Miracle-dz/UniFAR-FTUs huggingface dataset:
Cis-2-Decenoic Acid Interacts with Bacterial Cell Membranes to Potentiate Additive and Synergistic Responses against Biofilm

Musculoskeletal infection is a major risk in all wounds, especially orthopaedic procedures such as implants or bone grafts. Morbidity due to implant-associated infections has increased and the need for therapeutic strategies to prevent them is growing. Biofilm dispersal agent, cis-2-decenoic Acid (C2DA) may be used in conjunction with a variety of antibiotics to potentiate synergistic, additive and antagonistic responses against orthopaedic pathogens. Results demonstrate that C2DA exhibits additive and synergistic effects with tetracycline, amikacin and ceftazidime against both gram positive and gram negative bacteria. Uptake of a fluorescent probe 1-N-phenylnaphthylamine by S. aureus was doubled and uptake by P. aeruginosa was increased by over eight fold when exposed to varying concentrations of C2DA. Leakage of intracellular ATP also increased up to three times control values with P. aeruginosa and over 280 times control value with S. aureus. This suggests that the mechanism of C2DA additive and synergistic effects with antibiotics is in part due to increasing membrane permeability, allowing increased uptake of additional antimicrobials.
Bui 1 State of Power Prediction for Lithium-Ion Batteries in Electric Vehicles via Wavelet-Markov

—Electric vehicle (EV) power demands come from its acceleration/braking as well as consumptions of the components. The power delivered to meet any demand is limited to the available power of the battery. This makes the battery state of available power (SoAP) a critical variable for battery management purposes. This paper presents a novel approach for long-term SoAP prediction by supervising the working conditions for prediction of future load. Firstly, a battery equivalent circuit model (ECM) coupled with a thermal model is established to accurately capture the battery dynamics. The battery model is then connected to an EV model in order to interpret the working conditions to battery power demand. By supervising the historical usage conditions, a long-term load prediction mechanism is designed based on wavelet analysis and Markov models. This facilitates the separation of low and high frequency load demands and addresses future uncertainties. Finally, the SoAP prediction is put forward along with a sensitivity analysis with respect to battery model and load prediction mechanism parameters. It is demonstrated that compared to the existing approaches for load and SoAP prediction, the developed method is more practical and accurate. Co-simulations via MATLAB and AMESim as well as experiments on a set of commercially available Lithium-ion (Li-ion) cylindrical cells under real-world drive cycles prove the given concept and validate the performance of the method.
Curcumin Blocks Cytokine-Mediated NF-κB Activation and Proinflammatory Gene Expression by Inhibiting Inhibitory Factor I-κB Kinase Activity

NF-κB plays a critical role in the transcriptional regulation of proinflammatory gene expression in various cells. Cytokine-mediated activation of NF-κB requires activation of various kinases, which ultimately leads to the phosphorylation and degradation of IκB, the NF-κB cytoplasmic inhibitor. The food derivative curcumin has been shown to inhibit NF-κB activity in some cell types. In this report we investigate the mechanism of action of curcumin on cytokine-induced proinflammatory gene expression using intestinal epithelial cells (IEC). Curcumin inhibited IL-1β-mediated ICAM-1 and IL-8 gene expression in IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-κB DNA binding activity, RelA nuclear translocation, IκBα degradation, IκB serine 32 phosphorylation, and IκB kinase (IKK) activity were blocked by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited by curcumin treatment. In addition, mitogen-activated protein kinase/ERK kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol 12-myristate 13-acetate-responsive element-driven luciferase expression were inhibited by curcumin. However, IκBα degradation induced by ectopically expressed NF-κB-inducing kinase or IKK was not inhibited by curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-κB-inducing kinase and IKK. We conclude that curcumin potently inhibits cytokine-mediated NF-κB activation by blocking a signal leading to IKK activity.
It Is All about Metabolic Fluxes

