PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation

Характеристика экономических отношений на финансовом рынке Украины

Розглянуто проблеми, особливості функціонування та взаємодії учасників фінансового ринку України. Обґрунтовано наявність внутрішніх фінансових джерел формування ресурсного потенціалу вітчизняних банків, доведено їх пріоритетність для країни порівняно із зовнішніми джерелами. Окреслено причини, що зумовлюють дефіцит ресурсного потенціалу в банківській системі України. Ключові слова: заощадження, нагромадження, банки, економічне зростання, посередники, фінансовий ринок, ресурси, трансформація, інвестиційний потенціал.Рассмотрены проблемы, особенности функционирования и взаимодействия участников финансового рынка Украины. Обосновано наличие внутренних финансовых источников формирования ресурсного потенциала отечественных банков, доказана их приоритетность для страны по сравнению с внешними источниками. Очерчены причины, которые предопределяют дефицит ресурсного потенциала в банковской системе Украины. Ключевые слова: сбережения, накопления, банки, экономический рост, посредники, финансовый рынок, ресурсы, трансформация, инвестиционный потенциал.The present paper examines topical problems related to the specific aspects of economic relations in the financial market of Ukraine. The relevance and selection of the theme stem from the fact that financial market as a specific organization form of cash flows takes a leading place in the economic mechanism of market economy. Agents of this market are engaged in a whole range of complex economic relations which in their turn play a key role in securing a dynamic and sustainable economic growth of a country. Development of the financial market and creation of adequate flexible and adaptive economic relations between its players are critical for Ukraine. This is explained by specific aspects of the economic system formation and reforming, which are related to undergoing an intersystem transformation stage. The indicated circumstances predetermined the goal and objectives of the study pursued, which come to examination of economic relations in the financial market of Ukraine, identification of the interaction specificity of various financial intermediaries in the accumulation process of idle cash and its transformation into the investment capital of national economy. Based on the results of the analysis conducted, it is established that unlike countries with developed financial systems, where the majority of institutional participants of the capital market are proportionally developed, it is the banking sector that dominates in Ukraine and has a determinant role in financing the economic development of the state. The availability of domestic financial resources for forming the resource potential of banks is substantiated, and their priority versus external resources for Ukraine is proved. The comparison of gross savings and gross capital formation allowed identifying certain problems as to transformation of the former into investment resources in Ukraine. The paper outlines some causes of a poor resource potential of national banking institutions. Keywords: savings, accumulation, banks, economic growth, intermediaries, financial market, resources, transformation, investment potential

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Mixed model association scans of multi-environmental trial data reveal major loci controlling yield and yield related traits in Hordeum vulgare in Mediterranean environments

An association panel consisting of 185 accessions representative of the barley germplasm cultivated in the Mediterranean basin was used to localise quantitative trait loci (QTL) controlling grain yield and yield related traits. The germplasm set was genotyped with 1,536 SNP markers and tested for associations with phenotypic data gathered over 2 years for a total of 24 year × location combinations under a broad range of environmental conditions. Analysis of multi-environmental trial (MET) data by fitting a mixed model with kinship estimates detected from two to seven QTL for the major components of yield including 1000 kernel weight, grains per spike and spikes per m2, as well as heading date, harvest index and plant height. Several of the associations involved SNPs tightly linked to known major genes determining spike morphology in barley (vrs1 and int-c). Similarly, the largest QTL for heading date co-locates with SNPs linked with eam6, a major locus for heading date in barley for autumn sown conditions. Co-localization of several QTL related to yield components traits suggest that major developmental loci may be linked to most of the associations. This study highlights the potential of association genetics to identify genetic variants controlling complex traits

Advanced backcross-QTL analysis in spring barley (H. vulgare ssp. spontaneum) comparing a REML versus a Bayesian model in multi-environmental field trials

A common difficulty in mapping quantitative trait loci (QTLs) is that QTL effects may show environment specificity and thus differ across environments. Furthermore, quantitative traits are likely to be influenced by multiple QTLs or genes having different effect sizes. There is currently a need for efficient mapping strategies to account for both multiple QTLs and marker-by-environment interactions. Thus, the objective of our study was to develop a Bayesian multi-locus multi-environmental method of QTL analysis. This strategy is compared to (1) Bayesian multi-locus mapping, where each environment is analysed separately, (2) Restricted Maximum Likelihood (REML) single-locus method using a mixed hierarchical model, and (3) REML forward selection applying a mixed hierarchical model. For this study, we used data on multi-environmental field trials of 301 BC2DH lines derived from a cross between the spring barley elite cultivar Scarlett and the wild donor ISR42-8 from Israel. The lines were genotyped by 98 SSR markers and measured for the agronomic traits “ears per m²,” “days until heading,” “plant height,” “thousand grain weight,” and “grain yield”. Additionally, a simulation study was performed to verify the QTL results obtained in the spring barley population. In general, the results of Bayesian QTL mapping are in accordance with REML methods. In this study, Bayesian multi-locus multi-environmental analysis is a valuable method that is particularly suitable if lines are cultivated in multi-environmental field trials

Optimum allocation of resources for QTL detection using a nested association mapping strategy in maize

