bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rifaximin stimulates nitrogen detoxification by PXR‐independent mechanisms in human small intestinal organoids
Authors: de Wit Koos , Beuers Ulrich , Mukha Anna , Stigter Edwin C. A. , Gulersonmez M. Can , Ramos Pittol Jose M. , Middendorp Sabine , Takkenberg R. Bart , van Mil Saskia W. C. 
Published: December 2022

AbstractBackground and AimsRecurrent hepatic encephalopathy (HE) is characterized by hyperammonaemia in combination with neuropsychiatric abnormalities and is treated with lactulose and rifaximin. Rifaximin is a pregnane X receptor (PXR) agonist with low systemic and high intestinal bioavailability. The mechanisms by which it alleviates HE are unclear. We used human small intestinal (hSI) organoids to study whether rifaximin, via PXR activation, affects the epithelial biotransformation machinery, and to gain understanding of its low systemic availability.MethodsWe generated PXR knockdown hSI organoids via lentiviral delivery of short hairpin RNAs. Organoids were cultured for 24 h with rifaximin or rifampicin. RNA‐sequencing and metabolomics were performed to analyse gene expression and amino acid metabolism. Luminal rifaximin was quantified by photospectrometry.ResultsTreatment of wild‐type hSI organoids with rifaximin resulted in >twofold differential expression of 131 genes compared to DMSO. These effects were largely PXR independent and related to amino acid metabolism. Rifaximin decreased expression of glutaminase‐2 and increased expression of asparagine synthetase and solute carrier 7A11, thereby increasing intracellular glutamine and asparagine concentrations, indicating active ammonia detoxification. Rifaximin was apically excreted into the lumen in an ATP binding cassette B1 (ABCB1)‐dependent manner.ConclusionsRifaximin—after uptake into enterocytes—stimulates intracellular nitrogen detoxification by PXR‐independent mechanisms. Active apical excretion of rifaximin by ABCB1 into the intestinal lumen explains its low systemic bioavailability. Our study implies that rifaximin, next to modulation of the microbiome, has direct effects on ammonia scavenging in the human small intestinal epithelium.
Askival: An altered feldspathic cumulate sample in Gale crater
Authors: Bowden Donald Lewis , Bridges John C. , Cousin Agnes , Rapin William , Semprich Julia , Gasnault Olivier , Forni Olivier , Gasda Patrick , Das Debarati , Payré Valerie , Sautter Violaine , Bedford Candice C. , Wiens Roger C. , Pinet Patrick , Frydenvang Jens 
Published: December 2022

AbstractAskival is a light‐toned, coarsely crystalline float rock, which was identified near the base of Vera Rubin Ridge in Gale crater. We have studied Askival, principally with the ChemCam instrument but also using APXS compositional data and MAHLI images. Askival and an earlier identified sample, Bindi, represent two rare examples of feldspathic cumulate float rocks in Gale crater with >65% relict plagioclase. Bindi appears unaltered whereas Askival shows textural and compositional signatures of silicification, along with alkali remobilization and hydration. Askival likely experienced multiple stages of alteration, occurring first through acidic hydrolysis of metal cations, followed by deposition of silica and possible phyllosilicates at low T and neutral‐alkaline pH. Through laser‐induced breakdown spectroscopy compositional analyses and normative calculations, we suggest that an assemblage of Fe‐Mg silicates including amphibole and pyroxene, Fe phases, and possibly Mg‐rich phyllosilicate are present. Thermodynamic modeling of the more pristine Bindi composition predicts that amphibole and feldspar are stable within an upper crustal setting. This is consistent with the presence of amphibole in the parent igneous rocks of Askival and suggests that the paucity of amphiboles in other known Martian samples reflects the lack of representative samples of the Martian crust rather than their absence on Mars.
Insights into the petrogenetic history of the Northwest Africa 7635 augite‐rich shergottite
Authors: Herd Christopher D. K. 
Published: December 2022