In the field of genomics there has been a move towards the development of novel experimental techniques that enable analysis of all components of a certain kind in a biological system, and this has resulted in the appearance of new methods for analyzing the omes. Obviously, in a given cellular system it is attractive to measure all the mRNAs, all the proteins, a large number of the metabolites, a large fraction of protein-protein or protein-DNA interactions, and so on, but a fundamental problem in functional genomics is integration of the information obtained, i.e., how this information can be integrated and lead to new insights into the functioning of cellular processes. Bioinformatics and advanced computer models are continuously supplying new methods for integration of data, and surely progress in the field of systems biology will eventually result in an ability to describe cellular functions in silico. In the race to obtain large amounts of data for phenotypic characterization of different cellular systems, a relatively simple experimental technique for quantitative determination of metabolic fluxes has escaped the attention of a large part of the biological research community; this technique has been used primarily by researchers in the field of metabolic engineering (1). The technique is based on relatively old principles from biochemistry, namely, feeding of specifically C-labeled substrates to the cell for characterization of the metabolism. However, with the development of the necessary mathematical framework for analysis of data obtained from this type of analysis it has become possible to obtain estimates for the fluxes in the different parts of the central carbon metabolism. This information is obviously interesting in connection with improving metabolite production by a given microbial cell, but as demonstrated in a paper in this issue of Journal of Bacteriology (11), it also provides a very powerful tool for functional analysis of different mutant cells. In this short commentary the use of this technique for functional analysis and the advantages and limitations of different techniques for flux quantification are discussed, and some of the underlying methods are reviewed, Finally, some future perspectives are given.
Prevalence of active trachoma and its associated factors among 1–9 years of age children from model and non-model kebeles in Dangila district, northwest Ethiopia

Background Trachoma is the leading infectious disease that leads to blindness worldwide, especially in developing countries. Though Ethiopia had targeted a trachoma elimination program by 2020, the problem worsens, particularly in the Amhara Region. Even though sustained intervention measures are undertaken across the region, it is unclear why trachoma is still a significant public health problem. So, this study assessed the prevalence of active trachoma and associated factors among 1–9 years of age children from model and non-model kebeles in Dangila district Amhara Region, Northwest Ethiopia. Methods A community-based comparative cross-sectional study was conducted from 20th September 2019 to 29th October 2019. A multistage stratified random sampling technique was used to reach 704 children from model and non-model kebeles. Samples were allocated proportionally to model and non-model kebeles. A structured and pretested data collection tool and observational checklist was used to manage the necessary data. Data were coded and entered in Epidata version 4.6, and further analysis was done using SPSS version 20 software. Bivariable and multivariable logistic regression analysis was employed to identify factors associated with active trachoma. Adjusted Odds Ratios (AOR), p-value, and respected Confidence Interval (CI) were used to report the findings. Results Seven hundred four children were included in this study, with a response rate of 97.8%. The overall prevalence of active trachoma was 6% (95% CI: 4.5, 8.1). The prevalence of active trachoma among non-model and model Kebele was not significantly different. Still, the prevalence of active trachoma among children from model Kebele were [4.5%, (95% CI: 2.4%, 7.1%)] relatively lower compared with non-model kebeles, [7.6%, 95% CI: (4.9%, 10.9%)]. Moreover, not using latrine (AOR = 4.29, 95% CI: 1.96, 9.34), fly-eye contact (AOR = 2.59, 95% CI: 1.11, 6.03), presence of sleep in eyes (AOR = 2.46, 95% CI: 1.10, 5.47), presence of ocular discharge (AOR = 2.79, 95% CI: 1.30, 6.00), presence of nasal discharges (AOR = 2.67, 95% CI: 1.21, 5.90) and washing faces with soap (AOR = 0.22, 95% CI: 0.07, 0.69) were found significantly associated with the prevalence of active trachoma among children 1–9 years old. Conclusions The prevalence of active trachoma in the model and non-model kebeles was high and did not show a statistical difference. Attention to be given to latrine utilization, washing face with soap, and other personal hygiene activities.
Strategic complements: Poverty-targeted subsidy programs show additive benefits on household toilet purchases in rural Cambodia when coupled with sanitation marketing

