Abstract Folding of individual domains in large proteins during translation helps to avoid otherwise prevalent inter-domain misfolding. How folding intermediates observed in vitro for the majority of proteins relate to co-translational folding remains unclear. Combining in vivo and single-molecule experiments, we followed the co-translational folding of the G-domain, encompassing the first 293 amino acids of elongation factor G. Surprisingly, the domain remains unfolded until it is fully synthesized, without collapsing into molten globule-like states or forming stable intermediates. Upon fully emerging from the ribosome, the G-domain transitions to its stable native structure via folding intermediates. Our results suggest a strictly sequential folding pathway initiating from the C-terminus. Folding and synthesis thus proceed in opposite directions. The folding mechanism is likely imposed by the final structure and might have evolved to ensure efficient, timely folding of a highly abundant and essential protein.
Abstract Background In view of the harsh reality Chinese paediatricians face, the challenge of paediatric education is about instilling not only knowledge and clinical skills but also resilience and beliefs. The aim of the study is to explore a more effective method than the traditional lecture-based learning (LBL) model for optimizing educational outcomes by establishing an innovative, comprehensive, case-based learning (CBL) model combined with the micro-film technique (MF + CBL). This approach has four important components: interests (attraction), knowledge application, competency, and scenario coping skills. Methods Experimental research was conducted via a controlled parallel group study. The total sample of 104 senior-year students (Chinese) majoring in clinical medicine was randomly divided into two groups. The experimental group was exposed to the MF + CBL model and the control group to the LBL model. Overall, the results were assessed after an 8-week course via a student self-assessment questionnaire, a satisfaction survey and the final examination. Results The experimental group generally performed better than the control group on the student self-assessment (P<0.05), satisfaction survey (P<0.05), and final examination (80.02 ± 3.77 vs 73.65 ± 3.69, P = 0.000). The open question at the end of the questionnaire revealed that a small number of students did not favour the MF + CBL model due to its time- and energy-consuming features. Conclusions Compared with LBL, the MF + CBL model was an innovative teaching method that promoted more comprehensive quality development. It represents an alternative model for optimizing the capacity of future paediatric doctors.
Natural proteins have evolved to fold robustly along specific pathways. Folding begins during synthesis, guided by interactions of the nascent protein with the ribosome and molecular chaperones. However, the timing and progression of co-translational folding remain largely elusive, in part because the process is difficult to measure in the natural environment of the cytosol. We developed a high-throughput method to quantify co-translational folding in live cells that we term Arrest Peptide profiling (AP profiling). We employed AP profiling to delineate co-translational folding for a set of GTPase domains with very similar structures, defining how topology shapes folding pathways. Genetic ablation of major nascent chain-binding chaperones resulted in localized folding changes that suggest how functional redundancies among chaperones are achieved by distinct interactions with the nascent protein. Collectively, our studies provide a window into cellular folding pathways of complex proteins and pave the way for systematic studies on nascent protein folding at unprecedented resolution and throughput.
Background: N-terminal brain natriuretic peptide precursor (NT-proBNP) and brain natriuretic peptide (BNP) are mainly produced and secreted in the heart. In 2008, the European Heart Association recommended that serum BNP/NT-proBNP levels should be included in one of the diagnostic criteria of heart failure. Serum NT-proBNP is more stable than BNP, and the detection results are less affected by objective factors, so it is widely used. At present, NT-proBNP has long been beyond the scope of heart failure markers, and has a wide range of clinical value in the evaluation and prediction of some serious diseases. This study prospectively studied the predictive value of serum NT-proBNP in pediatric intensive care unit (PICU).Methods: This was a prospective study involving 375 children in the PICU. The patients were divided into three groups: non-risk, low-risk, and high-risk groups. Serum NT-proBNP levels and the 28-day mortality rate were analyzed.Results: The serum NT-proBNP levels and the mortality of the high-risk group was significantly higher than those of the low- and non-risk groups (P<0.01 in both cases). Receiver operating characteristic curve (ROC curve) analysis showed that the area under the curve was 0.705 (P<0.001, sensitivity =0.643, specificity =0.692). Death multivariate binary logistic regression analysis indicated that NT-proBNP was not an independent factor for 28-day mortality.Conclusions: Serum NT-proBNP was significantly correlated with the severity of illness for critically ill patients in PICU. Although high levels of NT-proBNP indicated greater severity, this was not an independent risk factor affecting the prognosis of patients.
