bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1
Authors: Birgy André , Roussel Clement , Kemble Harry , Mullaert Jimmy , Panigoni Karine , Chapron Audrey , Magnan Mélanie , Jacquier Hervé , Cocco Simona , Monasson Rémi , Tenaillon Olivier 
Published: January 2022

Abstract

Epistasis affects genome evolution together with our ability to predict individual mutation effects. The mechanistic basis of epistasis remains, however, largely unknown. To quantify and better understand interactions between fitness-affecting mutations, we focus on a 11 amino-acid α-helix of the protein β-lactamase TEM-1, and build a comprehensive library of more than 15,000 double mutants. Analysis of the growth rates of these mutants shows pervasive epistasis, which can be largely explained by a non-linear two-state model, where inactivating, destabilizing, neutral, or stabilizing mutations additively contribute to the phenotype. Hence, most epistatic interactions can be predicted by a non-linear model informed by single-point mutational measurements only. Deviations from the two-state model are consistently found for few pairs of residues, in particular when they are in contact. This result, as well as single-point mutation parameters, can be quantitatively found back through direct-coupling-analysis-based statistical models inferred from homologous sequence data. Our results thus shed light on the existence and the origins of the multiple determinants of the epistatic landscape, even at the level of small structural components of a protein, and suggest that the corresponding constraints shape the entire β-lactamase family.
Leukocyte inflammatory phenotype and function in migraine patients compared with matched non-migraine volunteers: A pilot study
Authors: Li Hongtao , Fu Qiang , Philips Kamaira , Sun Yufei , Faurot Keturah R. , Gaylord Susan A. , Mann John Douglas 
Published: January 2022

Abstract
Background: Migraine is a neurological condition characterized by chronic inflammation. However, not much is known about the potential role of peripheral blood immune cells in the pathophysiology of migraine.Methods: We investigated the status of peripheral blood immune cells of 15 adults with frequent episodic migraines recruited chronologically from a Randomized Clinical Trial (RCT) on Nutrition for Migraine (NCCIH 5R01AT007813-05) and 15 non-migraine, healthy volunteers (control) matched by age, gender, and Body Mass Index (BMI).Continuous variables were presented as means ± standard deviation, and comparisons between patients and healthy volunteers were performed with paired sample t-tests. Statistical analysis was performed using SPSS Statistics for Window, Version 17.0 (SPSS Inc., Chicago, IL). Fluorescence-Activated Cell Sorting (FACS) data were processed using FlowJo software (Ashland, OR: Becton, Dickenson and Company; 2019).Results: We observed that migraineurs had significantly higher percentages of classical monocytes (CD14++CD16-) and a significantly lower percentage of non-classical monocytes (CD14+CD16++) in blood circulation, compared to the control group. And the mean fluorescence intensity (MFI) level of CD36 on monocyte was significantly lowered in the migraine group. Migraineurs also showed a significantly lower percentage of blood CD3+CD4+ helper T cells and CD4+CD25+ regulatory T cells, compared to controls. Both CD4+ and CD8+ T cells displayed lower expression (MFI) of integrin CD18 in migraineurs vs. controls.Conclusions: Our results demonstrated that migraine is associated with dysregulated peripheral immune homeostasis that may play a role in its pathophysiology.
Green Synthesis of rGO-AgNP Composite Using Curcubita Maxima Extract for Enhanced Photocatalytic Degradation of the Organophosphate Pesticide Chlorpyrifos
Authors: Chinnappa Karthik , Ananthai Punnaivalavan Karuna , Sriniva Pandi Prabha , Bai Caroline Dharmaraj Glory 
Published: January 2022

