Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid typing of Bacillus subtilis strains by their secondary metabolites using matrix‐assisted laser desorption/ionization mass spectrometry of intact cells

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOFMS) has been used for rapid and efficient typing of Bacillus subtilis strains according to their secondary metabolite products using whole intact cells as targets. Cells were grown either in liquid media or on agar plates, respectively. Strains were classified by their unique spectra of bioactive peptides in the m/z range from 500 to 5000. The lipopeptide products surfactin, fengycin and the members of the iturin family were structurally characterized in situ by post-source decay (PSD) analysis. The potential of MALDI-MS for taxonomic studies, as well as for the investigation of the regulation and compartimentalization of secondary metabolites in the bacterial cell, is demonstrated. These achievements qualify this methodology for rapid screening of microorganisms to exploit bioactive compounds for biotechnological and pharmaceutical applications. Copyright © 1999 John Wiley & Sons, Ltd.
Relation Regularized Scene Graph Generation

Scene graph generation (SGG) is built on top of detected objects to predict object pairwise visual relations for describing the image content abstraction. Existing works have revealed that if the links between objects are given as prior knowledge, the performance of SGG is significantly improved. Inspired by this observation, in this article, we propose a relation regularized network (R2-Net), which can predict whether there is a relationship between two objects and encode this relation into object feature refinement and better SGG. Specifically, we first construct an affinity matrix among detected objects to represent the probability of a relationship between two objects. Graph convolution networks (GCNs) over this relation affinity matrix are then used as object encoders, producing relation-regularized representations of objects. With these relation-regularized features, our R2-Net can effectively refine object labels and generate scene graphs. Extensive experiments are conducted on the visual genome dataset for three SGG tasks (i.e., predicate classification, scene graph classification, and scene graph detection), demonstrating the effectiveness of our proposed method. Ablation studies also verify the key roles of our proposed components in performance improvement.
Clinical features and outcome of Streptococcus agalactiae bone and joint infections over a 6-year period in a French university hospital

Background Bone and joint infections (BJIs) due to Streptococcus agalactiae are rare but has been described to increase in the past few years. The objective of this study was to describe clinical features and outcomes of cases of S. BJIs. Methods We conducted a retrospective analysis of adult cases of S. agalactiae BJIs that occurred between January 2009 and June 2015 in a French university hospital. The treatment success was assessed until 24 months after the end of antibiotic treatment. Results Among the 26 patients included, 20 (77%) were male, mean age was 62 years ± 13 and mean Charlson comorbidity index score was 4.9 ± 3.2. Diabetes mellitus was the most common comorbidity (n = 14, 54%). Six had PJI (Prosthetic Joint Infections), five osteosynthesis-associated infections, 11 osteomyelitis and four native septic arthritis. Eleven patients had a delayed or late infection: six with a prosthetic joint infection and five with an internal fixation device infection. Sixteen patients (62%) had a polymicrobial BJI, most commonly with Gram-positive cocci (75%) notably Staphylococcus aureus (44%). Polymicrobial infections were more frequently found in foot infections (90% vs 44%, p = 0.0184). During the two-year follow-up, three patients died (3/25, 12%) and seven (7/25, 28%) had treatment failure. Conclusion Diabetes mellitus was the most common comorbidity. We observed an heterogenous management and a high rate of relapse.
Racial and ethnic differences in cognitive health appraisals: a comparison of non-Hispanic White, non-Hispanic Black, and Hispanic older adults

Abstract Objectives To investigate the relationship between cognitive performance and cognitive health appraisals across non-Hispanic White, non-Hispanic Black, and Hispanic older adults in the United States and to explore within-group variations by examining interactions between cognitive performance and background and health variables. Method The sample (N = 3,099) included 2,260 non-Hispanic White, 498 non-Hispanic Black, and 341 Hispanic adults aged 65 or older, from the 2016–2017 Harmonized Cognitive Assessment Protocol. Regression models of cognitive health appraisals, indicated by self-rated cognitive health, were examined in the entire sample and in racial and ethnic subgroups to test direct and interactive effects of cognitive performance, indicated by the Mini-Mental State Examination (MMSE). Results The regression model for the entire sample showed direct effects of cognitive performance and race/ethnicity on cognitive health appraisals, as well as a significant interaction between cognitive performance and being non-Hispanic Black. Cognitive performance and cognitive health appraisals were positively associated in non-Hispanic Whites but not significantly associated in non-Hispanic Blacks. Our subsequent analysis within each racial/ethnic group showed that the effect of cognitive performance in non-Hispanic Blacks and Hispanics became either reversed or nonsignificant when background and health variables were considered. Modification by age or chronic medical conditions in each racial and ethnic group was also observed. Conclusion Overall, these findings suggest that perceptions and appraisals of cognitive health vary by race and ethnicity and hold implications for how these differences should be considered in research and practice with diverse groups of older adults.
Limitations of animal epilepsy research models: Can epileptic human tissue provide translational benefit?

