Miracle-dz/UniFAR-FTUs huggingface dataset:
A complete bioconversion cascade for dehalogenation and denitration by bacterial flavin–dependent enzymes

Halogenated phenol and nitrophenols are toxic compounds that are widely accumulated in the environment. Enzymes in the had operon from the bacterium Ralstonia pickettii DTP0602 have the potential for application as biocatalysts in the degradation of many of these toxic chemicals. HadA monooxygenase previously was identified as a two-component reduced FAD (FADH−)–utilizing monooxygenase with dual activities of dehalogenation and denitration. However, the partner enzymes of HadA, that is, the flavin reductase and quinone reductase that provide the FADH− for HadA and reduce quinone to hydroquinone, remain to be identified. In this report, we overexpressed and purified the flavin reductases, HadB and HadX, to investigate their functional and catalytic properties. Our results indicated that HadB is an FMN-dependent quinone reductase that converts the quinone products from HadA to hydroquinone compounds that are more stable and can be assimilated by downstream enzymes in the pathway. Transient kinetics indicated that HadB prefers NADH and menadione as the electron donor and acceptor, respectively. We found that HadX is an FAD-bound flavin reductase, which can generate FADH− for HadA to catalyze dehalogenation or denitration reactions. Thermodynamic and transient kinetic experiments revealed that HadX prefers to bind FAD over FADH− and that HadX can transfer FADH− from HadX to HadA via free diffusion. Moreover, HadX rapidly catalyzed NADH-mediated reduction of flavin and provided the FADH− for a monooxygenase of a different system. Combination of all three flavin-dependent enzymes, i.e. HadA/HadB/HadX, reconstituted an effective dehalogenation and denitration cascade, which may be useful for future bioremediation applications.
Interarm Blood Pressure Difference is Associated with Early Neurological Deterioration, Poor Short-Term Functional Outcome, and Mortality in Noncardioembolic Stroke Patients

BACKGROUND AND PURPOSE Interarm differences in the systolic and diastolic blood pressures (IASBD and IADBD, respectively) are found in various populations, including stroke patients, but their significance for stroke outcomes has rarely been reported. We aimed to determine the associations of IASBD and IADBD with early neurological deterioration (END), functional outcome, and mortality. METHODS This study included 1,008 consecutive noncardioembolic cerebral infarction patients who were admitted within 24 hours of onset and had automatic measurements of blood pressures in the bilateral arms. END was assessed within 72 hours of stroke onset according to predefined criteria. A poor functional outcome was defined as a score on the modified Rankin Scale ≥3 at 3 months after the index stroke. All-cause mortality was also investigated during a median follow-up of 24 months. The absolute difference of blood pressure measurements in both arms were used to define IASBD and IADBD. RESULTS END occurred in 15.3% (155/1,008) of the patients. A multivariate analysis including sex, age, and variables for which the p value was <0.1 in a univariate analysis revealed that IASBD ≥10 mm Hg was significantly associated with END [odds ratio (OR)=1.75, 95% CI=1.02-3.01]. IADBD ≥10 mm Hg was also related to END (OR=3.11, 95% CI=1.61-5.99). Moreover, having both IASBD ≥10 mm Hg and IADBD ≥10 mm Hg was related to a poor functional outcome (OR=2.67, 95% CI=1.36-5.35) and mortality (hazard ratio=7.67, 95% CI=3.76-12.83) even after adjusting for END. CONCLUSIONS This study suggests that an interarm blood pressure difference of ≥10 mm Hg could be a useful indicator for the risks of END, poor functional outcome, and mortality.
Modulating long-range energetics via helix stabilization: a case study using T4 lysozyme

Cooperative protein folding requires distant regions of a protein to interact and provide mutual stabilization. The mechanism of this long-distance coupling remains poorly understood. Here, we use T4 lysozyme (T4L*) as a model to investigate long-range communications across a globular protein. T4L* is composed of two structurally distinct subdomains, although it behaves in a two-state manner at equilibrium. The subdomains of T4L* are connected via two topological connections: the N-terminal helix that is structurally part of the C-terminal subdomain (the A-helix) and a long helix that spans both subdomains (the C-helix). To understand the role that the C-helix plays in cooperative folding, we analyzed a circularly permuted version of T4L* (CP13*), whose subdomains are connected only by the C-helix. We demonstrate that when isolated as individual fragments, both subdomains of CP13* can fold autonomously into marginally stable conformations. The energetics of the N-terminal subdomain depend on the formation of a salt bridge known to be important for stability in the full-length protein. We show that the energetic contribution of the salt bridge to the stability of the N-terminal fragment increases when the C-helix is stabilized, such as occurs upon folding of the C-terminal subdomain. These results suggest a model where long-range energetic coupling is mediated by helix stabilization.
Neutrophils engage the kallikrein‐kinin system to open up the endothelial barrier in acute inflammation

