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Diagnostics for a troubled backbone:testing topological hypotheses of trapelioid lichenized fungi in a large-scale phylogeny of Ostropomycetidae(Lecanoromycetes)

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fungal Diversity 2015年第4期73卷 239-258页

作者： Philipp Resl Kevin Schneider Martin Westberg Christian Printzen Zdeněk Palice Göran Thor Alan fryday helmut Mayrhofer Toby Spribille Institute of Plant Sciences NAWI GrazUniversity of GrazHolteigasse 6A-8010 GrazAustria Department of Botany Swedish Museum of Natural HistoryP.O.Box 50007SE-10405 StockholmSweden Senckenberg forschungsinstitut und Naturmuseum Senckenberganlage 25D-60325 Frankfurt am MainGermany Institute of Botany Academy of Sciences of the Czech RepublicZámek 125243 PrůhoniceCzech Republic Department of Botany Faculty of SciencesCharles University in PragueBenátská212801 Praha 2Czech Republic Department of Ecology Swedish University of Agricultural SciencesP.O.Box 7044SE-75007 UppsalaSweden Herbarium Department of Plant BiologyMichigan State UniversityEast LansingMI 48824USA Division of Biological Sciences University of Montana32 Campus DriveMissoulaMT 59812USA

Trapelioid fungi constitute a widespread group of mostly crust-forming lichen mycobionts that are key to understanding the early evolutionary splits in the Ostropomycetidae,the second-most species-rich subclass of lichenized *** uncertain phylogenetic resolution of the approximately 170 species referred to this group contributes to a poorly resolved backbone for the entire *** on a data set including 657 newly generated sequences from four ribosomal and four protein-coding gene loci,we tested a series of a priori and new evolutionary hypotheses regarding the relationships of trapelioid clades within *** found strong support for a monophyletic group of nine core trapelioid genera but no statistical support to reject the long-standing hypothesis that trapelioid genera are sister to Baeomycetaceae or ***,we can reject a sister group relationship to Ostropales with high *** data also shed light on several longstanding questions,recovering Anamylopsoraceae nested within Baeomycetaceae,elucidating two major monophyletic groups within trapelioids(recognized here as Trapeliaceae and Xylographaceae),and rejecting the monophyly of the genus *** transfer eleven species of the latter genus to Lambiella and describe the genus Parainoa to accommodate a previously misunderstood species of *** phylogenetic studies in Ostropomycetidae have invoked Bdivergence order^for drawing taxonomic conclusions on higher level *** data show that if backbone support is lacking,contrasting solutions may be recovered with different or added *** accordingly urge caution in concluding evolutionary relationships from unresolved phylogenies.

关键词： Ascomycota fungi Lambiella Lecanoromycetes Ostropomycetidae Parainoa Paraphyly SOWH test Taxon sampling

Asymmetrical positive assortative mating induced by developmental lead （Pb2＋） exposure in a model system, Drosophila melanogaster

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Current Zoology 2017年第2期63卷 195-203页

作者： Elizabeth K. PETERSON Roman YUKILEVICH Joanne KEHLBECK Kelly M. LARUE Kyle fERRAIOLO Kurt HOLLOCHER helmut V.B. HIRSCH Bernard POSSIDENTE Department of Biological Sciences State University of New York at Albany Albany NY 12222 USA Department of Biology Union College Schenectady NY 12308 USA Department of Chemistry Union College Schenectady NY 12308 USA Department of Molecular Biology Princeton University Princeton NJ 08544 USA Department of Geology Union College Schenectady NY 12308 USA Department of Biology Skidmore College Saratoga Springs NY 12866 USA

Anthropogenic pollutants have the potential to disrupt reproductive strategies. Little is known about how lead （Pb2＋） exposure disrupts individual-level responses in reproductive behaviors, which are important for fitness. Drosophila melanogaster was used as a model system to deter- mine the effects of： 1） developmental lead exposure on pre-mating reproductive behaviors （i.e., mate preference）, and 2） lead exposure and mating preferences on fitness in the f0 parental generation and f1 un-exposed offspring. Wild-type strains of D. melanogaster were reared from egg stage to adulthood in control or leaded medium （250 μM PbAc） and tested for differences in： mate preference, male song performance, sex pheromone expression, fecundity, mortality, and body weight. f0 leaded females preferentially mated with leaded males （i.e., asymmetrical positive assortative mating） in 2-choice tests. This positive assortative mating was mediated by the females （and not the males） and was dependent upon context and developmental exposure to Pb. Neither the courtship song nor the sex pheromone profile expressed by control and leaded males medi- ated the positive assortative mating in leaded females. Leaded females did not incur a fitness cost in terms of reduced fecundity, increased mortality, or decreased body weight by mating with leaded males. These results suggest that sublethal exposure to lead during development can alter mate preferences in adults, but not fitness measures once lead exposure has been removed. We suggest that changes in mate preference may induce fitness costs, as well as long-term population and multi-generational implications, if pollution is persistent in the environment.

