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Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage

Neural Regeneration Research 2021年第12期16卷 2534-2541页

作者： Mohamed Tawfik Xiwei Zhang Lisa Grigartzik Peter Heiduschka Werner Hintz petra Henrich-Noack Berend van Wachem Bernhard A.Sabel Institute of Medical Psychology Otto von Guericke University of MagdeburgMagdeburgGermany Institute of Process Engineering Otto von Guericke University of MagdeburgMagdeburgGermany Department of Ophthalmology Münster University HospitalMünsterGermany Department of Neurology with Institute of Translational Neurology Münster University HospitalMünsterGermany Center of Behavioral Brain Sciences(CBBS) MagdeburgGermany

Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system *** developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve ***,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned *** non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological *** animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).

关键词： apoptosis brain caspase-3 drug delivery gene therapy in vivo confocal neuroimaging nanoparticles neurodegeneration neuroprotection retina siRNA

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A rice tubulin tyrosine ligase-like 12 protein affects the dynamic and orientation of microtubules

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Journal of Integrative Plant Biology 2021年第5期63卷 848-864页

作者： Kunxi Zhang Xin Zhu Steffen Durst petra Hohenberger Min‐Jung Han Gynheung An Vaidurya PSahi Michael Riemann Peter Nick Molecular Cell Biology Botanical InstituteKarlsruhe Institute of TechnologyKarlsruhe 76131Germany Aptamer Initiative Postech Biotech CenterPohang University of Science and TechnologyPohang‐siGyeongsangbuk‐do37673South Korea Department of Plant Molecular Systems Biotech Kyung Hee UniversityYongin 446‐701South Korea

The detyrosination/retyrosination cycle is the most common post-translational modification of α-*** of the conserved C-terminal tyrosine of α-tubulin by a still elusive tubulin tyrosine carboxypeptidase, and religation of this tyrosine by a tubulin tyrosine ligase(TTL), are probably common to all eukaryotes. Interestingly, for plants, the only candidates qualifying as potential TTL homologs are the tubulin tyrosine ligase-like 12 proteins. To get insight into the biological functions of these potential TTL homologs, we cloned the rice TTL-like 12 protein(Os TTLL12)andgeneratedoverexpression Os TTLL12-RFP lines in both rice and tobacco BY-2 cells. We found, unexpectedly, that overexpression of this Os TTLL12-RFP increased the relative abundance of detyrosinated α-tubulin in both coleoptile and seminal root, correlated with more stable microtubules. This was independent of the respective orientation of cortical microtubule, and followed by correspondingly changing growth of coleoptiles and seminal roots. A perturbed organization of phragmoplast microtubules and disoriented cell walls were further characteristics of this phenotype. Thus, the elevated tubulin detyrosination in consequence of Os TTLL12 overexpression affects structural and dynamic features of microtubules, followed by changes in the axiality of cell plate deposition and, consequently, plant growth.

关键词： microtubule phragmoplast rice tobacco BY-2 tubulin detyrosination tubulin tyrosine carboxypeptidase tubulin tyrosine ligase tubulin tyrosine ligase-like 12

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Long-lived electron emission reveals localized plasmon modes in disordered nanosponge antennas

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Light(Science & Applications) 2017年第1期6卷 458-465页

作者： Germann Hergert Jan Vogelsang Felix Schwarz Dong Wang Heiko Kollmann petra Groß Christoph Lienau Erich Runge Peter Schaaf Carl von Ossietzky Universität Institut für PhysikCenter of Interface ScienceD-26129 OldenburgNiedersachsenGermany Technische Universität Ilmenau Institut für Physik and Institut für Mikro-und Nanotechnologien MacroNano®D-98693 IlmenauThüringenGermany Technische Universität Ilmenau Institut für Mikro-und Nanotechnologien MacroNano®and Institut für WerkstofftechnikFachgebiet Werkstoffe der ElektrotechnikD-98693 IlmenauThüringenGermany Forschungszentrum Neurosensorik Carl von Ossietzky UniversitätD-26111 OldenburgNiedersachsenGermany

