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Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing

Bone Research 2022年第3期10卷 469-481页

作者： Mubashir Ahmad Benjamin Thilo Krüger Torsten Kroll Sabine Vettorazzi Ann-Kristin Dorn Florian Mengele Sooyeon Lee Sayantan Nandi Dilay Yilmaz Miriam Stolz Naveen Kumar Tangudu David Carro Vázquez Johanna Pachmayr Ion Cristian Cirstea maja vujic spasic Aspasia Ploubidou Anita Ignatius Jan Tuckermann Institute of Comparative Molecular Endocrinology(CME) Ulm UniversityHelmholtzstrasse 8/189081 UlmGermany Institute of Orthopedic Research and Biomechanics Ulm UniversityHelmholtzstrasse 1489081 UlmGermany Leibniz Institute on Aging–Fritz Lipmann Institute(FLI) Beutenbergstrasse 11D-07745 JenaGermany Praxisklinik für Orthopädie Unfall-und Neurochirurgie Prof.Bischoff/Dr.Spies/Dr.Mengele89231 Neu-UlmGermany Paracelsus Medizinische Privatuniverstät Institute of PharmacyStrubergasse 215020 SalzburgAustria Department of Endocrinology Ludwig Maximilians University MunichMunich 80336Germany Present address:Institute of Orthopedic Research and Biomechanics Ulm UniversityHelmholtzstrasse 1489081 UlmGermany Present address:UPMC Hillman Cancer Center Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh5115 Center Avenue15232 PittsburghPAUSA Present address:TAmiRNA GmbH Leberstrasse 201110 ViennaAustria

Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.

关键词： Cdk5 healing expression

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New strategy for reducing the EHL friction in steel contacts using additive-formed oleophobic boundary films

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Friction 2021年第6期9卷 1346-1360页

作者： Mitjan KALIN maja KUS Laboratory for Tribology and Interface Nanotechnology Faculty of Mechanical EngineeringUniversity of LjubljanaBogišićeva 81000 LjubljanaSlovenia

In this study we present a mechanism for the elastohydrodynamic(EHD)friction reduction in steel/steel contacts,which occurs due to the formation of oleophobic surface boundary layers from common boundary-lubrication *** simple organic additives(amine,alcohol,amide,and fatty acid)with different molecular structures were employed as the model *** was found that the stronger chemisorption at 100℃,rather than the physisorption at 25℃,is more effective in friction reduction,which reaches 22%.What is more,EHD friction reduction was obtained in steel/steel contacts without use of the diamond-like carbon(DLC)coatings with their wetting or thermal effect,which was previously suggested as possible EHD friction reduction mechanism;yet about the same friction reduction of about 20%was obtained here—but with much simpler and less expensive technology,namely with the adsorbed oleophobic surface layers.A small variation in the additive’s molecular structure results in significant changes to the friction,indicating good potential in future EHD lubrication technology,where these additives could be designed and well optimised for notable reduction of the friction losses in the EHD regime.

关键词： elastohydrodynamic(EHD) friction additives oleophobic layer boundary slip

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Ultrasound-triggered directional release from turmeric capsules

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Particuology 2021年第4期19卷 19-27页

作者： Tomasz Kubiak maja Zubko Arkadiusz Józefczak Chair of Acoustics Faculty of PhysicsAdam Mickiewicz University in PoznańUniwersytetu Poznańskiego 261-614 PoznańPoland Hipolit Cegielski State University of Applied Sciences Stefana Wyszyńskiego 3862-200 GnieznoPoland

The scientific interest in capsules with the shell composed of fused microparticles is still growing due to a large number of practical ***-designed capsules should ensure the safe cargo delivery and facilitate its controlled release on *** biocompatibility and biodegradability are additional essential features of structures intended for biomedical *** paper presents two kinds of ultrasound sensitive capsules:the first type with the homogeneous shell made of a monolayer of fine turmeric granules,and the other with Janus shell composed of two different materials *** granules and synthetic polystyrene *** demonstrated that plane ultrasonic waves with low intensity and high frequency and also focused ultrasound can act as a trigger for smooth liberation of a liquid cargo,in our case,the dispersion of probiotic *** ultrasound-induced puncture of the shell was followed by unidirectional and controlled release of encapsulated *** case of Janus structures,in addition to sonication time and ultrasound frequency,distinct mechanical properties of two shell regions also influenced the course of content liberation *** expect that the use of natural material such as turmeric granules for the formation of the shells of the ultrasound-responsive capsules can further increase the range of their potential applications.

