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Trypsin in pancreatitis:The culprit,a mediator,or epiphenomenon?

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World Journal of Gastroenterology 2024年第41期30卷 4417-4438页

作者： Anna S Gukovskaya markus m lerch Julia mayerle matthias Sendler Baoan Ji Ashok K Saluja Fred S Gorelick Ilya Gukovsky Department of medicine David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesCA 90073United States Department of MedicineVA Greater Los Angeles Healthcare System Los AngelesCA 90073United States Department of medicine Ludwig Maximilian University HospitalMunich 81377Germany Department of medicine II Ludwig Maximilian University of MunichMunich 81377Germany Department of medicine A University of GreifswaldGreifswald 17475Germany Department of Cancer Biology Mayo ClinicJacksonvilleFL 32224United States Department of Surgery University of Miami Miller School of MedicineMiamiFL 33136United States Departments of Cell Biology and Internal medicine Yale University School of Medicine and VA West HavenNew HavenCT 06519United States

Pancreatitis is a common,life-threatening inflammatory disease of the exocrine *** pathogenesis remains obscure,and no specific or effective treatment is *** and alcohol excess are major etiologies of pancreatitis;in a small portion of patients the disease is *** is believed to be initiated by injured acinar cells(the main exocrine pancreas cell type),leading to parenchymal necrosis and local and systemic *** primary function of these cells is to produce,store,and secrete a variety of enzymes that break down all categories of *** digestive enzymes,including all proteases,are secreted by acinar cells as inactive proforms(zymogens)and in physiological conditions are only activated when reaching the *** generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other *** was proposed that pancreatitis results from proteolytic autodigestion of the gland,mediated by premature/inappropriate trypsinogen activation within acinar *** intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis,and in human *** the basis of these observations,it has been considered the central pathogenic mechanism of pancreatitis-a concept with a century-old *** review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis,particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis;analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its’damaging effects;discusses the gaps in our knowledge,potential therapeutic approaches,and directions for future *** conclude that trypsin is not the culprit in the disease pathogenesis but,at most,a mediator of some pancreatitis ***,the search for effective therapies should

关键词： Pancreatic acinar cell Hereditary pancreatitis Autophagy Endolysosomal system Cholecystokinin Cerulein Cathepsin

Is hepatic steatosis associated with left ventricular mass index increase in the general population?

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World Journal of Hepatology 2017年第19期9卷 857-866页

作者： Katharina Piontek Carsten O Schmidt Sebastian E Baumeister markus m lerch Julia mayerle marcus Dorr Stephan B Felix Henry Volzke Institute for medical Psychology University Medicine Greifswald Institute for Community medicine University Medicine Greifswald Department of medicine A University Medicine Greifswald Department of Cardiology University Medicine Greifswald German Centre for Cardiovascular Research Partner site Greifswald

AIm To investigate the association between hepatic steatosis and change in left ventricular mass index(LVmI) over five years, and examine whether systolic and diastolic blood pressures are mediators of the association between hepatic steatosis and LVmI using a general population *** We analyzed data from the Study of Health in Pomerania. The study population comprised 1298individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels. Left ventricular mass was determined echocardiographically and indexed to height2.7. Path analyses were conducted to differentiate direct and indirect paths from hepatic steatosis to LVmI encompassing systolic and diastolic blood pressure as potential mediating *** Hepatic steatosis was a significant predictor for all measured echocardiographic characteristics at baseline. Path analyses revealed that the association of hepatic steatosis with LVmI change after five years was negligibly small(β =-0.12, s.e. = 0.21, P = 0.55). Systolic blood pressure at baseline was inversely associated with LVmI change(β =-0.09, s.e. = 0.03, P mI change was evident(β = 0.03, s.e. = 0.05, P = 0.56). The effect of the indirect path from hepatic steatosis to LVmI via systolic baseline blood pressure was small(β =-0.20, s.e. = 0.10, P = 0.07). No indirect effect was observed for the path via diastolic baseline blood pressure(β = 0.03, s.e. = 0.06, P = 0.60). Similar associations were observed in the subgroup of individuals not receiving beta-blockers, calcium channel blockers, or drugs acting on the reninangiotensin *** Baseline associations between hepatic steatosis and LVmI do not extend to associations with LVmI change after five years. more studies are needed to study the longitudinal effects of hepatic steatosis on LVmI.

