Weight Regulators Research Articles

Seed development-related genes contribute to high yield heterosis in integrated utilization of elite autotetraploid and neo-tetraploid rice.

Autotetraploid rice holds high resistance to abiotic stress and substantial promise for yield increase, but it could not be commercially used because of low fertility. Thus, our team developed neo-tetraploid rice with high fertility and hybrid vigor when crossed with indica autotetraploid rice. Despite these advances, the molecular mechanisms underlying this heterosis remain poorly understood. An elite indica autotetraploid rice line (HD11) was used to cross with neo-tetraploid rice, and 34 hybrids were obtained to evaluate agronomic traits related to yield. WE-CLSM, RNA-seq, and CRISPR/Cas9 were employed to observe endosperm structure and identify candidate genes from two represent hybrids. These hybrids showed high seed setting and an approximately 55% increase in 1000-grain weight, some of which achieved grain yields comparable to those of the diploid rice variety. The endosperm observations indicated that the starch grains in the hybrids were more compact than those in paternal lines. A total of 119 seed heterosis related genes (SHRGs) with different expressions were identified, which might contribute to high 1000-grain weight heterosis in neo-tetraploid hybrids. Among them, 12 genes had been found to regulate grain weight formation, including OsFl3, ONAC023, OsNAC024, ONAC025, ONAC026, RAG2, FLO4, FLO11, OsISA1, OsNF-YB1, NF-YC12, and OsYUC9. Haplotype analyses of these 12 genes revealed the various effects on grain weight among different haplotypes. The hybrids could polymerize more dominant haplotypes of above grain weight regulators than any homozygous cultivar. Moreover, two SHRGs (OsFl3 and SHRG2) mutants displayed a significant reduction in 1000-grain weight and an increase in grain chalkiness, indicating that OsFl3 and SHRG2 positively regulate grain weight. Our research has identified a valuable indica autotetraploid germplasm for generating strong yield heterosis in combination with neo-tetraploid lines and gaining molecular insights into the regulatory processes of heterosis in tetraploid rice.

Bisphenol A induces miR-708-5p through an ER stress-mediated mechanism altering neuronatin and neuropeptide Y expression in hypothalamic neuronal models

Bisphenol A (BPA) is an endocrine disrupting chemical that promotes obesity. It acts on the hypothalamus by increasing expression of the orexigenic neuropeptides, Npy and Agrp. Exactly how BPA dysregulates energy homeostasis is not completely clear. Since microRNAs (miRNA) have emerged as crucial weight regulators, the question of whether BPA could alter hypothalamic miRNA profiles was examined. Treatment of the mHypoA-59 cell line with 100 μM BPA altered a specific subset of miRNAs, and the most upregulated was miR-708-5p. BPA was found to increase the levels of miR-708-5p, and its parent gene Odz4, through the ER stress-related protein Chop. Overexpression of an miR-708-5p mimic resulted in a reduction of neuronatin, a proteolipid whose loss of expression is associated with obesity, and an increase in orexigenic Npy expression, thus potentially increasing feeding through converging regulatory pathways. Therefore, hypothalamic exposure to BPA can increase miR-708-5p that controls neuropeptides directly linked to obesity.

Endogenous and Synthetic Regulators of the Peripheral Components of the Hypothalamo-Hypophyseal-Gonadal and -Thyroid Axes

