Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into the Maturation of Hyperthermophilic Pyrolysin and the Roles of Its N-Terminal Propeptide and Long C-Terminal Extension

ABSTRACT Pyrolysin-like proteases from hyperthermophiles are characterized by large insertions and long C-terminal extensions (CTEs). However, little is known about the roles of these extra structural elements or the maturation of these enzymes. Here, the recombinant proform of Pyrococcus furiosus pyrolysin (Pls) and several N- and C-terminal deletion mutants were successfully expressed in Escherichia coli. Pls was converted to mature enzyme (mPls) at high temperatures via autoprocessing of both the N-terminal propeptide and the C-terminal portion of the long CTE, indicating that the long CTE actually consists of the C-terminal propeptide and the C-terminal extension (CTEm), which remains attached to the catalytic domain in the mature enzyme. Although the N-terminal propeptide deletion mutant PlsΔN displayed weak activity, this mutant was highly susceptible to autoproteolysis and/or thermogenic hydrolysis. The N-terminal propeptide acts as an intramolecular chaperone to assist the folding of pyrolysin into its thermostable conformation. In contrast, the C-terminal propeptide deletion mutant PlsΔC199 was converted to a mature form (mPlsΔC199), which is the same size as but less stable than mPls, suggesting that the C-terminal propeptide is not essential for folding but is important for pyrolysin hyperthermostability. Characterization of the full-length (mPls) and CTEm deletion (mPlsΔC740) mature forms demonstrated that CTEm not only confers additional stability to the enzyme but also improves its catalytic efficiency for both proteineous and small synthetic peptide substrates. Our results may provide important clues about the roles of propeptides and CTEs in the adaptation of hyperthermophilic proteases to hyperthermal environments.
Overexpression of Plastid Transketolase in Tobacco Results in a Thiamine Auxotrophic Phenotype[OPEN]

An unexpected phenotype caused by overexpression of the plastid transketolase enzyme provides evidence that transketolase activity is an important determinant of thiamine availability in the plant. To investigate the effect of increased plastid transketolase on photosynthetic capacity and growth, tobacco (Nicotiana tabacum) plants with increased levels of transketolase protein were produced. This was achieved using a cassette composed of a full-length Arabidopsis thaliana transketolase cDNA under the control of the cauliflower mosaic virus 35S promoter. The results revealed a major and unexpected effect of plastid transketolase overexpression as the transgenic tobacco plants exhibited a slow-growth phenotype and chlorotic phenotype. These phenotypes were complemented by germinating the seeds of transketolase-overexpressing lines in media containing either thiamine pyrophosphate or thiamine. Thiamine levels in the seeds and cotyledons were lower in transketolase-overexpressing lines than in wild-type plants. When transketolase-overexpressing plants were supplemented with thiamine or thiamine pyrophosphate throughout the life cycle, they grew normally and the seed produced from these plants generated plants that did not have a growth or chlorotic phenotype. Our results reveal the crucial importance of the level of transketolase activity to provide the precursor for synthesis of intermediates and to enable plants to produce thiamine and thiamine pyrophosphate for growth and development. The mechanism determining transketolase protein levels remains to be elucidated, but the data presented provide evidence that this may contribute to the complex regulatory mechanisms maintaining thiamine homeostasis in plants.
Model Transformation Modularization as a Many-Objective Optimization Problem

