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Atmospheric humidity regulates same-sex mating in Candida albicans through the trehalose and osmotic signaling pathways

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Science China(Life Sciences) 2023年第8期66卷 1915-1929页

作者： Chao Li Li Tao Guobo Guan Zhangyue Guan austin m.perry Tianren Hu Jian Bing ming Xu Clarissa J.Nobile Guanghua Huang Department of Infectious Diseases Huashan HospitalShanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic EngineeringSchool of Life SciencesFudan UniversityShanghai 200438China State Key Laboratory of mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of molecular and Cell Biology University of CaliforniaMercedMerced CA 95343USA Quantitative and Systems Biology Graduate Program University of CaliforniaMercedMerced CA 95343USA Health Sciences Research Institute University of CaliforniaMercedMerced CA 95343USA Shanghai Engineering Research Center of Industrial microorganisms Shanghai 200438China Shanghai Huashen Institute of microbes and Infections Shanghai 200052China

Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity.Environmental factors often have a direct impact on the occurrence and frequency of sexual reproduction in fungi.The regulatory effects of atmospheric relative humidity(RH)on sexual reproduction and pathogenesis in plant fungal pathogens and in soil fungi have been extensively investigated.However,the knowledge of how RH regulates the lifecycles of human fungal pathogens is limited.In this study,we report that low atmospheric RH promotes the development of mating projections and same-sex(homothallic)mating in the human fungal pathogen Candida albicans.Low RH causes water loss in C.albicans cells,which results in osmotic stress and the generation of intracellular reactive oxygen species(ROS)and trehalose.The water transporting aquaporin Aqy1,and the G-protein coupled receptor Gpr1 function as cell surface sensors of changes in atmospheric humidity.Perturbation of the trehalose metabolic pathway by inactivating trehalose synthase or trehalase promotes same-sex mating in C.albicans by increasing osmotic or ROS stresses,respectively.Intracellular trehalose and ROS signal the Hog1-osmotic and Hsf1-Hsp90 signaling pathways to regulate the mating response.We,therefore,propose that the cell surface sensors Aqy1 and Gpr1,intracellular trehalose and ROS,and the Hog1-osmotic and Hsf1-Hsp90 signaling pathways function coordinately to regulate sexual mating in response to low atmospheric RH conditions in C.albicans.

关键词： atmospheric relative humidity sexual reproduction same-sex mating Candida albicans trehalose metabolism osmotic stress

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Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： Dorothy Liu mark m Youssef Josephine A Grace marie Sinclair Department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTm)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(mPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or mPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIm To investigate the relative carcinogenicity of tacrolimus and mPA in solid organ transplantation.mETHODS A literature search was conducted using mEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of meSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonst

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus mycophenolate

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Differential signaling of Flt3 activating mutations in acute myeloid leukemia:a working model

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Protein & Cell 2011年第2期2卷 108-115页

作者： perry m.Chan Neuroscience Research Partnership Biomedical Sciences Instituteaffiliated with Institute of Molecular and Cell BiologyASTARSingapore 138673Singapore

Receptor tyrosine kinases couple a wide variety of extracellular cues to cellular responses.The class III subfamily comprises the platelet-derived growth factor receptor,c-Kit,Flt3 and c-Fms,all of which relay cell proliferation signals upon ligand binding.Accordingly,mutations in these proteins that confer ligand-independent activation are found in a subset of cancers.These mutations cluster in the juxtamembrane(Jm)and catalytic tyrosine kinase domain(TKD)regions.In the case of acute myeloid leukemia(AmL),the juxtamembrane(named ITD for internal tandem duplication)and TKD Flt3 mutants differ in their spectra of clinical outcomes.Although the mechanism of aberrant activation has been largely elucidated by biochemical and structural analyses of mutant kinases,the differences in disease presentation cannot be attributed to a change in substrate specificity or signaling strength of the catalytic domain.This review discusses the latest literature and presents a working model of differential Flt3 signaling based on mis-localized juxtamembrane autophosphorylation,to account for the disease variation.This will have bearing on therapeutic approaches in a complex disease such as AmL,for which no efficacious drug yet exists.