关键词： cuticular hydrocarbons positive assortative mating random mating species recognition system.

Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M

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World Journal of Hepatology 2016年第35期8卷 1547-1556页

作者： Vanessa Rausch Teresa Peccerella Carolin Lackner Eray Yagmur helmut-Karl Seitz Thomas Longerich Sebastian Mueller Salem Medical Center and Center for Alcohol Research University of Heidelberg Institute for Pathology Medical University Graz Laboratory Diagnostics Center RWTH-University Hospital Aachen Aachen and Medical Care Center Institute of Pathology RWTH-University Hospital Aachen

AIMTo investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODSCaucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (fibroscan, Echosens SA, Paris, france). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease (steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 patients. RESULTSThe PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis (r = 0.404, P r = 0.319, P r = 0.264, P r = 0.828, P r = 0.516, P r = 0.319, P vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the f4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to develop cirrhosis corrected for age, gender and body mass index was 1.295 (95%CI: 0.787-2.131) for CG + GG carriers. CONCLUSIONIn heavy drinkers, PNPLA3 GG primarily correlates with ballooning/steatohepatitis but not steatosis resulting in a delayed inflammation-associated resolution of LS. Consequently, sustained ballooning-associated LS elevation seems to be a potential risk factor for fibrosis progression in PNPLA3 GG carriers.

关键词： Liver stiffness Alcoholic liver disease Adiponutrin PNPLA3 Transient elastography Alcohol withdrawal Inflammation

Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

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World Journal of Gastroenterology 2010年第8期16卷 966-972页

作者： Sebastian Mueller Gunda Millonig Lucie Sarovska Stefanie friedrich frank M Reimann Maria Pritsch Silke Eisele felix Stickel Thomas Longerich Peter Schirmacher helmut Karl Seitz Department of Medicine and Center for Alcohol Research Salem Medical Center University of Heidelberg Institute of Medical Biometry and Informatics University of Heidelberg Institute of Clinical Pharmacology University of Bern Department of Pa-thology University of Heidelberg

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by fibroScan (fS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with f3and f4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by fS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower f3 fibrosis stage if LS measurements were restricted to patients with GOT f inflammation did not further improve the diagnostic accuracy of ***:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by fS during alcohol withdrawal until GOT decreases to f icantly improves the diagnostic accuracy.

关键词： Alcoholic liver disease Alcoholic steatohep-atitis Liver cirrhosis Bilirubin Tissue elasticity imaging fibroScan

Anti-Tuberculosis Drug Induced Liver Injury and Ursodeoxycholic Acid

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Journal of Tuberculosis Research 2020年第2期8卷 66-72页

作者： Susanne M. Lang Emad Al-Nemnem helmut Schiffl Klinik für Innere Medizin II Universit&#228 tsklinikum Jena Jena Germany Department of Pulmonary & Critical Care Medicine Clemenceau Medical Center DHCC Dubai United Arab Emirates Department of Internal Medicine IV University Hospital Munich Munich Germany

Hepatotoxicity induced by standard anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide) can result in significant morbidity and, rarely, even mortality. This major adverse side-effect of anti-tuberculosis treatment has a negative impact on patient adherence and patient outcomes as well as on tuberculosis control. Early recognition and prompt withdrawal of the offending drugs are the most critical interventions in the management of anti-tuberculosis drug-induced liver injury. No drug or herbal extract has been shown until recently to prevent or reverse anti-tuberculosis drug-induced hepatotoxicity. Ursodeoxycholic acid is the only fDA approved drug for the treatment of primary biliary cholangitis and has also been successfully used in various cholestatic liver diseases. Although still experimental, recent controlled clinical studies suggested that oral administration of ursodeoxycholic acid may prevent the onset of anti-tuberculosis drug-induced liver injury and accelerate the recovery of liver injury. These clinical data are supported by experimental models of anti-tuberculosis drug-induced hepatotoxicity. There is an urgent need for further randomized clinical trials to document the promising hepatoprotective properties of ursodeoxycholic acid.

关键词： Ursodeoxycholic Acid Hepatotoxicity Rifampicin Isoniazid Pyrazinamide Tuberculosis

Identification of galectin-3 as a novel potential prognostic/predictive biomarker and therapeutic target for cerebral cavernous malformation disease

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Genes & Diseases 2024年第1期11卷 67-71页