While poverty-targeted subsidies have shown promise as a means of reducing financial constraints on low-income populations to invest in new latrines, concerns have been raised about whether they may reduce demand for new latrines among non-eligible, non-poor populations, especially in geographically limited or closed markets. Using quasi experimental methods, we investigate the interaction effects of the “CHOBA” subsidy, a partial poverty-targeted monetary incentive to build a toilet, and a sanitation marketing program (SanMark) on new latrine uptake among households from different income segments in 110 rural villages across six Cambodian provinces. These programs were implemented either jointly with or independently. Overall, we find strong complementarity of the CHOBA subsidy with SanMark where the coupled implementation of the programs increased latrine uptake across all households as compared to exclusive deployment of the programs independently. Additionally, the CHOBA subsidy alone resulted in higher gains among the poor compared to SanMark suggesting that financial constraint is indeed a significant demand barrier for new latrines. The presence of the poverty-targeted subsidies did not reduce demand for new latrine purchases among ineligible households. Instead, we find some evidence for a positive spillover effect of subsidies on uptake of latrines among ineligible households in villages where both programs were implemented indicating that the presence of sanitation subsidies and the decision to purchase latrines among non-beneficiaries can be viewed as complements. We employ multivariate logistic regressions as well as further robustness checks to estimate the effects of the different interventions, with qualitatively consistent results.
Public engagement: Faculty lived experiences and perspectives underscore barriers and a changing culture in academia

The idea of faculty engaging in meaningful dialogue with different publics instead of simply communicating their research to interested audiences has gradually morphed from a novel concept to a mainstay within most parts of the academy. Given the wide variety of public engagement modalities, it may be unsurprising that we still lack a comprehensive and granular understanding of factors that influence faculty willingness to engage with public audiences. Those nuances are not always captured by quantitative surveys that rely on pre-determined categories to assess scholars’ willingness to engage. While closed-ended categories are useful to examine which factors influence the willingness to engage more than others, it is unlikely that pre-determined categories comprehensively represent the range of factors that undermine or encourage engagement, including perceptual influences, institutional barriers, and scholars’ lived experiences. To gain insight into these individual perspectives and lived experiences, we conducted focus group discussions with faculty members at a large midwestern land-grant university in the United States. Our findings provide context to previous studies of public engagement and suggest four themes for future research. These themes affirm the persistence of institutional barriers to engaging with the public, particularly the expectations in the promotion process for tenure-track faculty. However, we also find a perception that junior faculty and graduate students are challenging the status quo by introducing a new wave of attention to public engagement. This finding suggests a “trickle-up” effect through junior faculty and graduate students expecting institutional support for public engagement. Our findings highlight the need to consider how both top-down factors such as institutional expectations and bottom-up factors such as graduate student interest shape faculty members’ decisions to participate in public engagement activities.
Factor quinolinone inhibitors disrupt spindles and multiple LSF (TFCP2)-protein interactions in mitosis, including with microtubule-associated proteins

