A study on the flexibility of enzyme active sites

<p>Abstract</p> <p>Background</p> <p>A common assumption about enzyme active sites is that their structures are highly conserved to specifically distinguish between closely similar compounds. However, with the discovery of distinct enzymes with similar reaction chemistries, more and more studies discussing the structural flexibility of the active site have been conducted.</p> <p>Results</p> <p>Most of the existing works on the flexibility of active sites focuses on a set of pre-selected active sites that were already known to be flexible. This study, on the other hand, proposes an analysis framework composed of a new data collecting strategy, a local structure alignment tool and several physicochemical measures derived from the alignments. The method proposed to identify flexible active sites is highly automated and robust so that more extensive studies will be feasible in the future. The experimental results show the proposed method is (a) consistent with previous works based on manually identified flexible active sites and (b) capable of identifying potentially new flexible active sites.</p> <p>Conclusions</p> <p>This proposed analysis framework and the former analyses on flexibility have their own advantages and disadvantage, depending on the cause of the flexibility. In this regard, this study proposes an alternative that complements previous studies and helps to construct a more comprehensive view of the flexibility of enzyme active sites.</p

The effects of postintubation hypertension in severe traumatic brain injury

Introduction. The effect of post-intubation hypertension in severe traumatic brain injury (TBI) patients remains uncertain. We aimed to determine the relationship between post-intubation hypertension (mean arterial pressure (MAP) > 110mmHg) and outcomes in severe TBI. Methods. In this retrospective cohort study, adults who presented with isolated TBI and a MAP 70mmHg were assessed. Data were retrieved from our institutional trauma registry and the admission list of our neurosurgical intensive care unit (ICU). Results. We enrolled 126 patients, 81 of whom had a MAP 110 mmHg after intubation and were assigned to group 1; 45 patients who had a MAP > 110 mmHg were assigned to group 2. Only age (P = 0.008), heart rate (HR; P = 0.036), and MAP before intubation (P 110 mmHg, P < 0.034, OR 3.119, 95% CI 1.087–8.953). Conclusion. Post-intubation hypertension was associated with longer ventilator-dependent and ICU stays in patients with severe TBI

The effects of postintubation hypertension in severe traumatic brain injury

Introduction. The effect of post-intubation hypertension in severe traumatic brain injury (TBI) patients remains uncertain. We aimed to determine the relationship between post-intubation hypertension (mean arterial pressure (MAP) > 110mmHg) and outcomes in severe TBI. Methods. In this retrospective cohort study, adults who presented with isolated TBI and a MAP 70mmHg were assessed. Data were retrieved from our institutional trauma registry and the admission list of our neurosurgical intensive care unit (ICU). Results. We enrolled 126 patients, 81 of whom had a MAP 110 mmHg after intubation and were assigned to group 1; 45 patients who had a MAP > 110 mmHg were assigned to group 2. Only age (P = 0.008), heart rate (HR; P = 0.036), and MAP before intubation (P 110 mmHg, P < 0.034, OR 3.119, 95% CI 1.087–8.953). Conclusion. Post-intubation hypertension was associated with longer ventilator-dependent and ICU stays in patients with severe TBI

Web-based computer adaptive assessment of individual perceptions of job satisfaction for hospital workplace employees

<p>Abstract</p> <p>Background</p> <p>To develop a web-based computer adaptive testing (CAT) application for efficiently collecting data regarding workers' perceptions of job satisfaction, we examined whether a 37-item Job Content Questionnaire (JCQ-37) could evaluate the job satisfaction of individual employees as a single construct.</p> <p>Methods</p> <p>The JCQ-37 makes data collection via CAT on the internet easy, viable and fast. A Rasch rating scale model was applied to analyze data from 300 randomly selected hospital employees who participated in job-satisfaction surveys in 2008 and 2009 via non-adaptive and computer-adaptive testing, respectively.</p> <p>Results</p> <p>Of the 37 items on the questionnaire, 24 items fit the model fairly well. Person-separation reliability for the 2008 surveys was 0.88. Measures from both years and item-8 job satisfaction for groups were successfully evaluated through item-by-item analyses by using <it>t</it>-test. Workers aged 26 - 35 felt that job satisfaction was significantly worse in 2009 than in 2008.</p> <p>Conclusions</p> <p>A Web-CAT developed in the present paper was shown to be more efficient than traditional computer-based or pen-and-paper assessments at collecting data regarding workers' perceptions of job content.</p

Yang-Dan-Tang, Identified from 15 Chinese Herbal Formulae, Inhibits Human Lung Cancer Cell Proliferation via Cell Cycle Arrest

Lung cancer has long been one of the most deadly forms of cancer. The majority of lung cancers are of the non-small-cell lung cancer (NSCLC) type. Here we used the non-small-cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possible mechanisms of alternative medicine in lung cancer therapy. We identified three formulae (Formulae 3, 5, and 14) that substantially decreased the survival of A549 cells but did not affect MRC5 normal lung tissue cells. Formula 14, Yang-Dan-Tang, a modified decoction of Ramulus Cinnamomi Cassiae, was chosen for further characterization. Flow cytometry analysis showed that treatment of Formula 14 induced cell cycle arrest in G1 and G2 phase without causing significant cell death. These results were also confirmed by Western blot analysis, with decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. This study provides further insight into the possible working mechanism of Yang-Dan-Tang in patients

Effect of end-stage renal disease on long-term survival after a first-ever mechanical ventilation: a population-based study

