AIM: To analyze the biological role of the long non-coding RNA LINK-A. MATERIALS AND METHODS: An 850-bp segment from the second exon of LINK-A was removed using the CRISPR/Cas9 system in OVCA433 ovarian serous carcinoma cells. Spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity and expression of cell-signaling proteins were assessed in vitro. RESULTS: OVCA433 cells with LINK-A deletion were more invasive (p=0.0008) but had reduced migration and MMP9 secretion compared to controls (p=0.003 and p=0.005, respectively). LINK-A deletion did not affect proliferation but induced phosphorylation of extracellular signal-regulated kinase (10-fold; p=0.005). LINK-A knock out additionally reduced spheroid formation. CONCLUSION: Added to our previous data from analysis of clinical specimens, LINK-A is likely to be a tumor suppressor.
V. Stoeger, Holik, A.-K. , Hölz, K. , Dingjan, T. , Hans, J. , Ley, J.P. , Krammer, G.E. , Niv, M.Y. , Somoza, M.M. , ו Somoza, V. . 2020.
“Bitter-Tasting Amino Acids L-Arginine And L -Isoleucine Differentially Regulate Proton Secretion Via T2R1 Signaling In Human Parietal Cells In Culture”. Journal Of Agricultural And Food Chemistry, 68, 11, Pp. 3434-3444. doi:10.1021/acs.jafc.9b06285.
Publisher's Version This study aimed at identifying whether the bitter-tasting amino acids l-arginine (l-ARG) and l-isoleucine (l-ILE) differentially regulate mechanisms of gastric acid secretion in human parietal cells (HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in l-ARG and l-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a T2R1 CRISPR-Cas9 knock-out approach. Here, the effect of l-ARG on proton secretion decreased by 65.7 ± 21.9% and the effect of l-ILE increased by 93.2 ± 24.1% in HGT-1 T2R1 ko versus HGT-1 wt cells (p < 0.05). Overall, our results indicate differential effects of l-ARG and l-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets. Copyright © 2019 American Chemical Society.
Verena Stoeger, Holik, Ann-Katrin , Hölz, Kathrin , Dingjan, Tamir , Hans, Joachim , Ley, Jakob P, Krammer, Gerhard E, Niv, Masha Y. , Somoza, Mark Manuel , ו Somoza, Veronika . 2020.
“Bitter-Tasting Amino Acids L-Arginine And L-Isoleucine Differentially Regulate Proton Secretion Via T2R1 Signaling In Human Parietal Cells In Culture”. J Agric Food Chem, 68, 11, Pp. 3434-3444. doi:10.1021/acs.jafc.9b06285.
תקציר This study aimed at identifying whether the bitter-tasting amino acids l-arginine (l-ARG) and l-isoleucine (l-ILE) differentially regulate mechanisms of gastric acid secretion in human parietal cells (HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in l-ARG and l-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a CRISPR-Cas9 knock-out approach. Here, the effect of l-ARG on proton secretion decreased by 65.7 ± 21.9% and the effect of l-ILE increased by 93.2 ± 24.1% in HGT-1 T2R1 ko versus HGT-1 wt cells ( < 0.05). Overall, our results indicate differential effects of l-ARG and l-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets.
Public inquiries are ad hoc institutions, formally external to the executive branch, established by governments or a minister for the task of investigating crises, policy failures, or disasters. Inquiries play an important role in the aftermath of crisis by serving as instruments of accountability and policy learning. Yet the very existence and function of public inquiries are shaped by post crisis politics, in which public and politically independent inquiries create risks to potentially implicated players, who seek to avoid and mitigate potential blame. The blame-avoidance literature indeed provides a useful theoretical framework for the study of public inquiries. Empirical studies suggest that blame-attribution patterns are predictive of the political decision of whether to appoint an inquiry into a crisis. Studies of the effects of inquiries on public opinion show that, at the investigation stage, the institutional attributes of inquiries foster their legitimacy as a procedure for policy learning and accountability. However, after an inquiry reports its findings, members of the public can evaluate the report, rendering institutional attributes negligible in evaluating the inquiry. As for the effects of inquiries on the public agenda, existing evidence provides no support for a quantitative effect of inquiry appointment on the level of media coverage of a crisis. An integrated analysis of these findings offers an up-to-date theory of the political role of post crisis inquiries and points to some current gaps in our understanding of them.
Javier Diaz, Pinna, Marco , Zvelindovsky, Andrei V, Pagonabarraga, Ignacio , ו Shenhar, Roy . 2020.
“Block Copolymer&Ndash;Nanorod Co-Assembly In Thin Films: Effects Of Rod&Ndash;Rod Interaction And Confinement”. Macromolecules, 53, Pp. 3234-3249.
