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Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

Nano Research 2018年第2期11卷 913-928页

作者： Karin Kornmueller Bernhard Lehofer Gerd Leitinger Heinz Amenitsch Ruth Prassl institute of biophysics medical university of graz BioTechMed-Graz Graz Austria institute of Cell Biology Histology and Embryology Research Unit Electron Microscopic Techniques Medical University of Graz Graz Austria institute of Inorganic Chemistry graz university of Technology graz Austria

Lipids exhibit an extraordinary polymorphism in self-assembled mesophases, with lamellar phases as the most relevant biological representative. To mimic lipid lamellar phases with amphiphilic designer peptides, seven systematically varied short peptides were engineered. Indeed, four peptide candidates （V4D, V4WD, V4WD2, I4WD2） readily self-assembled into lamellae in aqueous solution. Small-angle X-ray scattering （SAXS） patterns revealed ordered lamellar structures with a repeat distance of 4-5 nm. Transmission electron microscopy （TEM） images confirmed the presence of stacked sheets. Two derivatives （V3D and V4D2） remained as loose aggregates dispersed in solution; one peptide （L4WD2） formed twisted tapes with internal lameUae and an antiparaUel -type monomer aligrtment. To understand the interaction of peptides with lipids, they were mixed with phosphatidylcholines. Low peptide concentrations （1.1 mM） induced the formation of a heterogeneous mixture of vesicular structures. Large multilamellar vesicles （MLV, d-spacing - 6.3 nm） coexisted with oligo- or unilamellar vesicles （- 50 nm in diameter） and bicelle-like structures （- 45 nm length, - 18 nm width）. High peptide concentrations （11 mM） led to unilamellar vesicles （ULV, diameter - 260-280 nm） with a homogeneous mixing of lipids and peptides. SAXS revealed the temperature-dependent fine structure of these ULVs. At 25 ℃ the bilayer is in a fully Interdigitated state （headgroup-to-headgroup distance dH, -2.9 nm）, whereas at 50 ℃this interdigitation opens up （dtm- 3.6 nm）. Our results highlight the versatility of self-assembled peptide superstructures. Subtle changes in the amino acid composition are key design elements in creating peptide- or lipid- peptide nanostructures with richness in morphology similar to that of naturally occurrin~ lioids.

关键词： amphiphilic designerpeptides lipids nanostructures lamellae small-angle X-rayscattering (SAXS) transmission electronmicroscopy (TEM)

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Optopharmacological control of TRPC channels by coumarin-caged lipids is associated with a phototoxic membrane effect

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Science China(Life Sciences) 2016年第8期59卷 802-810页

作者： Oleksandra Tiapko Bernadett Bacsa Gema Guedes de la Cruz Toma Glasnov Klaus Groschner institute of biophysics Medical University of GrazBio Tech Med-GrazHarrachgasse 21Graz 8010Austria institute of Chemistry University of GrazNAWI GrazBio Tech Med-GrazHeinrichstrasse 28Graz 8010Austria

Photouncaging of second messengers has been successfully employed to gain mechanistic insight of cellular signaling path- ways. One of the most enigmatic processes of ion channel regulation is lipid recognition and lipid-gating of TRPC channels, which represents pivotal mechanisms of cellular Ca2＋ homeostasis. Recently, optopharmacological tools including caged lipid mediators became available, enabling an unprecedented level of temporal and spatial control of the activating lipid species within a cellular environment. Here we tested a commonly used caged ligand approach for suitability to investigate TRPC sig- naling at the level of membrane conductance and cellular Ca2＋ handling. We report a specific photouncaging artifact that is triggered by the cage structure coumarin at UV illumination. Electrophysiological characterization identified a light-dependent membrane effect of coumarin. UV light （340 nm） as used for photouncaging, initiated a membrane conductance specifically in the presence of coumarin as low as 30 pmol L-1 concentrations. This conductance masked the TRPC3 conductance evoked by photouncaging, while TRPC-mediated cellular Ca2＋ responses were largely preserved. The observed light-induced membrane effects of the released caging moiety may well interfere with certain cellular functions, and prompt caution in using couma- fin-caged second messengers in cellular studies.