作者： Souvik Kar Andrea Perrelli Kiran Kumar Bali Raffaella Mastrocola Arpita Kar Bushra Khan Luis Gand Arnab Nayak Christian Hartmann Wolfram SKunz Amir Samii helmut Bertalanffy Saverio francesco Retta International Neuroscience Institute Rudolf-PichlmayrStrasse 4Hannover 30625Germany Department of Clinical and Biological Sciences University of TorinoOrbassano(TO)10043Italy CCM Italia Research Network National Coordination Center at the Department of Clinical and Biological SciencesUniversity of TorinoOrbassano(TO)10043Italy Department of Experimental Pain Research Mannheim Center for Translational Neuroscience(MCTN)Medical Faculty MannheimHeidelberg UniversityMannheim 68167Germany Department of Kidney Liver and Metabolic DiseasesChildren’s HospitalHannover Medical SchoolHannover 30625Germany Ricarda-Huch-Street-10B Hannover 30880Germany Institute of Molecular and Cell Physiology Hannover Medical SchoolHannover 30625Germany Department of Neuropathology Institute of PathologyHannover Medical SchoolHannover 30625Germany Institute of Experimental Epileptology and Cognition Research and Department of Epileptology University Hospital BonnVenusberg-Campus 1Bonn 53127Germany epartment of Pharmacology and Physiology University of Rochester Medical CenterRochesterNY 14642USA

cerebrovascular disease of genetic origin characterized by abnormally dilated capillaries and a wide spectrum of symptoms,including headaches,seizures,neurological deficits,and intracerebral *** unpredictable clinical course and the current lack of therapies make the identification of prognostic and predictive biomarkers an imperative research challenge.1 Herein,we provide evidence that galectin-3(Gal-3),a major tissue and circulating biomarker of oxidative stress and inflammation,is significantly up-regulated both in CCM patients and ***,wholetranscriptome sequencing,qRT-PCR,and Western blotting studies demonstrated a significant up-regulation of Gal-3 expression levels both in surgical CCM specimens and in blood samples of CCM patients.

关键词： inflammation cerebral dilated

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan helmut Dolznig Thomas Knosel friedrich Karl-Heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han Division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGfP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

Case Report: Bilateral Pneumothoraces due to Targeted Tumor Therapy with Regorafenib in a Young Woman with Metastatic Colorectal Cancer

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Case Reports in Clinical Medicine 2022年第5期11卷 139-145页

作者： Tobias Rachow Tim Sandhaus Thomas Ernst helmut Schiffl Susanne M. Lang Klinik für Innere Medizin II Universit&auml tsklinikum Jena Jena Germany Klinik für Innere Medizin V Universit&auml tsklinikum Jena Jena Germany Klinik für Herz- und Thoraxchirurgie Universit&auml tsklinikum Jena Jena Germany Medizinische Klinik IV LMU München München Germany

Background: Colorectal cancer is one of the most common cancer types, frequently metastasizing into the lungs. Treatment options have been vastly improved over the last years. With the increasing use of targeted therapies, novel and rare adverse effects can be seen. Case Presentation: A 43-year-old woman presented in our oncology department with chest pain and dyspnea. The patient was diagnosed with colorectal cancer seven years earlier and had received chemoradiation, surgery, and multiple chemotherapies before she was started on regorafenib because of progressive pulmonary metastases. Computed tomography scans demonstrated cavitation of former nodular bilateral pulmonary metastases. After drainage and resolution of the right-sided pneumothorax, the patient returned eleven days later with recurrent symptoms caused by left-sided tension pneumothorax. Video-assisted thoracoscopy and bilateral pleurodeses were performed. Persistent air leaks with severe pain and pulmonary infiltrates led to the death of the patient. Conclusions: This case demonstrates the efficacy of oral antiangiogenetic therapy in advanced metastatic colorectal cancer. Nevertheless, it also depicts an important potential side effect by transforming multiple solid lung metastases into cavitations which led to recurrent pneumothoraces. Special attention should be paid to this phenomenon as treatment of these complications can be challenging.

关键词： Regorafenib Pneumothorax Pulmonary Metastases Colorectal Cancer

Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer

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World Journal of Gastrointestinal Surgery 2009年第1期1卷 30-37页

作者： Joerg Theisen Bernd Krause Christian Peschel Roland Schmid Hans Geinitz helmut friess Department of Surgery Klinikum rechts der IsarTU Muenchen Department of Nuclear Medicine Klinikum rechts der IsarTU Muenchen Department of Oncology Klinikum rechts der IsarTU Muenchen Department of Gastroenterology Klinikum rechts der IsarTU Muenchen Department of Radiation Oncology Klinikum rechts der IsarTU Muenchen

Since the introduction of multimodal therapy regimens,the prognosis of esophageal cancer has *** is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or *** conclusions can be drawn from this regarding the indication for perioperative therapies,the radicality of surgery,or the surgical ***,most of the current research in this f ield is aimed at the early identif ication of this subset of patients,at the beginning of,or even before,neoadjuvant *** staging tools have failed to predict responses to neoadjuvant ***,molecular imaging methods,*** emission tomography(PET)-scans,have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy,allowing physicians to alter the treatment plan *** more desirable is the identif ication of potential responders before the start of neoadjuvant *** molecular data on biopsy specimens demonstrate the possibility of early response prediction in these *** present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.

关键词： Esophageal cancer Response prediction Individualized therapy