תקציר Simulations and experiments of nanorods (NRs) show that co-assembly with block copolymer (BCP) melts leads to the formation of a superstructure of side-to-side NRs perpendicular to the lamellar axis. A mesoscopic model is validated against scanning electron microscopy (SEM) images of CdSe NRs mixed with polystyrene-block-poly(methyl methacrylate). It is then used to study the co-assembly of anisotropic nanoparticles (NPs) with a length in the same order of magnitude as the lamellar spacing. The phase diagram of BCP/NP is explored as well as the time evolution of the NR. NRs that are slightly larger than the lamellar spacing are found to rotate and organize side-to-side with a tilted orientation with respect to the interface. Strongly interacting NPs are found to dominate the co-assembly, while weakly interacting nanoparticles are less prone to form aggregates and tend to form well-ordered configurations.
Y. Klein, Shani-Kdoshim, S. , Maimon, A. , Fleissig, O. , Levin-Talmor, O. , Meirow, Y. , Garber-Berkstein, J. , Leibovich, A. , Stabholz, A. , Chaushu, S. , ו Polak, D.. 2020.
“Bovine Bone Promotes Osseous Protection Via Osteoclast Activation”. J Dent Res, 99, Pp. 820-829. .
PubMed The current study aimed at investigating the long-term biological mechanisms governing bone regeneration in osseous defects filled with bovine bone (BB). Tooth extraction sockets were filled with BB or left unfilled for natural healing in a C57BL/6 mouse alveolar regeneration bone model (n = 12). Seven weeks later, the alveolar bone samples were analyzed histologically with hematoxylin/eosin and tartrate-resistant acid phosphatase staining. A separate group (n = 10) was used for RNA sequencing. Osteoclast inhibition was induced by zoledronic acid (ZA) administration at 2 wk postextraction in a third group (n = 28) for examination of osseous changes and cellular functions with micro-computed tomography and quantitative reverse transcription polymerase chain reaction, respectively. Histological and radiological osseous healing was observed in both BB-filled and normal-healing sockets. However, BB regenerated bone showed significant robust expression of genes associated with bone homeostasis and osteoclasts' function. Osteoclasts' inhibition in BB-filled sockets led to decreased bone resorption markers and reduced bone formation to a greater extent than that observed in osteoclasts' inhibition with natural healing. BB displays long-term biologically active properties, despite a naive osseous histological appearance. These include activation of osteoclasts, which in turn promotes osseous remodeling and maturation of ossified bone.
Karen M. Kapheim, Jones, Beryl M. , Søvik, Eirik , Stolle, Eckart , Waterhouse, Robert M. , Bloch, Guy , ו Ben-Shahar, Yehuda . 2020.
“Brain Micrornas Among Social And Solitary Bees”. Royal Society Open Science, 7, Pp. 200517. doi:10.1101/730317.
Publisher's Version תקציר Evolutionary transitions to a social lifestyle in insects are associated with lineage-specific changes in gene expression, but the key nodes that drive these regulatory changes are unknown. We examined the relationship between social organization and lineage-specific microRNAs (miRNAs). Genome scans across 12 bee species showed that miRNA copy-number is mostly conserved and not associated with sociality. However, deep sequencing of small RNAs in six bee species revealed a substantial proportion (20-35%) of detected miRNAs had lineage-specific expression in the brain, 24-72% of which did not have homologs in other species. Lineage-specific miRNAs disproportionately target lineage-specific genes, and have lower expression levels than shared miRNAs. The predicted targets of lineage-specific miRNAs are not enriched for genes with caste-biased expression or genes under positive selection in social species. Together, these results suggest that novel miRNAs may coevolve with novel genes, and thus contribute to lineage-specific patterns of evolution in bees, but do not appear to have significant influence on social evolution. Our analyses also support the hypothesis that many new miRNAs are purged by selection due to deleterious effects on mRNA targets, and suggest genome structure is not as influential in regulating bee miRNA evolution as has been shown for mammalian miRNAs.
Salomon Tom, Cohen, Adi , Barazany, Daniel , Ben-Zvi, Gal , BotvinikNezer, Rotem , Gera, Rani , Oren, Shiran , Roll, Dana , Rozic, Gal , Saliy, Anastasia , ו others, . 2020.
“Brain Volumetric Changes In The General Population Following The Covid-19 Outbreak And Lockdown (Preprint)”. Neuroimage, 239, 118311. .