AbstractThe petrogenesis of the Northwest Africa (NWA) 7635 Martian meteorite involved the entrainment of xenocrystic olivine grains into a relatively magnesian and oxidized melt, followed by a redox‐dependent reaction between olivine and melt that resulted in the crystallization of orthopyroxene and magnetite. Subsequent crystallization of the melt began with augite, plagioclase, and magnetite phenocrysts, and was followed by crystallization of augite, plagioclase, magnetite, ilmenite, and pyrrhotite in the groundmass, which took place under more rapid conditions of cooling, as reflected in the groundmass grain size. The petrogenetic history of NWA 7635 is similar in many ways to that of NWA 8159; this observation, coupled with similarities in geochemical and isotopic characteristics from other studies, suggests that the parent melts of the two rocks—as represented by all minerals except the xenocrystic olivine—were one and the same. The main distinctions between the two rocks are that their parent melts entrained xenocrystic olivine of different composition, and the cooling rate of the groundmass of NWA 7635 was more rapid than that of NWA 8159. The conclusion that the redox reaction took place between olivine and melt is in contrast to other work that suggests the reaction took place in the subsolidus, and has implications for the nature of the reaction in both NWA 7635 and NWA 8159.
A family perspective on parental psychosis: An interpretative phenomenological analysis study
Authors: Radley Jessica , Barlow Jane , Johns Louise C. 
Published: December 2022

AbstractObjectivesWhile one third of people with a psychotic disorder are a parent, there has been little research to date examining the consequences of this from a whole family perspective. This study investigates families where a parent has experienced an episode of psychosis and compares and contrasts the family members' perspectives.DesignThis study was rooted in phenomenology and data were derived from in‐depth semi‐structured interviews.MethodsParents with a psychotic disorder who had a child aged between 3 and 11 in a UK NHS Trust were invited to take part in the study. Semi‐structured interviews were conducted with these parents, with their child (if they were between the ages of 8 and 11), and with their partner or another close family member. Data were analysed using multiperspectival interpretive phenomenological analysis (m‐IPA).ResultsThirteen participants took part comprising of five parents, four children, three partners and one grandmother. Four themes were developed using m‐IPA: (1) Parental psychosis impacts the whole family, (2) Psychosis and my role as a parent, (3) Secrecy and concealment surrounding parental psychosis, and (4) Pressures and vulnerabilities within the family system.ConclusionPsychosis had a negative impact on all family members and secrecy existed between family members. The children in particular only had partial information about their parent's mental illness, which left them worried and confused. More work is needed to support these families to explain psychosis to the children.
Rationing scarce healthcare capacity: A study of the ventilator allocation guidelines during the COVID‐19 pandemic
Authors: Anderson David R. , Aydinliyim Tolga , Bjarnadóttir Margrét V. , Çil Eren B. , Anderson Michaela R. 
Published: December 2022

AbstractIn the United States, even though national guidelines for allocating scarce healthcare resources are lacking, 26 states have specific ventilator allocation guidelines to be invoked in case of a shortage. While several states developed their guidelines in response to the recent COVID‐19 pandemic, New York State developed these guidelines in 2015 as “pandemic influenza is a foreseeable threat, one that we cannot ignore.” The primary objective of this study is to assess the existing procedures and priority rules in place for allocating/rationing scarce ventilator capacity and propose alternative (and improved) priority schemes. We first build machine learning models using inpatient records of COVID‐19 patients admitted to New York‐Presbyterian/Columbia University Irving Medical Center and an affiliated community health center to predict survival probabilities as well as ventilator length‐of‐use. Then, we use the resulting point estimators and their uncertainties as inputs for a multiclass priority queueing model with abandonments to assess three priority schemes: (i) SOFA‐P (Sequential Organ Failure Assessment based prioritization), which most closely mimics the existing practice by prioritizing patients with sufficiently low SOFA scores; (ii) ISP (incremental survival probability), which assigns priority based on patient‐level survival predictions; and (iii) ISP‐LU (incremental survival probability per length‐of‐use), which takes into account survival predictions and resource use duration. Our findings highlight that our proposed priority scheme, ISP‐LU, achieves a demonstrable improvement over the other two alternatives. Specifically, the expected number of survivals increases and death risk while waiting for ventilator use decreases. We also show that ISP‐LU is a robust priority scheme whose implementation yields a Pareto‐improvement over both SOFA‐P and ISP in terms of maximizing saved lives after mechanical ventilation while limiting racial disparity in access to the priority queue.
Effects of intercropping and drought on soil aggregation and associated organic carbon and nitrogen
Authors: Peng Yumei , Xu Huasen , Wang Zi , Li Long , Shang Jianying , Li Baoguo , Wang Xiang 
Published: December 2022