Model transformation programs are iteratively refined, restructured, and evolved due to many reasons such as fixing bugs and adapting existing transformation rules to new metamodels version. Thus, modular design is a desirable property for model transformations as it can significantly improve their evolution, comprehensibility, maintainability, reusability, and thus, their overall quality. Although language support for modularization of model transformations is emerging, model transformations are created as monolithic artifacts containing a huge number of rules. To the best of our knowledge, the problem of automatically modularizing model transformation programs was not addressed before in the current literature. These programs written in transformation languages, such as ATL, are implemented as one main module including a huge number of rules. To tackle this problem and improve the quality and maintainability of model transformation programs, we propose an automated search-based approach to modularize model transformations based on higher-order transformations. Their application and execution is guided by our search framework which combines an in-place transformation engine and a search-based algorithm framework. We demonstrate the feasibility of our approach by using ATL as concrete transformation language and NSGA-III as search algorithm to find a trade-off between different well-known conflicting design metrics for the fitness functions to evaluate the generated modularized solutions. To validate our approach, we apply it to a comprehensive dataset of model transformations. As the study shows, ATL transformations can be modularized automatically, efficiently, and effectively by our approach. We found that, on average, the majority of recommended modules, for all the ATL programs, by NSGA-III are considered correct with more than 84 percent of precision and 86 percent of recall when compared to manual solutions provided by active developers. The statistical analysis of our experiments over several runs shows that NSGA-III performed significantly better than multi-objective algorithms and random search. We were not able to compare with existing model transformations modularization approaches since our study is the first to address this problem. The software developers considered in our experiments confirm the relevance of the recommended modularization solutions for several maintenance activities based on different scenarios and interviews.
On the influence of feature reduction for the classification of hyperspectral images based on the extended morphological profile

In this study we investigated the classification of hyperspectral data with high spatial resolution. Previously, methods that generate a so-called extended morphological profile (EMP) from the principal components of an image have been proposed to create base images for morphological transformations. However, it can be assumed that the feature reduction (FR) may have a significant effect on the accuracy of the classification of the EMP. We therefore investigated the effect of different FR methods on the generation and classification of the EMP of hyperspectral images from urban areas, using a machine learning-based algorithm for classification. The applied FR methods include: principal component analysis (PCA), nonparametric weighted feature extraction (NWFE), decision boundary feature extraction (DBFE), Gaussian kernel PCA (KPCA) and Bhattacharyya distance feature selection (BDFS). Experiments were run with two classification algorithms: the support vector machine (SVM) and random forest (RF) algorithms. We demonstrate that the commonly used PCA approach seems to be nonoptimal in a large number of cases in terms of classification accuracy, and the other FR methods may be more suitable as preprocessing approaches for the EMP.
Postoperative atrial fibrillation following cardiac surgery: a persistent complication

Abstract Postoperative atrial fibrillation (POAF) is a common, expensive and potentially morbid complication following cardiac surgery. POAF occurs in around 35% of cardiac surgery cases and has a peak incidence on postoperative day 2. Patients who develop POAF incur on average $10 000‐$20 000 in additional hospital treatment costs, 12‐24 h of prolonged ICU time, and an additional 2 to 5 days in the hospital. POAF has been identified as an independent predictor of numerous adverse outcomes, including a 2‐ to 4‐fold increased risk of stroke, reoperation for bleeding, infection, renal or respiratory failure, cardiac arrest, cerebral complications, need for permanent pacemaker placement, and a 2‐fold increase in all‐cause 30‐day and 6‐month mortality. The pathogenesis of POAF is incompletely understood but likely involves interplay between pre‐existing physiological components and local and systemic inflammation. POAF is associated with numerous risk factors including advanced age, pre‐existing conditions that cause cardiac remodelling and certain non‐cardiovascular conditions. Clinical management of POAF includes both prophylactic and therapeutic measures, although the efficacy of many interventions remains in question. This review provides a comprehensive and up‐to‐date summary of the pathogenesis of POAF, outlines current clinical guidelines for POAF prophylaxis and management, and discusses new avenues for further investigation.
Gap Junctions in the Sinoatrial Node:

Connexin43 (CX43) is the major constituent of gap junctions in working cardiac myocytes but has not been demonstrated in the sinoatrial (SA) node. In this issue of the Joumal of Cardiovascular Electrophysiology, Trabka-Janik and colleagues' describe for the Hrst time the presence of CX43 in the hamster SA node. This editorial discusses whether CX43 not being found in tbe SA node in other species may be due to different experimental tecbniques and/or interspecies differences. The implications of this finding for SA ntxial activation patterns are also discussed.
Keratin mutation in transgenic mice predisposes to Fas but not TNF‐induced apoptosis and massive liver injury