Neutrophil recruitment and plasma exudation are key elements in the immune response to injury or infection. Activated neutrophils stimulate opening of the endothelial barrier; however, the underlying mechanisms have remained largely unknown. In this study, we identified a pivotal role of the proinflammatory kallikrein‐kinin system and consequent formation of bradykinin in neutrophil‐evoked vascular leak. In mouse and hamster models of acute inflammation, inhibitors of bradykinin generation, and signaling markedly reduced plasma exudation in response to chemoattractant activation of neutrophils. The neutrophil‐driven leak was likewise suppressed in mice deficient in either the bradykinin B2 receptor or factor XII (initiator of the kallikrein‐kinin system). In human endothelial cell monolayers, material secreted from activated neutrophils induced cytoskeletal rearrangement, leading to paracellular gap formation in a bradykinin‐dependent manner. As a mechanistic basis, we found that a neutrophil‐derived heparin‐binding protein (HBP/azurocidin) displaced the bradykinin precursor high‐molecular‐weight kininogen from endothelial cells, thereby enabling proteolytic processing of kininogen into bradykinin by neutrophil and plasma proteases. These data provide novel insight into the signaling pathway by which neutrophils open up the endothelial barrier and identify the kallikrein‐kinin system as a target for therapeutic interventions in acute inflammatory reactions. —Kenne, E. , Rasmuson, J., Renné, T. , Vieira, M. L. , Müller‐Esterl, W. , Herwald, H. , Lindbom, L. Neutrophils engage the kallikrein‐kinin system to open up the endothelial barrier in acute inflammation. FASEB J. 33, 2599–2609 (2019). www.fasebj. org
Frequency Analysis of Memristor Based Low Pass Bessel Filter

Bessel filter is a type of linear form filter, which is widely used for applications where constant group delay response is required. Such implementation allows to avoid linear distortion. It is believed that recent realization of memristor element can significantly affect filter's performance by being able to adjust filter gain and cut-off frequency. Therefore, this paper presents a memristor based active low pass Bessel filter, where resistor elements were replaced by memristors. The circuit is analysed by on frequency response. Memristor resistances are to be adjusted by means of tuning circuits. Overall, memristive circuit resulted in slight deviation from the original circuit with the same power consumption and verified adjustability of several filter characteristics.
Risk of Progression to Alzheimer’s Disease for Different Neuropsychological Mild Cognitive Impairment Subtypes: A Hierarchical Meta-Analysis of Longitudinal Studies

Mild Cognitive Impairment (MCI) is a heterogeneous condition between normal aging and dementia. Upon neuropsychological testing, MCI can be divided into 4 groups: single-domain amnestic MCI (sd-aMCI), multiple-domain amnestic MCI (md-aMCI), single- and multiple-domain nonamnestic MCI (sd-naMCI, md-naMCI). Some controversy exists about whether the risk of progression to Alzheimer’s disease (risk-AD) is increased in all MCI subtypes. We meta-analyzed the risk-AD for 4 MCI groups using random-effects metaregression with the Hierarchical Robust Variance Estimator and sample size, criterion for objective cognitive impairment, length of follow-up and source of recruitment as covariates. From a pool of 134 available studies, 81 groups from 33 studies (N = 4,907) were meta-analyzed. All the studies were rated as having a high risk of bias. aMCI is overrepresented in studies from memory clinics. Multivariate analyses showed that md-aMCI had a similar risk-AD relative to sd-aMCI, whereas both sd-naMCI and md-naMCI showed a lower risk-AD compared with sd-aMCI. The risk-AD was significantly associated with differences in sample sizes across studies and between groups within studies. md-aMCI had a similar risk-AD relative to sd-aMCI in studies from memory clinics and in studies in the community. Several potential sources of bias such as blindness of AD diagnosis, the MCI diagnosis approach and the reporting of demographics were associated with the risk-AD. This work provides important data for use in both clinical and research scenarios.
“I Feel Sorry for Them”: Australian Meat Consumers’ Perceptions about Sheep and Beef Cattle Transportation