Factor quinolinone inhibitors (FQIs), a first-in-class set of small molecule inhibitors targeted to the transcription factor LSF (TFCP2), exhibit promising cancer chemotherapeutic properties. FQI1, the initial lead compound identified, unexpectedly induced a concentration-dependent delay in mitotic progression. Here, we show that FQI1 can rapidly and reversibly lead to mitotic arrest, even when added directly to mitotic cells, implying that FQI1-mediated mitotic defects are not transcriptionally based. Furthermore, treatment with FQIs resulted in a striking, concentration-dependent diminishment of spindle microtubules, accompanied by a concentration-dependent increase in multi-aster formation. Aberrant γ-tubulin localization was also observed. These phenotypes suggest that perturbation of spindle microtubules is the primary event leading to the mitotic delays upon FQI1 treatment. Previously, FQIs were shown to specifically inhibit not only LSF DNA-binding activity, which requires LSF oligomerization to tetramers, but also other specific LSF-protein interactions. Other transcription factors participate in mitosis through non-transcriptional means, and we recently reported that LSF directly binds α-tubulin and is present in purified cellular tubulin preparations. Consistent with a microtubule role for LSF, here we show that LSF enhanced the rate of tubulin polymerization in vitro, and FQI1 inhibited such polymerization. To probe whether the FQI1-mediated spindle abnormalities could result from inhibition of mitotic LSF-protein interactions, mass spectrometry was performed using as bait an inducible, tagged form of LSF that is biotinylated by endogenous enzymes. The global proteomics analysis yielded expected associations for a transcription factor, notably with RNA processing machinery, but also to nontranscriptional components. In particular, and consistent with spindle disruption due to FQI treatment, mitotic, FQI1-sensitive interactions were identified between the biotinylated LSF and microtubule-associated proteins that regulate spindle assembly, positioning, and dynamics, as well as centrosome-associated proteins. Probing the mitotic LSF interactome using small molecule inhibitors therefore supported a non-transcriptional role for LSF in mediating progression through mitosis.
Efficacy of Cabbage Leaf versus Cooling Gel Pad or Diclofenac Gel for Patients with Knee Osteoarthritis: A Randomized Open-Labeled Controlled Clinical Trial

Background Osteoarthritis (OA) is one of the most common joint degeneration ailments adversely affecting the elderly population by impairing their physical movements and quality of life. This study aimed to establish the efficacy of cabbage leaf application in alleviating pain-related distress and positively improving OA conditions. Materials and Methods Patients with moderate to severe (grades 3-4) OA by the Kellgren and Lawrence grading system with a poor to good Oxford Knee Score were selected for enrollment in this clinical trial. The participants were divided into three intervention groups: the cooling gel pad group for 20 minutes duration once a day (n = 20), the diclofenac gel group for 4 times a day (n = 20) as the control group (total n = 40), and the cabbage leaf group for 1-hour duration once a day (n = 20) as the experimental group (total n = 20). All trial participants were trained to record their Numerical Rating Scale (NRS) pain score and Oxford Knee Score and were advised to undergo weekly follow-ups and assessment of the outcome at 4 weeks. Data were analyzed by the paired t-test and analysis of variance (ANOVA). Results The cabbage leaf group and cooling gel pad group showed a significant difference in both the Oxford Knee Score (p < 0.001 in both groups) and NRS score (p < 0.001 in both groups) before and after the intervention, by using the paired t-test. The three study procedures were found to be significantly different with respect to both the Oxford Knee Score (p=0.012) and NRS score (p < 0.001), by using ANOVA. Conclusion This study clinically demonstrated that cabbage leaf application and cooling gel pad application showed similar improvements in reducing OA symptoms in terms of the overall NRS score and Oxford Knee Score. Their therapeutic effectiveness was better than that of diclofenac gel.
Penalties for industrial accidents: The impact of the Deepwater Horizon accident on BP’s reputation and stock market returns

Do visible industrial accidents damage firms’ reputations and depress their stock market returns, and do these penalties spill over to other firms in the industry? On April 20, 2010, the Deepwater Horizon offshore oil rig in the Gulf of Mexico leased by BP exploded and sank, causing 11 deaths and the largest marine oil spill in US history. We examine the impact of this accident on BP’s reputation and stock market performance using data from YouGov’s BrandIndex and Capital IQ’s financial data for the period 2007–2017. We employ a synthetic control analysis to examine the extent and duration of these penalties. We find that in the aftermath of the Deepwater accident, BP’s reputation declined by approximately 50% relative to the synthetic control, and this decline persisted through the end of 2017. Yet, in terms of financial market returns, though the stock price dropped drastically in the first two months, we do not find a statistically significant decline in the stock market returns either in the mid-term (1–2 years) or the long term (2–7 years). In terms of spillover effects, we find no evidence of reputational damage or a decline in stock market returns for other oil and gas firms. These findings suggest that while environmental accidents invite swift and lasting reputational penalties, they might not depress the stock market performance in the long run. Moreover, the impact either on reputation or stock market returns does not necessarily spill over to other firms in the same industry.
PR interval duration is associated with the presence of white matter hyperintensities: Insights from the epidemiologic LIFE-Adult Study