关键词： caged diacylglycerols TRPC channels Ca2+ signaling optopharmacology

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Tracking morphologies at the nanoscale： Self-assembly of an amphiphilic designer peptide into a double helix superstructure

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Nano Research 2015年第6期8卷 1822-1833页

作者： Karin Kornmueller Ilse Letofsky-Papst Kerstin Gradauer Christian Mikl Fernando Cacho-Nerin Mario Leypold Walter Keller Gerd Leitinger Heinz Amenitsch Ruth Prassl institute of biophysics Medical University ofGraz BioTechMed-Graz 8010 Graz Austria institute for Electron Microscopy and Nanoanalysis Graz University of Technology and Graz Centre for Electron Microscopy 80 10 Graz A us tria institute of Inorganic Chemistry Graz University of Technology 8010 Graz Austria institute of Organic Chemistry Graz University of Technology 8010 Graz Austria institute for Molecular Biosciences KarI-Franzens-University Graz 8010 Graz Austria Research Unit Electron Microscopic Techniques Institute of Cell Biology Histology and Embryology Medical University of Graz 80 10 Graz A us tria Center for medical Research Medical University of Graz 8010 Graz Austria

Hierarchical self-assembly is a fundamental principle in nature, which gives rise to astonishing supramolecular architectures that are an inspiration for the development of innovative materials in nanotechnolog）a Here, we present the unique structure of a cone-shaped amphiphilic designer peptide. While tracking its concentration-dependent morphologies, we observed elongated bilayered single tapes at the beginning of the assembly process, which further developed into novel double-helix-like superstructures at high concentrations. This architecture is characterized by a tight intertwisting of two individual helices, resulting in a periodic pitch size over their total lengths of several hundred nanometers. Solution X-ray scattering data revealed a marked 2-layered internal organization. All these characteristics remained unaltered for the investigated period of almost three months. In their collective morphology, the assemblies are integrated into a network with hydrogel characteristics. Such a peptide-based structure holds promise as a building block for next-generation nanostructured biomaterials.

关键词： double helix amphiphilic designerpeptide self-assembl)~SAXS TEM spectroscopy

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Lymph node staging in colorectal cancer:Old controversies and recent advances

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World Journal of Gastroenterology 2013年第46期19卷 8515-8526页

作者： Annika Resch Cord Langner institute of Pathology Medical University of Graz

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal *** affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node *** addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node *** include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be *** to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone *** prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved *** invasion has been identified as additional prognostic *** step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological *** clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.

关键词： Colon cancer Rectum cancer Tumor stag-ing Lymph node metastasis Prognosis Sentinel lymph node Lymph node ratio Extracapsular invasion Im-munohistochemistry Molecular analysis

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Rarity among benign gastric tumors: Plexiform fibromyxoma-Report of two cases

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World Journal of Gastroenterology 2017年第31期23卷 5817-5822页

作者： Kinga Szurian Holger Till Eva Amerstorfer Nicole Hinteregger Hans-Jorg Mischinger Bernadette Liegl-Atzwanger Iva Brcic institute of Pathology Medical University of Graz Department of Paediatric and Adolescent Surgery Medical University of Graz Department of Radiology Division of NeuroradiologyVascular and Interventional RadiologyMedical University of Graz Department of Surgery Medical University of Graz