关键词： Hepatic steatosis Left ventricular mass index Blood pressure General Population Study of Health in Pomerania

Embracing substrate multispecificity in plant ABC transporters

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molecular Plant 2024年第7期17卷 990-992页

作者： markus m.Geisler Department of Biology University of Fribourg1700 FribourgSwitzerland

By analogy,the first plant ATP-binding cassette(ABC)transporters were identified as vacuolar detoxifiers transporting glutathione conjugates into the vacuole(martinoia et al.,1993).This somewhat negative image as"unspecific detoxifiers"still clings to plant ABC transporters today,although they have since been described to be involved in completely different programs,including development and defense(Park et al.,2017).In this context,some key plant ABC transporters have been shown to own exceptionally high substrate *** example,the transporter of the native auxin indole-3-acetic acid(IAA),Arabidopsis ABCB1,has been shown to also export the synthetic auxin 1-naphtaleneacetic acid but is even able to distinguish this substrate from its structural isomer,2-naphtaleneacetic acid(Geisler et al.,2005).Likewise,ABCG36 and ABCG37,which are known to have a broader substrate portfolio(Park et al.,2017;Aryal et al.,2023),export IBA but do not touch IAA(Aryal et al.,2023).Recently,several reports have challenged our current view on the reported high substrate specificity of plant ABCs,which requires clarification.

关键词： specificity analogy exceptional

Glucocorticoids and nervous system plasticity

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Neural Regeneration Research 2016年第1期11卷 37-41页

作者： Kathryn m.madalena Jessica K.lerch Center for Brain and Spinal Cord Repair The Ohio State University Department of Neuroscience Wexner Medical Center at The Ohio State University

Glucocorticoid and glucocorticoid receptor（GC/GR） interactions alter numerous aspects of neuronal function. These consequences（e.g., anti-inflammatory vs. pro-inflammatory） can vary depending on the duration of GC exposure or central nervous system（CNS） injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.

关键词： glucocorticoids plasticity stress neuropathic pain

Quantification of human telomerase RNA(hTR)and human telomerase reverse transcriptase(hTERT)mRNA in testicular tissue of infertile patients

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Asian Journal of Andrology 2001年第4期3卷 263-270页

作者： mark Schrader markus müller Rüdiger Heicappell Bernd Straub Kurt miller Department of Urology Universitatsklinikum Benjamin FranklinFreie Universitat BerlinHindenburgdamm 3012200 BerlinGermany

Aim:To evaluate the quantitative detection of human telomerase RNA(hTR)and human telomerase reverse tran-scriptase(hTERT)mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients presentingwith non-obstructive ***:hTR and hTERT mRNA expression were quantified in 38 cryopre-served testicular tissue specimens by fluorescence real-time reverse transcription-polymerase chain reaction(RT-PCR)in a LightCycler(r).This was paralleled by conventional histological workup in all tissue specimens and additionalsemithin sectioning preparation in cases with maturation arrest(n=12)and Sertoli-cell-only syndrome(n=12).Re-sults;The average normalized hTERT expression(N_(hTERT))was 131.9±48.0 copies(mean±SD)in tissue speci-mens with full spermatogenesis,N_(hTERT)=51.2±17.2 copies in those with maturation arrest and N_(hTERT)=2.7±2.4copies in those with Sertoli-cell-only syndrome(SCOS).The discriminant analysis showed that detection of N_(hTERT)(N_(hTR))had a predictive value of 86.8%(55.3%)for correct classification in one of the three histological ***;Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue en-ables a molecular-diagnostic classification of *** detection of hTERT in testicular biopsies isthus well suited for supplementing the histopathological evaluation.

关键词： spermatogenesis human telomerase reverse transcriptase human telomerase RNA fertility

The influence of terrain age and altitude on the arthropod communities found on recently deglaciated terrain

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Current Zoology 2014年第2期60卷 203-220页

作者： markus FRANZEN Petra DIEKER UFZ Helmholtz-Centre for Environmental Research Department of Community Ecology Theodor-Lieser-Strasse 4 D-06120Halle (Saale) Germany Centre for methods Leuphana University Lfineburg Scharnhorststrage 1 D-21335 Liineburg Germany