关键词： acute myeloid leukemia receptor tyrosine kinase oncogenic mutation autoinhibition intracellular traf-ficking

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Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: A prospective study in healthcare workers using self-administered testing

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2022年第3期8卷 249-256页

作者： austin C.Cao Zachary m.Nimmo Natasha mirza Noam A.Cohen Robert m.Brody Richard L.Doty Perelman School of medicine University of PennsylvaniaPhiladelphiaPAUSA Department of Otorhinolaryngology-Head and Neck Surgery University of PennsylvaniaPhiladelphiaPAUSA Corporal michael J.Crescenz Veterans Administration medical Center PhiladelphiaPAUSA monell Chemical Senses Center PhiladelphiaPAUSA

Background: Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory dysfunction.Objectives: The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare workers.methods: Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were completed.Results: Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (mpared to other subjects. There was a time-dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.Conclusion: Healthcare workers with recent SARS-CoV-2 infection had reduced olfaction and normal gustation on self-administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.

关键词： Anosmia Brief Smell Identification Test Chemosensory dysfunction COVID-19 Dysgeusia Gustation Healthcare workers Objective testing Olfaction Screening University of Pennsylvania Smell Identification Test

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Genetic parameters of drinking and feeding traits of wean-to-finish pigs under a polymicrobial natural disease challenge

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Journal of Animal Science and Biotechnology 2022年第1期13卷 17-35页

作者： Jian Cheng austin m.Putz John C.S.Harding michael K.Dyck Frederic Fortin Graham S.Plastow Pig Gen Canada Jack C.m.Dekkers Department of Animal Science Iowa State UniversityAmesIA 50011USA Hendrix Genetics Swine Business UnitBoxmeerThe Netherlands 5831CK Department of Large Animal Clinical Science University of SaskatchewanSaskatoonSK S7N 5A2Canada Department of Agriculture Food and Nutritional ScienceUniversity of AlbertaEdmontonAB T6G 2R3Canada Centre de Developpement du Porc du Quebec Inc. Quebec City G1V 4M6Canada PigGen Canada Research Consortium GuelphOntario N1H4G8Canada

Background:The pork industry faces unprecedented challenges from disease,which increases cost of production and use of antibiotics,and reduces production efficiency,carcass quality,and animal wellbeing.One solution is to improve the overall resilience of pigs to a broad array of common diseases through genetic selection.Behavioral changes in feeding and drinking are usually the very first clinical signs when animals are exposed to stressors such as disease.Changes in feeding and drinking behaviors in diseased pigs may reflect the way they cope with the challenge and,thus,could be used as indicator traits to select for disease resilience.The objectives of this study were to estimate genetic parameters of feeding and drinking traits for wean-to-finish pigs in a natural polymicrobial disease challenge model,to estimate genetic correlations of feeding and drinking traits with growth rate and clinical disease traits,and to develop indicator traits to select for disease resilience.Results:In general,drinking traits had moderate to high estimates of heritability,especially average daily water dispensed,duration,and number of visits(0.44 to 0.58).Similar estimates were observed for corresponding feeding traits(0.35 to 0.51).most genetic correlation estimates among drinking traits were moderate to high(0.30 to 0.92)and higher than among feeding traits(0 to 0.11).Compared to other drinking traits,water intake duration and number of visits had relatively stronger negative genetic correlation estimates with treatment rate and mortality,especially across the challenge nursery and finisher(−0.39 and−0.45 for treatment rate;−0.20 and−0.19 for mortality).Conclusion:most of the recorded drinking and feeding traits under a severe disease challenge had moderate to high estimates of heritability,especially for feed or water intake duration and number of visits.Phenotypic and genetic correlations among the recorded feeding traits under disease were generally low but drinking traits showed high correlations with each other.Water intak

关键词： Disease resilience Feeding and drinking behavior Genetic parameters Pigs

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Development and application of feature engineered geological layers for ranking magmatic,volcanogenic,and orogenic system components in Archean greenstone belts

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Geoscience Frontiers 2024年第2期15卷 251-273页

作者： R.m.montsion S.Perrouty m.D.Lindsay m.W.Jessell R.Sherlock mineral Exploration Research Centre Harquail School of Earth SciencesGoodman School of MinesLaurentian UniversitySudburyOntario P3E 2C6Canada Centre for Exploration Targeting School of Earth SciencesThe University of Western Australia35 Stirling HighwayCrawley 6009Australia Commonwealth Scientific and Industrial Research Organization Mineral Resources26 Dick Perry AveKensingtonWA 6151Australia ARC Centre for Data Analytics for Resources and Environments(DARE) Perth and SydneyAustralia

