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Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori

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Gastroenterology Report 2019年第1期7卷 42-49,I0002页

作者： Eng-Guan Chua Aleksandra W.Debowski KMary Webberley Fanny Peters Binit Lamichhane Mun-Fai Loke jamuna Vadivelu Chin-Yen Tay Barry j.Marshall michael j.wise The Marshall Centre for Infectious Diseases Research and Training University of Western AustraliaPerthWestern AustraliaAustralia School of Biomedical Sciences Faculty of Health and Medical SciencesUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Medical Microbiology University of MalayaKuala LumpurWilayah PersekutuanMalaysia Shenzhen Dapeng New District Kuichong People Hospital ShenzhenGuangdongChina UM Marshall Centre University of MalayaKuala LumpurWilayah PersekutuanMalaysia School of Computer Science and Software Engineering University of Western AustraliaPerthWestern AustraliaAustralia

Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori ***,the global emergence of metronidazole resistance in Hp poses a major challenge to health *** of RdxA is known to be a major mechanism of conferring metronidazole resistance in ***,metronidazole resistance can also arise in *** strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this ***:We performed whole-genome sequencing on 121 *** clinical strains,among which 73 were ***-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was *** sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in ***:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant *** of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole *** sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in *** that merit further investigation.

关键词： Helicobacter pylori metronidazole antibiotic resistance whole-genome sequencing core protein clusters sequence alignment

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael j.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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Identifying suitable areas for plenter forest management

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FOREST ECOSYSTEMS 2025年第1期12卷 83-92页

作者： Leiter, Mathias Pucher, Christoph Kessler, michael Hoeuronigsberger, Ferdinand Lexer, Manfred j. Vacik, Harald Hasenauer, Hubert Univ Nat Resources & Life Sci BOKU Inst Silviculture Peter Jordan Str 82 A-1190 Vienna Austria Univ Nat Resources & Life Sci BOKU Inst Forest Engn Peter Jordan Str 82 A-1190 Vienna Austria

Plenter forests, also known as uneven-aged or continuous cover forests enhance forest resilience and resistance against disturbances compared to even-aged forests. They are considered as an adaptation option to mitigate climate change effects. In this study, we present a conceptual approach to determine the potentially suitable area for plenter forest management within central European mixed species forests and apply our approach to the case study area in Styria, the south-eastern Province of Austria. The concept is based on ecological and technical-economic constraints and considers expected future climate conditions and its impact on plenter forest management. For each 1 ha forest pixel, we assess the ecological conditions for plenter forest management according to the autecological growth conditions of silver fir, and at least one additional shade tolerant tree species. The technical-economic constraints are defined by slope (<= 30%) and distance to the next forest road (<= 100 m) to ensure cost-efficient harvesting. The results show that under current climate conditions 28.1% or 305,349 ha of the forests in Styria are potentially suitable for plenter forest management. For the years 2071-2100 and under the climate change scenario RCP 4.5, the potential area decreases to 286,098 ha (26.3% of the total forest area) and for the scenario RCP 8.5 to 208,421 ha (19.1% of the total forest area). The main reason for these changes is the unfavourable growing conditions for silver fir in the lowlands, while in the higher elevations silver fir is likely to expand. Our results may serve forest managers to identify areas suitable for plenter forests and assist in the transformation of even-aged pure forests to uneven-aged forests to increase resistance, resilience, and biodiversity under climate change.

关键词： Plenter forest Uneven-aged forest management Tree species suitability Tree harvesting Transformation

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The hydrodynamic RAM effect:Review of historic experiments,model developments and simulation

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Defence Technology(防务技术) 2025年第2期44卷 150-178页

作者： Georg A.Heilig michael May Fraunhofer Institute for High-Speed Dynamics Ernst-Mach-Institute(EMI)Ernst-Zermelo-Strasse 4Freiburg 79104Germany

The Hydrodynamic Ram(HRAM)effect occurs when a high kinetic energy projectile penetrates a fluid filled area,e.g.,a liquid filled *** projectile transfers its momentum and kinetic energy to the fluid,what causes a sudden,local pressure rise,further expanding as primary shock wave in the fluid and developing a *** is possible that the entire tank ruptures due to the loads transferred through the fluid to its surrounding *** the past decades,additionally to experimental investigations,HRAM has been studied using various computational approaches particularly focusing on the description of the Fluid-Structure Interaction(FSI).This article reviews the published experimental,analytical and numerical results and delivers a chronological overview since the end of World War ***,HRAM mitigation measures are highlighted,which have been developed with the experimental,analytical and numerical toolboxes matured over the past 80 years.

关键词： Fluid-structure-interaction(FSI) Euler-Lagrange-Coupling Hydrodynamic RAM effect HRAM

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Identifying suitable areas for plenter forest management

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Forest Ecosystems 2025年第01期 83-92页

作者： Mathias Leiter Christoph Pucher michael Kessler Ferdinand H?nigsberger Manfred j.Lexer Harald Vacik Hubert Hasenauer Institute of Silviculture University of Natural Resources and Life Sciences (BOKU) Institute of Forest Engineering University of Natural Resources and Life Sciences (BOKU)

