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CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

Cellular & molecular Immunology 2023年第2期20卷 201-213页

作者： Ana jordan-Paiz Glòria martrus Fenja L.Steinert max Kaufmann Adrian F.Sagebiel Renée R.C.E.Schreurs Anne Rechtien martin E.Baumdick johannes m.jung kimberly j.möller Lucy Wegner Cordula Grüttner Laura Richert Roland Thünauer jennifer Schroeder-Schwarz johannes Bvan Goudoever Teunis B.H.Geijtenbeek marcus Altfeld Steven T.Pals Daniel Perez Paul L.Klarenbeek Christian Tomuschat Guido Sauter Ingo Königs Udo Schumacher manuel A.Friese Nathaniel melling Konrad Reinshagen madeleine j.Bunders Department of Virus Immunology Leibniz Institute of VirologyHamburg20251Germany University medical Center Hamburg-Eppendorf Hamburg20246Germany Institute of Neuroimmunology and multiple Sclerosis Center for Molecular Neurobiology HamburgUniversity Medical Center Hamburg-EppendorfHamburg20251Germany Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburg20246Germany Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterUniversity of Amsterdam and Vrije Universiteit AmsterdamAmsterdam1105 AZThe Netherlands I.Department of medicine University Medical Center Hamburg-EppendorfHamburg20246Germany Partner Site Hamburg-Lübeck-Borstel-Riems German Center for Infection Research(DZIF)Hamburg20246Germany University of Bordeaux Institut National de la Santéet de la Recherche MédicaleBordeaux Population Health Research Center UMR1219 and INRIA SISTM TeamBordeaux33000France Institute of Anatomy and Experimental morphology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pathology Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Rheumatology and Clinical Immunology and Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1007 MBThe Netherlands Amsterdam Rheumatology&Immunology Center Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburg20246Germany Institute of Pathology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pediatric Surgery Altona Children’s HospitalHamburg22763Germany III.Department of medicine University M

Gastrointestinal infections are a major cause for serious clinical complications in *** induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human *** CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to *** findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to ***-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B *** together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

关键词： TFH cells B cells Antibodies Intestine Pediatrics

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Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

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世界胃肠病学杂志:英文版 2023年第33期29卷 4991-5004页

作者： Kendra L Francis kimberly m Alonge maria Cristina Pacheco Shannon j Hu Cody A Krutzsch Gregory j.morton michael W Schwartz jarrad m Scarlett Department of Pediatric Gastroenterology and Hepatology Seattle Children’s HospitalSeattleWA 98105United States 不详 Department of medicinal Chemistry University of WashingtonSeattleWA 98195United States Department of Laboratory medicine and Pathology Seattle Children's HospitalSeattleWA 98105United States

BACKGROUND The increased prevalence of inflammatory bowel disease(IBD)among patients with obesity and type 2 diabetes suggests a causal link between these diseases,potentially involving the effect of hyperglycemia to disrupt intestinal barrier *** To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced *** mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range *** weeks later,dextran sodium sulfate was given to induce *** select experiments,a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis *** included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier *** In mice given a high-fat diet,but not chow-fed animals,diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease *** was also associated with a decrease in key components that regulate colonic epithelial barrier integrity(colonic mucin layer content and epithelial tight junction proteins)in diet-induced obese *** of these effects of diabetes in diet-induced obese mice was ameliorated by restoring *** In obese mice,diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of ***-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis *** findings suggest that effective diabetes management may decrease the clinical severity of IBD.