The 30-day, 6-month, and 1-, 2-, 5-, and 10-year survival rate differences in the ESRD Pos and ESRD Neg groups from the beginning. (DOCX 17 kb

Experience of patients with inflammatory bowel disease in using a home fecal calprotectin test as an objective reported outcome for self-monitoring

Background/Aims Fecal calprotectin (fC) level is a predictive marker of mucosal healing for patients with inflammatory bowel disease (IBD). Home fC tests are now available. We evaluated the performance of the smartphone-based IBDoc home testing system in patients with IBD and obtained their feedback as an objective patient-reported outcome. Methods This prospective study enrolled consecutive patients with IBD in clinical remission. fC in the same stool sample was assessed by using both the laboratory test (Quantum Blue calprotectin test) and home test (IBDoc). The correlation between the 2 tests was analyzed using the Pearson method. In addition, the patients were asked to fill a questionnaire based on their experience. Results Fifty-one patients with IBD (68 tests and 49 questionnaires) were included. The correlation between Quantum Blue test and IBDoc was good (r=0.776, P70%) probability to use it for future monitoring if the price was acceptable. By using 250 μg/g as the cutoff, the agreement between home test and laboratory results was 80%, and by using 600 μg/g as the cutoff, the agreement increased to 92%. Conclusions The correlation between the laboratory and home tests was good. Most patients found the home test to be feasible and easy to use and preferred it over laboratory test and endoscopy for monitoring. Therefore, the home test could be used as an objective patient-reported outcome

Multiple upstream modules regulate zebrafish myf5 expression

BACKGROUND: Myf5 is one member of the basic helix-loop-helix family of transcription factors, and it functions as a myogenic factor that is important for the specification and differentiation of muscle cells. The expression of myf5 is somite- and stage-dependent during embryogenesis through a delicate regulation. However, this complex regulatory mechanism of myf5 is not clearly understood. RESULTS: We isolated a 156-kb bacterial artificial chromosome clone that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish myf5 and generated a transgenic line carrying this 156-kb segment fused to a green fluorescent protein (GFP) reporter gene. We find strong GFP expression in the most rostral somite and in the presomitic mesoderm during segmentation stages, similar to endogenous myf5 expression. Later, the GFP signals persist in caudal somites near the tail bud but are down-regulated in the older, rostral somites. During the pharyngula period, we detect GFP signals in pectoral fin buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and superior oblique muscles, a pattern that also corresponds well with endogenous myf5 transcripts. To characterize the specific upstream cis-elements that regulate this complex and dynamic expression pattern, we also generated several transgenic lines that harbor various lengths within the upstream 80-kb segment. We find that (1) the -80 kb/-9977 segment contains a fin and cranial muscle element and a notochord repressor; (2) the -9977/-6213 segment contains a strong repressive element that does not include the notochord-specific repressor; (3) the -6212/-2938 segment contains tissue-specific elements for bone and spinal cord; (4) the -2937/-291 segment contains an eye enhancer, and the -2937/-2457 segment is required for notochord and myocyte expression; and (5) the -290/-1 segment is responsible for basal transcription in somites and the presomitic mesoderm. CONCLUSION: We suggest that the cell lineage-specific expression of myf5 is delicately orchestrated by multiple modules within the distal upstream region. This study provides an insight to understand the molecular control of myf5 and myogenesis in the zebrafish

Automatic Precipitation Measurement Based on Raindrop Imaging and Artificial Intelligence

Rainfall measurement is subjected to various uncertainties due to the complexity of measurement techniques and atmosphere characteristics associated with weather type. Thus, this article presents a video-based disdrometer to analyze raindrop images by introducing artificial intelligence technology for the rainfall rate. First, a high-speed CMOS camera is integrated into a planar LED as a backlight source for appropriately acquiring falling raindrops in different positions. The falling raindrops can be illuminated and used for further image analysis. Algorithms developed for raindrop detection and trajectory identification are employed. In a field test, a rainfall event of 42 continuous hours has been measured by the proposed disdrometer that is validated against a commercial PARSIVEL² disdrometer and a tipping bucket rain gauge at the same area. In the evaluation for 5-min rainfall images, the results of the trajectory identification are within the precision of 87.8%, recall of 98.4%, and F1 score of 92.8%, respectively. Furthermore, the performance exhibits that the rainfall rate and raindrop size distribution (RSD) obtained by the proposed disdrometer are remarkably consistent with those of PARSIVEL² disdrometer. The results suggest that the proposed disdrometer based on the continuous movements of the falling raindrops can achieve accurate measurements and eliminate the potential errors effectively in the real-time monitoring of rainfall

TTBK2: A Tau Protein Kinase beyond Tau Phosphorylation

Tau tubulin kinase 2 (TTBK2) is a kinase known to phosphorylate tau and tubulin. It has recently drawn much attention due to its involvement in multiple important cellular processes. Here, we review the current understanding of TTBK2, including its sequence, structure, binding sites, phosphorylation substrates, and cellular processes involved. TTBK2 possesses a casein kinase 1 (CK1) kinase domain followed by a ∼900 amino acid segment, potentially responsible for its localization and substrate recruitment. It is known to bind to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. In addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. Mutations of TTBK2 are associated with spinocerebellar ataxia type 11. In addition, TTBK2 is essential for regulating the growth of axonemal microtubules in ciliogenesis. It also plays roles in resistance of cancer target therapies and in regulating glucose and GABA transport. Reported sites of TTBK2 localization include the centriole/basal body, the midbody, and possibly the mitotic spindles. Together, TTBK2 is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its functions