Hepatocytes express keratins 8 and 18 (K8/18) as their only cytoskeletal intermediate filament (IF) proteins, and K8/18 mutations predispose their carriers to liver cirrhosis. Transgenic mice that overexpress mutant human K18 (Arg89→Cys [R89C]) develop mild chronic hepatitis, hepatocyte fragility, keratin filament disruption, and increased susceptibility to drug‐induced liver injury. K18 is a major caspase substrate during apoptosis, and K8‐ or K18‐null mice are significantly predisposed to Fas‐ and possibly tumor necrosis factor (TNF)‐mediated apoptosis in the liver. Here we tested the potential role of the K18 R89C mutation on Fas‐ or TNF‐mediated apoptotic liver injury by injecting Fas antibody (Ab) or TNF‐α plus actinomycin D into mice that overexpress wild‐type (WT) human K18 (with intact filament network, termed TG2 mice) or into K18 R89C mice (with disrupted filament network). K18 R89C mice are significantly more susceptible to Fas‐mediated liver injury compared with nontransgenic and TG2 mice. This included differences in lethality, histology, apoptosis, and serum transaminase levels. In contrast, K18 WT and R89C mice manifest similar sensitivity to TNF‐induced injury. Both Fas‐ and TNF‐induced apoptosis in liver tissues are associated with caspase‐mediated K18 degradation and increased keratin phosphorylation on several but not all sites. In conclusion, transgenic mouse K18 mutation and its consequent keratin filament disruption predispose hepatocytes to Fas‐ but not TNF‐mediated apoptotic injury. This supports the association of keratin mutations with cirrhosis in patients with liver disease and suggests that keratins modulate apoptosis induced by Fas but not TNF.
E3 Ubiquitin ligase RNF183 Is a Novel Regulator in Inflammatory Bowel Disease.

BACKGROUND AND AIMS Specific members of the RING finger [RNF] protein family serve as E3 ubiquitin ligases and play important roles in the regulation of inflammation. However, their roles in the pathogenesis of inflammatory bowel disease [IBD] have not been explored. METHODS Genomic microarray of inflamed colon samples from Crohn's disease [CD] patients was performed to identify potential up-regulated genes. Expression of the identified highly up-regulated RNF183 gene was subsequently examined by quantitative reverse transcription polymerase chain reaction [qRT-PCR], western blotting and immunohistochemistry of the intestinal tissues of IBD patients and the colons of trinitrobenzene sulphonic acid [TNBS]-induced colitic mice. RNF183-mediated interaction with the NF-κB pathway and ubiquitination of IκBα were examined by siRNA, plasmid transfection, and immunoprecipitation. The miRNA predicted to target RNF183 was explored and its role in the RNF183/ NF-κB pathway was investigated. RESULTS RNF183 was up-regulated in intestinal epithelial cells in IBD patients and in colitic mice. RNF183 promoted intestinal inflammation via the activation of the NF-κB pathway by increasing the ubiquitination and degradation of IκBα. Computational analysis identified putative binding of miR-7 to RNF183. Transfection of intestinal cells with a miR-7 mimic or inhibitor confirmed its negative regulatory effect on RNF183 expression and ubiquitination of IκBα. miR-7 was down-regulated in inflamed colon tissues of IBD patients and colitic mice. CONCLUSIONS RNF183, which is negatively regulated by miR-7, is a novel regulator promoting intestinal inflammation by increasing the ubiquitination and degradation of IκBα, thereby inducing NF-κB activation. The interaction between RNF183-mediated ubiquitination and miRNA may be an important novel epigenetic mechanism in the pathogenesis of IBD.
On demand: the singular rht net, an ideal blueprint for the construction of a metal-organic framework (MOF) platform.