关键词： Inflammatory bowel disease Type 2 diabetes Obesity Intestinal barrier Hyperglycemia Colitis in mice Tight junction proteins

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Improving detection of cerebral small vessel disease aetiology in patients with isolated lobar intracerebral haemorrhage

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Stroke & Vascular Neurology 2023年第1期8卷 26-33页

作者： Alvin S Das Elif Gokcal Robert W Regenhardt mitchell j Horn Kristin Schwab Nader Daoud Anand Viswanathan W Taylor kimberly joshua N Goldstein Alessandro Biffi Natalia Rost jonathan Rosand Lee H Schwamm Steven m Greenberg m Edip Gurol Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMassachusettsUSA Department of Neurology Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Department of Neurosurgery Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Department of Emergency medicine Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA

Background and purpose We evaluate whether non-haemorrhagic imaging markers(NHIm)(white matter hyperintensity patterns,lacunes and enlarged perivascular spaces(EPVS))can discriminate cerebral amyloid angiopathy(CAA)from hypertensive cerebral small vessel disease(HTN-cSVD)among patients with isolated lobar intracerebral haemorrhage(isolated-LICH).methods In patients with isolated-LICH,four cSVD aetiologic groups were created by incorporating the presence/distribution of NHIm:HTN-cSVD pattern,CAA pattern,mixed NHIm and no *** pattern consisted of patients with any combination of severe centrum semiovale EPVS,lobar lacunes or multiple subcortical spots ***-cSVD pattern consisted of any HTN-cSVD markers:severe basal ganglia PVS,deep lacunes or peribasal ganglia white matter hyperintensity *** NHIm consisted of at least one imaging marker from either *** hypothesis was that patients with HTN-cSVD pattern/mixed NHIm would have a higher frequency of left ventricular hypertrophy(LVH),which is associated with *** In 261 patients with isolated-LICH,CAA pattern was diagnosed in 93 patients,HTN-cSVD pattern in 53 patients,mixed NHIm in 19 patients and no NHIm in 96 *** frequency of LVH was similar among those with HTN-cSVD pattern and mixed NHIm(50%vs 39%,p=0.418)but was more frequent in HTN-cSVD pattern compared with CAA pattern(50%vs 20%,pmodel,HTN-cSVD pattern(OR:7.38;95%CI 2.84 to 19.20)and mixed NHIm(OR:4.45;95%CI 1.25 to 15.90)were found to be independently associated with *** Among patients with isolated-LICH,NHIm may help differentiate HTN-cSVD from CAA,using LVH as a marker for HTN-cSVD.

关键词： patients cerebral hypertensive

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Understanding the agronomic impacts of defoliation strategies in“Bulldog 805”Alfalfa+“Tifton 85”bermudagrass mixed stands

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Grassland Research 2023年第4期2卷 251-259页

作者： Lisa L.Baxter justin C.Burt mary kimberly mullenix Sydney L.Payne Kaylyn R.Reagin Katie m.mason Chris G.Prevatt jennifer j.Tucker Department of Crop and Soil Science University of GeorgiaTiftonGeorgiaUSA Department of Animal Science Auburn UniversityAuburnAlabamaUSA Department of Animal Science University of TennesseeKnoxvilleTennesseeUSA Beef Cattle and Forage Commodity Director Alabama Farmers Federation MontgomeryMontgomeryAlabamaUSA Department of Animal and Dairy Science University of GeorgiaTiftonGeorgiaUSA

Background:The incorporation of legumes,specifically alfalfa(medicago sativa L.),into bermudagrass(Cynodon spp.)-based pasture systems in the southeastern United States has increased in recent years as an alternative to synthetic nitrogen(N)***:A small plot evaluation was conducted in Shorter,Alabama,and Tifton,Georgia,USA,to evaluate the impact of harvest height(HH)and harvest frequency(HF)on agronomic characteristics of alfalfa+bermudagrass mixtures in southeastern United ***:Results from both locations revealed that the longer the HF and the shorter the HH,the greater the alfalfa retention was in the stand(pmpact any of the reported nutritive value parameters,while longer HF resulted in lower total digestible nutrients,lower crude protein,higher acid detergent fiber,and lower 48 h in vitro dry matter digestibility(pmpacted forage accumulation at both locations(pmed recent findings from comparable evaluations in the southeastern United States,in that increasing HH and decreasing HF improved alfalfa retention while having a negligible effect on nutritive value or forage accumulation.