We report long-lived,highly spatially localized plasmon states on the surface of nanoporous gold nanoparticles—nanosponges—with high excitation *** is well known that disorder on the nanometer scale,particularly in two-dimensional systems,can lead to plasmon localization and large field enhancements,which can,in turn,be used to enhance nonlinear optical effects and to study and exploit quantum optical ***,we introduce promising,three-dimensional model systems for light capture and plasmon localization as gold nanosponges that are formed by the dewetting of gold/silver bilayers and *** study light-induced electron emission from single nanosponges,a nonlinear process with exponents of n≈5...7,using ultrashort laser pulse excitation to achieve femtosecond time *** long-lived electron emission process proves,in combination with optical extinction measurements and finite-difference time-domain calculations,the existence of localized modes with lifetimes of more than 20 *** electrons couple efficiently to the dipole antenna mode of each individual nanosponge,which in turn couples to the ***,individual gold nanosponges are cheap and robust disordered nanoantennas with strong local resonances,and an ensemble of nanosponges constitutes a meta material with a strong polarization independent,nonlinear response over a wide frequency range.

关键词： disorder-induced plasmon localization nanoantennas nanoporous gold nanoparticles ultrafast photoemission spectroscopy

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Morphological characteristics of blood cells in monitor lizards:is erythrocyte size linked to actual body size?

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Integrative Zoology 2013年第1期8卷 39-45页

作者： petra FRÝDLOVÁ Jan HNÍZDO Lenka CHYLÍKOVÁ OlgaŠIMKOVÁ Veronika CIKÁNOVÁ Petr VELENSKÝ Daniel FRYNTA Department of Zoology Charles University in PraguePragueCzech Republic Animal Clinic PragueCzech Republic Prague Zoo PragueCzech Republic

Blood cell morphology and count are not uniform across ***,between-species comparisons revealed that the size of red blood cells is associated with body size in some lizard taxa,and this finding was interpreted in the context of the metabolic *** the present study,we examined the numbers and the size of blood cells in 2 species of monitor lizards,the mangrove-dwelling monitor(Varanus indicus)and the savannah monitor(***),and we compared these traits in individuals of different body *** results revealed that during the course of ontogeny,the size of red blood cells increases with body *** the mass-specific metabolic rate decreases with body size and the cell volume-to-surface ratio decreases with the cell size,changes in the erythrocyte size might be the result of oxygen transport adjustment.

关键词： blood parameters body size erythrocyte size metabolic theory Varanidae

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Pancreatic Castleman disease treated with laparoscopic distal pancreatectomy

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 332-334页

作者： Filip ecka Alexander Ferko Bohumil Jon Zdeněk ubrt petra Kaparová Rudolf Repák Department of Surgery Faculty of Medicine and University Hospital Hradec Králové Department of Field Surgery Military Health Science Faculty Hradec Králové Defence University Brno Fingerland Department of Pathology Faculty of Medicine and University Hospital Hradec Králové Second Department of Internal Medicine Faculty of Medicine and University Hospital Hradec Králové

BACKGROUND: Castleman disease is an uncommon lympho-proliferative disorder most frequently occurring in the mediastinum. Abdominal forms are less frequent, with pancreatic localization of the disease in particular being extremely rare. Only seventeen cases have been described in the world literature. METHOD: This report describes an interesting and unusual case of pancreatic Castleman disease treated with laparoscopic resection. RESULTS: A 48-year-old woman presented with epigastric pain. CT scan showed a well-encapsulated mass on the ventral border of the pancreas. Endosonography with fine needle aspiration biopsy was performed. Biopsy showed lymphoid elements and structures of a normal lymph node. The patient was treated with laparoscopic distal pancreatectomy. The pancreas was transected with a Ligasure device and the pancreatic stump was secured with a manual suture. One year after surgery the patient was complaint-free and showed no signs of recurrence of the disease. CONCLUSIONS: Laparoscopic distal pancreatectomy is a feasible and safe method for the treatment of lesions in the body and tail of the pancreas. Transection of the pancreas with a Ligasure device offers the advantages of low bleeding and low risk of pancreatic fistula.