The need for tunable functional solid-state materials is ever increasing because of the growing demand to address persisting challenges in global energy issues, environmental sustainability, and others. [1] It is practical and preferable for such materials to be pre-designed and constructed to contain the desired properties and specific functionalities for a given targeted application. An emerging unique class of solid-state materials, namely metal–organic frameworks (MOFs), has the desired attributes and offers great promise to unveil superior materials for many lasting challenges [2] since desired functionality can be introduced pre- and/or post-synthesis. [3] A remarkable feature of MOFs is the ability to build periodic structures with in-built functional properties using the molecular building block (MBB) approach, which utilizes pre-selected organic and inorganic MBBs, with desired function, that are judiciously chosen to possess the proper geometry, shape, and directionality required to target given underlying nets. [4]
Diabetes, colorectal cancer and cyclooxygenase 2 inhibition

Diabetes is a risk factor for cancer and specifically colorectal cancer. It is also associated with increased cancer mortality. Aspirin, non‐steroidal anti‐inflammatory drugs (NSAIDs) and cyclooxygenase 2 (Cox‐2) inhibitors have been shown to decrease the incidence of colorectal cancer. This effect may be mediated by inhibiting prostaglandin synthesis. Long‐term use of high‐dose aspirin and NSAIDs is associated with significant gastrointestinal side effects. Unfortunately, the use of Cox‐2 inhibitors is associated with an increased incidence of acute myocardial infarction and death from cardiovascular disease. The increased risk of cardiovascular disease in patients with diabetes results in the loss of the potential to use Cox‐2 inhibitors for cancer chemoprophylaxis. Until a safer type of Cox‐2 inhibitor is available, or low‐dose aspirin is evaluated for chemoprophylaxis, a more intense screening programme for colorectal cancer may be appropriate for patients with diabetes, especially men. Healthcare professionals managing patients with diabetes should be aware of the increased risk of this type of cancer.
Contextual factors influencing research use in nursing.

BACKGROUND Contextual factors are perceived to be significant barriers to research-utilisation-related activity, but little is known about how context impacts on specific research-based decisions, or how the individual interacts with the organisation in the requirement for research-based change. AIM This study describes the impact of contextual factors on the practical reasoning of nurse specialists in the construction of policy for practice. METHODS Three groups of clinical nurse specialists were observed during a series of meetings convened to construct evidence-based guidelines for nursing practice. Transcripts of the meetings were analysed to identify and categorise the physical, social, political, and economic influences on 31 nursing issues. FINDINGS Multiple contextual factors influenced each decision made, with decisions about nursing practice bounded by setting and system considerations, relationships with others in the care team, and resource constraints. Practitioners were involved in weighing up alternative scenarios, contexts, and contingencies for each decision, requiring strategies to adapt and reconstruct the nature of care, to influence others, and to affect organisational decision-making processes. DISCUSSION The practical accomplishment of evidence-based practice required diverse skills: translating between evidence and practice; mediating the values, preferences, and working practices of multiple stakeholders; negotiating organisational complexity and the management of boundaries; and coordinating inter-organisational and inter-agency working. Nurse specialists in this study had a significant role in instigating, fuelling, and coordinating policy review, predominantly by communication across professional and organisational boundaries. IMPLICATIONS/CONCLUSIONS Clinical specialists acting as organisational boundary spanners require skills in the informal cultural work of organising, facilitating, and maintaining links across professional, team, and organisational boundaries. If their role in the negotiation of evidence-based practice patterns across professional and organisational boundaries is to be successful, wider skills than information management need to be recognised and their development and enactment supported.
Longitudinal assessment of white matter abnormalities following sports‐related concussion