Simple Summary Understanding what concerns about animal welfare are most prominent among members of the public is critical to improve processes in the meat production industry. Hence, this study uses qualitative data to explore how Australian meat consumers viewed one aspect of the production process, livestock transportation. Participants in this study were concerned about the close packing of animals into trucks and ships, and their experiences during long-distance voyages; their views on this topic may be motivated by genuine concerns about animal welfare, together with anthropomorphic tendencies to project human feelings onto these animal experiences and emotional responses, due to transport being associated with slaughter. Given the importance of transport to the Australia red-meat production industry, we argue that public views should be considered as the sector modifies its practices; in addition, higher levels of transparency and communication about practices associated with good animal welfare are needed. Abstract Concern for livestock welfare is significantly increasing in many parts of the world. One area of concern is the transportation of livestock. Using qualitative research methods, this research explores the concerns of Australian meat consumers related to livestock transportation practices, both on land by truck and on sea by ship. Participants were predominantly concerned about animals being “crammed” into trucks and ships, and the long distances over which livestock were transported. Likely contributors to these reactions are the high visibility of truck transport in urban areas, and recent media and political attention to the live-export issue in Australia. We argue that participants’ concerns about transport are arising for a variety of reasons, including anthropomorphic tendencies, genuine concern for the welfare of farm animals, and emotional responses related to the discomfort experienced by meat consumers when they are reminded of the meat-animal connection. Given the importance of transport to the red-meat production industry, these results suggest that the sector may need to reconsider some of their practices and increase transparency and communication about the practices, which they utilise to ensure good animal welfare.
Transcriptional regulation of the matrix protein Shematrin-2 during shell formation in pearl oyster

The molluscan shell is a fascinating biomineral consisting of a highly organized calcium carbonate composite. Biomineralization is elaborately controlled and involves several macromolecules, especially matrix proteins, but little is known about the regulatory mechanisms. The matrix protein Shematrin-2, expression of which peaks in the mantle tissues and in the shell components of the pearl oyster Pinctada fucata, has been suggested to be a key participant in biomineralization. Here, we expressed and purified Shematrin-2 from P. fucata and explored its function and transcriptional regulation. An in vitro functional assay revealed that Shematrin-2 binds the calcite, aragonite, and chitin components of the shell, decreases the rate of calcium carbonate deposition, and changes the morphology of the deposited crystal in the calcite crystallization system. Furthermore, we cloned the Shematrin-2 gene promoter, and analysis of its sequence revealed putative binding sites for the transcription factors CCAAT enhancer–binding proteins (Pf-C/EBPs) and nuclear factor-Y (NF-Y). Using transient co-transfection and reporter gene assays, we found that cloned and recombinantly expressed Pf-C/EBP-A and Pf-C/EBP-B greatly and dose-dependently up-regulate the promoter activity of the Shematrin-2 gene. Importantly, Pf-C/EBP-A and Pf-C/EBP-B knockdowns decreased Shematrin-2 gene expression and induced changes in the inner-surface structures in prismatic layers that were similar to those of antibody-based Shematrin-2 inhibition. Altogether, our data reveal that the transcription factors Pf-C/EBP-A and Pf-C/EBP-B up-regulate the expression of the matrix protein Shematrin-2 during shell formation in P. fucata, improving our understanding of the transcriptional regulation of molluscan shell development at the molecular level.
Asymmetrical Ride-Through and Grid Support in Converter-Interfaced DG Units Under Unbalanced Conditions

Increasing penetration level of distributed generation (DG) units necessitates their participation in supporting power system stability and providing ancillary services. This paper highlights the necessity of supporting the connection voltage by these units under short-term unbalanced voltage sags. To address this, a new regulation scheme, named asymmetrical ride-through (ART), is proposed in this paper. The proposed scheme enforces DG units to properly regulate the voltage within the dynamic limits for three important voltage parameters: positive sequence, negative sequence, and phase voltage magnitude. The main advantages of applying the ART scheme are avoiding unnecessary outages due to temporary unbalanced faults and enhancing the grid stability. As the second contribution, an advanced dynamic voltage support method is also proposed to accurately address the specifications determined in the ART scheme. The successful results of the ART regulation scheme and the proposed dynamic voltage support method are verified using simulation and experimental test cases.
Survey on Sentiment Analysis using Twitter Dataset

Social networking sites like twitter have millions of people share their thoughts day by day as tweets. As tweet is characteristic short and basic way of expression. So in this review paper we focused on sentiment analysis of Twitter data. The Sentiment Analysis sees as area of text data mining and NLP. The research of sentiment analysis of Twitter data can be performed in different aspects. This paper shows sentiment analysis types and techniques used to perform extraction of sentiment from tweets. In this survey paper, we have taken comparative study of different techniques and approaches of sentiment analysis having twitter as a data.
Membrane sweeping at term to promote spontaneous labour and reduce the likelihood of a formal induction of labour for postmaturity: a systematic review and meta-analysis