Activity in the peripheral components of the hypothalamo-hypophyseal-gonadal and -thyroid axes is regulated by hypophyseal hormones – gonadotropins and thyrotropic hormones (thyroid-stimulating hormone, TSH), which are secreted by specialized cells in the adenohypophysis. Luteinizing hormone (LH) and its homolog chorionic gonadotropin (CG) realize their steroidal effects by binding to LH/CG receptors on the surfaces of Leydig cells in the testes and theca cells and granulosa cells in mature follicles in the ovaries. Follicle-stimulating hormone (FSH) binds FSH receptors on Sertoli cells in the testes and granulosa cells in primordial and maturing follicles in the ovaries, controlling the processes of folliculogenesis, spermatogenesis, and steroidogenesis. TSH, via activation of TSH receptors, stimulates the synthesis of thyroid hormones by thyrocytes in the thyroid gland. Gonadotropins (LH, CG, and FSH) and TSH, which bind with high affinity to the extracellular domains of specific G protein-coupled receptors, directly activate various signal cascades operating via different types of G-proteins and β-arrestins. Recombinant gonadotropins and gonadotropins extracted from natural sources and used for the treatment of reproductive dysfunction and as assisted reproduction technologies have a number of drawbacks, which has led to the development of peptide and low molecular weight regulators of LH/CG and FSH receptors which interact with allosteric sites on the transmembrane or cytoplasmic domains of the receptors. Wide perspectives in the regulation of reproductive functions and the control of fertility are opened up by the use of adipokines, peptides of the insulin and relaxin families, and the antidiabetic drug metformin, which not only regulate and modify the responses of the gonads to gonadotropins, but also themselves influence steroidogenesis and gamete maturation. In the case of TSH receptors, the most acute problem is that of reversing increases in their activity in autoimmune and oncological diseases of the thyroid gland and in endocrine ophthalmopathy. The greatest potential in this direction lies in the ongoing development of low molecular weight inverse agonists and neutral antagonists, which interact with an allosteric site located in the transmembrane domain of the TSH receptor. The present review addresses contemporary advances in the development and study of endogenous and synthetic regulators and modulators of gonadotrophic and TSH receptors, along with their influences on the peripheral components of the hypothalamo-hypophyseal-gonadal and -thyroid axes.

Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus

Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and as a consequence, the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (TH) are used to correct functions of the thyroid system. However, they are characterized by many side effects, such as their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to disturb insulin-producing function of pancreas, exacerbating thereby diabetic pathology. Therefore, the analogues of TH, selective for certain types of TH receptors, that do not have these side effects, are being developed. The peptide and low-molecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, metformin therapy and drugs with antioxidant activity are effective for the treatment of thyroid pathology in types 1 and 2 DM. In the review, the literature data and the results of own investigations on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM are summarized and analyzed.

Low molecular weight regulators of the intracellular insulin signal transduction as a correction method of the insulin resistance in the treatment of type 2 diabetes

Insulin resistance is the characteristic feature of type 2 diabetes. This condition is manifested in the reduction of peripheral tissues sensitivity to the biological action of insulin and is expressed in the inhibition of cellular glucose absorption and metabolism in response to hormonal stimulation. At the cellular level, disorders which are realized both at the receptor and the postreceptor levels can serve a prerequisite to the formation of insulin resistance and are associated with a change in the amount or dysfunction of major molecular signaling cascade. Thus, the insulin receptor, as well as the other related signaling molecules can be considered as ideal therapeutic targets for the correction of insulin resistance and thus low molecular weight effectors which act on the individual links of insulin signaling cascade may be positioned as a new generation of anti-diabetic agents. This report provides information on the regulators of insulin receptor cascade, main advantages and disadvantages of their impact on biological targets and prospects for their therapeutic use as anti-diabetic drugs.

Thienopyrimidines - the new class of low molecular weight regulators of the female reproductive system

The authors analyse the original and literature data concerning thienopyrimidine derivatives showing the activity of luteinizing hormone (LH) receptor agonists. These compounds are known to specifically interact with the allosteric site of LH receptors localized in the transmembrane channels and activate the LH-sensitive adenylate cyclase signal system. The thienopyrimidine derivatives were shown to stimulate steroidogenesis and ovulation both in vitro and in vivo by acting on the cells that have not only normal but also mutant receptors. The thienopyrimidine derivatives are believed to be efficacious inducers of ovulation in the women.