In quantitative trait locus (QTL) mapping studies, it is mandatory that the available financial resources are spent in such a way that the power for detection of QTL is maximized. The objective of this study was to optimize for three different fixed budgets the power of QTL detection 1 − β* in recombinant inbred line (RIL) populations derived from a nested design by varying (1) the genetic complexity of the trait, (2) the costs for developing, genotyping, and phenotyping RILs, (3) the total number of RILs, and (4) the number of environments and replications per environment used for phenotyping. Our computer simulations were based on empirical data of 653 single nucleotide polymorphism markers of 26 diverse maize inbred lines which were selected on the basis of 100 simple sequence repeat markers out of a worldwide sample of 260 maize inbreds to capture the maximum genetic diversity. For the standard scenario of costs, the optimum number of test environments (Eopt) ranged across the examined total budgets from 7 to 19 in the scenarios with 25 QTL. In comparison, the Eopt values observed for the scenarios with 50 and 100 QTL were slightly higher. Our finding of differences in 1 − β* estimates between experiments with optimally and sub-optimally allocated resources illustrated the potential to improve the power for QTL detection without increasing the total resources necessary for a QTL mapping experiment. Furthermore, the results of our study indicated that also in studies using the latest genomics tools to dissect quantitative traits, it is required to evaluate the individuals of the mapping population in a high number of environments with a high number of replications per environment

Tumor Progression Locus 2 (Tpl2) Deficiency Does Not Protect against Obesity-Induced Metabolic Disease

Obesity is associated with a state of chronic low grade inflammation that plays an important role in the development of insulin resistance. Tumor progression locus 2 (Tpl2) is a serine/threonine mitogen activated protein kinase kinase kinase (MAP3K) involved in regulating responses to specific inflammatory stimuli. Here we have used mice lacking Tpl2 to examine its role in obesity-associated insulin resistance. Wild type (wt) and tpl2−/− mice accumulated comparable amounts of fat and lean mass when fed either a standard chow diet or two different high fat (HF) diets containing either 42% or 59% of energy content derived from fat. No differences in glucose tolerance were observed between wt and tpl2−/− mice on any of these diets. Insulin tolerance was similar on both standard chow and 42% HF diets, but was slightly impaired in tpl2−/− mice fed the 59% HFD. While gene expression markers of macrophage recruitment and inflammation were increased in the white adipose tissue of HF fed mice compared with standard chow fed mice, no differences were observed between wt and tpl2−/− mice. Finally, a HF diet did not increase Tpl2 expression nor did it activate Extracellular Signal-Regulated Kinase 1/2 (ERK1/2), the MAPK downstream of Tpl2. These findings argue that Tpl2 does not play a non-redundant role in obesity-associated metabolic dysfunction

Extent and structure of linkage disequilibrium in canola quality winter rapeseed (Brassica napus L.)

Linkage disequilibrium was investigated in canola quality winter rapeseed to analyze (1) the prospects for whole-genome association analyses and (2) the impact of the recent breeding history of rapeseed on linkage disequilibrium. A total of 845 mapped AFLP markers with allele frequencies ≥0.1 were used for the analysis of linkage disequilibrium in a population of 85 canola quality winter rapeseed genotypes. A low overall level of linkage disequilibrium was found with a mean r2 of only 0.027 over all 356,590 possible marker pairs. At a significance threshold of P = 2.8 × 10−7, which was derived by a Bonferroni correction from a global α-level of 0.1, only 0.78% of the marker pairs were in significant linkage disequilibrium. Among physically linked marker pairs, the level of linkage disequilibrium was about five times higher with more than 10% of marker pairs in significant linkage disequilibrium. Linkage disequilibrium decayed rapidly with distance between linked markers with high levels of linkage disequilibrium extending only for about 2 cM. Owing to the rapid decay of linkage disequilibrium with distance association analyses in canola quality rapeseed will have a significantly higher resolution than QTL analyses in segregating populations by interval mapping, but much larger number of markers will be necessary to cover the whole genome. A major impact of the recent breeding history of rapeseed on linkage disequilibrium could not be observed

Efficient QTL detection for nonhost resistance in wild lettuce: backcross inbred lines versus F2 population

In plants, several population types [F2, recombinant inbred lines, backcross inbred lines (BILs), etc.] are used for quantitative trait locus (QTL) analyses. However, dissection of the trait of interest and subsequent confirmation by introgression of QTLs for breeding purposes has not been as successful as that predicted from theoretical calculations. More practical knowledge of different QTL mapping approaches is needed. In this recent study, we describe the detection and mapping of quantitative resistances to downy mildew in a set of 29 BILs of cultivated lettuce (L. sativa) containing genome segments introgressed from wild lettuce (L. saligna). Introgression regions that are associated with quantitative resistance are considered to harbor a QTL. Furthermore, we compare this with results from an already existing F2 population derived from the same parents. We identified six QTLs in our BIL approach compared to only three in the F2 approach, while there were two QTLs in common. We performed a simulation study based on our actual data to help us interpret them. This revealed that two newly detected QTLs in the BILs had gone unnoticed in the F2, due to a combination of recessiveness of the trait and skewed segregation, causing a deficit of the wild species alleles. This study clearly illustrates the added value of extended genetic studies on two different population types (BILs and F2) to dissect complex genetic traits

Russia’s Legal Transitions: Marxist Theory, Neoclassical Economics and the Rule of Law

We review the role of economic theory in shaping the process of legal change in Russia during the two transitions it experienced during the course of the twentieth century: the transition to a socialist economy organised along the lines of state ownership of the means of production in the 1920s, and the transition to a market economy which occurred after the fall of the Soviet Union in the 1990s. Despite differences in methodology and in policy implications, Marxist theory, dominant in the 1920s, and neoclassical economics, dominant in the 1990s, offered a similarly reductive account of law as subservient to wider economic forces. In both cases, the subordinate place accorded to law undermined the transition process. Although path dependence and history are frequently invoked to explain the limited development of the rule of law in Russia during the 1990s, policy choices driven by a deterministic conception of law and economics also played a role.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s40803-015-0012-