Plexiform fibromyxoma is a very rare mesenchymal tumor of the stomach, found almost exclusively in the antrum/pylorus region. The most common presenting symptoms are anemia, hematemesis, nausea and unintentional weight loss, without sex or age predilection. We describe here two cases of plexiform fibromyxoma, involving a 16-year-old female and a 34-year-old male. Both patients underwent complete resection(R0) by distal gastrectomy and retrocolic gastrojejunostomy(according to Billroth 2); for both, the postoperative course was uneventful. Histology showed multiple intramural and subserosal nodules with characteristic plexiform growth, featuring bland spindle cells situated in an abundant myxoid stroma with low mitotic activity. Immunohistochemistry showed α-smooth muscle actin-positive spindle cells, focal positivity for CD10, and negative staining for KIT, DOG1, CD34, S100, β-catenin, STAT-6 and anaplastic lymphoma kinase. One of the cases showed focal positivity for h-caldesmon and desmin. Upon followup, no sign of disease was found. In the differential diagnosis of plexiform fibromyxoma, it is important to exclude the more common gastrointestinal stromal tumors as they have greater potential for aggressivebehavior. Other lesions, like neuronal and vascular tumors, inflammatory fibroid polyps, abdominal desmoid-type fibromatosis, solitary fibrous tumors and smooth muscle tumors, must also be excluded.

关键词： Plexiform fibromyxoma Plexiform angiomyxoid myofibroblastic tumor Gastrointestinal stromal tumor Stomach Benign gastric tumor

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From contraction to gene expression:nanojunctions of the sarco/endoplasmic reticulum deliver site-and function-specific calcium signals

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Science China(Life Sciences) 2016年第8期59卷 749-763页

作者： A.Mark Evans Nicola Fameli Oluseye A.Ogunbayo Jingxian Duan Jorge Navarro-Dorado Centre for Integrative Physiology College of Medicine and Veterinary MedicineHugh Robson BuildingUniversity of EdinburghEdinburgh EH8 9XDUK institute of biophysics Medical University of GrazGraz 8010Austria

Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2 b and Ry R1 are preferentially targeted to the sarcoplasmic reticulum(SR) proximal to the plasma membrane(PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2 a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. Ry R3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of Ry R2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear Ry R3 s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via Ry R2 in order to elicit contraction. Data also suggest that unique SERCA and Ry R are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades.

关键词： calcium nanojunction ryanodine receptor sarco/endoplasmic reticulum calcium ATPase smooth muscle gene expression contraction

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Co-occurrence of carbohydrate malabsorption and primary epiploic appendagitis

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World Journal of Gastroenterology 2015年第35期21卷 10242-10245页

作者： Wolfgang J Schnedl Peter Kalmar Harald Mangge Robert Krause Sandra J Wallner-Liebmann Practice for General Internal Medicine Department of Radiology Medical University of Graz Clinical institute for medical and Chemical Laboratory Diagnosis MUG Coordinator BioTechMed GrazMedical University of Graz Department of Internal Medicine Medical University of Graz institute of Pathophysiology Centre for Molecular MedicineMedical University of Graz

Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with hydrogen(H2) breath tests and correlated to carbohydrate malabsorption. During performing these H2-breath tests the patient presented with an acute, localized, non-migratory pain in the left lower abdominal quadrant. Primary epiploic appendagitis is a rare cause of abdominal acute or subacute complaints and diagnosis of primary epiploic appendagitis(PEA) is made when computed tomography reveals a characteristic lesion. We report on a patient with cooccurrence of lactose and fructose malabsorption, which was treated successfully with a diet free of culprit carbohydrates, with PEA recovering without medication or surgical treatment within few days. Since the abdominal unspecific symptoms had been present for months, they appeared not to be correlated to the acute localized abdominal pain, therefore we speculate on a random co-occurrence of combined carbohydrate malabsorption and PEA.

