Finite Hilbert stability of (bi)canonical curves

We prove that a generic canonically or bicanonically embedded smooth curve has semistable m-th Hilbert points for all m. We also prove that a generic bicanonically embedded smooth curve has stable m-th Hilbert points for all m \geq 3. In the canonical case, this is accomplished by proving finite Hilbert semistability of special singular curves with G_m-action, namely the canonically embedded balanced ribbon and the canonically embedded balanced double A_{2k+1}-curve. In the bicanonical case, we prove finite Hilbert stability of special hyperelliptic curves, namely Wiman curves. Finally, we give examples of canonically embedded smooth curves whose m-th Hilbert points are non-semistable for low values of m, but become semistable past a definite threshold. (This paper subsumes the previous submission and arXiv:1110.5960).Comment: To appear in Inventiones Mathematicae, 2012. The final publication is available at http://www.springerlink.co

Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice

Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG) were decreased with 14% (

PREPARATION AND PROPERTIES OF MURINE ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES RECOGNIZING PRIMARY RABBIT POLYCLONAL ANTIBODIES AGAINST MORPHINE DERIVATIVES

Anti-idiotypic antibodies (Ab2), according to the network theory of Jerne, are second-generation immunoglobulins that are produced against the idiotype of an antibody to a specific antigen. Despite the large number of works devoted to the study of the properties of these proteins, their role in the regulation of the immune system is not fully known. It may consist in maintaining or blocking a minimal immune response to the antigen. The study of Ab2 is of great practical and scientific importance. The special properties of Ab2, namely, the ability to partially reproduce the structure of the primary antigen and, upon immunization, induce the appearance of tertiary antibodies, which, like first-generation antibodies, can bind to the antigen, have found application in the development of Ab2-based vaccines, in particular, for the treatment of tumors. In view of the presence of a number of limitations on research related to psychoactive substances, the development of Ab2- based vaccines against drug addiction also seems promising. To example, anti-idiotypic antibodies obtained for this purpose possessing a cocaine-like structure are described in the literature. In this work, murine monoclonal anti-idiotypic antibodies (mAb2) mimicking the structure of various morphine derivatives were obtained. Rabbit polyclonal antibodies to the 6-hemisuccinyl derivative of morphine conjugated with bovine serum albumin isolated by affinity chromatography were used as primary antibodies for immunization. Four hybridoma clones were obtained as a result of the fusion of immunized mice lymphocytes with mouse Sp2/0 mouse myeloma cells by the Milstein-Köhler method. After growth in animals, mAb2 produced by hybridoma cells were affinity purified. We investigated the physicochemical and antigenic properties of the isolated antibodies. It was shown that the obtained mAb2 differ in immunological specificity, competing in different degree with morphine derivatives for binding to first-generation antibodies. We tested the possibility of using the obtained mAb2 as antigen analogues in the solid-phase enzyme-linked immunosorbent assay to determine the titer of primary antibodies against morphine in the blood serum of laboratory animals immunized with morphine derivatives. Based on the obtained anti-idiotypic antibodies, it is proposed to develop test systems to determine the serum opiate-specific antibodies in people after specific vaccination for therapeutic or prophylactic purposes to avoid the use of drugs as antigens immobilized on the solid phase in the analysis

Preparation of polyclonal and monoclonal anti-idiotypic antibodies against morphine-specific immunoglobulins

The preparation and study of anti-idiotypic (secondary) antibodies (Ab2) against monoclonal primary antibodies (Ab1) specific to biologically active molecules with a known structure is of great scientific and practical importance. Due to partial antigenic similarity of Ab2 and the initial antigen structures, these antibodies can be the basis of the vaccine, if the antigen usage is not possible, or is limited by law. In particular, one may create Ab2-based preparations, designed for immunization, in order to prevent and treat the drug addiction. The value of Ab2 properties increases even more if Ab1, used to obtain them, recognize different parts of the antigen molecule, which makes it possible to obtain second-generation antibodies with a wide range of specificity. In this work, the morphine-like polyclonal and monoclonal Ab2 were obtained. In each case, as the first-generation immunoglobulins for immunization, we used two murine monoclonal antibodies (mAbs) specific to different morphine derivatives: 3K11 antibodies to 3-0-carboxymethyl (CMM) and 2-p-carboxyphenylazomethyl (FAM) derivatives, as well as 6G1 antibodies to 6-hemisuccinyl derivative (GSM). After immunization of the horse with Ab1 and development of immune response, three pools of specific polyclonal antibodies were isolated from the animal blood serum: horse anti-species antibodies to the total mouse immunoglobulins (HAM); horse anti-idiotypic antibodies against 3K11 antibodies (HAM-K11), and against 6G1 antibodies (HAM-G1). In parallel, immunization of mice with 3K11 and 6G1 antibodies and fusion of obtained lymphocytes with Sp2/0 mouse myeloma cells by the Milstein-Köhler method resulted in three producers of anti-idiotypic antibodies: a clone producing mouse monoclonal Ab2 specific for mAb-6G1 (AIG1), as well as clones producing anti-mAb-3K11 antibodies (AI-K11A and AI-K11B). The physico-chemical and antigenic properties of all the Ab2 obtained were characterized. It was shown that the horse anti-idiotypic immunoglobulins not only belong to different classes, but are also polyvalent, while all monoclonal Ab2 obtained are represented by IgM immunoglobulins, being also strictly specific to the corresponding first-generation antibodies. Subsequently, the morphine-like properties of the first domestic polyclonal and monoclonal Ab2 obtained in the work will be investigated in a cellular model. Likewise, we shall study their ability to induce Ab3 as well as morphine-specific Ab1

Construction of a map-based reference genome sequence for barley, Hordeum vulgare L.

Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and raw material for the malting industry. The map-based reference genome sequence of barley cv. `Morex' was constructed by the International Barley Genome Sequencing Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the experimental and computational procedures to (i) sequence and assemble more than 80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path of a genome-wide physical map, (ii) find and validate overlaps between adjacent BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing clusters of overlapping BACs, and (iv) order and orient these BAC clusters along the seven barley chromosomes using positional information provided by dense genetic maps, an optical map and chromosome conformation capture sequencing (Hi-C). Integrative access to these sequence and mapping resources is provided by the barley genome explorer (BARLEX).Peer reviewe

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

BACKGROUND: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. METHODOLOGY: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. RESULTS/CONCLUSION: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery