44 research outputs found
Differentiation of mouse embryonic stem cells along a hepatocyte lineage
No full textThe development of implantable engineered liver tissue constructs, ex vivo hepatocyte based therapeutic devices and drug discovery studies are limited by an inadequate hepatocyte cell source. Embryonic stem (ES) cells, characterized by their self-renewing and multi-lineage differentiating capabilities, represent a promising mature cell source required for these applications. Previous research has utilized embryoid body (EB) formation in both guided, through extracellular matrix and growth factor supplementation, and unguided, or spontaneous, differentiation to generate hepatocyte like cells. However, these characterizations have been limited to only one or several lineage specific protein or gene expression patterns. In addition, there have been few reports of long term propagation or characterization of long term function for ES cell derived hepatocyte precursors. In this thesis, we have implemented a platform for the long term propagation and augmentation of functional hepatocytes generated from murine ES cell sources. We first utilize a controlled, reproducible, EB mediated differentiation system to characterize efficiency of hepatocyte lineage commitment in four parallel culture configurations. These studies have shown that, EB mediated stem cell differentiation spontaneously yield populations of hepatocyte lineage cells expressing mature hepatocyte markers such as albumin (ALB) and Cytokeratin 18 (CK-18). We then used secondary culture configurations to study the effects of collagen sandwich culture and Oncostatin-M (OSM) or S-nitroso-N-acetylpenicillamine (SNAP) supplementation of EB derived hepatocyte-lineage cell function. The results of these studies suggest that SNAP, independent of the collagen supplementation, maintains the highest levels of ALB expression, however mature liver specific CK-18 is only expressed in the presence of both gel sandwich culture supplemented with SNAP. In addition, albumin secretion and Cytochrome P450 detoxification studies indicated that this condition was the best for the augmentation of hepatocyte-like function. Maintenance and augmentation of hepatocyte-like cells isolated from heterogeneous EB cell populations will be a critical step in generating large numbers of functional differentiated cells for therapeutic use.Ph.D.Includes bibliographical references (p. 45-48)
Ethnic affiliation, common memory and traditional culture of Macedonian Muslims in Albania: adaptating and preserving the identity (fieldworks of 2008-2010)
No full textThe paper is devoted to the question of ethnic affiliation of Macedonian Muslims in conditions of combined ethnical neighborhood. There are around ten settlements with Macedonian population in the Eastern part of the Republic of Albania (Mac. Golo Brdo, Alb. Golloborda). Five scientific researchers from St. Petersburg: Andrej Sobolev, Alexander Novik, Denis Ermolin, Maria Morozova and Alexandra Dugushina (Institute of Linguistic Studies of the Russian Academy of Sciences, Peter the Great Museum of Anthropology and Ethnography and St. Petersburg State University) had organized fieldwork in the villages Trebisht, Klenje, Ostren etc. in 2008-2010. The author puts into academic context a new description of almost unexplored Macedonian community. The data have been obtained during the fieldworks in Eastern Albania. In conditions of long-term neighborhood with other languages and religious denominations, the adapting mechanisms have worked out specific approaches to preserving ethnical identity and traditional culture, perceiving their value and necessity of translating to descendants. Materials of fieldwork include data about identity, language, culture of Macedonian community in different periods of the state of Albania (Osmanli time, Royal Albania, Enver Hoxha monism period, post-communist transition, modern republic). These expedition materials are archived in the Kunstkamera (Museum of Anthropology and Ethnography of the Russian Academy of Sciences). The founds of the Museum have traditional clothes of Macedonian Muslims from Golo Brdo which are collected during the fieldworks 2008-201
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Long-term hepatitis B infection in a scalable hepatic co-culture system.