Publisher's Version תקציר
Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. Photocleavage from intact porous polystyrene beads is not optimal because light cannot penetrate into the beads and the surface area exposed to irradiation is limited. Thus, hazardous, technically challenging and expensive setups are used for photocleavage from intact beads. We developed a new concept in which grinding the beads during or prior to irradiation is employed as an essential part of the photocleavage process. By grinding the beads we are exposing more surface area to the light source, hence, photocleavage can be performed even using a simple benchtop LED setup. This approach proved very efficient for photocleavage of various model compounds including fully protected oligosaccharides.
What role do Brazil, Russia, India, China, and South Africa (BRICS) play in the global investment regime and what policies do they espouse? How can we account for similarities among and differences across these countries with respect to their approach to international investment agreements (IIAs) and investment arbitration? What are their implications for the future of this regime? This study addresses these questions by situating emerging market economies in the persistent North-South divide, that is endemic to the global politics of foreign direct investment (FDI). Surveying the policies of the five countries since the 1980s, it shows that all were initially motivated to provide foreign investors with protection against political risk in order to attract FDI. As their own position in the global economy has changed and the rules of the regime itself have evolved, the investment policies of the BRICS countries have transformed, albeit in distinct ways. China and, to a lesser extent, Russia appear broadly content with the current state of affairs. Brazil, India, and South Africa, on the other hand, seem to object to current rules, which they view as overly protective of foreign investors at the expense of host state regulatory space. I argue and show that two factors – the amount of FDI outflows and regime type – usefully account for the observed variation across BRICS’ international investment policies, but that more research is needed to fully understand this matter. Regardless its sources, the diversity between the BRICS countries suggests that the prospects of them shaping the rules of the global investment regime, either individually or collectively, are rather bleak.
D. Robinson, Ritter, S. , Zadik-Weiss, L. , Ounallah-Saad, H. , Abu-Ahmad, N. , Kashkoosh, R. , Yassin, M. , ו Or, R.. 2020.
“Bridging The Accessibility Gap Of Cannabinoid Medicine And Arabic Culture”. Rambam Maimonides Medical Journal, 11, 1. doi:10.5041/RMMJ.10392.
Publisher's Version Arabs are a large minority group in the Israeli society. With the increasing use of medical cannabis throughout Israel due to changing governmental policies, the interactions of the Arab society with medical cannabis becomes of scientific and medical relevance. Recreational cannabis use is considered haram (forbidden) in Islam. However, most religious scholars agree that medical cannabis usage might be justified as zarurat (emergency and life-saving, therefore allowed) use. Obstacles to medical cannabis use within the Arabic population may relate to language barrier and/or cultural barriers. There are few Arabic-speaking web-based medical-cannabis support groups, and little official information about it is available in the Arabic language. In order for the full benefits of medical cannabis to reach the entire Israeli population, a government-sponsored web-based educational program is necessary in Hebrew and Arabic, both of which are among the nation's official languages, thereby contributing to the equalization of health resource accessibility. © 2020 Robinson et al. This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License (
http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The Ancient Throne provides readers with a collection of articles that either study specific thrones known from historical texts, artistic depictions or excavations, or offer an overview of the role of thrones from as early as ancient Mesopotamia in the 3rd millennium BCE to as late as Iran and China in the 14th century CE. The volume thus collates the work of scholars who specialise in diverse cultures and who have all found thrones to be helpful
vehicles for promoting unique inquiries into such issues as royalty, society, ritual, and religion within their areas of expertise. The breadth of their collective efforts offers a comparative view through which the dissemination of political and ideological concepts may be better explored. The following collection of articles, however, does not attempt to provide a single answer to the question of what a throne is or is not, but instead presents the authors’ individual – and sometimes conflicting – outlooks. While the volume is far from being a comprehensive survey of thrones in Eurasian cultures across the ages, it nevertheless offers readers a specialised bibliography and draws attention to scholarly trends that will be useful to future studies on thrones in general. Most of all, the volume cohesively suggests that thrones have been a meaningful category of material culture throughout history, one that may inspire both inter-cultural and intra-cultural studies of the ways in which types of chairs can embody, execute or induce notions of kingship and a
range of concepts pertaining to the religious, ideological, and social spheres.
Do budget institutions play a role in explaining why government effectiveness is higher in some advanced countries than in others? Employing an original panel dataset that covers four different years (1991, 2003, 2007 and 2012), we find that budget centralization has a negative and significant effect on government effectiveness in OECD countries after accounting for a list of control variables, such as GDP per capita, government expenditure and country- and year-fixed effects. We show that less centralized countries display significantly better performance in health and infrastructure and a similar effectiveness in tax collections. The negative impact of budget centralization seems to manifest especially at the execution stage of the budgeting process, while it is not significant at the formulation and legislation stages. These results survive a list of sensitivity tests.