AbstractDrought has significant effects on soil physicochemical properties and thereby crop productivity. Intercropping is a traditional agricultural practice with a good ecological effect and can improve soil structure. However, the effects of intercropping on soil aggregate distribution and associated organic carbon (OC) and nitrogen (N) compared with monoculture under drought remains unclear. Therefore, a two‐year controlled rainfall field (i.e., 30–40 days of 100% rainfall reduction during crop growth) was carried out to examine the effects of intercropping and short‐term drought on soil aggregate stability and associated OC and N in Northeast China. Results showed that soil OC and N were predominant in macroaggregates (2–0.25 mm), accounting for 39%–51% of SOC, 36%–51% of N at 0–10 cm depth, and 44%–67% of SOC, 43%–66% of N at 10–20 cm depth. After 2 years of a rainfall reduction treatment, large macroaggregates (>2 mm) increased by 84.7% at 0–10 cm and the aggregate stability improved. There was no difference in the mass of aggregates between monoculture and intercropping, but short‐term drought increased >0.25 mm aggregates and stability in intercropping soil at 0–10 cm depth. Moreover, drought significantly increased bulk soil OC in 10–20 cm but decreased the OC and N concentrations in large macroaggregates and silt + clay fractions (<0.053 mm) in 0–10 cm. Compared with the monoculture, intercropping enhanced OC and N concentrations in aggregates, and decreased soil C/N ratio. Therefore, these findings provide insights into how intercropping and short‐term drought interactively influence soil aggregation, and C and N processes.
Changes in operation of postural networks in rabbits with postural functions recovered after lateral hemisection of the spinal cord
Authors: Zelenin Pavel V. , Lyalka Vladimir F. , Deliagina Tatiana G. 
Published: December 2022

AbstractAcute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Here, to reveal changes in the operation of postural networks underlying the recovery, male rabbits with recovered postural functions after LHS at T12 (R‐rabbits) were used. After decerebration, we characterized the responses of individual spinal interneurons from L5 along with hindlimb EMG responses to stimulation causing postural limb reflexes (PLRs) that substantially contribute to postural corrections in intact animals. The data were compared with those obtained in our previous studies of rabbits with the intact spinal cord and rabbits after acute LHS. Although, in R‐rabbits, the EMG responses to postural disturbances both ipsilateral and contralateral to the LHS (ipsi‐LHS and co‐LHS) were only slightly distorted, PLRs on the co‐LHS side (unaffected by acute LHS) were distorted substantially and PLRs on the ipsi‐LHS side (abolished by acute LHS) were close to control. Thus, in R‐rabbits, plastic changes develop in postural networks both affected and unaffected by acute LHS. PLRs on the ipsi‐LHS side recover mainly as a result of changes at brainstem–cerebellum–spinal levels, whereas the forebrain is substantially involved in the generation of PLRs on the co‐LHS side. We found that, in areas of grey matter in which the activity of spinal neurons of the postural network was significantly decreased after acute LHS, it recovered to the control level, whereas, in areas unaffected by acute LHS, it was significantly changed. These changes underlie the recovery and distortion of PLRs on the ipsi‐LHS and co‐LHS sides, respectively.
imageKey points
After lateral hemisection of the spinal cord (LHS), postural functions recover over time. The underlying changes in the operation of postural networks are unknown.
We compared the responses of individual spinal neurons and hindlimb muscles to stimulation causing postural limb reflexes (PLRs) in recovered LHS‐rabbits with those obtained in rabbits with the intact spinal cord and rabbits after acute LHS.
We demonstrated that changes underlying the recovery of postural functions take place not only in postural networks that are severely impaired, but also in those that are almost unaffected by acute LHS.
PLRs on the LHS side recover mainly as a result of changes at brainstem–cerebellum–spinal levels, whereas the forebrain is substantially involved in the generation of PLRs contralateral to the LHS.
Mechanisms underlying divergent relationships between Ca2+ and YAP/TAZ signalling
Authors: Khalilimeybodi A. , Fraley S.I. , Rangamani P. 
Published: December 2022