Low molecular weight regulators of the intracellular insulin signal transduction as the method of correction of insulin resistance in the treatment of type 2 diabetes mellitus

Insulin resistance is the characteristic feature of type 2 diabetes mellitus. This condition is manifested in decreased sensitivity of peripheral tissues to the biological action of insulin and is expressed in the inhibition of cell glucose uptake and metabolism in response to the hormonal stimulation. At the cellular level, impairments realized both at the receptor and the postreceptor levels and associated with changes in the content or dysfunction of the main molecules of the signal cascade can serve a molecular prerequisite to the formation of insulin resistance. Thus, the insulin receptor, as well as the other related signaling molecules can be considered as ideal therapeutic targets for the correction of insulin resistance and low molecular weight effectors, which act on the individual links of the insulin signaling cascade, may be positioned as a new generation of anti-diabetic agents. This review summarizes current knowledge on regulators of the insulin receptor cascade, main advantages and disadvantages of their effects on biological targets and prospects for their therapeutic use as anti-diabetic agents.

Self-perceived successful weight regulators are less affected by self-regulatory depletion in the domain of eating behavior

Weight loss and maintenance goals are highly prevalent in many affluent societies, but many weight regulators are not successful in the long term. Research started to reveal psychological mechanisms that help successful weight regulators in being successful. In the present study, we tested the assumption that these mechanisms facilitate successful self-regulation particularly under conditions of self-regulatory depletion. Participants exerted or did not exert self-control in a first task before engaging in a taste test of a tempting but unhealthy food. Participants who had initially exerted self-control ate more than participants in the control condition. This effect was reduced in self-perceived successful weight regulators as compared to perceived unsuccessful self-regulators. A reduced susceptibility to self-regulatory depletion may be an important contributor to long-term weight regulation success in successful weight regulators.

Adipose Tissue Hormones and Appetite and Body Weight Regulators an Insulin Resistance / Гормоны Жировой Ткани И Регуляторы Аппетита И Массы Тела При Инсулиновой Резистентности

Impaired sensitivity to insulin (the so called insulin resistance, IR) occurs in a number of genetic and acquired conditions, including obesity, non-insulin dependent diabetes mellitus, polycystic ovary syndrome (PCOS) and metabolic syndrome (MS). In this review we discuss the correlation between IR, the adipose tissue hormones and appetite and body weight regulators. Leptin acts as a major adipostat: it suppresses food intake and activates catabolic pathways associated with increased energy production. It improves the peripheral insulin sensitivity and affects beta-cell function. Adiponectin is the only adipocytokine discovered so far that has anti-atherogenic properties. There is a reverse correlation between the serum adiponectin levels and the degree of obesity, IR, impaired glucose tolerance, dyslipidemia and atherosclerosis. Ghrelin stimulates food intake; of all circulating orexigenic hormones ghrelin is the most thoroughly studied. Ghrelin levels are decreased in MS and PCOS patients as this hormone is negatively correlated with body mass. Resistin is a hormone secreted by adipose tissues; a growing body of evidence suggests that it might be implicated in the link between obesity and diabetes. It has been found that the hormone's levels are significantly higher in obese people than those in normal body mass people. The recently discovered adipose tissue hormones, vaspin, visfatin, omentin-1 and their effect on IR development, have been increasingly researched.

Too tempting to resist? Past success at weight control rather than dietary restraint determines exposure-induced disinhibited eating

As the prevalence of obesity is increasing, many people resort to dieting to achieve a healthy body weight. Such dietary restraint has been suggested to cause counterproductive effects leading to disinhibited eating. However, it is more likely that dietary restraint is a by-product of previous difficulties in weight control and disinhibited eating. If so, disinhibition should be related more strongly to unsuccessful weight control than dietary restraint. This possibility was examined in the present study. Participants were exposed to palatable food or to neutral objects. Before and after exposure, we measured craving, general inhibitory control and inhibition of food-related responses with the Stop-Signal Task (SST), and food consumption during a taste test. Results showed that exposure increased craving in both successful and unsuccessful weight regulators. People who were successful at controlling their weight, however, were better able to regulate this temptation compared to unsuccessful weight regulators: while exposure to palatable food reduced inhibitory control over food-related responses and increased food consumption in unsuccessful weight regulators, successful weight regulators did not show such disinhibition. Dietary restraint did not influence any of these findings. Further, the exposure-induced difference in inhibition between successful and unsuccessful weight regulators was specific for food-related responses, as regulatory success did not influence general inhibitory control. Thus, while successful and unsuccessful weight regulators seem equally tempted by palatable food, those who are successful in controlling their weight seem better able to resist these temptations by exerting inhibitory control over appetitive responses toward palatable food.