关键词： Castleman disease pancreas laparoscopic distal pancreatectomy Ligasure

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Implementing BIM in the German Architecture, Engineering and Construction Market---A Survey about the Potentials and Barriers

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Journal of Civil Engineering and Architecture 2013年第7期7卷 812-820页

作者： petra von Both Building Lifecycle Management Department Karlsruhe Institute of Technology Karlsruhe 76131 Germany

The research project ＂BIM--Potentials and Barriers＂ aims to analyze existing BIM practice and the barriers to the implementation of the approach in Germany. Overseen by an ＂advisory board＂ with high-profile field, public-authority and AEC （architecture, engineering and construction market） association representatives, a set of hypotheses has been drawn up and subjected to evaluation by means of a detailed survey. The survey, having identified the relevant stakeholders, first attempts to discover how BIM （building information modeling） is currently used. The potentials of the application of BIM in the different processes and target groups are also determined, as well as the barriers and constraints. Enhancement of the considered areas is an important project solution approach： Besides technological aspects, the analysis also focuses on contracting, norms and processes, as well as education, knowledge and role perception.

关键词： BIM survey collaborative engineering virtual engineering product modelling.

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Patient age and duration of colonoscopy are predictors for adenoma detection in both proximal and distal colon

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World Journal of Gastroenterology 2015年第2期21卷 525-532页

作者： Peter Klare Stefan Ascher Alexander Hapfelmeier petra Wolf Analena Beitz Roland M Schmid Stefan von Delius Ⅱ.Medizinische Klinik Klinikum rechts der IsarTechnischen Universit?t München81675 MunichGermany Institut für Medizinische Statistik und Epidemiologie Klinikum rechts der IsarTechnische Universit?t München81675 MunichGermany

AIM: To investigate the relation of patient characteristics and procedural parameters to the endoscopic detection rate of colonic adenomas. Further to study,which factors may be capable to predict the localization of adenomatous ***: We used the data base of a prospective randomized colonoscopy study(The Colo Cap trial) to identify patients being diagnosed with colon adenoma. Logistic regression analysis was conducted to reveal predictors for adenoma detection in the entire colon and also with respect to the proximal and distal part. Covariates including age, gender, duration of colonoscopy and comorbidities were defined to determine association between predictors and adenoma ***: Equal numbers of adenomas were detected in the proximal and distal side of the splenic flexure [126(57%) vs 94(43%), P = 0.104]. Simultaneous occurrence of adenomas in both sides of the colon was rare. The appearance of both proximal and distal adenoma was associated with increasing age(P = 0.008 and P = 0.024) and increasing duration of colonoscopy(P < 0.001 and P = 0.001). Male gender was a predictor for adenoma detection in the proximal colon(P = 0.008) but statistical significance was slightly missed with respect to the distal colon(P = 0.089). Alcohol abuse was found to be a predictor for the detection of distal adenoma(P = 0.041). CONCLUSION: Increasing age and longer duration of colonoscopy are factors with a strong impact on adenoma detection both in the proximal and distal colon. Since proximal adenomas occurred in absence of distal adenomas, complete colonoscopy should be performed for screening.

关键词： Adenoma Colorectal carcinoma Distal Colonoscopy Pr

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Colorectal cancer screening:20 years of development and recent progress

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World Journal of Gastroenterology 2014年第14期20卷 3825-3834页

作者： Miroslav Zavoral Stepan Suchanek Ondrej Majek Premysl Fric petra Minarikova Marek Minarik Bohumil Seifert Ladislav Dusek Department of Medicine 1st Faculty of MedicineMilitary University HospitalCharles University Institute of Biostatistics and Analyses Masaryk University Genomac Research Institute Centre for Applied Genomics of Solid Tumors Institute of General Medicine 1st Faculty of MedicineCharles University

Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily *** trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality *** year,approximately 8000 people are diagnosed with CRC and some 4000 die from this *** years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in ***,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT *** program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of *** the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening *** overall program expanded to cover 25.0%of the target population by ***,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.