Abstract
Chlorpyrifos is a broad-spectrum organophosphate pesticide widely used for agricultural and non-agricultural applications that can highly intervene and impact with the ecosystem and affects both biotic and abiotic components. Photocatalytic degradation process using nanoparticles and nanocomposites are more fascinating as they are rapid and efficient than the existing other degradation routes. In this study, Curcubita maxima leaves are used as a novel source for green synthesis of reduced graphene oxide - silver composite in a single pot. Characterization of the novel phyto source driven composite was performed by UV-visible spectroscopy, Fourier transform infrared analysis, X-ray diffraction analysis and field emission scanning electron microscopic methods. The assessment of degradation effect of chlorpyrifos by the synthesized nanocomposite was performed. The photocatalytic activity of the composite was demonstrated through two different process as adsorption under room temperature and photocatalysis in the presence of sunlight. Different parameters such as pH, time, photocatalyst dose and pesticide concentration were optimized. The adsorption isotherms governing the photocatalytic adsorption process were investigated to predict the adsorption capacity of the synthesized nanocomposite. In addition, the results of antimicrobial activity of the nanocomposite against gram-positive, gram-negative bacteria and antifungal activity were also been found to be highly promising to utilize this composite for the removal of microbial contaminations in wastewater treatment.
Efficacy of Electromechanical-Assisted Gait Training on Walking Ability and Symmetry After Brain Injury: A Multicenter Randomized Controlled Trial
Authors: Nam Yeon-Gyo , Ko Mun jung , Bok Soo Kyung , Paik Nam-Jong , Lim Chi-Yeon , Lee Jin Won , Kwon Bum Sun 
Published: January 2022

Abstract
Background: Electromechanical-assisted gait training might be one of the most effective interventions to promote motor recovery after brain injury. But many studies still have difficulties to clarify the difference with conventional gait training.Objective: To evaluate the effectiveness of electromechanical-assisted gait training compared to conventional gait training on walking ability and symmetry in stroke patients.Methods: Patients with stroke (n = 144) were randomly assigned to control (physical therapist-assisted gait training) and experimental groups (electromechanical gait training). Both types of gait training were performed for 30 minutes each day, 5 days a week for 4 weeks. Main outcome measures are changes in functional ambulatory category (FAC). Secondary outcomes were walking abilities and walking symmetries of swing time and step length. Results: FAC showed significant improvement after 4 weeks intervention in both groups. Walking abilities showed significant improvement after intervention, but, walking symmetries did not in both groups. According to sub-group analysis of stroke duration of 90 days, FAC and walking abilities in both groups showed significant improvement in subacute group compared to chronic group. However, walking symmetries did not show any significant changes in subacute and chronic group. Swing time asymmetry in the experimental group showed significant improvement in chronic group while it did not in the control group.Conclusion: Electromechanical-assisted gait training by Exowalk® was shown to be as effective as conventional gait training with a physiotherapist. Electromechanical-assisted gait training for four weeks can change gait patterns close to normal by reducing swing time asymmetry in chronic stroke patients.Trial registration: KCT0003411 Clinical Research Information Service (CRIS), Republic of Korea.
The Use of Co-production, Co-design and Co-creation to Mobilise Knowledge in the Management of Health Conditions: A Systematic Review
Authors: Grindell Cheryl , Coates Elizabeth , Croot Liz , O’Cathain Alicia 
Published: January 2022

Abstract
Background Knowledge mobilisation is a term used in healthcare research to describe the process of generating, sharing and using evidence. ‘Co’approaches, such as co-production, co-design and co-creation, have been proposed as a way of overcoming the knowledge to practice gap. There is a need to understand why researchers choose to adopt these approaches, how they achieve knowledge mobilisation in the management of health conditions, and the extent to which knowledge mobilisation is accomplished. Methods Studies that explicitly used the terms co-production, co-design or co-creation to mobilise knowledge in the management of health conditions were included. Web of Science, EMBASE via OvidSP, MEDLINE via OvidSP and CINHAL via EBSCO databases were searched up to April 2021. Quality assessment was carried out using the Joanna Briggs Institute qualitative quality assessment checklist. Pluye and Hong’s seven steps for mixed studies reviews were followed. Data were synthesised using thematic synthesis. Results 24 international studies were included. These were qualitative studies, case studies and study protocols. Key aspects of ‘co’approaches were bringing people together as active and equal partners, valuing all types of knowledge, using creative approaches to understand and solve problems, and using iterative prototyping techniques. Authors articulated mechanisms of action that included developing a shared understanding, identifying and meeting needs, giving everyone a voice and sense of ownership, and creating trust and confidence. They believed these mechanisms could produce interventions that were relevant and acceptable to stakeholders, more useable and more likely to be implemented in healthcare. Varied activities were used to promote these mechanisms such as interviews and creative workshops. There appeared to be a lack of robust evaluation of the interventions produced so little evidence in this review that ‘co’approaches improved the management of health conditions. Conclusion Those using ‘co’approaches believed that they could achieve knowledge mobilisation through a number of mechanisms, but there was no evidence that these led to improved health. The framework of key aspects and mechanisms of ‘co’approaches developed here may help researchers to meet the principles of these approaches. There is a need for robust evaluation to identify whether ‘co’approaches produce improved health outcomes. Registration: PROSPERO CRD42020187463
IMPLANT: a new technique for transgene copy number estimation in plants using a single end-point PCR reaction
Authors: De Saeger Jonas , Park Jihae , Thoris Kai , Chung Hoo Sun , Inzé Dirk , Depuydt Stephen 
Published: January 2022