Abstract The aim of this study was to evaluate the efficacy and the safety of membrane sweeping in promoting spontaneous labour and reducing a formal induction of labour for postmaturity. Based on articles published between 2005 and 2016, 12 electronic databases were searched. Relative risk (RR) and its 95% confidence interval (CI) were used as pooled statistics. A total of seven studies consisting of 2252 participants were selected for the review and meta-analysis. The results revealed that membrane sweeping is advantageous in promoting spontaneous labour (RR = 1.205, 95% CI: 1.133–1.282, p = <.001), and reducing the formal induction of labour for postmaturity (RR = 0.523, 95% CI: 0.409–0.669, p = <.001). The studies reported several varying outcomes for both maternal and foetal morbidities; meta-analyses were performed where possible on each of these and found there to be no statistically significant differences in outcome between the intervention and control groups. Impact Statement What is already known on this subject? Research suggests that a pregnancy which exceeds 42 weeks of gestation is associated with an increased risk of perinatal morbidity and mortality (Gulmezoglu et al. 2012). Consequently, a formal induction of labour is usually offered to low-risk pregnant women between 41 and 42 weeks of pregnancy. However, all of the induction methods carry some degree of risk in terms of the associated morbidities and effectiveness (Cunningham 2005; Simpson and James 2008; Thomas et al. 2014), as well as having an impact on NHS resources (Department of Health 2015), and the birth experience of women (Gatward et al. 2010). For these reasons, it is currently recommended by The National Institute for Health and Care Excellence (NICE 2008) that women are offered a membrane sweep to promote spontaneous labour prior to arranging a formal induction of labour. What the results of this study add? The results from this meta-analysis add to the body of existing evidence around membrane sweeping. This study clearly demonstrates that membrane sweeping is effective in promoting a spontaneous labour and thereby reducing the need for a formal induction of labour. However, the results of this review suggest that this effect is significant from 38 weeks of gestation, and is not dependent upon the number or timing of membrane sweeps performed. What the implications are of these findings for clinical practice and/or further research? There is no evidence supporting any increase in maternal or foetal morbidity suggesting that membrane sweeping is a safe procedure to offer to all low risk pregnant women. We recommend therefore that there could be a reduction in the gestation at which membrane sweeping is offered from 40 weeks for primiparous women and 41 weeks for multiparous women to 38 weeks onwards for all low risk women without any increased risk of maternal or foetal morbidity. This may result in a decreased risk of requiring a formal induction of labour for postmaturity.
Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

Atrial fibrillation (AF) is commonly associated with heart failure. A bidirectional relationship exists between the two—AF exacerbates heart failure causing a significant increase in heart failure symptoms, admissions to hospital and cardiovascular death, while pathological remodeling of the atria as a result of heart failure increases the risk of AF. A comprehensive understanding of the pathophysiology of AF is essential if we are to break this vicious circle. In this review, the latest evidence will be presented showing a fundamental role for calcium in both the induction and maintenance of AF. After outlining atrial electrophysiology and calcium handling, the role of calcium-dependent afterdepolarizations and atrial repolarization alternans in triggering AF will be considered. The atrial response to rapid stimulation will be discussed, including the short-term protection from calcium overload in the form of calcium signaling silencing and the eventual progression to diastolic calcium leak causing afterdepolarizations and the development of an electrical substrate that perpetuates AF. The role of calcium in the bidirectional relationship between heart failure and AF will then be covered. The effects of heart failure on atrial calcium handling that promote AF will be reviewed, including effects on both atrial myocytes and the pulmonary veins, before the aspects of AF which exacerbate heart failure are discussed. Finally, the limitations of human and animal studies will be explored allowing contextualization of what are sometimes discordant results.
Integrating viability and fecundity selection to illuminate the adaptive nature of genetic clines

Genetically based trait variation across environmental gradients can reflect adaptation to local environments. However, natural populations that appear well‐adapted often exhibit directional, not stabilizing, selection on ecologically relevant traits. Temporal variation in the direction of selection could lead to stabilizing selection across multiple episodes of selection, which might be overlooked in short‐term studies that evaluate relationships of traits and fitness under only one set of conditions. Furthermore, nonrandom mortality prior to trait expression can bias inferences about trait evolution if viability selection opposes fecundity selection. Here, we leveraged fitness and trait data to test whether phenotypic clines are genetically based and adaptive, whether temporal variation in climate imposes stabilizing selection, and whether viability selection acts on adult phenotypes. We monitored transplants of the subalpine perennial forb, Boechera stricta (Brassicaceae), in common gardens at two elevations over 2–3 years that differed in drought intensity. We quantified viability, and fecundity fitness components for four heritable traits: specific leaf area, integrated water‐use efficiency, height at first flower, and flowering phenology. Our results indicate that genetic clines are maintained by selection, but their expression is context dependent, as they do not emerge in all environments. Moreover, selection varied spatially and temporally. Stabilizing selection was most pronounced when we integrated data across years. Finally, viability selection prior to trait expression targeted adult phenotypes (age and size at flowering). Indeed, viability selection for delayed flowering opposed fecundity selection for accelerated flowering; this result demonstrates that neglecting to account for viability selection could lead to inaccurate conclusions that populations are maladapted. Our results suggest that reconciling clinal trait variation with selection requires data collected across multiple spatial scales, time frames, and life‐history stages.