Bempedoic acid suppresses diet-induced hepatic steatosis independently of ATP-citrate lyase.

ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in metabolic dysfunction-associated steatotic liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol-lowering drug bempedoic acid (BPA), which also improves steatosis in mice. While BPA potently suppresses hepatic DNL and increases fat catabolism, it is unclear if ACLY is its primary molecular target in reducing liver triglyceride.

Societal benefits of floodplains in the Chesapeake Bay and Delaware River watersheds: Sediment, nutrient, and flood regulation ecosystem services.

Floodplains provide critical ecosystem services to people by regulating floodwaters and retaining sediments and nutrients. Geospatial analyses, field data collection, and modeling were integrated to quantify a portfolio of services that floodplains provide to downstream communities within the Chesapeake Bay and Delaware River watersheds. The portfolio of services included floodplain sediment and nutrient retention and flood regulation.

Glucose-Induced Activation of mTORC1 is Associated with Hexokinase2 Binding to Sestrins in HEK293T Cells.

Background: Sestrins (SESN1-3) act as proximal sensors in leucine-induced activation of the protein kinase mechanistic target of rapamycin (mTOR) in complex 1 (mTORC1), a key regulator of cell growth and metabolism.

Objective: In the present study, the hypothesis that SESNs also mediate glucose-induced activation of mTORC1 was tested.

Methods: Rats underwent overnight fasting, and in the morning, either saline or a glucose solution (4 g⋅kg BW/10 mL⋅kg) was administered by oral gavage; mTORC1 activation in the tibialis anterior muscle was assessed.

Serum Fibroblast Growth Factor 21 Is Markedly Decreased following Exercise Training in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis.

Background And Aims: Exercise remains a key component of nonalcoholic fatty liver disease (NAFLD) treatment. However, mechanisms underpinning the improvements in NAFLD seen with exercise are unclear. Exercise improved liver fat and serum biomarkers of liver fibrosis in the NASHFit trial.

An integrative approach to assessing effects of a short-term Western diet on gene expression in rat liver.

Consumption of a diet rich in saturated fatty acids and carbohydrates contributes to the accumulation of fat in the liver and development of non-alcoholic steatohepatitis (NASH). Herein we investigated the hypothesis that short-term consumption of a high fat/sucrose Western diet (WD) alters the genomic and translatomic profile of the liver in association with changes in signaling through the protein kinase mTORC1, and that such alterations contribute to development of NAFLD. The results identify a plethora of mRNAs that exhibit altered expression and/or translation in the liver of rats consuming a WD compared to a CD.

Global-run on sequencing identifies as an Akt-dependent long noncoding RNA involved in insulin sensitivity.

The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) to measure the nascent transcriptional response to fasting and refeeding as well as define the specific role of hepatic Akt and FoxO1 signaling in mediating this response. We identified 599 feeding-regulated transcripts, as well as over 6,000 eRNAs, and mapped their dependency on Akt and FoxO1 signaling.

HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence.

During metastasis cancer cells must adapt to survive loss of anchorage and evade anoikis. An important pro-survival adaptation is the ability of metastatic tumor cells to increase their antioxidant capacity and restore cellular redox balance. Although much is known about the transcriptional regulation of antioxidant enzymes in response to stress, how cells acutely adapt to alter antioxidant enzyme levels is less well understood.

Gas exchange measurements in the unsteady state.

Leaf level gas exchange is a widely used technique that provides real-time measurement of leaf physiological properties, including CO assimilation (A), stomatal conductance to water vapour (g ) and intercellular CO (C ). Modern open-path gas exchange systems offer greater portability than the laboratory-built systems of the past and take advantage of high-precision infrared gas analyzers and optimized system design. However, the basic measurement paradigm has long required steady-state conditions for accurate measurement.

Retinol-binding protein 4 mRNA translation in hepatocytes is enhanced by activation of mTORC1.

Increased expression of the peptide hormone retinol-binding protein 4 (RBP4) has been implicated in the development of insulin resistance, type 2 diabetes, and visual dysfunction. Prior investigations of the mechanisms that influence RBP4 synthesis have focused solely on changes in mRNA abundance. Yet, the production of many secreted proteins is controlled at the level of mRNA translation, as it allows for a rapid and reversible change in expression.

Glucagon-Dependent Suppression of mTORC1 is Associated with Upregulation of Hepatic FGF21 mRNA Translation.

Fibroblast growth factor 21 (FGF21) is a peptide hormone that acts to enhance insulin sensitivity and reverse many of the metabolic defects associated with consumption of a high-fat diet. Recent studies show that the liver is the primary source of FGF21 in the blood, and that hepatic FGF21 expression is upregulated by glucagon. Interestingly, glucagon acts to upregulate FGF21 production by primary cultures of rat hepatocytes and H4IIE and HepG2 hepatocarcinoma cells independent of changes in FGF21 mRNA abundance, suggesting that FGF21 protein expression is regulated post-transcriptionally.

Closing in on maximum yield of chlorophyll fluorescence using a single multiphase flash of sub-saturating intensity.