关键词： alfalfa+bermudagrass mixtures defoliation management forage management

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Dynamics and mechanisms of permethrin resistance in a field population of the horn fly, Haematobia irritans irritans

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Insect Science 2009年第2期16卷 175-184页

作者： Andrew Y. Li kimberly H. Lohmeyer j. Allen miller USDA ARS Knipling-Bushland US Livestock Insects Research Laboratory 2700 Fredericksburg Road Kerrville TX 78028 USA

A study was conducted at the Pressler ranch, near Kerrville, Texas, USA between 2002 and 2006 to determine the dynamics and mechanisms of resistance to permethrin in a field population of the horn fly, Haematobia irritans irritans （L.）. Changes of resistance to pyrethroid insecticide associated with use of a pour-on formulation of cyfluthrin in 2002 and use of diazinon ear tags in subsequent years were studied using a filter paper bioassay technique and a polymerase chain reaction assay that detects two sodium channel mutations, kdr and super-kdr resistance alleles. A maximum of 294-fold resistance to permethrin was observed in the summer of 2002. A significant decrease in the resistance level was observed in spring 2003, and resistance continued to decline after animals were treated with diazinon ear tags. In response to pyrethroid treatments, the allelic kdr and super-kdr frequency increased from 56.3% to 93.8% and from 7.5% to 43.8%, respectively in 2002, and decreased significantly in 2003 when the pyrethroid insecticide was no longer used to treat animals. Females were found to have a higher allelic super-kdr frequency than males in 2002, while no difference was detected between males and females in the allelic kdr frequency. There was a significant positive correlation between frequencies of the sodium channel mutations and levels ofpermethrin resistance, suggesting that the sodium channel mutations, kdr and super-kdr, are the major mechanisms of resistance to pyrethroids in this horn fly population. Results of synergist bioassays also indicated possible contributions of two metabolic detoxification mechanisms, the mixed function oxidases （mFO） and glutathione S-trans- ferases （GST）. Compared to a horn fly infestation of an untreated herd, treatments with the pyrethroid pour-on formulation failed to control horn flies at the Pressler ranch in 2002. Sustained control of horn flies was achieved with the use of diazinon ear tags in 2003 and subsequent years.

关键词： efficacy horn fly insecticide resistance PCR permethrin pyrethroids

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Another look at silent circulation of poliovirus in small populations

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Infectious Disease modelling 2018年第1期3卷 107-117页

作者： Dominika A.Kalkowska Radboud j.Duintjer Tebbens kimberly m.Thompson Kid Risk Inc.605 N.High St.#253ColumbusOH 43215USA

Background:Silent circulation of polioviruses complicates the polio endgame and motivates analyses that explore the probability of undetected circulation for different scenarios.A recent analysis suggested a relatively high probability of unusually long silent circulation of polioviruses in small populations(defined as 10,000 people or smaller).methods:We independently replicated the simple,hypothetical model by Vallejo et al.(2017)and repeated their analyses to explore the model behavior,interpretation of the results,and implications of simplifying ***:We found a similar trend of increasing times between detected cases with increasing basic reproduction number(R0)and population ***,we found substantially lower estimates of the probability of at least 3 years between successive polio cases than they reported,which appear more consistent with the prior *** small and isolated populations may sustain prolonged silent circulation,our reanalysis suggests that the existing rule of thumb of less than a 5%chance of 3 or more years of undetected circulation with perfect surveillance holds for most conditions of the model used by Vallejo et *** most realistic ***:Avoiding gaps in surveillance remains critical to declaring wild poliovirus elimination with high confidence as soon as possible after the last detected poliovirus,but concern about transmission in small populations with adequate surveillance should not significantly change the criteria for the certification of wild polioviruses.

