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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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Perforated duodenal ulcer:An unusual manifestation of allergic eosinophilic gastroenteritis

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World journal of Gastroenterology 2015年第44期21卷 12709-12712页

作者： Kevin m Riggle Ghassan Wahbeh Elizabeth m Williams kimberly j Riehle Department of General Surgery University of Washington Seattle Division of Gastroenterology Seattle Children’s Hospital Seattle Division of Pathology Seattle Children’s Hospital Seattle Division of Pediatric General and Thoracic Surgery Seattle Children’s Hospital

Spontaneous perforation of a duodenal ulcer secondary to allergic eosinophilic gastroenteritis(EGE) has not been previously reported. We present such a case in a teenager who presented with peritonitis. After exploration and operative repair of his ulcer, he continued to experience intermittent abdominal pain, and further evaluation revealed eosinophilic gastroenteritis in the setting of multiple food allergies. His EGE resolved after adhering to a restrictive diet. Both duodenal ulcers and EGE are very rarely seen in pediatric patients. EGE has a variable presentation depending on the layer(s) of bowel wall affected and the segment of the gastrointestinal tract that is involved. Once diagnosed, it may respond to dietary changes in patients with recognized food allergies, or to steroids in patients in whom an underlying cause is not identified. Our case highlights the need to keep EGE in the differential diagnosis when treating pediatric patients with duodenal ulcers. The epidemiology, pathophysiology, and treatment of EGE are also discussed, along with a review of the current literature.

关键词： Pediatric Duodenal ulcer Eosinophilic Gastroenteri

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Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

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World journal of Gastroenterology 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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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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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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Treatment of distal femur fractures in a regional Australian hospital

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World journal of Orthopedics 2014年第3期5卷 379-385页

作者： Ewan Batchelor Clare Heal j kimberly Haladyn Herwig Drobetz Department of General Practice and Rural medicine James Cook University School of Medicine and DentistryLevel 1Building KMackay Base HospitalMackay QLD 4740Australia Department of Orthopaedic Surgery Mackay Base HospitalMackay QLD 4740Australia

AIm:To review our outcomes and compare the results of the Less Invasive Stabilization System(LISS)to other implants for distal femur fracture management at a regional Australian ***:The LISS is a novel implant for the management of distal femur *** is,however,technically demanding and treatment results have not yet been assessed outside tertiary ***-seven patients with 28 distal femur fractures who had been managed surgically at the mackay Base Hospital from january 2004 to December 2010 were retrospectively enrolled and assessed clinically and *** were union,pain,Lysholm score,knee range of motion,and complication ***:Twenty fractures were managed with the LISS and eight fractures were managed with alternative *** of the surgical techniques re-vealed that 11 fractures managed with the LISS were performed according to the recommended principles(LISS-R)and 9 were not(LISS-N).Union occurred in67.9%of fractures overall:9/11(82%)in the LISS-R group vs 5/9(56%)in the LISS-N group and 5/8(62.5%)in the alternative implant *** was no statistically significant difference between pain,Lysholm score,and complication rates between the ***,there was a trend towards the LISS-R group having superior outcomes which were clinically *** was a statistically significant greater range of median knee flexion in the LISS-R group with compared to the LISS-N group(P=0.0143)and compared with the alternative implant group(P=0.0454).CONCLUSION:The trends towards the benefits of the LISS procedure when correctly applied would suggest that not only should the LISS procedure be performed for distal femur fractures,but the correct principle of insertion is important in improving the patient’s outcome.

关键词： Distal femur fracture Less Invasive Stabilization System Locking plates Retrospective Operative technique

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Increased Benthic Algal Primary Production in Response to the Invasive Zebra mussel (Dreissena polymorpha) in a Productive Ecosystem,Oneida Lake,New York

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journal of Integrative Plant Biology 2008年第11期50卷 1452-1466页

作者： Rebecca K.Cecala Christine m.mayer kimberly L.Schulz Edward L.mills Biology Department Syracuse University Biology Deptartment Department of Environmental Sciences and Lake Erie Center University of Toledo State University of New York School of Environmental Science and Forestry Cornell Biological Field Station and Department of Natural Resources Cornell University

