bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse mechanisms control amino acid-dependent environmental alkalization byCandida albicans
Authors: Silao Fitz Gerald S. , Valeriano Valerie Diane , Uddström Erika , Falconer Emilie , Ljungdahl Per O. 
Published: August 2023

AbstractCandida albicanshas the remarkable capacity to neutralize acidic growth environments by releasing ammonia derived from the catabolism of amino acids. The molecular components and mechanisms controlling this capacity remain poorly understood. Here, we present an integrative model with the cytosolic NAD+-dependent glutamate dehydrogenase (Gdh2) as the principal component. We show that the alkalization defect of a strain lacking the SPS-sensor regulated transcription factorSTP2is due to the inability to fully derepressGDH2and the two proline catabolic enzymes,PUT1andPUT2. Notably, the Stp2-dependent regulation ofPUT1andPUT2occurs independent of Put3, the proline-dependent activator. Accordingly, astp2-/– put3-/-strain is unable to derepress the expression of these enzymes resulting in a severe alkalization defect that nearly phenocopies the abrogated alkalization of agdh2-/-strain. In wildtype cells, alkalization is tightly dependent on mitochondrial activity and occurs as long as conditions permit respiratory growth. As alkalization proceeds, Gdh2 levels decrease and glutamate is transiently extruded from cells. Together these two processes constitute a rudimentary regulatory system enabling cells to prevent the rapid intracellular build-up of ammonia. Similar toC. albicans, Gdh2-dependent alkalization is dispensable forC. glabrataandC. aurisvirulence as assessed using a whole-blood infection model. Intriguingly, fungal-dependent alkalization does not influence the growth or proliferation ofLactobacillus crispatus, a potent antagonist ofC. albicansthat normally resides in the acidic vaginal microenvironment. Our data suggest that it is time to reconsider the idea that pH modulation driven by pathogenic fungi plays a crucial role in shaping the architecture and dynamics of (poly)microbial communities. Other factors are likely to be more critical in contributing to dysbiosis and that favor virulent growth.
Label-free citrate-stabilized silver nanoparticles-based highly sensitive, cost-effective and rapid visual method for differential detection ofMycobacterium tuberculosisandMycobacterium bovis
Authors: Patnaik Naresh , Dey Ruchi Jain 
Published: August 2023

AbstractTuberculosis poses a global health challenge, demanding improved diagnostics and therapies. Distinguishing betweenMycobacterium tuberculosis(M. tb) andMycobacterium bovis(M. bovis) infections holds critical “One Health” significance due to zoonotic nature of these infections and inherent resistance ofM. bovisto pyrazinamide, a key part of Directly Observed Treatment, Short-course (DOTS) regimen. Furthermore, most of the currently used molecular detection methods fail to distinguish between the two species. To address this, our study presents an innovative molecular-biosensing strategy. We developed a label-free citrate-stabilized silver nanoparticle aggregation assay, offering sensitive, cost-effective, and swift detection. For molecular detection, genomic markers unique toM. tbandM. boviswere targeted using species-specific primers. In addition to amplifying species-specific regions, these primers also aid detection of characteristic deletions in each of the mycobacterial species. Post polymerase chain reaction (PCR), we compared two highly sensitive visual detection methods with respect to the traditional agarose gel electrophoresis. The paramagnetic bead-based bridging flocculation assay, successfully discriminatesM. tbfromM. boviswith a sensitivity of ~40 bacilli. The second strategy exploits citrate-stabilized silver nanoparticle which aggregates in the absence of amplified dsDNA on addition of sodium chloride (NaCl). This technique enables precise, sensitive and differential detection of as few as ~4 bacilli. Our study hence advances tuberculosis detection, overcoming challenges ofM. tbandM. bovisdifferentiation offering a quicker alternative to time-consuming methods.
Resistance and resilience of soil microbiomes under climate change
Authors: Boyle Julia A. , Murphy Bridget K. , Ensminger Ingo , Stinchcombe John R. , Frederickson Megan. E. 
Published: August 2023