Background PR interval prolongation is a preliminary stage of atrial cardiomyopathy which is considered as an intermediate phenotype for atrial fibrillation (AF). AF is a known risk factor for cerebrovascular adverse outcomes including stroke. Cerebral ischemia is one cause of white matter hyperintensities (WMHs), and cognitive dysfunction. Aim To analyze the relationship between PR interval and WMHs. Materials and methods We performed a cross-sectional analysis with individuals from the LIFE-Adult-Study (a population-based cohort study of randomly selected individuals from Leipzig, Germany) with available brain MRI and ECG. The Fazekas stages were used to quantify WMHs (0 = none; 1 = punctate foci; 2 = beginning confluence; 3 = large confluent areas). Stages 2–3 were defined as advanced WMHs. The PR interval was measured from resting 12-lead ECG. PR duration >200ms was defined as PR interval prolongation. We used a binary logistic regression for statistical analysis. We examined the relationship between MRI and ECG measures and adjusted them for clinical risk factors. Results We included 2464 individuals (age 59±15 years, 47% women) into analyses. The median PR interval was 160ms (interquartile range 143–179), and 319 (13%) individuals with advanced WMHs, were significantly older, had more cardiovascular comorbidities and risk factors compared to individuals without WMHs (all p<0.005). On univariable analysis, PR interval duration (OR 1.01, 95%CI 1.01–1.02, p≤0.001) and PR interval ≥160 ms (OR 2.1, 95%CI 1.6–2.7, p≤0.001) were associated with advanced WMHs. In multivariable analysis, while PR interval duration was not associated with WMHs in the whole cohort, individuals with PR ≥160ms had higher risk for WMHs. Conclusion PR interval duration is associated with advanced WMHs beside advanced age, hypertension, and history of stroke. Further research is needed to determine whether changes in PR interval indices are clinically relevant for changes in WMHs.
Dokmegang, Joel and Nguyen, Hanh and Kardash, Elena and Savy, Thierry and Cavaliere, Matteo and Peyriéras, Nadine and Doursat, René (2021) Quantification of cell behaviors and computational modelling show that cell directional behaviors drive zebrafish pectoral fin

Motivation: Understanding the mechanisms by which the zebrafish pectoral fin develops is expected to produce insights on how vertebrate limbs grow from a 2D cell layer to a 3D structure. Two mechanisms have been proposed to drive limb morphogenesis in tetrapods: a growth-based morphogenesis with a higher proliferation rate at the distal tip of the limb bud than at the proximal side, and directed cell behaviors that include elongation, division and migration in a nonrandom manner. Based on quantitative experimental biological data at the level of individual cells in the whole developing organ, we test the conditions for the dynamics of pectoral fin early morphogenesis. Results: We found that during the development of the zebrafish pectoral fin, cells have a preferential elongation axis that gradually aligns along the proximodistal axis (PD) of the organ. Based on these quantitative observations, we build a center-based cell model enhanced with a polarity term and cell proliferation to simulate fin growth. Our simulations resulted in 3D fins similar in shape to the observed ones, suggesting that the existence of a preferential axis of cell polarization is essential to drive fin morphogenesis in zebrafish, as observed in the development of limbs in the mouse, but distal tip-based expansion is not. Availability: Upon publication, biological data will be available at http://bioemergences.eu/modelingFin, and source code at https://github.com/guijoe/MaSoFin. Contact: joel.dokmegang-kassap@stu.mmu. ac.uk, nadine.peyrieras@cnrs.fr or rene.doursat@iscpif.fr Supplementary information: Supplementary data are included in this manuscript.