Increased water clarity associated with zebra mussel （Dreissena polymorpha） populations may favor benthic algal primary production in freshwater systems previously dominated by pelagic phytoplankton production. While zebra mussel-mediated water clarity effects on benthic primary production have been implicated in published reports, few production estimates are available. This study estimates benthic primary production in Oneida Lake, NY before and after zebra mussel invasion （1992）, using measured photosynthetic parameters （P^Bmax, α^β and β） from sampled benthic algal communities. In the summers of 2003 and 2004, primary production was measured as O2 evolution from algal communities on hard （cobble） and soft （sediment） substrate from several depths. We also backcast estimates of benthic primary production from measurements of light penetration since 1975. Estimates of whole-lake epipelic and epilithic algal primary production showed a significant （4%） increase and exhibited significantly less interannual variability subsequent to the establishment of zebra mussels. We applied our model to two lakes of differing trophic status; the model significantly overestimated benthic primary production in a hypereutrophic lake, but there was no significant difference between the actual and predicted primary production values in the oligotrophic lake. The hypereutrophic lake had higher zebra mussel densities than Oneida （224 vs. 41 per sample respectively）. Though total community respiration （measured in total darkness） was factored into our model predictions of production, our model may need modification when heterotrophic respiration is a large portion of total community metabolism.

关键词： Dreissena ecosystem engineering nonindigenous species Oneida Lake periphyton primary production.

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methods for engineering therapeutic peptides

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Chinese Chemical Letters 2018年第7期29卷 1074-1078页

作者： Yaohao Li kimberly A.Clark Zhongping Tan Department of Chemistry and Biochemistry and BioFrontiers Institute University of Colorado

Peptides are a class of drugs that have become increasingly important and influential for the treatment of many human diseases. Compared to traditional small molecule drugs, peptides have the potential for higher target specificity and potency, along with better safety profiles. On the other hand, the complex and fragile nature of peptides poses significant challenges for their administration. Of particular concern is that they are often unstable and can be rapidly degraded by various proteases after dosing. To address these inherent problems of peptides, many different methods have been attempted. Here, we briefly review these methods, with an emphasis on the effect of each method.

关键词： Therapeutic peptides Engineering Half-life Stability Solubility Aggregation Permeability

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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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Spatiotemporal microRNA profile in peripheral nerve regeneration:miR-138 targets vimentin and inhibits Schwann cell migration and proliferation

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Neural Regeneration Research 2018年第7期13卷 1253-1262页

作者： Travis B.Sullivan Litchfield C.Robert Patrick A.Teebagy Shannon E.morgan Evan W.Beatty Bryan j.Cicuto Peter K.Nowd kimberly m.Rieger-Christ David j.Bryan Department of Translational Research Lahey Hospital & Medical Center Tissue Engineering Laboratory Lahey Hospital & Medical Center Department of Plastic and Reconstructive Surgery Lahey Hospital & Medical Center

While the peripheral nervous system has regenerative ability,restoration of sufficient function remains a *** has been shown to be localized in axonal growth fronts and associated with nerve regeneration,including myelination,neuroplasticity,kinase signaling in nerve axoplasm,and cell migration;however,the mechanisms regulating its expression within Schwann cell（SC） remain *** aim of this study was to profile the spatial and temporal expression profile of micro RNA（mi RNA） in a regenerating rat sciatic nerve after transection,and explore the potential role of mi R-138-5 p targeting vimentin in SC proliferation and migration.A rat sciatic nerve transection model,utilizing a polyethylene nerve guide,was used to investigate mi RNA expression at 7,14,30,60,and 90 days during nerve *** levels of mi RNA expression were determined using microarray analysis and subsequently validated with quantitative real-time polymerase chain *** vitro assays were conducted with cultured Schwann cells transfected with mi RNA mimics and assessed for migratory and proliferative *** top seven dysregulated mi RNAs reported in this study have been implicated in cell migration elsewhere,and GO and KEGG analyses predicted activities essential to wound *** of one of these,mi RNA-138-5 p,into SCs reduced cell migration and *** R-138-5 p has been shown to directly target vimentin in cancer cells,and the luciferase assay performed here in rat Schwann cells confirmed *** results detail a role of mi R-138-5 p in rat peripheral nerve regeneration and expand on reports of it as an important regulator in the peripheral nervous system.

关键词： non-coding RNA neural regeneration nerve guide sciatic nerve transection peripheral nerve injury wound healing Gene Ontology processes Kyoto Encyclopedia of Genes and Genomes pathways microarray luciferase assay

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