Mechanism of geroprotective action of delta-sleep inducing peptide

Subcutaneous injections of exogenous delta-sleep inducing peptide (DSIP) to rats aged 2–24 months (100 μg/kg body weight, 5-day series of injections) have been shown to efficiently prevent oxidative damage to lipids and malonic dialdehyde accumulation in the tissues and blood plasma of rats of different ages. DSIP has a strong antioxidant effect mediated by the activation of various endogenous mechanisms of antioxidant protection both in cells and in the intercellular liquid containing high molecular weight and low molecular weight regulators of free-radical processes. DSIP has a stimulatory effect on the activity of superoxide dismutase, catalase, and ceruloplasmin, and affects the concentration of nonenzymatic antioxidantsurea and ureic acid; the physiological aging of the organism is accompanied by suppression of antioxidant protection mechanisms. DSIP increases the capacity of endogenous antioxidant protection systems in the tissues and blood, mostly by stimulating the components of the enzymatic antioxidant system, especially in late ontogenesis.

Methyltrioxorhenium Catalyzed Synthesis of Dinitrones from Primary Diamines and Non-Enolizable Aldehydes

Green Chemistry is the design of chemicals and processes that reduce or eliminate the use and generation of hazardous substances, and consequently reduce the risk to human health and the environment. Nitrones have various applications, such as building blocks in the synthesis of natural and biologically active compounds and molecular weight regulators in radical polymerization. In this work, dinitrones were successfully synthesized in a one-pot process from primary diamines and proper aromatic aldehydes employing methyltrioxorhenium (MTO) as catalyst and urea-hydrogen peroxide adduct (UHP) as oxidizing agent. Diamines, such as 1,6-diaminohexane and 1,12-diaminododecane were reacted with benzaldehydes bearing various substituent, such as 4-chloro, 4-nitro, 4-methoxybenzaldehyde, and also furfural. The resulting N,N' -bis (benzylidene)-1,6-hexanediamine N,N' -dioxides or N,N' -bis (benzylidene)-1,12-dodecanediamine N,N' -dioxides (or substituted benzylidenes) were separated with 45-60 % yields. The main advantage of the one-pot process is the elimination of need for several separation and purification steps and reduction in consumption of chemicals and waste production. The products selectively were characterized by 1H-NMR, 13C-NMR, FT-IR spectroscopies, and elemental analysis (CHNS).

Performance-Based Design of an Innovative Truck-Trailer Configuration

This paper describes the process whereby one of Australia's major fuel distributors recently gained approval to operate an innovative truck-trailer configuration that was needed to overcome some prescriptive truck size and weight limits and to satisfy the company's new policy on the improvement of fleet safety. Using Australia's newly developed performance-based standards for truck size and weight regulation as the design driver, the process began with field testing of the company's safest existing vehicles, went on to the iterative design of an improved concept by vehicle dynamics simulation, and ended with field testing and calibrated computer simulation of a prototype vehicle for certification. While demonstrating a quantum improvement in dynamic stability, the concept also offers a substantial increase in payload capacity. The process was a valuable learning experience for Australia's truck size and weight regulators and performance-based standards practitioners and is expected to pave the way for continued innovation by this company and others.

Performance-Based Design of an Innovative Truck-Trailer Configuration: Safer and More Efficient Distribution of Liquid Fuel in Australia

This paper describes the process whereby one of Australia's major fuel distributors recently gained approval to operate an innovative truck-trailer configuration that was needed to overcome some prescriptive truck size and weight limits and to satisfy the company's new policy on the improvement of fleet safety. Using Australia's newly developed performance-based standards for truck size and weight regulation as the design driver, the process began with field testing of the company's safest existing vehicles, went on to the iterative design of an improved concept by vehicle dynamics simulation, and ended with field testing and calibrated computer simulation of a prototype vehicle for certification. While demonstrating a quantum improvement in dynamic stability, the concept also offers a substantial increase in payload capacity. The process was a valuable learning experience for Australia's truck size and weight regulators and performance-based standards practitioners and is expected to pave the way for con...