Climate warming has been more pronounced in the Arctic than elsewhere, resulting in a recent rapid glacial retreat. Over 85% of the Almajallojekna glacier has disappeared over the last 115 years and it is one of the fastest retreating glaciers in Sweden. In 2011 and 2012, at 18 sites in the vicinity of the remaining glacier network, we sampled arthropods and related the species richness, abundance and proportion of herbivores to altitude （ranging from 824 to 1,524 m.a.s.1.） and the age of the site （ranging from 0 to 〉 115 years）. Temperature was measured at six sites and the average annual air temperature ranged from -3.7℃ to 1.1℃. In total, we recorded 3,705 arthropods from 117 species in nine different taxonomic groups. The most abundant and species-rich group was Coleoptera （1,381 individuals, 41 species） followed by Araneae （1,050 individuals, 15 species） and macrolepidoptera （732 individuals, 17 species）. Only at lower altitudes did the abundance and species richness of arthropods increase with increasing age of the site. The results were consistent among the studied taxonomic groups and when controlling for sam- piing intensity using two different approaches. The proportion of herbivores decreased with increasing age of the site and with increasing altitude. Clearly, altitude appears more important than the age of the site and, at higher altitudes, abundance, species richness and herbivory are low [Current Zoology 60 （2）： 203-220, 2014].

关键词： Climate change Glacier foreland Emerging communities Insects and arachnids Subarctic environment Speciesrichness

Saturated Hydraulic Conductivity from Field measurements Compared to Pedotransfer Functions in a Heterogeneous Arable Landscape

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Journal of Earth Science 2010年第6期21卷 923-930页

作者： Florian Winter markus Disse Institute of Hydro Sciences Universitt der Bundeswehr München

A high degree of uncertainty with regard to soil parameterisation limits the significance of physically-based simulation of distributed flood control measures, which affect the runoff generation process, such as land-use changes or differing soil tillage practices. In this study, the soil measurement data from the hillslope scale at the Scheyern research farm were compared to demonstrate this uncertainty. To account for the spatial variability of soils in the investigation area of Scheyern, different approaches were applied to estimate soil hydraulic properties and saturated hydraulic conductivity, and were compared to field measurements

关键词： hydraulic conductivity pedotransfer function hood infiltrometer uncertainty distributed flood control measures.

Single-mode and tunable VCSELs in the near-to mid-infrared Invited Paper

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Chinese Optics Letters 2008年第10期6卷 743-747页

作者： markus-Christian Amann Werner Hofmann Walter Schottky Institut Technische Universitt MnchenD-85748 GarchingGermany

Single-mode, long-wavelength vertical-cavity surface-emitting lasers （VCSELs） in the near- to mid-infrared covering the wavelength range from 1.3 to 2.3 μm are presented. This wide spectral emission range opens applications in gas sensing and optical interconnects. All these lasers are monolithically grown in the InGaAlAs-InP material system utilizing a buried tunnel junction （BTJ） as current aperture. Fabricated with a novel high-speed design with reduced parasitics, bandwidths in excess of 10 GHz at 1.3 and 1.55 μm have been achieved. Therefore, the coarse wavelength division multiplexing （CWDm） wavelength range of 1.3 to 1.6 μm at 10 Gb/s can be accomplished with one technology. Error-free data-transmission at 10 Gb/s over a fiber link of 20 km is demonstrated. One-dimensional arrays have been fabricated with emission wavelengths addressable by current tuning. micro-electro-mechanical system （mEmS） tunable devices provide an extended tuning range in excess of 50 nm with high spectral purity. All these devices feature continuous-wave （CW） operation with typical single-mode output powers exceeding 1 mW. The operation voltage is around 1 - 1.5 V and power consumption is as low as 10 - 20 mW. Furthermore, we have also developed VCSELs based on GaSb, targeting functionality of tunable diode laser spectroscopy （TDLS） applying a 1.84-μm VCSEL. at the wavelength range from 2.3 to 3.0 μm. The systems is shown by presenting a laser hygrometer

关键词： mode VCSEL Single-mode and tunable VCSELs in the near-to mid-infrared Invited Paper

River Stabilisation by Breach-ramps and Widening

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四川大学学报（工程科学版） 2005年第S1期37卷 34-40页

作者： markus AUFLEGER Tobias HAFNER Andreas NIEDERmAYR Iint.of Hydraulic and Water Resources Eng. Technische Universitt MünvhenGermany

Numerous gravel-bed rivers are affected by unceasing degradation problems,mostly caused or in- creased by technical measures *** Germany removing the bank fixations is regarded as a concept to dissolve the *** allowing lateral erosion and in consequence river widening the bed load transport ca- pacity will be *** the eroded bank material will serve as additional sediment influx. Nevertheless in some cases additional measures are required for a sustainable stabilization o...

关键词： river widening breach-ramps