No full textVolume 8, Issue 1, 1 December 2017, Article number 125, pgs. 1-11. Authors: Benjamin Y. Winer, Tiffany S. Huang, Eitan Pludwinski, Brigitte Heller, Felix Wojcik, Gabriel E. Lipkowitz, Amit Parekh, Cheul Cho, Anil Shrirao, Thomas W. Muir (Tom W. Muir), Eric Novik & Alexander Ploss.Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system. Importantly, infection can be established without antiviral immune suppression, and susceptibility is not donor dependent. The platform is scalable to microwell formats, and we provide proof-of-concept for its use in testing entry inhibitors and antiviral compounds.The lack of models that mimic hepatitis B virus (HBV) infection in a physiologically relevant context has hampered drug development. Here, Winer et al. establish a self-assembling, primary hepatocyte co-culture system that can be infected with patient-derived HBV without further modifications
Abstract 584: From code to cure: Computational discovery of novel immune checkpoints
No full textAbstract
Antibody blockade of CTLA4 and PD-1 immune checkpoints emerged as an effective treatment modality for cancer. However, the majority of patients do not achieve sustained long term benefit, suggesting a need for targeting of additional immune checkpoints. To identify additional B7/CD28 immune checkpoint targets, we developed a unique compendium of computational algorithms that identified multiple novel targets including TIGIT in 2008, which was an unknown protein at the time of discovery [Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17858-63], and PVRIG which we recently disclosed. Since their initial discovery, these targets have been functionally validated and anti-tumor activity was demonstrated with antibodies that target them.
In this presentation, we will describe the computational algorithms that led to the discovery of these novel immune checkpoints. These algorithms combine two complementary aspects: (i) endogenous immune checkpoint function prediction and (ii) prediction of immuno-modulatory activity in cancer. Immune checkpoint function was predicted based on gene structure similarity to B7/CD28 family members that is reminiscent of ancient common evolutionary origins. A gene structure alignment tool was developed to identify functional homologs of B7/CD28 genes even in the absence of sequence similarity. Next, the expression profile of these candidates was modeled and compared to profiles of known immune checkpoints in normal and cancer tissues. We will review the details of TIGIT and PVRIG discovery, which were among the immune checkpoints predicted in this process.
Our approach demonstrates the powerful ability of computational biology to translate genomic knowledge into rational and reliable drug target discovery.
Citation Format: Yair Benita, Amit Novik, Gady Cojocaru, Itamar Borukhov, Assaf Wool, Yossef Kliger, Tomer Zekharya, Zurit Levine, Sergey Nemzer, Ofer Levy, Amir Toporik. From code to cure: Computational discovery of novel immune checkpoints [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 584. doi:10.1158/1538-7445.AM2017-584</jats:p
Follow the Leader: Preference for Specific Amino Acids Directly Following the Initial Methionine in Proteins of Different Organisms
No full textAbstractIt is well established that the vast majority of proteins of all taxonomical groups and species are initiated by an AUG codon, translated into the amino acid methionine (Met). Many attempts were made to evaluate the importance of the sequences surrounding the initiation codon, mostly focusing on the RNA sequence. However, the role and importance of the amino acids following the initiating Met residue were rarely investigated, mostly in bacteria and fungi. Herein, we computationally examined the protein sequences of all major taxonomical groups represented in the Swiss-Prot database, and evaluated the preference of each group to specific amino acids at the positions directly following the initial Met. The results indicate that there is a species-specific preference for the second amino acid of the majority of protein sequences. Interestingly, the preference for a certain amino acid at the second position changes throughout evolution from lysine in prokaryotes, through serine in lower eukaryotes, to alanine in higher plants and animals
Discourses of biopolitics and human security in the context of new challenges and threats to humanity
No full textThe research aims at explicating two discourses that are most important for solving global problems of humanity: biopolitics and human security. The similarity of the studied concepts is revealed. According to the authors, it consists in the sameness of their object, and the differences - in its interpretation. Biopolitics sees its interest in finding ways to control the impersonal “man in General”, and human security - in its individuation. The measure of correlation of these concepts and their relation to the philosophical discourse about freedom is revealed. The author traces the dialectics of biopolitics and human security, the moments when the biopolitical discourse of “insured” and “uninsured” life intersects with the “colonizing” discourse. It is concluded that the conflict of interests of the studied discourses is inevitable, none of them is able to “rise above the fray”, having the opportunity to answer complex questions of human security. The measure of their effectiveness as an intellectual tool and practical mechanism for solving problems is illustrated by “fragile States” (the case of sub-Saharan Africa) and in the context of the COVID-19 pandemic
Balkan Colonists in the Azov Region: Diversity of Identities and Demise of the Ethnic Paradigm
No full textThrough his work, the author analyzes the influence of state ideology and cultural codes on the ethnic and national self-identification of the migrants from Southeastern Europe to the Azov region of Russia. Through his research, he has revealed the degree of influence of various factors contributing to the sustainable preservation or loss of ethnic, regional, linguistic and religious identities within the framework of the development of a separate multi-ethnic territory. The source base for the study is the documents of the State Archive of the Rostov Region and the materials of complex expeditions, the Archive of the Museum of Anthropology and Ethnography of the Russian Academy of Sciences. The author comes to the conclusion, that at the present, most residents of the villages on the shores of the Taganrog Bay are well aware of the history of their settlements; many are ready to claim that they have Greek/ Arnaut roots, and therefore they resolutely declare their “autochthony.” However, there are no attempts to revitalize this traditional culture or it’s holidays - “like in Greece or Albania” (as it is happening in the Zaporozhye and Donetsk regions). In the region, belonging to one’s people, by those born and living there, is perceived as a more significant marker than ethnic origin, ethnic self-identification and declaration of ethnic preferences
Socio-humanitarian knowledge and education: development paradoxes / E. K. Novik
No full textРассматриваются проблемы развития системы образования в Республике Беларусь. Анализируются упущения и просчеты реформирования социального гуманитарного блока дисциплин, связанные с вступлением в болонский процесс, переходом к централизованному тестированию, модульной системе обучения. Внесены предложения по совершенствованию действующей системы высшего образования.The problems of the development of the education system in the Republic of Belarus are considered, omissions and miscalculations of the reform of the social humanitarian block of disciplines, connected with entering the Bologna process, the transition to centralized testing, the modular system of education are analyzed. The author makes proposals on improving the current system of higher education
Socio-humanitarian knowledge and education: development paradoxes / E. K. Novik
No full textРассматриваются проблемы развития системы образования в Республике Беларусь. Анализируются упущения и просчеты реформирования социального гуманитарного блока дисциплин, связанные с вступлением в болонский процесс, переходом к централизованному тестированию, модульной системе обучения. Внесены предложения по совершенствованию действующей системы высшего образования.The problems of the development of the education system in the Republic of Belarus are considered, omissions and miscalculations of the reform of the social humanitarian block of disciplines, connected with entering the Bologna process, the transition to centralized testing, the modular system of education are analyzed. The author makes proposals on improving the current system of higher education
Meeting under the Plane Tree: Violation or Upholding of Tradition? The Ritual Year among the Himara Greeks
No full textThis study is dedicated to analysing the Himariot tradition of villagers meeting for coffee in the main square for the celebration of important feasts or family occasions. The cultural code of the population of Himara, which consists mostly of Orthodox Greeks and Orthodox and Muslim Albanians, has undergone major transformation in the twentieth century due to social and political reasons, including the persecution of religious institutions which reached its peak in the 1960s. Churches, formerly the main place for celebrating main feasts and family ceremonies as well as exchanging local news, were closed or destroyed. Instead, the café/kafenio/lokal in the center of the village (usually near the closed-down church) became the sacred meeting place for the villagers, while the barman/waiter/cook became the gatekeeper (according to the gatekeeping theory supported by the author), who allowed or refused to grant community members entrance to the inner circle (those who make the decision for the entire community). The transformations in the 1990s and 2000s gave a start to new or forgotten ritual practices and pastimes, as well as an entirely new organization of community life. The change of ritual practices was considerably influenced by: 1) the factor of prestige of the sacred locus in the people’s mind; 2) the revitalization of tradition starting in case of an intrusion in the people’s ritual sphere; 3) a conscious or unconscious wish of many of the communities to museify the past, in spite of the challenges of the present