Plenter forests, also known as uneven-aged or continuous cover forests enhance forest resilience and resistance against disturbances compared to even-aged forests. They are considered as an adaptation option to mitigate climate change effects. In this study, we present a conceptual approach to determine the potentially suitable area for plenter forest management within central European mixed species forests and apply our approach to the case study area in Styria, the south-eastern Province of Austria. The concept is based on ecological and technicaleconomic constraints and considers expected future climate conditions and its impact on plenter forest management. For each 1 ha forest pixel, we assess the ecological conditions for plenter forest management according to the autecological growth conditions of silver fir, and at least one additional shade tolerant tree species. The technical-economic constraints are defined by slope(≤30%) and distance to the next forest road(≤100 m) to ensure cost-efficient harvesting. The results show that under current climate conditions 28.1% or 305,349 ha of the forests in Styria are potentially suitable for plenter forest management. For the years 2071–2100 and under the climate change scenario RCP 4.5, the potential area decreases to 286,098 ha(26.3% of the total forest area)and for the scenario RCP 8.5 to 208,421 ha(19.1% of the total forest area). The main reason for these changes is the unfavourable growing conditions for silver fir in the lowlands, while in the higher elevations silver fir is likely to expand. Our results may serve forest managers to identify areas suitable for plenter forests and assist in the transformation of even-aged pure forests to uneven-aged forests to increase resistance, resilience, and biodiversity under climate change.

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Seismites of the Late Triassic Lockatong Formation,Pennsylvania,USA:implications for Newark Basin border fault movement

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journal of Palaeogeography 2025年第1期14卷 1-14页

作者： Edward L.Simpson michael C.Wizevich David L.Fillmore Department of Physical Sciences Kutztown University of Pennsylvania Department of Earth and Space Sciences Central Connecticut State University

Numerous soft-sediment deformation structures(SSDS) within thin-bedded, heterolithic lacustrine shoreline deposits of the Upper Triassic Tumble Falls Member, Lockatong Formation of eastern Pennsylvania, demonstrate liquefaction, fluidization and shearing features processes affecting sediment. This study employs thin-section analysis of SSDS to interpret them as probable seismites from the Triassic-jurassic Newark Basin. Sedimentary structures include right-lateral offset of desiccation cracks and ichnofossils, thrust,reverse, and normal faults with mm-scale offsets, horsts and grabens, lateral spreads, and single and complex multiple networks of dikes and sills and associated sedimentary volcanoes, thin mudflows on a paleosurface linked to sediment dikes, load and flame structures, ball and pillow structures, recumbent folds, and incipient breccias. Dike fill consists of mudstone, angular sedimentary clasts, sandstone margins with mudstone cores,and plastically deformed sediment fill. The SSDS indicate that Late Triassic lacustrine shoreline sediments were subjected to forces, probably compressive with a minimal shear component reflected in the offset of the dikes and ichnofossils, that induced liquefaction followed by fluidization and vertical movement of *** forces that altered sediment vertical stability, leading to deformation of the sediment included gravitationally unstable density gradients, vertical shear stress, and gravitational body forces. SSDS can be induced by seismic and aseismic processes. However, this unique combination of forces and resulting sedimentary structures indicate an origin by earthquake activity, likely produced by the nearby, active Newark Basin border fault system. The Lockatong Formation SSDS seismites improve our understanding via thin section analysis of the rheology and preservation potential of SSDS in lacustrine shoreline deposits, critical for the geologic history of Newark Basin, as well as the refinement for paleos

关键词： Seismites Triassic Lockatong Formation Lacustrine Soft-sediment deformation structures

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Modeling compositional heterogeneity resolves deep phylogeny of flowering plants

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Plant Diversity 2025年第1期47卷 13-20页

作者： Yongli Wang Yan-Da Li Shuo Wang Erik Tihelka michael S.Engel Chenyang Cai Biofuels Institute School of Environmental and Safety EngineeringJiangsu UniversityZhenjiang 212013China Key Laboratory of Palaeobiology and Petroleum Stratigraphy Nanjing Institute of Geology and PalaeontologyChinese Academy of SciencesNanjing 210008China School of Earth Sciences University of BristolLife Sciences BuildingTyndall AvenueBristol BS81TQUnited Kingdom College of Marine Science and Biological Engineering Qingdao University of Science and TechnologyQingdao 266042China Division of Invertebrate Zoology American Museum of Natural HistoryNew YorkNY 10024-5192USA Facultad de Ciencias Biologicas Universidad Nacional Mayor de San MarcosLima 15081Peru Departamento de Entomología Museo de Historia NaturalUniversidad Nacional Mayor de San MarcosLima 15072Peru

Angiosperms experienced one of the most remarkable radiations of land plants and are now the dominant autotrophs in terrestrial *** phylogenomic studies based on large-scale data from plastid,mitochondrial,or nuclear transcriptomes/genomes and increased taxon sampling have provided unprecedent resolution into the phylogeny of flowering ***,owing to ancient rapid radiations,the interrelationships among the five lineages of Mesangiospermae,the vast majority of angiosperms,remain *** we show that,although plastid and mitochondrial genomes lack sufficient phylogenetic signal for resolving deeper phylogeny,the relationships among five mesangiosperm lineages can be confidently resolved under better-fitting models using genome-scale *** to our Bayesian cross-validation and model test in a maximum likelihood framework,siteheterogeneous models(e.g.,CAT-GTR+G4,LG+C20+F+G)outperform site-homogeneous or partition models often used in previous *** site-heterogeneous models,the approximately unbiased test favored our preferred tree recovered from various datasets:Ceratophyllales(coontails)are robustly recovered as sister to monocots,and they together are sister to the clade comprising magnoliids,Chloranthales,and *** phylogenomic analyses resolve the last enigma of the deeper phylogeny of angiosperms and emphasize the efficacy of modeling compositional heterogeneity in resolving rapid radiations of plants.

关键词： Angiosperms Ceratophyllales Phylogenomics Radiation Methodological factors CAT model

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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