Abstract
Background

Copy number determination is one of the first steps in the characterization of transgenic plant lines. The classical approach to this, Southern blotting, is time-consuming, expensive and requires massive amounts of high-quality genomic DNA. Other PCR-based techniques are either inaccurate, laborious, or expensive.
Results
Here, we propose a new technique, IMPLANT (Insertion of competitive PCR calibrator for copy number estimation), a competitive PCR-based technique in which the competitor (based on an endogenous gene) is also incorporated in the T-DNA, which then gets integrated in the genome together with the gene of interest. As the number of integrated competitor molecules directly corresponds to the number of transgene copies, the transgene copy number can be determined by a single PCR reaction. We demonstrate that the results of this technique closely correspond with those obtained by segregation analysis in Arabidopsis and digital PCR In rice, indicating that it is a powerful alternative for other techniques for copy number determination.
Conclusions

We show that this technique is not only reliable, but is also faster, easier, and cheaper as compared with other techniques. Accurate results are obtained in both Arabidopsis and rice, but this technique can be easily extended to other organisms and as such can be widely adopted in the field of biotechnology.
CYP19A1 Is Regulated by BRD4 and Suppresses Castration-resistant Prostate Cancer Cell Invasion and Proliferation by Decreasing AR Expression
Authors: Chen Xi , Xu Chengdang , Wang Xinan , Yao Yicong , Wu Gnag , Wu Denglong 
Published: January 2022

Abstract
BackgroundCastration-resistant prostate cancer (CRPC) is the final stage of prostate cancer (PCa). Thus far, there is no effective method for CRPC treatment. Androgen and androgen receptor (AR) play a vital role in CRPC occurrence and drug tolerance. Testosterone is the main androgen in males. CYP19A1 can encode aromatase, a key enzyme that can catalyze the conversion of testosterone to estrogen, and may affect both androgen and AR. CYP19A1 may play a role in the occurrence of CRPC; however, the function of CYP19A1 in CRPC remain unclear.MethodsUsing data from public databases and clinical samples, we analyzed the expression of CYP19A1 in PCa and CRPC specimens. In addition, the influence of CYP19A1 on cell invasion and proliferation was detected in vivo and vitro. The affect of BRD4 on CYP19A1 and AR was detected by qRT-PCR and western blot experiments.ResultsWe found that CYP19A1 was downregulated in CRPC samples and cells. CYP19A1 overexpression decreased CRPC cell invasion and proliferation. In addition, CYP19A1 expression was negatively correlated with AR expression. CYP19A1 affected CRPC cell invasion and proliferation ability by suppressing the expression of AR, and this may be attributed to the metabolism of testosterone by CYP19A1. Moreover, the BRD4 inhibitor-JQ1 induced the expression of CYP19A1 and suppressed the expression of AR. Following BRD4 knockdown, CYP19A1 showed a higher expression level, and, AR expression was decreased. ConclusionsIn conclusion, our findings demonstrated that CYP19A1 could reduce CRPC cell invasion and proliferation by targeting AR, and this process could be regulated by BRD4. The BRD4-CYP19A1-AR pathway may be a potential cause of CRPC occurrence. Therefore, CYP19A1 may be a potential therapeutic target for treating CRPC.
Pan-Cancer Analysis Based on Gene Mutation and Epigenetic Modification Explains The Value of HJURP in The Tumor Microenvironment
Authors: Li Junwu , Zhang Ronggui , Zhang Weili , Zhang Junyong , Zheng Jun , Zhang Yuanfeng 
Published: January 2022