There is great interest in developing physiological‐based biomarkers such as diffusion tensor imaging to aid in the management of concussion, which is currently entirely dependent on clinical judgment. However, the time course for recovery of white matter abnormalities following sports‐related concussion (SRC) is unknown. We collected diffusion tensor imaging and behavioral data in forty concussed collegiate athletes on average 1.64 days (T1; n = 33), 8.33 days (T2; n = 30), and 32.15 days post‐concussion (T3; n = 26), with healthy collegiate contact‐sport athletes (HA) serving as controls (n = 46). We hypothesized that fractional anisotropy (FA) would be increased acutely and partially recovered by one month post‐concussion. Mood symptoms were assessed using structured interviews. FA differences were assessed using both traditional and subject‐specific analyses. An exploratory analysis of tau plasma levels was conducted in a subset of participants. Results indicated that mood symptoms improved over time post‐concussion, but remained elevated at T3 relative to HA. Across both group and subject‐specific analyses, concussed athletes exhibited increased FA in several white matter tracts at each visit post‐concussion with no longitudinal evidence of recovery. Increased FA at T1 and T3 was significantly associated with an independent, real‐world outcome measure for return‐to‐play. Finally, we observed a nonsignificant trend for reduced tau in plasma of concussed athletes at T1 relative to HA, with tau significantly increasing by T2. These results suggest white matter abnormalities following SRC may persist beyond one month and have potential as an objective biomarker for concussion outcome. Hum Brain Mapp 37:833–845, 2016. © 2015 Wiley Periodicals, Inc.
Factors associated with asthma in adolescents in the city of Fortaleza, Brazil

Abstract Objective: Asthma is a chronic inflammatory airway disease. In Brazil, little is known about factors associated with this disease. This study aimed to identify factors associated with asthma in 13- to 14-year-old adolescents in Fortaleza, Ceará, Brazil. Methods: It is a cross-sectional population-based study, with a probability sample of 3015 students in 2006–2007. We used the questionnaires about asthma, rhinitis and socio-demographic/environmental factors from the International Study for Asthma and Allergies in Childhood (ISAAC) protocol. Current asthma was defined as physician-diagnosed asthma and wheezing in the previous 12 months. Bivariate analysis was performed between asthma and factors included in the study, using prevalence ratio and Chi-square test. Confidence intervals (95%) and odds ratio (OR) were also calculated. Factors associated with asthma in bivariate analysis were then assessed using logistic regression. Results: Final sample was composed by 694 adolescents, 179 with asthma. Rhinoconjunctivitis and consumption of stuffed biscuits and fried snacks three or more times per week were independently and positively associated with asthma; consumption of fruits three or more times per week was negatively associated with asthma. Conclusions: Dietary factors were the most associated with asthma in this study. Besides rhinoconjunctivitis, consumption of stuffed biscuits and fried snacks (foods with high content of saturated fat) three or more times per week were independently associated with asthma as aggravating factors, while the consumption of fruits three or more times per week was associated with asthma as protective factor. Interventions acting on these factors may decrease the occurrence of asthma in this population.
Studies of Hurst Index for Different Regions of Genes

Hurst indexes of exon, intron and promoter sequences were studied based on Z-curve. For z variable of Z-curve, Hurst index distribution curves of the exons and introns had a great difference, and the distribution curve of the promoters overlapped with those of exons and introns. For other viable y and x of Z-curve, the exons, introns and promoters had a similar Hurst index distribution. It was also found that reverse Z-curve had the similar characteristic with Z-curve on the aspect of Hurst index.
On the normal modes of free vibration of inhomogeneous and anisotropic elastic objects ß

The Hamilton's principle approach to the calculation of vibrational modes of elastic objects with free boundaries i exploited to compute the resonance frequencies of a variety of anisotropic elastic objects, including spheres, hemispheres, pheroids, ellipsoids, cylinders, eggs, shells, bells, sandwiches, parallelepipeds, cones, pyramids, prisms, tetrahedra, octahedra, and potatoes. The paramount feature of this calculation, which distinguishes it from previous ones, is the choice of products of powers of the Cartesian coordinates as a basis for expansion of the displacement in a truncated complete set, enabling one to analytically evaluate the required matrix elements for these systems. Because these basis functions are products of powers of x, y, and z, this scheme is called the xyz algorithm. The xyz algorithm allows a general anisotropic elastic tensor with any position dependence and any shape with arbitrary density variation. A number of plots of resonance spectra of families of elastic objects are displayed as functions of relevant parameters, and, to illustrate the versatility of the method, the measured resonant frequencies of a precision machined but irregularly shaped sample of aluminum (called a potato) are compared with its computed normal modes. Applications to materials science and to seismology are mentioned.