AbstractSoil microbiomes play key roles in plant productivity and nutrient cycling, and we need to understand whether and how they will withstand the effects of global climate change. We exposedin situsoil microbial communities to multiple rounds of heat, drought, or both treatments, and profiled microbial communities with 16S rRNA and ITS amplicon sequencing during and after these climatic changes, and then tested how domain and symbiotic lifestyle affected responses. Fungal community composition strongly shifted due to drought and its legacy. In contrast, bacterial community composition resisted change during the experiment, but still was affected by the legacy of drought. We identified fungal and bacterial taxa with differential abundance due to heat and drought and found that taxa affected during climate events are not necessarily the taxa affected in recovery periods, showing the complexity and importance of legacy effects. Additionally, we found evidence that symbiotic groups of microbes important to plant performance respond in diverse ways to climate treatments and their legacy, suggesting plants may be impacted by past climatic events like drought and warming even if they do not experience the event themselves.
How do biomarkers dance? Specific moves of defense and damage biomarkers for biological interpretation of dose-response model trends
Authors: Colas Simon , Le Faucheur Séverine 
Published: August 2023

AbstractOmics and multi-omics studies are currently increasingly used in ecotoxicology to highlight the induction of known or new biomarkers when an organism is exposed to one (or more) contaminant(s). Although it is virtually impossible to identify all biomarkers from all possible organisms, biomarkers can be grouped into two categories, defense or damage biomarkers and they have a limited number of response trends. Our working hypothesis is that defense and damage biomarkers show different dose-response patterns. A meta-analysis of 156 articles and 2,595 observations of dose-response curves of well-known defense and damage biomarkers was carried out in order to characterize the response trends of these biological parameters in a large panel of living organisms (18 phyla) exposed to a wide variety of inorganic or organic contaminants. Defense biomarkers describe biphasic responses (bell-shaped and U-shaped) to a greater extent than damage biomarkers. In contrast, damage biomarkers varied mainly monotonically (decreasing or increasing). Neither the nature of the contaminant nor the type of organisms, whatever the kingdom (Plantae, Animalia, Chromista or Bacteria), influence these specific responses. This result suggests that cellular defense and damage mechanisms are not specific to stressors and are conserved throughout life. The meta-analysis results confirm the usefulness of trend analysis in dose-response models as a biological interpretation of biomarkers in large dataset and their application in determining the concentration ranges inducing defense responses (CRIDeR) and the concentration ranges inducing damage responses (CRIDaR) regardless of the contaminant tested or the organism studied.HighlightsWe interpreted 2,595 biomarker dose-response curves generated by chemical exposure.Defense biomarkers mainly describe biphasic (bell- or U-shaped) trends.Damage biomarkers mainly describe monotonic (decreasing or increasing) trends.Cellular defense and damage responses appear to have been conserved during evolution.Response trend analysis is a promising tool for environmental risk assessment.Graphical abstract
Protein interaction network analysis of mTOR signaling reveals modular organization
Authors: Wehle Devin T. , Bass Carter S. , Sulc Josef , Mirzaa Ghayda , Smith Stephen E.P. 
Published: August 2023

AbstractThe mammalian target of rapamycin (mTOR) is a serine-threonine kinase that acts as a central mediator of translation, and plays important roles in cell growth, synaptic plasticity, cancer, and a wide range of developmental disorders. The signaling cascade linking lipid kinases (PI3Ks), protein kinases (AKT) and translation initiation complexes (EIFs) to mTOR has been extensively modeled, but does not fully describe mTOR system behavior. Here, we use quantitative multiplex co-immunoprecipitation to monitor a protein interaction network (PIN) composed of 300+ binary interactions among mTOR-related proteins. Using a simple model system of serum deprived or fresh-media-fed mouse 3T3 fibroblasts, we observed extensive PIN remodeling involving 27+ individual protein interactions after one hour, despite phosphorylation changes observed after only five minutes. Using small molecule inhibitors of PI3K, AKT, mTOR, MEK and ERK, we define subsets of the PIN, termed ‘modules’, that respond differently to each inhibitor. Using primary fibroblasts from individuals with overgrowth disorders caused by pathogenicPIK3CAorMTORvariants, we find that hyperactivation of mTOR pathway components is reflected in a hyperactive PIN. Our data define a “modular” organization of the mTOR PIN in which coordinated groups of interactions respond to activation or inhibition of distinct nodes, and demonstrate that kinase inhibitors affect the modular network architecture in a complex manner, inconsistent with simple linear models of signal transduction.
Oligomerization and positive feedback on membrane recruitment encode dynamically stable PAR-3 asymmetries in theC. eleganszygote
Authors: Lang Charlie , Maxian Ondrej , Anneken Alexander , Munro Edwin 
Published: August 2023