Abstract
Objective: To analyze expression levels, prognostic value and immune infiltration association of Holliday junction protein (HJURP) as well as its feasibility as a pan-cancer biomarker for different cancers. Methods: The Protter online tool was utilized to obtain the protein structure and localization of HJURP in diverse tumors, then the mutation and methylation of HJURP in tumors were further explored. Thereafter, the mRNA data and clinical characteristics of 33 tumor types from TCGA database were obtained for investigating HJURP levels within different tumor types and different tumor stages and its prognostic relation. Finally, the composition pattern and immune infiltration of HJURP in different tumors were detected in Tumor Immune Estimation Resource. Results: HJURP was abnormally expressed in most of the cancer types and subtypes in TCGA database. Also, it was related to metastasis, tumor stage, and poor prognosis of different cohorts. Moreover, HJURP was related to tumor immune escape through diverse mechanisms, including T cell rejection and methylation within diverse cancers. Besides, the methylation of HJURP was inversely proportional to mRNA expression levels, which mediated the dysfunctional phenotypes of T cells and poor prognosis of different cancer types. Patients with HJURP mutations had a higher tumor mutation load than those with no HJURP mutations. Alternatively, based on this work, HJURP level was related to immune cell infiltration within diverse cancers. Conclusions: HJURP may serve as an oncogenic molecule, and its expression and immune infiltration characteristics can be used as the diagnostic, prognostic marker and therapeutic target.
Effect of Black Seeds (Nigella sativa) on Inflammatory and Immunomodulatory Markers in Plasmodium berghei-Infected Mice
Authors: Ojueromi Opeyemi Oluwafemi , Oboh Ganiyu , Ademosun Ayokunle 
Published: January 2022

Abstract
N.sativa, a core dietary supplement and food additive in folklore is one of the most broadly studied seed plants in the global nutraceutical sector. Malaria infection impairs the ability of principal cells of the immune system to trigger an efficient inflammatory and immune response. Ninety-six mice weighing (20-25g) were grouped into twelve consisting of eight animals each. The mice were infected with standard inoculum of the strain NK65 P.berghei (chloroquine sensitive) and the percentage parasitemia suppression were evaluated. The individual effect of black seed supplemented diet and its combinatory effect with chloroquine (CQ) were investigated on the glutathione peroxidase(GPx), reduced glutathione(GSH), glutathione-S-transferase (GST), serum immunoglobulins (IgG and IgM), and the hematological parameters (haemoglobin, packed cell volume and red blood cell count) in P.berghei infected mice. The inflammatory cytokines; Tumor necrosis factor (TNF-α), C-reactive protein (CRP), Interleukin (IL-6 and IL-10) as well as IgG and IgM were assayed in the serum. The mice temperature and behavioural changes were observed. Infected mice treated with the dietary supplementation of black seed with a percentage inclusion (2.5%, 5% and 10%) showed significantly decreased parasitemia levels (p<0.05) compared with the untreated mice. The result demonstrated a significant suppression in the pro-inflammatory cytokines (TNF-α, CRP, IL-6) levels and a notable elevation in the anti- inflammatory cytokine (IL-10), antioxidant markers as well as the immunoglobulin levels of the P.berghei-infected mice treated with black seed. The study revealed that black seed enhanced host antioxidant status, modulated inflammatory and immune response by regulating some inflammatory cytokines and immunomodulatory mediators.
Modified Pseudo-Dynamic Bearing Capacity of Shallow Foundations Subjected to Inclined-Eccentric Combined Loading
Authors: Tavakoli Maedeh Akhavan , Fathipour Hessam , Payan Meghdad , Chenari Reza Jamshidi , Ahmadi Hadi 
Published: January 2022