Estimation of the maximum chlorophyll fluorescence yield under illumination, or Fm', by traditional single saturation pulse (SP) methodology is prone to underestimation error because of rapid turnover within photosystem (PS) II. However, measurements of fluorescence yield during several single pulses of variable intensity describes the irradiance dependence of apparent Fm', from which estimates of Fm' at infinite irradiance can be derived. While such estimates have been shown to result in valid approximations of Fm', the need to apply several single pulses limits its applicability.

Design, synthesis and identification of a new class of triarylmethyl amine compounds as inhibitors of apolipoprotein E production.

We have identified a new class of triarylmethyl amine compounds that can inhibit apolipoprotein E (apoE) production. ApoE is a cholesterol- and lipid-carrier protein implicated in aging, atherosclerosis, Alzheimer's Disease (AD), and other neurological and lipid-related disorders. Attenuation of apoE production is generally considered to be of therapeutic value.

The gel microdrop secretion assay: Identification of a low productivity subpopulation arising during the production of human antibody in CHO cells.

The long-term stability of high-level expression is the mostimportant factor to consider when choosing cell lines for the expression of recombinant proteins. Declining volumetricyields in large-scale fermentation can be caused by changes affecting the cell population as a whole such as loss in viability, depletion of nutrients or accumulation of metabolites affecting cell growth. Alternatively, geneticinstability may lead to the outgrowth of a less productive,metabolically favored sub-population.

Complex-type N-linked oligosaccharides of gp120 from human immunodeficiency virus type 1 contain sulfated N-acetylglucosamine.

The major envelope glycoproteins gp120 and gp41 of human immunodeficiency virus type 1, the causative agent for human AIDS, contain numerous N-linked oligosaccharides. We report here our discovery that N-acetylglucosamine residues within the complex-type N-linked oligosaccharides of both gp120 and its precursor, gp160, are sulfated. When human Molt-3 cells persistently infected with human T-cell leukemia virus IIIB were metabolically radiolabeled with 35SO4, gp160, gp120, and to some extent gp41 were radiolabeled.

gp160 of HIV-I synthesized by persistently infected Molt-3 cells is terminally glycosylated: evidence that cleavage of gp160 occurs subsequent to oligosaccharide processing.

The envelope glycoprotein of HIV-I in infected, cultured human T cells is synthesized as a precursor of apparent Mr 160 kDa (gp160) and is cleaved to two glycoproteins, gp120 and gp41, which are the mature envelope glycoproteins in the virus. Neither the temporal and spatial features of glycosylation nor the oligosaccharide processing and proteolytic cleavage of the envelope glycoprotein are well understood. To understand more about these events, we investigated the glycosylation and cleavage of the envelope glycoproteins in the CD4+ human cell line, Molt-3, persistently infected with HIV-I (HTLV IIIB).

Transcellular transactivation by the human immunodeficiency virus type 1 tat protein.

The human immunodeficiency virus type 1 (HIV-1) transactivator (tat) protein produced in one cell activated HIV-1 promoter-directed gene expression in a second cell, provided the cells were in direct contact with one another. This observation suggests that the tat protein produced in HIV-1-infected cells has a physiological effect on neighboring cells.

The maternal erotic countertransference.

This paper reviews literature on countertransference erotism and perversion, and offers our conception of the maternal erotic countertransference. We stress that sado-masochistic issues are not only issues of aggression, but represent pre-oedipal erotism as well. The analyst's struggle with these issues may contribute to a perverse misalliance instead of a creative coupling.

The maternal erotic transference.

After reviewing literature on gender and erotic transferences, which have often been treated as primarily problematic, this paper offers a positive and transformational view of aspects of what is called the maternal erotic transference (MET). Rooted in mother and baby's earliest sensual contacts, it manifests in concrete transferences to the real parts of the body of the therapist; its expressions are typically inhibited as preverbal and/or defended against out of shame and fear of humiliation. Analysts of both genders who have access to their own maternal erotic countertransferences and their patients' matching transferences may enable their patients' acceptance of and immersion in the maternal erotic transference in its loving and sado-masochistic permutations and thus foster the making of a sense of wholeness, and connectedness to living.

Toxicologic evaluation of cefamandole nafate in laboratory animals.

The safety of cefamandole nafate in laboratory animals was evaluated in six species. The acute toxicity of cefamandole after intravenous or subcutaneous administration was similar to that of cephalothin sodium. The subacute and chronic toxicity of cefamandole was studied in rats and dogs for periods of two weeks to six months at doses of 250--1,000 mg/kg per day in rats and 125--1,500 mg/kg per day in dogs.

Aspects of the pharmacology and toxicology of tobramycin in animals and humans.

The pharmacology and toxicology of tobramycin in animals and humans are reviewed. After intramuscular and intravenous administration, tobramycin diffuses throughout most body tissues and tissue fluids. Therapeutic concentrations can be obtained by intravitreal or intradural injections.

New synthetic antibacterial compound, 1-(2-hydroxyethyl)-3-nitro-4-pyrazole carboxamide.

A series of 3-nitropyrazole compounds represent a new class of synthetic antibacterial agents. One member of this series, 1-(2-hydroxyethyl)-3-nitro-4-pyrazolecarboxamide, exhibited an antibacterial spectrum similar to that of nitrofurantoin. The inhibitory concentrations of this nitropyrazole were lower than those required for nitrofurantoin.