The mitotic chromosomes of Cansumys canus , from Ningshan,Shaanxi P rovi nce of China were analyzed by conventional, C banding, and Silver staining tec hn iques The species has a diploid number of 24, consists of 16 metacentrics, 4 s ubmetacentrics,2 subtelocetrics and 2 telocentrics Because of no male specime ns it is not determined the sex chromosomes Centromeric C bands were found in 2 pairs of chromosomes and a large heterochromatin block in long arm of one pair of subtelocentric chromosomes Silver stained NORs were found on the three to four pairs of chromosomes As the comparisons of the results with the chromosom e of the species Tscherskia (Cricetulus) triton [2n=28, 22 t + 4 m + XY (s t, m )] and other species in the Genus Cricetulus , there are several differences amo ng them in the diploid chromosome number and karyotypes We suggest that Cans umys canus should be one valid species
To investigate the clinical features of invasive pulmonary fungal infections (IPFIs) after biliary atresia (BA) surgery and related risk factors.A retrospective analysis was performed for the clinical data of 49 children with IPFIs after BA surgery, including clinical features, lung imaging findings, and pathogenic features. The risk factors for IPFIs after BA surgery were also analyzed.The most common pathogens of IPFIs after BA surgery was Candida albicans (17 strains, 45%), followed by Candida tropicalis (7 strains, 18%), Aspergillus (6 strains, 16%), Candida krusei (3 strains, 8%), Candida glabrata (3 strains, 8%), and Candida parapsilosis (2 strains, 5%). Major clinical manifestations included pyrexia, cough, and shortness of breath, as well as dyspnea in severe cases; the incidence rate of shortness of breath reached 78%, and 35% of all children had no obvious rale. The multivariate logistic regression analysis showed that age at the time of surgery, time of glucocorticoid application, cumulative time of the application of broad-spectrum antibiotics, and recurrent cholangitis were major risk factors for IPFIs after BA surgery.The three most common pathogens of IPFIs after BA surgery are Candida albicans, Candida tropicalis, and Aspergillus. It is important to perform surgery as early as possible, avoid recurrent cholangitis, and shorten the course of the treatment with broad-spectrum antibiotics and glucocorticoids for decreasing the risk of IPFIs.
Peptide hormones are decorated with post-translational modifications (PTMs) that are crucial for receptor recognition. Tyrosine sulfation on plant peptide hormones is, for example, essential for plant growth and development. Measuring the occurrence and position of sulfotyrosine is, however, compromised by major technical challenges during isolation and detection. Nanopores can sensitively detect protein PTMs at the single-molecule level. By translocating PTM variants of the plant pentapeptide hormone phytosulfokine (PSK) through a nanopore, we here demonstrate the accurate identification of sulfation and phosphorylation on the two tyrosine residues of PSK. Sulfation can be clearly detected and distinguished (>90%) from phosphorylation on the same residue. Moreover, the presence or absence of PTMs on the two close-by tyrosine residues can be accurately determined (>96% accuracy). Our findings demonstrate the extraordinary sensitivity of nanopore protein measurements, providing a powerful tool for identifying position-specific sulfation on peptide hormones and promising wider applications to identify protein PTMs.
Abstract Background: By establishing an innovative teaching model, teachers and students can optimize the education outcome. Lecture-Based Learning (LBL) model has long been widely used as main teaching method in medical course in Chinese culture with a positive result of grades, however, negative of practice. Case-Based Learning (CBL) model modified it by focusing on clinical case study, yet with its limitations. The aim of our study is to discuss the effect of applying a comprehensive renewal CBL model: Micro-Film Case Based Learning (MF+CBL) Model, in pediatrics theoretical course in senior year students under Chinese culture.Methods: Experimental research was conducted by parallel group control study. The total sample was 104 senior year students (Chinese) majoring in clinical medicine from Guangxi Medical University. The experimental group was intervened by MF+CBL model, while the control group by LBL model. Both process and result were assessed after 8-week courses, by questionnaires of Student Self-Assessment, Satisfaction Survey and Final examination.Results: The outcome of experimental group generally surpassed control group in Student Self-Assessment, Satisfaction Survey, and Final examination. The open question at the end of the questionnaire yet unfolded a fact that a small number of students were not used to the MF+CBL model due to its time and energy consuming feature.Conclusions: MF+CBL model was an innovative teaching method, compared with LBL, with a better contribution of comprehensive quality development，which offered an alternative model to optimize the capacity of future pediatrics doctors.
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