AbstractStudies of PAR polarity have emphasized a paradigm in which mutually antagonistic PAR proteins form complementary polar domains in response to transient cues. A growing body of work suggests that the oligomeric scaffold PAR-3 can form unipolar asymmetries without mutual antagonism, but how it does so is largely unknown. Here we combine single molecule analysis and modeling to show how the interplay of two positive feedback loops promote dynamically stable unipolar PAR-3 asymmetries in earlyC. elegansembryos. First, the intrinsic dynamics of PAR-3 membrane binding and oligomerization encode negative feedback on PAR-3 dissociation. Second, membrane-bound PAR-3 promotes its own recruitment through a mechanism that requires the anterior polarity proteins CDC-42, PAR-6 and PKC-3. Using a kinetic model tightly constrained by our experimental measurements, we show that these two feedback loops are individually required and jointly sufficient to encode dynamically stable and locally inducible unipolar PAR-3 asymmetries in the absence of posterior inhibition. Given the central role of PAR-3, and the conservation of PAR-3 membrane-binding, oligomerization, and core interactions with PAR-6/aPKC, these results have widespread implications for PAR-mediated polarity in metazoa.
Using human genetics to develop strategies to increase erythropoietic output from genome-edited hematopoietic stem and progenitor cells
Authors: Luna Sofia E. , Camarena Joab , Hampton Jessica P. , Majeti Kiran R. , Charlesworth Carsten T. , Soupene Eric , Selvaraj Sridhar , Jia Kun , Sheehan Vivien A. , Cromer M. Kyle , Porteus Matthew H. 
Published: August 2023

AbstractHuman genetic polymorphisms result in a diversity of phenotypes. Some sequences are pathologic and lead to monogenic diseases, while others may confer beneficial traits. Genome editing is a powerful tool to recreate genotypes found in the population, including the ability to correct pathologic mutations. One of the best characterized naturally occurring mutations causing congenital erythrocytosis arises from a truncation in the erythropoietin receptor (tEPOR) which can result in non-pathogenic hyper-production of red blood cells (RBCs). Using the precision of CRISPR/Cas9 genome editing, we have recreated tEPOR and studied the effect of variations of the genotype on RBC development. We then combined tEPOR with a correction strategy developed for β-thalassemia and demonstrated that coupling the two genome editing events gave RBCs a significant selective advantage. This demonstrates the potential of combining human genetics with the precision of genome editing to enable safer and more effective genome editing therapies for patients with serious genetic diseases.
Method for Evaluating Cortical Bone Young's Modulus: Numerical Twin Reconstruction, Finite Element Calculation, and Microstructure Analysis
Authors: Kurtz T. , Woitrain T. , Godio-Raboutet Y. , Ribeiro F. L. B. , Arnoux P.-J. , Tailhan J.-L. 
Published: August 2023