Abstract
Shallow foundations are commonly subjected to simultaneous inclined and eccentric combined loadings exerted by the overlying superstructure and geo-environmental sources. The performance of such footings in seismic-prone areas is a topic of great interest in geotechnical engineering practice. In this paper, a comprehensive parametric study is conducted to evaluate the seismic bearing capacity of shallow strip foundations overlying dry and cohesionless granular soil under the action of vertical-horizontal-moment combined loading. For this purpose, a systematic combination of the lower-bound theorems of the limit analysis, the finite element method, and the nonlinear programming is implemented. The second-order cone programming (SOCP) is adopted for efficient optimization purposes so as to model the actual nonlinear form of the universal Mohr-Coulomb yield function. In addition, the equilibrium equations associated with the combined loading are incorporated into the lower bound formulations. The seismic condition is simulated by the well-established modified pseudo-dynamic approach by accounting for the significant influence of phase difference as well as the primary and shear waves propagation through applying non-uniform inertia forces along the vertical and horizontal directions, respectively. The employed formulations are rigorously validated against a majority of high-quality studies in the literature in the static combined loading condition. The results of the seismic bearing capacity are presented in the forms of spectral responses and failure envelopes for the eccentric and inclined loadings. Accordingly, the influences of non-dimensional frequency, induced seismic acceleration and material damping on the ultimate bearing capacity of eccentrically and obliquely loaded strip footings are thoroughly examined and discussed. The results show that the most critical responses of the shallow foundation are captured in the resonance condition of earthquake excitation. As the seismic intensity decreases and the damping ratio increases, the spectral vertical, horizontal and moment bearing capacities of surface footings become smoother. In addition, the failure envelopes of the shallow foundation subjected to either inclined or eccentric loading significantly shrink with the increase in the earthquake accelerations and decrease in the material damping of the underlying soil mass. The amount of changes in the size of failure envelopes in the normalized V - H and V - M spaces due to the variation of seismic intensity and material damping depends directly on the non-dimensional frequency of the earthquake excitation.
Bacillus siamensis I7B strain as heavy metal quencher and probiotics; isolated from gut of Stolepherous commersonni
Authors: Selta Daniel Raja Femil , BS SABNA , MAHENDRAN RAMASAMY , THANKAPPAN BENCY , MUTHUSAMY GAYATHRI , BALASUBRAMANIAN VINOTH , JAYARAMAN ANGAYARKANNI , kavitha Rangasamy 
Published: January 2022

Abstract
Probiotic products have been administered in food, medicine, dairy and fermentation industry to enhance the beneficial functions in the host. In the present study gut bacteria of stolepherous commersonnii have been isolated and subjected to screening for heavy metal resistance. A potent heavy metal resistant bacterial strain of gut microbiota was subjected to assessment for its probiotic and antioxidant potential. Four bacterial strains namely I7A, I7B, I7C, and I8 were isolated and the strain I7B showed heavy metal resistant potential (upto 20 mg/ml of Cr, Cr, and Pb). The strain I7B showed high sensitivity to Streptomycin (10 μg), low sensitivity to Rifampin (5 μg) and resistant to pencillin (2 μg, 10 μg). Atomic absorption spectrometry studies showed that the I7B strain possess maximum heavy metal (Cu) removal ability of 81.64 % in textile dye effluent and the strain was identified as Bacillus siamensis by 16S rRNA gene sequencing studies. Hence I7B strain was named as Bacillus siamensis I7B and has been submitted in NCBI with accession number MN404539. Bacillus siamensis 17B strain possess high acid tolerance (90.9 %), high bile tolerance (96.9 %) and nonhemolytic. The17B strain showed auto aggregation (28±0.011%) and coaggregation potential (27±0.16 %) which could be a feasible characteristic of potent probiotic strain. Cell free Supernatant of Bacillus siamensis I7B strain possess good DPPH free radical scavenging ability (59.43±0.002 %) and moderate hydroxyl radical scavenging ability (27.6±0.010 %). Biopreservation effect of Bacillus siamensis I7B strain on tomato puree showed 72 % growth inhibition against A. niger for 15 days.
Toughness improvement of epoxy composites using a kind of environment-friendly bio-based polyester polyol
Authors: Shang Xinyu , Xue Lei , Zhang Yanhua 
Published: January 2022

Abstract
Epoxy resin (EP) is a thermosetting resin with prominent performances and wide applications. However, the inherent brittleness limits its development in the engineering materials area. A liquid bio-based polyester polyol (LLP) with flexible long chains was synthesized in this study by melt polycondensation of corn straw lignin. After being compounded with EP (LLP/EP), the mechanical property, micromorphology and thermal behavior of the composite were evaluated. The experimental result indicated that the fracture brittleness of EP composite was decreased by importing the LLP. The bending and impact strength were up to 113.67 MPa and 51.29 kJ/m2 for 10%-LLP/EP, which were 5.25% and 27% higher than those of unmodified EP. The results of this work build new avenues for the efficient utilization of lignin and the development of low-cost, high-performance and well environmentally adaptable EP composite by renewable resources.