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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

Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer barry j.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： barry S. Schifrin Brian j. Koos Wayne R. Cohen Department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The David Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Injury Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

Cell-cell interactions and communication dynamics in lung fibrosis

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Chinese Medical journal Pulmonary and Critical Care Medicine 2024年第2期2卷 63-71页

作者： Ting Xie jiurong Liang barry Stripp Paul W.Noble Division of Pulmonary and Critical Care Medicine Department of MedicineWomen’s Guild Lung InstituteCedars-Sinai Medical CenterLos AngelesCA 90048USA

Cell-cell interactions are essential components of coordinated cell function in lung *** diseases involve altered cell-cell interactions and communication between different cell types,as well as between subsets of cells of the same *** identification and understanding of intercellular signaling in lung fibrosis offer insights into the molecular mechanisms underlying these interactions and their implications in the development and progression of lung fibrosis.A comprehensive cell atlas of the human lung,established with the facilita-tion of single-cell RNA transcriptomic analysis,has enabled the inference of intercellular communications using ligand-receptor *** this review,we provide a comprehensive overview of the modified cell-cell commu-nications in lung *** highlight the intricate interactions among the major cell types within the lung and their contributions to *** insights presented in this review will contribute to a better understand-ing of the molecular mechanisms underlying lung fibrosis and may guide future research efforts in developing targeted therapies for this debilitating disease.

关键词： Cell–cell interaction Lung fibrosis Lung homeostasis Targeted therapies

Robustness Assessment and Adaptive FDI for Car Engine

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International journal of Automation and computing 2008年第2期5卷 109-118页

作者： Mahavir Singh Sangha j.barry Gomm Control Systems Research Group School of EngineeringLiverpool John Moores University

A new on-line fault detection and isolation （FDI） scheme proposed for engines using an adaptive neural network classifier is evaluated for a wide range of operational modes to check the robustness of the scheme in this paper. The neural classifier is adaptive to cope with the significant parameter uncertainty, disturbances, and environment changes. The developed scheme is capable of diagnosing faults in on-line mode and the FDI for the closed-loop system with can be directly implemented in an on-board crankshaft speed feedback is investigated by diagnosis system （hardware）. The robustness of testing it for a wide range of operational modes including robustness against fixed and sinusoidal throttle angle inputs, change in load, change in an engine parameter, and all these changes occurring at the same time. The evaluations are performed using a mean value engine model （MVEM）, which is a widely used benchmark model for engine control system and FDI system design. The simulation results confirm the robustness of the proposed method for various uncertainties and disturbances.

关键词： On-board fault diagnosis automotive engines adaptive neural networks (ANNs) fault classification robustness assessment

Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease

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World journal of Gastroenterology 2014年第27期20卷 8751-8763页

作者： Ahmed Tawfik Paul K Flanagan barry j Campbell Department of Gastroenterology Institute of Translational Medicine University of Liverpool

Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn’s disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn’s pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.

关键词： Crohn's disease Inflammatory bowel disease Escherichia coli Intra-macrophage survival and replication Phagolysosome Autophagy

Control of the carrier-envelope phases of a synchronously pumped femtosecond optical parametric oscillator and its applications

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Chinese Science Bulletin 2008年第5期53卷 642-651页

作者： SUN jingHua barry j S Gale Derryck T Reid Ultrafast Optics Group School of Engineering and Physical Sciences Heriot-Watt University Edinburgh EH14 4AS UK Laboratory of Optical Physics Institute of Physics Chinese Academy of Sciences Beijing 100080 China

The intrinsic synchronization, multi-color outputs and related carrier-envelope phases (CEP) among pulses bring advantages to synchronously pumped femtosecond optical parametric oscillators and the pumping sources for broadband frequency comb generation and ultrashort waveform coherent syn-thesis. In this paper, we discuss our latest research results in this field, which cover the following as-pects: the phase relationship and energy conservation law in an OPO and related experimental verifi-cation; control of the pumping Ti:sapphire femtosecond laser's CEP by self-referencing technology, and its repetition-rate locking by piezoelectric transducer (PZT); CEP locking of the pulses from the OPO by beating the non-phase-matched visible outputs against pump supercontinuum to obtain a driving signal for a fast PZT on the OPO end mirror; the generation of a broadband frequency comb spanning from 400 nm to 2.4 μm with 1.2 kHz bandwidth; and the realization of coherent interference between phase controlled pump pulses and signal second harmonic pulses.

关键词：光学参数振荡器载波包络相同步控制超短光脉冲

THIGEMINAL MECHANISMS OF OROFACIAL PAIN

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神经解剖学杂志 2001年第B7期17卷 35-36页

作者： barry j. SESSLE Department of Physiology Faculty of Dentistry University of Toronto Canada BDS BSc MDS PhD FRSC

Difficulties with the diagnosis and management of acute and chronic pain conditions stem largely from uncertainties of the aetiology or pathogenesis of the conditions. Recent studies have provided some important new insights into the peripheral and central processes underlying pain, and this presentation will review some of the recent advances in our knowledge of the neural processes involved in pain of the orofacial region.

关键词：口面部疼痛机制三叉神经中枢损伤感受器

A preliminary study of sperm identification in microdissection testicular sperm extraction samples with deep convolutional neural networks

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Asian journal of Andrology 2021年第2期23卷 135-139页

作者： Daniel j Wu Odgerel Badamjav Vikrant V Reddy Michael Eisenberg barry Behr Department of Computer Science Stanford UniversityStanfordCA 94305USA Department of Urology University of Utah HealthSalt Lake CityUT 84108USA Department of Obstetrics and Gynecology Stanford Children’s HealthStanfordCA 94305USA Department of Urology Stanford University School of MedicineStanfordCA 94305USA

Sperm identification and selection is an essential task when processing human testicular samples for in vitro *** and identifying sperm cell(s)in human testicular biopsy samples is labor intensive and time *** developed a new computer-aided sperm analysis(CASA)system,which utilizes deep learning for near human-level performance on testicular sperm extraction(TESE),trained on a custom *** system automates the identification of sperm in testicular biopsy samples.A dataset of 702 de-identified images from testicular biopsy samples of 30 patients was *** image was normalized and passed through glare filters and diffraction *** data were split 80%,10%,and 10%into training,validation,and test sets,***,a deep object detection network,composed of a feature extraction network and object detection network,was trained on this *** model was benchmarked against embryologists’performance on the detection *** deep learning CASA system achieved a mean average precision(mAP)of 0.741,with an average recall(AR)of 0.376 on our *** proposed method can work in real time;its speed is effectively limited only by the imaging speed of the *** results indicate that deep learning-based technologies can improve the efficiency of finding sperm in testicular biopsy samples.

关键词： artificial intelligence computer vision male infertility microdissection testicular sperm extraction sperm