Advancement of understanding the etiology and treatment of epilepsy has largely depended on the use of acute and chronic animal models. An alternative approach, which is being increasingly used by a select number of laboratories worldwide, is to make functional mechanistic studies in brain slices of living human tissue, resected during surgery for drug resistant epilepsies. Pharmacoresistant epilepsy is a major clinical problem with a significant proportion of patients not receiving any symptomatic benefit from available anti-epileptic drugs. Animal models of epilepsy have dominated the landscape with regard to research and development, however they have failed to deliver new agents that would provide seizure control in patients with drug refractory epilepsy. Moreover, these models have considerable issues with respect to validity and animal welfare considerations. A compelling alternative is the use of live human epileptic tissue which recapitulates a number of key features of refractory epilepsy. The use of live epileptic human tissue offers unprecedented opportunities to understand the mechanisms associated with difficult to treat epilepsy whilst also permitting studies of efficacy of novel agents that are being developed to alleviate epilepsy in drug resistant patients.
Does education of primary care professionals promote patient self-management and improve outcomes in chronic disease? An updated systematic review

Background Primary care has a vital role in supporting patient autonomy to enable people with long-term conditions to manage their own health and wellness. Evidence is needed on whether education and training of health professionals helps support patient self-management and improves outcomes. The authors' first systematic review included only two articles showing patient outcomes following health professional training for promoting patient self-management. Aim To present an updated review undertaken from September 2013 to August 2018. Design & setting A systematic review was undertaken using the PRISMA guidelines, following the methodology of the first review and is outlined in the PROSPERO registered protocol. Method Six databases were searched — Cochrane Library, PubMed, ERIC, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO — in addition to web searches, hand searches, and bibliographies for articles published from 1 September 2013 to 31 August 2018. Results The updated systematic review showed more evidence is now available with 18 articles in the 5-year period from the 4284 abstracts located. Twelve of these articles showed a difference between intervention and control groups. Of the 18 articles identified, 11 were assessed as having a low risk of bias and five overall were rated of weak quality. The educational interventions with health professionals spanned a range of techniques and modalities, and many incorporated multiple interventions including patient components. There may be a lack of adoption owing to several challenges, including that complex interventions may not be delivered as planned and are difficult to assess, and owing to patient engagement and the need for ongoing follow-up. Conclusion More high-quality research is needed on what methods work best, for which patients, and for what clinical conditions in the primary care setting. The practical implications of training healthcare professionals require specific attention.
Induction of Apoptosis in Hepatocellular Carcinoma Cell Lines by Novel Indolylacrylamide Derivatives: Synthesis and Biological Evaluation

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and one of the leading causes of cancer associated death worldwide. This is due to the highly resistant nature of this malignancy and the lack of effective treatment options for advanced stage HCC patients. The hyperactivity of PI3K/Akt and Ras/Raf/MEK/ERK signaling pathways contribute to the cancer progression, survival, motility, and resistance mechanisms, and the interaction of these two pathways are responsible for the regulation of cancer cell growth and development. Therefore, it is vital to design and develop novel therapeutic options for HCC treatment targeting these hyperactive pathways. For this purpose, novel series of trans‐indole‐3‐ylacrylamide derivatives originated from the lead compound, 3‐(1H‐indole‐3‐yl)‐N‐(3,4,5‐trimethoxyphenyl)acrylamide, have been synthesized and analyzed for their bioactivity on cancer cells along with the lead compound. Based on the initial screening, the most potent compounds were selected to elucidate their effects on cellular signaling activity of HCC cell lines. Cell cycle analysis, immunofluorescence, and Western blot analysis revealed that lead compound and (E)‐N‐(4‐tert‐butylphenyl)‐3‐(1H‐indole‐3‐yl)acrylamide induced cell cycle arrest at the G2/M phase, enhanced chromatin condensation and PARP‐cleavage, addressing induction of apoptotic cell death. Additionally, these compounds decreased the activity of ERK signaling pathway, where phosphorylated ERK1/2 and c‐Jun protein levels diminished significantly. Relevant to these findings, the lead compound was able to inhibit tubulin polymerization as well. To conclude, the novel trans‐indole‐3‐ylacrylamide derivatives inhibit one of the critical pathways associated with HCC which results in cell cycle arrest and apoptosis in HCC cell lines.
High precision numerical estimates of acoustic phonon frequencies of nonspherical nanoparticles