Purine Inhibitors of Cyclin-Dependent Kinase and Their Apoptosis and Cytotoxicity Mechanisms.

INTRODUCTION. The importance of cell cycle regulatory proteins, their direct interaction with oncogenes and the tumour suppressor pRb and their frequent deregulation in human tumours has encouraged an active search for low-molecular weight regulators of these proteins. Among them the chemical inhibitors of cyclin-dependent kinases were the first discovered. These inhibitors are anti-mitotic and display very interesting anti-tumour activities.

Synthesis of oligo(phenylene oxides) with identical functional end groups

Linear α,ω-dibromo- and α-hydroxy-ω-methoxy-oligo(phenylene oxides) with different degrees of polycondensation corresponding closely to the monomer: regulator molar ratio, have been prepared by polycondensation by the Uhlman method of potassium p-bromophenolate in the presence of p-dibromobenzene or the monomethyl ether of hydroquinone as molecular weight regulators. It was found that traces of oxygen promote a free radical side reaction—oxidative polycondensation—resulting in formation of branched and crosslinked products.

Carboxylic acids used as molecular weight regulators for polycaproamide

Carboxylic acids used as molecular weight regulators for polycaproamide

Relationship between the solubility of water vapour in caprolactam and its partial pressure and temperature

It has been shown that the solubility of water vapour in a caprolactam melt decreases sharply with an increase in temperature, and also in the presence of acetic acid and a protective gas. Therefore, to increase the concentration of water in a caprolactam melt it is advantageous to use non-volatile molecular weight regulators and water vapour as the protective gas in the first section of a continuous polymerization tube.

Polymerization of ethylene with a preactivated aluminum‐titanium(IV) chloride catalyst and a statistical study of the polymerization variables

AbstractConversion of ethylene to a high‐density polymer was readily effected at low pressures and temperatures with the use of a catalyst consisting initially of a mixture of aluminum and titanium(IV) chloride. The principal factors influencing the polymerization and properties of the resulting polyethylene were investigated. These reactions at preferred catalyst concentrations were always preceded by a prolonged induction period; consequently, a means of reducing this period was developed. Factors influencing the polymerization included the nature of the aluminum in the catalyst, type of solvent, and molecular weight regulators. The effects of pressure, temperature, aluminum concentration, and Al/TiCl4 mole ratio on induction period, reaction rate, and polymer properties were determined from a factorial experiment in which each factor was investigated at two levels. The polymerization could be initiated at low catalyst concentrations and temperatures by preactivating the Al‐TiCl4 mixture, that is, partially converting it to aluminum chloride and titanium(III) chloride. Optimum catalyst efficiency was obtained at an Al/TiCl4 mole ratio of 0.5 to 1.0; the aluminum concentration was 0.0028 to 0.04% based on weight of solvent. Polyethylene yields as great as 1873 parts/part total catalyst were obtained at aluminum concentrations of 0.0028 to 0.008% and ethylene pressures of 150 to 280 psi. Liquid aliphatic hydrocarbons were more effective than aromatic hydrocarbons as media for the polymerization. Low molecular weight polymers and high‐density waxes were produced when hydrogen was used in the polymerization. The statistical study showed that the induction period was reduced by increasing the ethylene pressure and by decreasing the Al/TiCl4 mole ratio. The average reaction rate was increased by increasing the pressure, temperature, and aluminum concentration. A kinetic analysis of the data showed that the length of the induction period was inversely proportional to the first power of the pressure and titanium(IV) chloride concentration. The rate equation for the polymerization was found to be where P is the ethylene pressure. Formation of high molecular weight polymers was favored by high monomer concentrations and low titanium(IV) chloride concentrations. High‐density polyethylene (0.950–0.960 g./cc.) can be produced conveniently, safely, and economically at low pressures (40 to 280 psi) and low temperatures (50 to 85°C.) with the use of preactivated Al‐TiCl4 catalyst.