关键词： Polio Small populations Silent circulation Stochastic modeling

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Improving bermudagrass in the Southeastern United States with alfalfa as an alternative nitrogen source in grazing systems

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Grassland Research 2022年第4期1卷 280-289页

作者： justin C.Burt Lisa L.Baxter Christopher G.Prevatt mary kimberly mullenix R.Lawton Stewart jr. jennifer j.Tucker Department of Animal and Dairy Science University of GeorgiaTiftonGeorgiaUSA Department of Crop and Soil Science University of GeorgiaTiftonGeorgiaUSA Regional Specialized Agent Range Cattle RECUniversity of FloridaGainesvilleFloridaUSA Department of Animal Science Auburn UniversityAuburnAuburnUSA Department of Animal and Dairy Science University of GeorgiaAthensGeorgiaUSA

Background Bermudagrass(Cynodon spp.)is one of the most common perennial warm-season forages grown in the Southeastern United *** incorporation of alfalfa(medicago sativa)into bermudagrass pastures could serve as an alternative source of nitrogen(N)while also improving the nutritive value of the forage *** A 2-year grazing evaluation arranged in a randomized complete block design was conducted from may to September 2018(Year 1)and may–August 2019(Year 2)in Tifton,GA,*** objective was to compare the production of alfalfa–bermudagrass mixed pastures(BGA)with bermudagrass monoculture pastures with(BGN)or without(BG)the application of synthetic nitrogen on forage production and stocker cattle *** Differences were observed for average daily gain(p=0.10),gain per hectare(p=0.02)and stocking rate(p=0.01),in that BGA was greatest compared to BGN and BG,which did not differ from each ***,BGA had increased forage crude protein(p=0.01)and total digestible nutrients(p=0.01)compared to BGN and ***,BGA provided the greatest economic return per hectare compared to BG or *** These data illustrate improved animal performance and forage nutritive value using alfalfa–bermudagrass systems and offer a viable option for producers seeking alternatives to synthetic N sources for bermudagrass pastures in the Southeastern United States.

关键词： alfalfa-bermudagrass mixtures forage management grazing management

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Phase transitions between tropical,subtropical,and extratropical cyclones:A review from IWTC-10

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Tropical Cyclone Research and Review 2023年第4期12卷 294-308页

作者： kimberly Wood Wataru Yanase jack Beven Suzana j.Camargo joseph B.Courtney Chris Fogarty junya Fukuda Naoko Kitabatake matthew Kucas Ron mcTaggart-Cowan michelle Simoes Reboita jacopo Riboldi The University of Arizona ArizonaUSA meteorological Research Institute IbarakiJapan National Hurricane Center MiamiUSA Lamont-Doherty Earth Observatory Columbia UniversityPalisadesUSA Bureau of meteorology MelbourneAustralia Canadian Hurricane Center Nova ScotiaCanada japan meteorological Agency TokyoJapan meteorological College ChibaJapan joint Typhoon Warning Center HonoluluUSA Environment and Climate Change Gatineau QuebecCanada Federal University of Itajuba ItajubaBrazil ETH Zurich ZurichSwitzerland

This review,which was adapted from a Tenth International Workshop on Tropical Cyclones(IWTC-10)report,discusses research findings and operational practices relevant to cyclone types and phase transitions(extratropical,subtropical,and tropical).The cyclone phase space(CPS)method is widely used in both historical investigations and real-time evaluation of cyclone type and transition;however,CPS parameter values depend on input data resolution,and universal thresholds do not currently exist to delineate when a cyclone transitions from one type to *** of phase transitions in a changing climate highlight potential latitude shifts in extratropical transition and increased potential for tropical transition,but realistic projections of future trends likely require high-resolution simulations that can capture the cyclone warm *** meteorological centers apply varied approaches to cyclone classification via CPS parameters and other criteria,some of which depend on the tropical basin,yet these approaches cannot fully address challenges in operational classification and subsequently in communicating risks associated with these phase *** recommend a multivariate historical assessment of tropical and subtropical cyclones across all basins in which they occur,including the South Atlantic Ocean and the mediterranean Sea,to identify the potential for a more universal cyclone classification approach that meets operational needs.