We introduce an adapted method for calculating the acoustic vibrational frequencies of arbitrarily shaped nanoparticles to high precision. Molecular dynamics simulation results are tested against exact solutions for a free sphere, a hollow sphere and a spheroid. This permits theoretical predictions of the frequencies of peaks in low frequency Raman spectra. Our results demonstrate that vibrational frequencies can be calculated for a wide range of low frequency modes with accuracies on the order of a tenth of a percent.
Natural Transformation in a Classical-Biotype Vibrio cholerae Strain

Natural transformation (uptake of exogenous DNA) in Vibrio cholerae has contributed to the evolution of these human pathogens. Classical biotype V. cholerae strains were responsible for the first six cholera pandemics but were replaced by El Tor biotype V. cholerae in the current pandemic. ABSTRACT Vibrio cholerae causes the gastrointestinal illness cholera, which spreads throughout the globe in large pandemics. The current pandemic is caused by O1 El Tor biotype strains, whereas previous pandemics were caused by O1 classical biotype strains. El Tor V. cholerae is noted for its ability to acquire exogenous DNA through chitin-induced natural transformation, which has been exploited for genetic manipulation of El Tor strains in the laboratory. In contrast, the prototypical classical strain O395 lacks this ability, which was suspected to be due to a mutation in the regulatory gene hapR. HapR and the regulator TfoX control expression of a third competence regulator, QstR. We found that artificial induction of both TfoX and QstR in the presence of HapR in O395 was required for efficient DNA uptake. However, natural transformation in the classical strain is still orders of magnitude below that of an El Tor strain. O395 expressing HapR could also undergo natural transformation after growth on chitin, which could be increased by artificial induction of TfoX and/or QstR. A plasmid that expresses both TfoX and QstR was created that allowed for consistent DNA uptake in O395 carrying a hapR plasmid. This technique was also used to facilitate cotransformation into O395 of unmarked DNA (ΔlacZ, ΔflaA, ΔflgG) for multiplex genome editing by natural transformation (MuGENT). These results demonstrate that the classical biotype O395 strain is functionally capable of DNA uptake, which allows for the rapid genetic manipulation of its genome. IMPORTANCE Natural transformation (uptake of exogenous DNA) in Vibrio cholerae has contributed to the evolution of these human pathogens. Classical biotype V. cholerae strains were responsible for the first six cholera pandemics but were replaced by El Tor biotype V. cholerae in the current pandemic. This study demonstrates that classical V. cholerae is functionally capable of natural transformation, but inactivation of the transformation regulator HapR and inherent levels of transformation that are lower than those of El Tor V. cholerae suggest that the classical biotype may be less able to utilize natural transformation for horizontal gene transfer.
Evolution of eggshell structure in relation to nesting ecology in non‐avian reptiles