Geologically representative feature engineering is a crucial component in geoscientific applications of machine learning.many commonly applied feature engineering techniques used to produce input variables for machine learning apply geological knowledge to generic data science techniques,which can lead to ambiguity,geological oversimplification,and/or compounding subjective bias.Workflows that utilize minimally processed input variables attempt to overcome these issues,but often lead to convoluted and uninterpretable results.To address these challenges,new and enhanced feature engineering methods were developed by combining geological knowledge,understanding of data limitations,and a variety of data science techniques.These include non-Euclidean fluid pre-deformation path distance,rheological and chemical contrast,geologically constrained interpolation of characteristic host rock geochemistry,interpolation of mobile element gain/loss,assemblages,magnetic intensity,structural complexity,host rock physical properties.These methods were applied to compiled open-source and new field observations from Archean greenstone terranes in the Abitibi and western Wabigoon sub-provinces of the Superior Province near Timmins and Dryden,Ontario,respectively.Resulting feature maps represent conceptually significant components in magmatic,volcanogenic,and orogenic mineral systems.A comparison of ranked feature importance from random forests to conceptual mineral system models show that the feature maps adequately represent system components,with a few exceptions attributed to biased training data or limited constraint data.The study also highlights the shared importance of several highly ranked features for the three mineral systems,indicating that spatially related mineral systems exploit the same features when available.Comparing feature importance when classifying orogenic Au mineralization in Timmins and Dryden provides insights into the possible cause of contrasting endowment being related to fluid source.The study demonstrat

关键词： machine learning Random forests mineral systems magmatic Ni-Cu-PGE Volcanogenic massive Sulfide(VmS)Cu-Zn-Pb-Ag(-Au) Orogenic Au Abitibi Wabigoon

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Assessing the Performance of a Dynamical Downscaling Simulation Driven by a Bias-Corrected CmIP6 Dataset for Asian Climate

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Advances in Atmospheric Sciences 2024年第5期41卷 974-988页

作者： Zhongfeng XU Ying HAN meng-Zhuo ZHANG Chi-Yung TAm Zong-Liang YANG Ahmed m.EL KENAWY Congbin FU Institute of Atmospheric Physics Chinese Academy of SciencesBeijing 100029China School of Atmospheric Sciences Nanjing UniversityNanjing 210093China Earth System Science Programme The Chinese University of Hong KongHong KongChina Department of Geological Sciences Jackson School of GeosciencesThe University of Texas at AustinAustinTexasUSA Instituto Pirenaico de Ecología Consejo Superior de Investigaciones Científicas(CSIC)Campus de Aula Dei1005Zaragoza 50059Spain Department of Geography Mansoura UniversityMansoura 35516Egypt

In this study,we aim to assess dynamical downscaling simulations by utilizing a novel bias-corrected global climate model(GCm)data to drive a regional climate model(RCm)over the Asia-western North Pacific region.Three simulations were conducted with a 25-km grid spacing for the period 1980–2014.The first simulation(WRF_ERA5)was driven by the European Centre for medium-Range Weather Forecasts Reanalysis 5(ERA5)dataset and served as the validation dataset.The original GCm dataset(mPI-ESm1-2-HR model)was used to drive the second simulation(WRF_GCm),while the third simulation(WRF_GCmbc)was driven by the bias-corrected GCm dataset.The bias-corrected GCm data has an ERA5-based mean and interannual variance and long-term trends derived from the ensemble mean of 18 CmIP6 models.Results demonstrate that the WRF_GCmbc significantly reduced the root-mean-square errors(RmSEs)of the climatological mean of downscaled variables,including temperature,precipitation,snow,wind,relative humidity,and planetary boundary layer height by 50%–90%compared to the WRF_GCm.Similarly,the RmSEs of interannual-tointerdecadal variances of downscaled variables were reduced by 30%–60%.Furthermore,the WRF_GCmbc better captured the annual cycle of the monsoon circulation and intraseasonal and day-to-day variabilities.The leading empirical orthogonal function(EOF)shows a monopole precipitation mode in the WRF_GCm.In contrast,the WRF_GCmbc successfully reproduced the observed tri-pole mode of summer precipitation over eastern China.This improvement could be attributed to a better-simulated location of the western North Pacific subtropical high in the WRF_GCmbc after GCm bias correction.

关键词： bias correction multi-model ensemble mean dynamical downscaling interannual variability day-to-day variability validation

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Investigation of effect of near-fault motions on substandard bridge structures

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Earthquake Engineering and Engineering Vibration 2011年第1期10卷 1-11页

作者： austin Brown m. Saiid Saiidi Dynamic Certification Laboratories Department of Civil & Environmental Engineering

The objective of this study was to investigate the effects of near-fault ground motions on substandard bridge columns and piers. To accomplish these goals, several large scale reinforced concrete models were constructed and tested on a shake table using near- and far-field ground motion records. Because the input earthquakes for the test models had different characteristics, three different measures were used to evaluate the effect of the input earthquake. These measures are peak shake table acceleration, spectral acceleration at the fundamental period of the test specimens, and the specimen drift ratios. For each measure, force-displacement relationships, strains, curvatures, drift ratios, and visual damage were evaluated. Results showed that regardless of the measure of input or response, the near-fault record generally led to larger strains, curvatures, and drift ratios. Furthermore, residual displacements were small compared to those for columns meeting current seismic code requirements.