Abstract
The determination of bone mechanical properties remains crucial, especially to feed up numerical models. An original methodology of inverse analysis has been developed to determine the longitudinal elastic modulus of femoral cortical bone. The method is based on a numerical twin of a specific three-point bending test. It has been designed to be reproducible on each test result. In addition, the biofidelity of the geometric acquisition method has been quantified. As the assessment is performed at the scale of a bone shaft segment, the Young's modulus values obtained (between 9518.29 MPa and 14181.15 MPa) are considered average values for the whole tissue, highlighting some intersubject variability. The material microstructure has also been studied through histological analysis, and bone-to-bone comparisons highlighted discrepancies in quadrants microstructures. Furthermore, significant intrasubject variability exists since differences between the bone's medial-lateral and anterior–posterior quadrants have been observed. Thus, the study of microstructures can largely explain the differences between the elastic modulus values obtained. However, a more in-depth study of bone mineral density would also be necessary and would provide some additional information. This study is currently being setup, alongside an investigation of the local variations of the elastic modulus.
The Effect of Menopause on Vaginal Tissue Mechanics: A Brief Review
Authors: Gimenez Clara , Alperin Marianna , De Vita Raffaella 
Published: August 2023

AbstractOften called “the change of life,” menopause affects every part of a woman's body. As the sex hormones decrease, the reproductive organs experience the most remarkable changes, with the vagina becoming thinner, drier, and less elastic. Despite the important implications of these changes in genitourinary conditions, there are only a few experimental studies that focus on quantifying the effect of menopause on the mechanical properties of the vagina. These studies are mostly conducted using uniaxial tests on strips of vaginal tissues isolated from rats, rabbits, and sheep and, in only a few cases, from humans. The purpose of this article is to present a systematic review of experimental protocols, methods, and results that are currently published on how menopause alters the mechanical behavior of the vagina. This review will enable new investigators in the biomechanics field to identify important gaps and frame research questions that inform the design of new treatment options for menopausal symptoms.
Development of Analysis Tools for Heat Pipes Used in Small Modular Reactors: Sodium Property Correlations
Authors: Beuthe Thomas , Vasić Aleksandar , Azih Chukwudi , Maqueo Pablo D. G. 
Published: August 2023

Abstract
Advanced small modular reactors strive to improve reactor safety through increased utilization of passive heat transport and safety systems. An innovative means of meeting this design goal is to use alkali metal heat pipes to cool the reactor under both normal and abnormal operating conditions. A heat pipe model has been added to the ARIANT thermalhydraulic code to enable reactor modeling and support the design and licensing of new reactors. Saturation fluid properties are a fundamental input to this model. Consequently, this article provides a comprehensive comparative overview of the best available sodium saturation property correlations developed over the past century. The results show most of the sodium property correlations needed to model a heat pipe are relatively well-defined and recommendations for their use can be provided.
Mechanical Response of an Industrial Piping System Under Strong Cyclic Loading
Authors: Karvelas C. G. , Chatzopoulou G. , Zervaki A. D. , Karamanos S. A. , Strepelias E. , Palios X. , Bousias S. N. 
Published: August 2023

Abstract
The paper presents a combined experimental and numerical investigation of cyclic loading response of an internally pressurized 8-inch-diameter steel piping system. The piping system comprises three elbows and is subjected to quasi-static end-displacement excitation. Global deformation and local strain measurements are obtained, indicating significant strain ratcheting at critical locations of the elbows. The piping system failed under low-cycle fatigue undergoing through-thickness cracking at the flank of the most strained elbow, after 129 loading cycles with measured strain range of approximately 3%. Postfatigue metallographic examination of the elbows indicated that fatigue cracking initiates from the inner surface of the pipe elbow. In all elbows, several microcracks develop along the inner surface of elbow flanks, whereas the outer surface remained practically intact before through-thickness cracking occurred. Finite element simulations, with a cyclic-plasticity model calibrated properly in terms of small-scale material tests, provide very good predictions in terms of local strain evolution at critical locations. Numerical results at the intrados and the extrados of the critical elbow of the piping system verify strain ratcheting and the location of crack initiation observed in the experiments. This paper can be used as a reference for future experiments on cyclic loading of piping components, and for benchmarking constitutive modeling for simulating ratcheting.
Optimal Transient Energy Growth of Two-Dimensional Perturbation in a Magnetohydrodynamic Plane Poiseuille Flow of Casson Fluid
Authors: Basavaraj M. S. , Shivaraj Kumar D. L. 
Published: August 2023