Amniotic eggs are multifunctional structures that enabled early tetrapods to colonize the land millions of years ago, and are now the reproductive mode of over 70% of all terrestrial amniotes. Eggshell morphology is at the core of animal survival, mediating the interactions between embryos and their environment, and has evolved into a massive diversity of forms and functions in modern reptiles. These functions are critical to embryonic survival and may serve as models for new antimicrobial and/or breathable membranes. However, we still lack critical data on the basic structural and functional properties of eggs, particularly of reptiles. Here, we first characterized egg shape, shell thickness, porosity, and mineralization of eggs from 91 reptile species using optical images, scanning electron microscopy, and micro computed tomography, and collected data on nesting ecology from the literature. We then used comparative analyses to test hypotheses on the selective pressures driving their evolution. We hypothesized that eggshell morphology has evolved to protect shells from physical damage and desiccation, and, in support, found a positive relationship between thickness and precipitation, and a negative relationship between porosity and temperature. Although mineralization varied extensively, it was not correlated with nesting ecology variables. Ancestral state reconstructions show thinning and increased porosity over evolutionary time in squamates, but the opposite in turtles and crocodilians. Egg shape, size, porosity and calcification were correlated, suggesting potential structural or developmental tradeoffs. This study provides new data and insights into the morphology and evolution of reptile eggs, and raises numerous questions for additional research.
Molecular Force Measurement with Tension Sensors.

The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. In this review, we discuss the physical principles, advantages, and limitations of this increasingly popular method. By highlighting current examples from the literature, we demonstrate how molecular tension sensors can be utilized to obtain access to previously unappreciated biophysical parameters that define the propagation of mechanical forces on molecular scales. We discuss how the methodology can be further developed and provide a perspective on how the technique could be applied to uncover entirely novel aspects of mechanobiology in the future. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Multiplexing physical stimulation on single human induced pluripotent stem cell-derived cardiomyocytes for phenotype modulation

Traditional in vitro bioengineering approaches whereby only individual biophysical cues are manipulated at any one time are highly inefficient, falling short when recapitulating the complexity of the cardiac environment. Multiple biophysical cues are present in the native myocardial niche and are essential during development, as well as in maintenance of adult cardiomyocyte (CM) phenotype in both health and disease. This study establishes a novel biofabrication workflow to study and manipulate hiPSC-CMs and to understand how these cells respond to a multiplexed biophysical environment, namely 3D shape and substrate stiffness, at a single cell level. Silicon masters were fabricated and developed to generate inverse patterns of the desired 3D shapes in bas relief, which then were used to mold the designed microwell arrays into a hydrogel. Polyacrylamide (PAAm) was modified with the incorporation of acrylic acid to provide a carboxylic group conjugation site for adhesion motifs, without compromising capacity to modulate stiffness. In this manner, two individual parameters can be finely tuned independently within the hydrogel: the shape of the 3D microwell and its stiffness. The design allows the platform to isolate single hiPSC-CMs to study solely biophysical cues in the absence of cell-cell physical interaction. Under physiologic-like physical conditions (3D shape resembling that of adult CM and 9.83 kPa substrate stiffness that mimics muscle stiffness), isolated single hiPSC-CMs exhibit increased Cx-43 density, cell membrane stiffness and calcium transient amplitude; co-expression of the subpopulation-related MYL2-MYL7 proteins; and higher anisotropism than cells in pathologic-like conditions (flat surface and 112 kPa substrate stiffness). This demonstrates that supplying a physiologic or pathologic microenvironment to an isolated single hiPSC-CM in the absence of any physical cell-to-cell communication in this biofabricated platform leads to a significantly different set of cellular features, thus presenting a differential phenotype. Importantly, this demonstrates the high plasticity of hiPSC-CMs even in isolation. The ability of multiple biophysical cues to significantly influence isolated single hiPSC-CM phenotype and functionality highlights the importance of fine-tuning such cues for specific applications. This has the potential to produce more fit-for-purpose hiPSC-CMs. Further understanding of human cardiac development is enabled by the robust, versatile and reproducible biofabrication techniques applied here. We envision that this system could be easily applied to other tissues and cell types where the influence of cellular shape and stiffness of the surrounding environment is hypothesized to play an important role in physiology.
Optical properties of irregularly shaped particles

The phase matrix of irregularly shaped randomly oriented large fractal particles is studied in the framework of the ray tracing approach for various refractive indices. The fractal particle model can be used for modelling local optical characteristics of various natural light scattering media with irregular particles, including oceanic water, crystalline clouds and solid aerosols. For nonabsorbing large particles the theory does not contain any fitting parameters except the refractive index of particles, which is either known (ice clouds) or has generally unknown distribution in a local volume of a scattering medium (dust aerosols and oceanic suspensions).
Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo

The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti‐senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of “cellular aging”: the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.