Abstract The coupling of protein synthesis and folding is a crucial yet poorly understood aspect of cellular protein folding. Over the past few years, it has become possible to experimentally follow and define protein folding on the ribosome, revealing principles that shape co‐translational folding and distinguish it from refolding in solution. Here, we highlight some of these recent findings from biochemical and biophysical studies and their potential significance for cellular protein biogenesis. In particular, we focus on nascent chain interactions with the ribosome, interactions within the nascent protein, modulation of translation elongation rates, and the role of mechanical force that accompanies nascent protein folding. The ability to obtain mechanistic insight in molecular detail has set the stage for exploring the intricate process of nascent protein folding. We believe that the aspects discussed here will be generally important for understanding how protein synthesis and folding are coupled and regulated.
Wilson's disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children.The data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points.Fifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001).Our study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.
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Mild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes.A total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers.DMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors.DMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.
Abstract Background To explore t function of peroxisome proliferator-activated receptor γ(PPARγ) in renal tissue in acute hypoxic renal rat model injury. Methods 24 male SD rats were randomly divided into normal control group, PPARγ agonist group (rosiglitazone 10 mg/kg.d), PPARγ inhibitor group༈GW9662,1mg/kg·d༉and hypoxia injury group, with six rats in each group. The normal control group without any treatment, the other three groups were exposed to 7500 m altitude for seven hours of acute hypobaric hypoxia. The mRNA and protein expressions of PPARγ, superoxide dismutase (SOD), interleukin-1 β༈IL-1β༉ and renal endothelin(ET-1) in renal tissue were detected by using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting. The kidney’s morphology was observed by light microscope and electron microscope. Results The mRNA and protein expression levels of PPARγ and SOD in hypoxia injury group decreased significantly (P < 0.05), while the mRNA and protein expression levels of IL-1 β and ET-1 increased significantly compared with the normal control group (P < 0.05). After intervention with PPAR agonists, the PPARγ and SOD were elevated significantly, while IL-1 β and ET-1 were decreased significantly compared to the hypoxia injury group. The renal tubule epithelial cells (RTEC) were less damaged and abscission was reduced. Conclusions PPARγ protect renal tubular epithelial cells from hypoxia-induced injury. PPARγ agonists can be used as potential target interventions to alleviate acute hypoxic kidney injury.
Rare mutations in the ATP-binding cassette (ABC) transporter A3 (ABCA3) gene are associated with neonatal respiratory distress syndrome (RDS). The contribution of common single nucleotide polymorphisms (SNPs) to preterm RDS differs between ethnicities and remains unclear in Chinese infants. This study evaluated whether common SNPs and consequent haplotypes increase susceptibility to RDS in a population of preterm infants from the Guangxi Zhuang Autonomous Region of China.Using a tagging SNP (tSNP) strategy and real-time polymerase chain reaction, we genotyped four tSNPs (i.e., rs150929, rs4787273, rs11867129, and rs17135889) and one coding SNP (p.F353F) of the ABCA3 gene in preterm infants with RDS (n = 83) and without RDS (n = 83). We predicted the haplotypes. Minor allele frequencies (MAFs) and haplotype distributions were compared between the two groups. We analyzed correlations between the clinical data and the genotypes.Seven haplotypes existed at a frequency of 0.01 or greater. The haplotype TGGAG was significantly more frequent in RDS infants than in non-RDS infants (p = 0.026; odds ratio 3.41; 95% confidence interval 1.088-10.685). The MAF of rs17135889 SNP, a crucial SNP of the haplotype TGGAG located in the transcription factor binding site of ABCA3, was significantly higher in RDS infants (p < 0.05); however, the Bonferroni correction test showed no significant difference (p > 0.05). No significant correlation existed between the rs17135889 genotypes (AG/GG) and any clinical characteristic (e.g., oxygen supplementation duration and hospitalization, requirement for ventilation, bronchopulmonary dysplasia complications, and mortality rate).The TGGAG haplotype may be a risk factor for RDS in preterm infants in this Chinese population. Further study is needed with a larger sample size to verify the association between the rs17135889 SNP and increased risk of RDS in preterm infants, and to determine whether rs17135889 can be a reference in further population-based studies of ABCA3.
Glycogen storage disease (GSD) type VI is a rare disease caused by the inherited deficiency of liver phosphorylase.The proband, a 61-month-old Chinese boy, manifested intermittent hematochezia, growth retardation, hepatomegaly, damage of liver function, mild hypoglycemia, and hyperlactatemia. The other patient was a 107-month-old Chinese girl with growth retardation, hepatomegaly, mild hypoglycemia, and hyperlactatemia. In order to further confirm the diagnosis, we conducted a liver biopsy and detected blood samples for their gene using IDT exon chip capture and high-throughput sequencing.According to the clinical symptoms, physical examination, laboratory examinations, liver biopsy, and the genetic test finding, the 2 patients were diagnosed GSD VI.They were treated mainly with uncooked cornstarch.There were 2 mutations of PYGL gene in this pedigree. c.2467C>T (p. Q823X) and c.2178-2A>C occurred both in the proband and his second sister.As a novel mutation, c.2178-2A>C enriches the mutation spectrum of PYGL gene. The different degrees of elevated lactate is an unusual phenotype in GSD VI patients. It is not clear if this is caused by the new mutation of c. 2178-2A > C. Long-term complications remains to be observed.
PURPOSE To investigate the imaging characteristics of ultrasound biomicroscope (UBM) in the different stages and evaluate preliminary application of UBM in diagnosis of senile cataract. METHODS Using UBM to examine 80 eyes, which were diagnosed senile cataract by slit-lamp microscope (20 eyes, incipient stage; 20 eyes, intumescent stage; 20 eyes, mature stage; 20 eyes, hypermature stage). RESULTS The UBM image of senile cataract is distinguished in the different stages. In incipient stage, it shows sporadic flake high echo areas in equator of the lens. In intumescent stage, it shows flake high echo areas and low echo areas interlace each other, and the thickness of equator increases. In mature stage, it shows symmetrical high echo areas in cortex of the lens and higher echo areas in nucleus of the lens sometimes. In hypermature stage, it shows irregular echo (heterogeneous high density glisten) areas of the lens, heterogeneous incrassation and strong echo areas of anterior capsule. Characteristic high echo granules were found in the anterior chamber. The granules may obstruct the anterior chamber angle. CONCLUSION The UBM examination can be an assistant diagnostic method for senile cataract, especially for the patients whose refractive media of ocular anterior segment is opacity or the pupil is very small.
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