关键词： Ultrasound-responsive capsules Turmeric shells Janus capsules Controlled release

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Multi-Objective Hybrid Sailfish Optimization Algorithm for Planetary Gearbox and Mechanical Engineering Design Optimization Problems

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Computer Modeling in Engineering & Sciences 2025年第2期142卷 2111-2145页

作者： Miloš Sedak maja Rosic Božidar Rosic Faculty of Mechanical Engineering University of BelgradeBelgrade11000Serbia

This paper introduces a hybrid multi-objective optimization algorithm,designated HMODESFO,which amalgamates the exploratory prowess of Differential Evolution(DE)with the rapid convergence attributes of the Sailfish Optimization(SFO)*** primary objective is to address multi-objective optimization challenges within mechanical engineering,with a specific emphasis on planetary gearbox *** algorithm is equipped with the ability to dynamically select the optimal mutation operator,contingent upon an adaptive normalized population spacing *** efficacy of HMODESFO has been substantiated through rigorous validation against estab-lished industry benchmarks,including a suite of Zitzler-Deb-Thiele(ZDT)and Zeb-Thiele-Laumanns-Zitzler(DTLZ)problems,where it exhibited superior *** outcomes underscore the algorithm’s markedly enhanced optimization capabilities relative to existing methods,particularly in tackling highly intricate multi-objective planetary gearbox optimization ***,the performance of HMODESFO is evaluated against selected well-known mechanical engineering test problems,further accentuating its adeptness in resolving complex optimization challenges within this domain.

关键词： Multi-objective optimization planetary gearbox gear efficiency sailfish optimization differential evolution hybrid algorithms

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In polytocous mammals,weakling neonates,but not their stronger littermates,benefit from specialized foraging

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Current Zoology 2019年第6期65卷 675-683页

作者： Janko SKOK maja PREVOLNIK POVSE Faculty of Agriculture and Life Sciences University of Maribor2311 HoceSlovenia

Adjusting foraging strategies is a common phenomenon within groups of animals competing for the same *** polytocous mammals,neonates concurrently compete for limited milk and alternate between two foraging(suckling)strategies:adaptable exploratory foraging with random sampling of teats,and ordered foraging with a tendency towards exploiting a particular suckling *** theoretical(game theory)models have shown that weaker siblings in particular benefit from foraging specialization(suckling order).Neonate piglets establish a well-defined suckling order that develops gradually and fluctuates throughout the lactation period,implying the existence of inter-individual differences in foraging *** therefore analyzed suckling behavior in pigs to determine whether one foraging strategy was more beneficial to neonates in terms of their body weight and foraging *** found that intermediate and heavy littermates tended to adjust their suckling strategy according to the foraging environment;however,the selected foraging strategy did not affect their overall growth *** individuals that consumed significantly less milk did not greatly alternate their foraging strategy according to the foraging environment but their growth rate was significantly higher whenever they performed less-exploratory foraging *** suckling order appeared to be a relatively stable behavioral phenotype,it was beneficial exclusively for *** results confirm theoretical predictions and indicate that specializing in a suckling position is a beneficial strategy for weaker,light *** findings suggest that physically weaker neonates might have driven the evolution of neonatal foraging specialization.

关键词： neonatal foraging strategy pig polytocous mammals suckling

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On ε-Derivations and Local ε-Derivations

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Acta Mathematica Sinica,English Series 2010年第8期26卷 1555-1566页

作者： Ajda FONER maja FONER Faculty of Management University of Primorska Faculty of Logistics University of Maribor

In this paper, we describe ∈-derivations in certain graded algebras by their actions on elements satisfying some special conditions. One of the main results is applied to local ∈-derivations on some certain graded a... 详细信息

关键词： Graded algebras graded prime algebras graded semiprime algebras ∈-derivations local ∈-derivations

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Inflammatory bowel disease in liver transplanted patients

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World Journal of Gastroenterology 2017年第18期23卷 3214-3227页

作者： Tajana Filipec Kanizaj maja Mijic Department of Gastroenterology University Hospital MerkurSchool of MedicineUniversity of Zagreb University Hospital Merkur

Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Antitumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.

关键词： Inflammatory bowel disease Anti-TNF alpha therapy Liver transplantation Immunomodulatory therapy Immunosuppression Proctoproctocolectomy Risk factors

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Asynchronus bilateral ovarian torsions in girls-systematic review

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World Journal of Pediatrics 2017年第5期13卷 416-420页

作者： maja Raicevic Amulya Kumar Saxena Clinic for Pediatric Surgery and Orthopedic Nis Clinical Center NisSerbia Department of Pediatric Surgery Chelsea Children's HospitalChelsea and Westminster NHS Fdn TrustImperial College LondonUnited Kingdom