Yes‐associated protein (YAP) and its homologue TAZ are transducers of several biochemical and biomechanical signals, integrating multiplexed inputs from the microenvironment into higher level cellular functions such as proliferation, differentiation and migration. Emerging evidence suggests that Ca2+ is a key second messenger that connects microenvironmental input signals and YAP/TAZ regulation. However, studies that directly modulate Ca2+ have reported contradictory YAP/TAZ responses: in some studies, a reduction in Ca2+ influx increases the activity of YAP/TAZ, while in others, an increase in Ca2+ influx activates YAP/TAZ. Importantly, Ca2+ and YAP/TAZ exhibit distinct spatiotemporal dynamics, making it difficult to unravel their connections from a purely experimental approach. In this study, we developed a network model of Ca2+‐mediated YAP/TAZ signalling to investigate how temporal dynamics and crosstalk of signalling pathways interacting with Ca2+ can alter the YAP/TAZ response, as observed in experiments. By including six signalling modules (e.g. GPCR, IP3‐Ca2+, kinases, RhoA, F‐actin and Hippo‐YAP/TAZ) that interact with Ca2+, we investigated both transient and steady‐state cell response to angiotensin II and thapsigargin stimuli. The model predicts that stimuli, Ca2+ transients and frequency‐dependent relationships between Ca2+ and YAP/TAZ are primarily mediated by cPKC, DAG, CaMKII and F‐actin. Simulation results illustrate the role of Ca2+ dynamics and CaMKII bistable response in switching the direction of changes in Ca2+‐induced YAP/TAZ activity. A frequency‐dependent YAP/TAZ response revealed the competition between upstream regulators of LATS1/2, leading to the YAP/TAZ non‐monotonic response to periodic GPCR stimulation. This study provides new insights into underlying mechanisms responsible for the controversial Ca2+–YAP/TAZ relationship observed in experiments.
imageKey points
YAP/TAZ integrates biochemical and biomechanical inputs to regulate cellular functions, and Ca2+ acts as a key second messenger linking cellular inputs to YAP/TAZ.
Studies have reported contradictory Ca2+–YAP/TAZ relationships for different cell types and stimuli.
A network model of Ca2+‐mediated YAP/TAZ signalling was developed to investigate the underlying mechanisms of divergent Ca2+–YAP/TAZ relationships.
The model predicts context‐dependent Ca2+ transient, CaMKII bistable response and frequency‐dependent activation of LATS1/2 upstream regulators as mechanisms governing the Ca2+–YAP/TAZ relationship.
This study provides new insights into the underlying mechanisms of the controversial Ca2+–YAP/TAZ relationship to better understand the dynamics of cellular functions controlled by YAP/TAZ activity.
The Homotopy Analysis Method for Solving Differential Equations With Generalized Caputo-Type Fractional Derivatives
Authors: Fafa Wafia , Odibat Zaid , Shawagfeh Nabil 
Published: December 2022

Abstract
This study expands and modifies the homotopy analysis method to handle differential equations with generalized Caputo-type fractional derivatives. Analytical approximate solutions for such models were successfully provided using the proposed modification. The determination of the valid region of convergence for the proposed method, with respect to the auxiliary control parameter, was discussed when using fractional operators. Then, mainly, the accuracy and effectiveness of the proposed method was verified through illustrative examples and comparisons with the predictor corrector method and RK4 method. Finally, it is expected that the studied generalized operators and the suggested method can be widely applied in the field of fractional calculus.
Can Recombinant Tree Shrew (Tupaia belangeri chinensis) Chymosin Coagulate Cow (Bos taurus) Milk?
Authors: Balabova D. V. , Belenkaya S. V. , Volosnikova E. A. , Hermes T. , Chirkova V. Y. , Sharlaeva E. A. , Shcherbakov D. N. , Belov A. N. , Koval A. D. , Elchaninov V. V. 
Published: December 2022