Abstract
The study investigates the influence of the Casson fluid parameter and the spanwise uniform magnetic field on the onset of instability against infinitesimal disturbances in an electrically conducting fluid flow between two parallel nonconducting rigid plates. The fourth-order linearized disturbance equation governing stability is solved using the spectral collocation method with Chebyshev-based polynomials. The aim is to analyze in detail the effect of the parameters involved in the problem using both modal and nonmodal linear stability analysis. The modal analysis provides accurate values of the critical Reynolds number, critical wave number, and critical wave speed, denoted as critical triplets (Rc, αc, cc). Additionally, it examines the eigen-spectrum, growth rate curves, and neutral stability curves. On the other hand, the nonmodal analysis investigates the transient energy growth G(t) of two-dimensional (2D) optimal perturbations, the pseudospectrum of the non-normal Orr–Sommerfeld (O–S) operator (ℒ), and the regions of stability, instability, and potential instability of the fluid flow system. The extensive examination of both long-term behavior through modal analysis and short-term behavior through nonmodal analysis reveals that the Hartmann number (Ha) acts as a stabilizing agent, delaying the onset of instability. Conversely, the Casson parameter (η) acts as a destabilizing agent, advancing the onset of instability. The results obtained here are verified to be in good agreement with the existing literature in the absence of the Casson fluid flow parameter.
Applications of the Linear Quadratic Regulator Optimal Control With Completely and Partially Observed Markovian Switching
Authors: Beatris Escobedo-Trujillo , Javier Garrido 
Published: August 2023

Abstract
We study optimal control problems where the dynamic system evolves according to a linear stochastic differential equation with (a) multiplicative and additive white noise, (b) a mixture of white noise, and (c) white noise and colored noise. The drift rate and the diffusion matrix of the linear dynamic system depend on a continuous-time Markov chain with finite state space that is (I) partially observed and (II) completely observed. Using the results of Wonham filter theory, we reduce the partially observed problems to one with complete observation. We solve the control optimal problems explicitly with the help of dynamic programing technique, and three applications are presented to illustrate our theoretical results.
Three-Dimensional, Right Ventricular Surface Strain Computation From Three-Dimensional Echocardiographic Images From Patients With Pediatric Pulmonary Hypertension
Authors: Kundu Priyamvada , Schäfer Michal , Le Lisa , Thomas Thomas , Jone Pei-Ni , Hunter Kendall S. 
Published: August 2023

Abstract
Right Ventricular (RV) dysfunction is routinely assessed with echocardiographic-derived global longitudinal strain (GLS). GLS is measured from a two-dimensional echo image and is increasingly accepted as a means for assessing RV function. However, any two-dimensional (2D) analysis cannot visualize the asymmetrical deformation of the RV nor visualize strain over the entire RV surface. We believe three-dimensional surface (3DS) strain, obtained from 3D echo will better evaluate myocardial mechanics. Components of 3DS strain (longitudinal, LS; circumferential, CS; longitudinal-circumferential shear, ɣCL; principal strains PSMax and PSMin; max shear, ɣMax; and principal angle θMax) were computed from RV surface meshes obtained with 3D echo from 50 children with associated pulmonary arterial hypertension (PAH), 43 children with idiopathic PAH, and 50 healthy children by computing strains from a discretized displacement field. All 3DS freewall (FW) normal strain (LS, CS, PSMax, and PSMin) showed significant decline at end-systole in PH groups (p &lt; 0.0001 for all), as did FW-ɣMax (p = 0.0012). FW-θMax also changed in disease (p &lt; 0.0001). Limits of agreement analysis suggest that 3DS LS, PSMax, and PSMin are related to GLS. 3DS strains showed significant heterogeneity over the 3D surface of the RV. Components of 3DS strain agree with existing clinical strain measures, well classify normal -versus- PAH subjects, and suggest that strains change direction on the myocardial surface due to disease. This last finding is similar to that of myocardial fiber realignment in disease, but further work is needed to establish true associations.