Background:Bilateral ovarian torsions with complete loss of ovaries is *** study analyzed the literature on bilateral ovarian torsions in girls to evaluate surgical options and ***:Literature was searched on Pubmed(R)(1987-2014) using terms 'bilateral','adnexal','ovary','torsion' and 'children'.Data were collected on age,surgical preference,pathology and ***:Thirteen articles were identified,and 9 met the inclusion criteria (5 case reports,4 original articles);and analyzed 17 girls (mean age:8.75 years,range:1-16).Bilateral oophorectomies (n=4),ipsilateral oophorectomy of severely affected ovary and contralateral oophoropexy (n=10),and detorsion of bilateral ovaries and bilateral oophoropexy (n=3) were *** torsion recurrence occurred after two *** and open surgery was done in 2 and 15 girls,*** etiology,there were simple tubo-ovarian torsions (n=8),polycystic ovary (n=1),polycystic ovary associated with Down syndrome (n=1) and corpus luteum cyst (n=1).No tumors were *** ultrasound follow-ups of ipsilateral oophorectomy and contralateral oophoropexy (n=5) confirmed follicular function (n=4) and viability and position of the ovary (n=l).Conclusions:Though extremely rare,school age girls present bilateral ovarian torsion,Ipsilateral oophorectomy and contralateral detorsion with oophoropexy has been the preferred approach.

关键词： asynchronous bilateral outcomes ovarian torsion surgery

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Language of plants: Where is the word?

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Journal of Integrative Plant Biology 2016年第4期58卷 343-349页

作者： maja impraga Junji Takabayashi Jarmo K.Holopainen Botanical Garden Faculty of Science Ghent University Department of Environmental Science University of Eastern Finland Center for Ecological Research Kyoto University

Plants emit biogenic volatile organic compounds（BVOCs） causing transcriptomic, metabolomic and behavioral responses in receiver organisms. Volatiles involved in such responses are often called ＂plant language＂. Arthropods having sensitive chemoreceptors can recognize language released by plants. Insect herbivores, pollinators and natural enemies respond to composition of volatiles from plants with specialized receptors responding to different types of compounds. In contrast, the mechanism of how plants＂hear＂ volatiles has remained obscured. In a plant-plant communication, several individually emitted compounds are known to prime defense response in receiver plants with a specific manner according to the chemical structure of each volatile compound. Further, composition and ratio of volatile compounds in the plant-released plume is important in plantinsect and plant-plant interactions mediated by plant volatiles. Studies on volatile-mediated plant-plant signaling indicate that the signaling distances are rather short, usually not longer than one meter. Volatile communication from plants to insects such as pollinators could be across distances of hundreds of meters. As many of the herbivore induced VOCs have rather short atmospheric life times, we suggest that in long-distant communications with plant volatiles,reaction products in the original emitted compounds may have additional information value of the distance to emission source together with the original plant-emitted compounds.

关键词： Green leaf volatiles plant-insect communication plant language semiochemicals volatiles

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Molecular heterogeneity of gelatin-binding proteins from human seminal plasma

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Asian Journal of Andrology 2010年第3期12卷 363-375,I0010页

作者： maja M. Kosanovic Miroslava M. Jankovic Department for Immunochemistry and Glycobiology Institute for the Application of Nuclear Energy-INEP University of Belgrade Banatska 31b Zemun-Belgrade 11080 Serbia

Defining the molecular characteristics of seminal plasma proteins is essential for understanding their function in physiological and pathological conditions. Starting from the predicted importance of human seminal plasma gelatin-binding proteins, comprising fibronectin （FN） and FN-related molecules, for male fertility, this study aims at gaining insight into their immuno-glycobiochemical properties. Human seminal plasma from subjects with normal semen parameters were separated on a gelatin-Sepharose column and analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis and immunoblotting using antibodies against distinct FN forms. Heterogeneity of the isolated molecular species was examined by protein chip arrays combined with surface-enhanced laser desorption/ionization time of flight mass spectrometry, on normal, metal and hydrophobic surfaces. Carbohydrate composition was investigated using mannose-, fucose- and sialic acid-specific plant lectins and galectin-1. The results obtained indicated a pattern of isolated proteins corresponding to that of known FN fragments, as confirmed by immunoreactivity. Among them heparin-binding ability was preferentially associated with low molecular mass species. As for posttranslational modifications, phosphorylation and glycosylation of distinct fragments were revealed. Lectin binding to fragments containing the gelatin-binding domain, particularly with Ricinus communis agglutinin I, was stronger than to fragments containing the cell-binding site of FN. A low level of sialylation and distinctive concanavalin A- and Lens culinaris agglutinin-reactive species were also observed. Galectin-1 did not interact with the isolated preparation. Resolving the molecular heterogeneity of normal human seminal plasma FN and gaining initial insight into possible similarities/differences with known FN molecular species may be considered a prerequisite step preceding challenging the clinical usefulness of these molecular properties.

关键词： fibronectin gelatin-binding glycosylation heparin-binding human seminal plasma

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