关键词： near-fault reinforced concrete bridge columns dynamic response

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Use of the O-Z flap as an alternative to free tissue transfer for reconstruction of large scalp defects

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2022年第4期8卷 355-360页

作者： austin C.Cao Ryan m.Carey mitali Shah Kevin Chorath Robert m.Brody Steven B.Cannady Jason G.Newman Rabie m.Shanti Karthik Rajasekaran Perelman School of medicine University of PennsylvaniaPhiladelphia19104PA Department of Otorhinolaryngology-Head and Neck Surgery University of PennsylvaniaPhiladelphia19104PA Drexel University College of medicine Drexel UniversityPhiladelphia19102PA Department of Oral and maxillofacial Surgery University of PennsylvaniaPhiladelphia19104PA Leonard Davis Institute of Health Economics University of PennsylvaniaPhiladelphiaPA

Objective:The reconstruction of large scalp defects poses both functional and cosmetic challenges.While free tissue transfer remains the standard for defects larger than 30 cm^(2),prolonged anesthesia and postoperative complications remain significant limitations.The purpose of this study is to evaluate the use of O-Z flaps for the reconstruction of large scalp defects and to describe the techniques employed.methods:This is a retrospective analysis of ten patients who underwent reconstructive surgery using an O-Z flap approach for large scalp defects between July 2017 and June 2019.The parameters included in this study were patient demographics,tumor characteristics,and postoperative management,collected for at least a year after surgery.Results:In this cohort,the mean age was 76.1 years and 90%were male.All patients were treated for neoplastic skin lesions,with 70%located on the vertex and 30%located on the temporoparietal region.The mean size of defect was 52.0 cm^(2)(range:38.6 to 63.8 cm^(2)).The maximum hospital stay was two days,and no patients were readmitted within 30 days of surgery.There were no cases of wound infection or flap necrosis.All patients reported pain control with acetaminophen and ibuprofen.Four patients received adjuvant radiation,and there was no delay to receiving treatment following surgery.Conclusions:The O-Z flap is a reliable alternative for the reconstruction of non-irradiated scalp defects in the vertex and temporoparietal regions up to 63 cm^(2).This technique provides advantages for patients,including hairline preservation,shorter hospital stays,and decreased postoperative complications.

关键词： Scalp reconstruction Local flaps Free flap reconstruction Facial plastics microvascular surgery Head and neck cancer

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Compositional Effect of ZrO_2 Nanofillers on a PVDF-co-HFP Based Polymer Electrolyte System for Solid State Zinc Batteries

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Chinese Journal of Polymer Science 2016年第3期34卷 332-343页

作者： m.Johnsi S.austin Suthanthiraraj Department of Energy University of MadrasGuindy Campus

Composite polymer electrolytes（CPEs） comprising poly（vinilydene fluoride-hexafluoro propylene）, PVDF-coHFP and zinc triflate, Zn（CF3SO3）2 with varying concentrations of ZrO_2 nanofillers were prepared by solution casting technique with N,N-dimethyl formamide（DmF） as the common solvent. The polymer electrolyte specimen with the particular composition 75 wt% PVDF-co-HFP： 25 wt% Zn Tf ＋ 7 wt% Zr O2 showed the highest conductivity of 4.6 × 10-4 S/cm at 298 K as confirmed from impedance measurements and favored by the rich amorphous phase of the CPE revealed from room temperature X-ray diffraction analysis（XRD）. The electrical conductivity relaxation time and its distribution within the materials have been evaluated from the electric modulus m 2 and impedance Z＂ data which showed the occurrence of non-Debye type of relaxation phenomenon. The changes in the surface morphology of the CPEs were examined using scanning electron microscopy（SEm）. The electrochemical stability window of CPE is found to be 2.6 V with a thermal stability up to 300 °C. An electrochemical cell has been fabricated based on Zn/mnO_2 electrode couple under a constant load of 1 mΩ and its discharge characteristics have been evaluated.

关键词： Nanocomposites Dielectric properties Thermal stability Electrochemical stability Batteries

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