel and concrete and compared with the experiments, which showed good agreement and clarified the load transfer mechanism. A trial design with the SRC highway bridge was carried out, confirmed that the applicable span length can be extended to 50 m. Seismic performance of the SRC system was verified by dynamic analysis, showed sufficient strength and ductility for strong earthquake with peak acceleration of 810 m/s2. Cross beams were eliminated in the new SRC bridge because the girder height was low, which was verified by FEM analysis with the full bridge model.

Background One genomic breakpoint can result in variable BCR - ABL1 transcript types due to alternative splicing. The influence of different BCR - ABL1 transcript types on clinical outcome is still controversial. Aim of the study The objective of this analysis was to determine the impact of transcript type on response, clinical outcome, recurrence risk after treatment with Imatinib mesylate in Chronic Myeloid Leukemia (CML) patients. Methods Sixty CML patients in chronic phase were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and banding standard protocols. Results There was a significant difference in collective incidence of complete cytogenetic response (CCR) between the e14a2 and e13a2 groups ( P = 0.04). The median time to achieve CCR was shorter in e14a2 patients than to e13a2 ( P = 0.01). This finding is paralleled by the molecular response where the median of the BCR - ABL1 / ABL1 expression levels were significantly lower in e14a2 transcript compared to e13a2 type at 3, 6, 9 and 12 months from the start of therapy ( P χ 2 = 5.49; P = 0.01; OR: 9.33; 95% CI: 1.59, 54.67). No significant difference was observed regarding overall survival (OS), although Patients with e14a2 transcript displayed a significant tendency toward a higher event free survival (EFS) ratio ( P = 0.03). Conclusion We found that patients with the e14a2 transcript achieved better and faster responses to Imatinib mesylate. In this study, parallel data regarding molecular and cytogenetic responses, impact of transcript type on the probability of recurrence might suggest a general outcome that the type of transcript can be used as a prognostic marker at diagnosis.

Thermostable enzymes are currently being investigated to improve industrial processes of starch saccharification. A novel glucoamylase was purified to electrophoretic homogeneity from the culture supernatant of Fusarium solani on a fast protein liquid chromatographic system (FPLC). The recovery of glucoamylase after gel filtration on FPLC was 31.8% with 26.2-fold increase in specific activity. The enzyme had a molecular mass of 40 kDa by SDS-PAGE and 41 kDa by gel filtration. The glucoamylase exhibited optimum activity at pH 4.5. The Kcat and Km were 441/min and 1.9 mg/ml, respectively, for soluble starch, specificity constant (Kcat/Km) was 232. The enzyme was thermally stable at 50 °C and retained 79% activity after 60 min at this temperature. The half-life of the enzyme was 26 min at 60°C. The enzyme was slightly stimulated by Cu2+ and Mg2+ and strongly inhibited by Hg2+, Pb2+, Zn2+, Ni2+ and Fe3+.