关键词： Colorectal cancer Population-based screening program Colonoscopy Fecal occult blood test

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Hepatic phenotypes of HNF1B gene mutations:A case of neonatal cholestasis requiring portoenterostomy and literature review

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World Journal of Gastroenterology 2015年第8期21卷 2550-2557页

作者： Radana Kotalova petra Dusatkova Ondrej Cinek Lenka Dusatkova Tomas Dedic Tomas Seeman Jan Lebl Stepanka Pruhova Department of Pediatrics 2nd Faculty of Medicine Charles University in Prague and University Hospital Motol

Hepatocyte nuclear factor 1-β(HNF1B)defects cause renal cysts and diabetes syndrome(RCAD),or HNF1B-maturity-onset diabetes of the ***,the hepatic phenotype of HNF1B variants is not well *** present a female neonate born small for her gestational age[birth weight 2360 g;-2.02standard deviations(SD)and birth length 45 cm;-2.40 SD at the 38th gestational week].She developed neonatal cholestasis due to biliary atresia and required surgical intervention(portoenterostomy)when 32-d *** the operation,icterus resolved,but laboratory signs of liver dysfunction *** had hyperechogenic kidneys prenatally with bilateral renal cysts and pancreatic hypoplasia postnatally that led to the diagnosis of an HNF1B *** represents the most severe hepatic phenotype of an HNF1B variant recognized thus far.A review of 12 published cases with hepatic phenotypes of HNF1B defects allowed us to distinguish three severity levels,ranging from neonatal cholestasis through adult-onset cholestasis to noncholestatic liver impairment,all of these are associated with congenital renal cysts and mostly with diabetes later in *** conclude that to detect HNF1B variants,neonates with cholestasis should be checked for the presence of renal cysts,with special focus on those who are born small for their gestational ***,patients with diabetes and renal cysts at any age who develop cholestasis and/or exocrine pancreatic insufficiency should be tested for HNF1B variants as the true etiological factor of all disease *** observations are needed to confirm the potential reversibility of cholestasis in infancy in HNF1B mutation/deletion carriers.

关键词： Hepatocyte nuclear factor 1-β Renal cysts and diab

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Contrast-enhanced ultrasonography in the evaluation of incidental focal liver lesions: A cost-effectiveness analysis

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World Journal of Gastroenterology 2016年第38期22卷 8605-8614页

作者： Miriama Smajerova Hana petrasova Jirina Little petra Ovesna Tomas Andrasina Vlastimil Valek Eva Nemcova Barbora Miklosova Department of Radiology University Hospital Brno Faculty of Medicine Masaryk University Institute of Biostatistics and Analyses Masaryk University

AIM To determine whether contrast-enhanced ultrasonography(CEUS) as the first-line method is more costeffective in evaluating incidentally discovered focal liver lesions(FLLs) than is computed tomography(CT) and magnetic resonance imaging(MRI). METHODS Between 2010 and 2015, our prospective study enrolled 459 patients with incidentally found FLLs. The biological nature of FLLs was assessed by CEUS in all patients. CT or MRI examinations were added in unclear cases. The sensitivity and specificity of CEUS were calculated. The total costs of CEUS examinations and of the added examinations performed in inconclusive cases were calculated. Afterwards, the theoretical expenses for evaluating incidentally discovered FLLs using CT or MRI as the first-line method were calculated. The resultswere compared. RESULTS The total cost of the diagnostic process using CEUS for all enrolled patients with FLLs was 75884 USD. When the expenses for additional CT and MRI examinations performed in inconclusive cases were added, the total cost was 90540 US dollar(USD). If all patients had been examined by CT or MR as the first-line method, the costs would have been 78897 USD or 384235 USD, respectively. The difference between the cost of CT and CEUS was 3013 USD(4%) and that between MRI and CEUS was 308352 USD(406.3%). We correctly described 97.06% of benign or malignant lesions, with 96.99% sensitivity and 97.09% specificity. Positive predictive value was 94.16% and negative predictive value was 98.52%. In cases with 4 and more lesions, malignancy is significantly more frequent and inconclusive findings significantly less frequent(P < 0.001).CONCLUSION While the costs of CEUS and CT in evaluating FLLs are comparable, CEUS examination is far more costeffective in comparison to MRI.

关键词： Contrast-enhanced ultrasonography Focal liver lesion Computed tomography Magnetic resonance imaging Economic analysis

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