关键词： Tropical cyclone Subtropical cyclone Extratropical transition Tropical transition

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Brain-targeting,acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery

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Bioactive materials 2022年第10期7卷 57-65页

作者： Shenqi Zhang Bin Peng Zeming Chen jiang Yu Gang Deng Youmei Bao Chao ma Fengyi Du Wendy C.Sheu W.Taylor kimberly j.marc Simard Daniel Coman Qianxue Chen Fahmeed Hyder jiangbing Zhou Kevin N.Sheth Department of Neurosurgery USA Department of Biomedical Engineering USA Department of Radiology and Biomedical Imaging USA Department of Neurology Yale UniversityNew HavenCT06510USA Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei430060China Department of Neurology Division of Neurocritical CareMassachusetts General HospitalBostonMAUSA Department of Neurosurgery University of Maryland School of MedicineBaltimoreMD21201USA

Stroke is the leading cause of death and ***,there is no effective pharmacological treatment for this disease,which can be partially attributed to the inability to efficiently deliver therapeutics to the *** we report the development of natural compound-derived nanoparticles(NPs),which function both as a potent therapeutic agent for stroke treatment and as an efficient carrier for drug delivery to the ischemic ***,we screened a collection of natural nanomaterials and identified betulinic acid(BA)as one of the most potent antioxidants for stroke ***,we engineered BA NPs for preferential drug release in acidic ischemic tissue through chemically converting BA to betulinic amine(BAm)and for targeted drug delivery through surface conjugation of AmD3100,a CXCR4 *** resulting AmD3100-conjugated BAm NPs,or A-BAm NPs,were then assessed as a therapeutic agent for stroke treatment and as a carrier for delivery of NA1,a neuroprotective *** show that intravenous administration of A-BAm NPs effectively improved recovery from stroke and its efficacy was further enhanced when NA1 was *** to their multifunctionality and significant efficacy,we anticipate that A-BAm NPs have the potential to be translated both as a therapeutic agent and as a drug carrier to improve the treatment of stroke.

关键词： Drug delivery Acid-triggered release Antioxidant nanoparticles NA1 Ischemic stroke

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The lncRNA BORG: a novel inducer of TNBC metastasis, chemoresistance, and disease recurrence

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journal of Cancer metastasis and Treatment 2019年第5期4卷 48-61页

作者： Alex j.Gooding kimberly A.Parker Saba Valadkhan William P.Schiemann Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA Department of molecular Biology and microbiology Case Western Reserve UniversityClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA

Although greater than 90% of breast cancer-related mortality can be attributed to metastases, the molecular mechanisms underpinning the dissemination of primary breast tumor cells and their ability to establish malignant lesions in distant tissues remain incompletely understood. Genomic and transcriptomic analyses identified a class of transcripts called long noncoding RNA (lncRNA), which interact both directly and indirectly with key components of gene regulatory networks to alter cell proliferation, invasion, and metastasis. We identified a pro-metastatic lncRNA BmP/OP-Responsive Gene (BORG) whose aberrant expression promotes metastatic relapse by reactivating proliferative programs in dormant disseminated tumor cells (DTCs). BORG expression is broadly and strongly induced by environmental and chemotherapeutic stresses, a transcriptional response that facilitates the survival of DTCs. Transcriptomic reprogramming in response to BORG resulted in robust signaling via survival and viability pathways, as well as decreased activation of cell death pathways. As such, BORG expression acts as a (1) marker capable of predicting which breast cancer patients are predisposed to develop secondary metastatic lesions;and (2) unique therapeutic target to maximize chemosensitivity of DTCs. Here we review the molecular and cellular factors that contribute to the pathophysiological activities of BORG during its regulation of breast cancer metastasis, chemoresistance, and disease recurrence.

关键词： BORG chemoresistance disease recurrence dormancy long noncoding RNA metastasis triple-negative breast cancer

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