Abstract
Genetically engineered chymosin from the tree shrew (Tupaia belangeri chinensis) has been obtained and partially characterized for the first time. The target enzyme was produced in Escherichia coli, strain BL21(DE3). It was shown that tree shrew recombinant chymosin coagulates cow milk (Bos taurus). The total and specific milk-clotting activity of the obtained enzyme was 0.7–5.3 IMCU/mL and 8.8–16.6 IMCU/mg. The nonspecific proteolytic activity of tree shrew recombinant chymosin in relation to total bovine casein was 30 and 117% higher than that of recombinant chymosin of cow and of single-humped camel respectively. It was found that in comparison with most of the known genetically engineered chymosins, the tree shrew enzyme showed exceptionally low thermal stability. After heating at 45°C, the coagulation ability of tree shrew recombinant chymosin decreased by more than 40%, and at 50°C the enzyme lost more than 90% of the initial milk-clotting activity. The Michaelis constant (Km), enzyme turnover number (kcat), and catalytic efficiency (kcat/Km) for genetically engineered chymosin from the tree shrew were 6.3 ± 0.1 µM, 11 927 ± 3169 s–1 and 1968 ± 620 µM–1 s–1, respectively. Comparative analysis showed that the primary structure of the chymosin-sensitive site of cow kappa-casein and the supposed similar sequence of tree shrew kappa-casein differed by 75%. The ability of tree shrew recombinant chymosin to coagulate cow’s milk, along with a low thermal stability and high catalytic efficiency with respect to the substrate, imitating the chymosin-sensitive site of cow kappa-casein, suggests that this enzyme is of potential interest for cheese making.
The Thermostability of Nucleoside Phosphorylases from Prokaryotes. I. The Role of the Primary Structure of the N-terminal fragment of the Protein in the Thermostability of Uridine Phosphorylases
Authors: Veiko V. P. , Antipov A. N. , Mordkovich N. N. , Okorokova N. A. , Safonova T. N. , Polyakov K. M. 
Published: December 2022

AbstractMutant uridine phosphorylase genes from Shewanella oneidensis MR-1 (S. oneidensis) were constructed by site-directed mutagenesis and strains-producers of the corresponding recombinant (F5I and F5G) proteins were obtained on the basis of Escherichia coli cells. The mutant proteins were purified and their physicochemical and enzymatic properties were studied. It was shown that the N-terminal fragment of uridine phosphorylase plays an important role in the thermal stabilization of the enzyme as a whole. The role of the aminoacid (a.a.) residue phenylalanine (F5) in the formation of thermotolerance of uridine phosphorylases from gamma-proteobacteria was revealed.
25 years of cross-fertilization between HADES and Mont Terri rock laboratory
Authors: Nussbaum Christophe , Bernier Frédéric , Bleyen Nele , Bossart Paul , Bruggeman Christophe , De Cannière Pierre , Fierz Thomas , Jaeggi David , Neerdael Bernard , Valcke Elie , Volckaert Geert 
Published: December 2022

Abstract
The collaboration between HADES and the Mont Terri rock laboratory started in 1995, when granite was considered the most suitable host rock for radioactive waste disposal in Switzerland. When an alternative host formation was looked for by NAGRA, the choice of clay as host rock became rapidly clear. It was then decided to build an underground research laboratory in the Opalinus Clay taking advantage of the excavation of a motorway tunnel crossing the Mont Terri anticline. Exchanges of knowledge and experience on the behaviour of argillaceous formations were focused on the feasibility of constructing a safe geological repository for high-level radioactive waste: from excavation and gallery lining techniques to geochemistry, diffusion of radionuclides and coupled thermo-hydro-mechanical processes. The research programme at Mont Terri and the growing numbers of partners from four up to nine countries worldwide led to successive extensions of the galleries. The scientific and technical advances made possible by the collaboration between both laboratories dealt with the development of common methods and joint experimental and modelling efforts. This review article summarizes the main scientific lessons learned during these exchanges, stressing the added values of the knowledge transfer between partners and the overall cross-fertilization between HADES and Mont Terri.