关键词： Carbohydrate malabsorption Fructose malabsorption

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Degradation behavior and osseointegration of Mg-Zn-Ca screws in different bone regions of growing sheep:a pilot study

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Regenerative Biomaterials 2023年第1期10卷 1-14页

作者： Romy Marek Hanna C´wieka Nicholas Donohue Patrick Holweg Julian Moosmann Felix Beckmann Iva Brcic Uwe Yacine Schwarze Kamila Iskhakova Marwa Chaabane Sandra Sefa Berit Zeller-Plumhoff Annelie-Martina Weinberg Regine Willumeit-Ro¨mer Nicole Gabriele Sommer Department of Orthopaedics and Traumatology Medical University of Graz8010 GrazAustria institute of Metallic Biomaterials Helmholtz-Zentrum Hereon GmbH21502 GeesthachtGermany National institute for Bioprocessing Research and Training University College DublinDublin 4Ireland institute of Materials Physics Helmholtz-Zentrum Hereon GmbH21502 GeesthachtGermany D&R institute of Pathology Medical University of Graz8010 GrazAustria Department of Dental Medicine and Oral Health Medical University of Graz8010 GrazAustria SCANCO medical AG 8306 Wangen-BruttisellenSwitzerland

Magnesium(Mg)-based implants are highly attractive for the orthopedic field and may replace titanium(Ti)as support for fracture *** determine the implant-bone interaction in different bony regions,we implanted Mg-based alloy ZX00(Mg<0.5 Zn<0.5 Ca,in wt%)and Ti-screws into the distal epiphysis and distal metaphysis of sheep *** implant degradation and osseointegration were assessed in vivo and ex vivo after 4,6 and 12weeks,using a combination of clinical computed tomography,medium-resolution micro computed tomography(mCT)and high-resolution synchrotron radiation mCT(SRmCT).Implant volume loss,gas formation and bone growth were evaluated for both implantation sites and each bone region ***,histological analysis of bone growth was performed on embedded hard-tissue *** demonstrate that in all cases,the degradation rate of ZX00-implants ranges between 0.23 and 0.75mm/*** highest degradation rates were found in the ***-to-implant contact varied between the time points and bone types for both ***,bone-volume-to-total-volume was higher around ***,we found an increased cortical thickness around the ZX00-screws when compared with the *** results showed the suitability of ZX00-screws for implantation into the distalmeta-and epiphysis.

关键词： biodegradable implants magnesium-based alloys computed tomography Mg-Zn-Ca sheep histology

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Isospin Dependence of Fragmentation Cross Sections in Collisions of Neutron-Rich Ca Isotopes with ^(12)C

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Plasma Science and Technology 2012年第5期14卷 396-398页

作者：马春旺张艳芳金婵 Department of Physics Henan Normal University institute of biophysics the Second Military Medical University

The cross sections of fragments （δf） produced in the even 36～52Ca projectile frag- mentation reactions at 80 AMeV are calculated in the framework of the statistical abrasion- ablation model. The distributions of af are investigated. Linear correlations between the peak positions of the distributions and charge numbers of the fragment isotopes are found.

关键词： heavy-ion collisions neutron density distribution neutron-rich nucleus

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Executionary pathway for apoptosis: lessons from mutant mice

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Cell Research 2000年第4期10卷 267-278页

作者： WOO MINNA RAZQALLAH HAKEM TAK W. MAK Amgen institute and Ontario Cancer institute, Departments of Immunology and medical biophysics, university of Toronto, Canada 1Amgen institute and Ontario Cancer institute Departments of Immunology and Medical Biophysics University of Toronto Canada 1Amgen institute and Ontario Cancer institute Departments of Immunology and Medical Biophysics University of Toronto Canada 1Amgen institute and Ontario Cancer institute Departments of Immunology and Medical Biophysics University of Toronto Canada

Apoptosis or programmed cell death (PCD) is an evolutionarily conserved cellular process that is essential for normal development and homeostasis of multicellular organisms. Defects in the apoptosis signaling result in many diseases including autoimmune diseases and cancer. The apoptosis signaling pathway was first described genetically in the nematode Caenorhabditis elegans which serves as a framework for the more complex apoptotic pathways that exist in mammals. In this review, we will discuss the apoptotic pathways that are emerging in mammals as elucidated by studies of gene-targeted mutant mice.

关键词： Apoptosis progammed cell death caspases death receptors mitochondri?

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