Cold molecular welding study Final report, Jun. 15, 1966 - Jun. 14, 1967

Cold molecular welding characteristics of metal pellets on stainless steel wear plate

Cold molecular welding study in ultra-high vacuum Final report, 8 Oct. 1964 - 17 Dec. 1965

Cold molecular welding in ultrahigh vacuum of metals for use in Apollo projec

The normalization of sibling violence: Does gender and personal experience of violence influence perceptions of physical assault against siblings?

Despite its pervasive and detrimental nature, sibling violence (SV) remains marginalized as a harmless and inconsequential form of familial aggression. The present study investigates the extent to which perceptions of SV differ from those of other types of interpersonal violence. A total of 605 respondents (197 males, 408 females) read one of four hypothetical physical assault scenarios that varied according to perpetrator–victim relationship type (i.e., sibling vs. dating partner vs. peer vs. stranger) before completing a series of 24 attribution items. Respondents also reported on their own experiences of interpersonal violence during childhood. Exploratory factor analysis reduced 23 attribution items to three internally reliable factors reflecting perceived assault severity, victim culpability, and victim resistance ratings. A 4 × 2 MANCOVA—controlling for respondent age—revealed several significant effects. Overall, males deemed the assault less severe and the victim more culpable than did females. In addition, the sibling assault was deemed less severe compared to assault on either a dating partner or a stranger, with the victim of SV rated just as culpable as the victim of dating, peer, or stranger-perpetrated violence. Finally, respondents with more (frequent) experiences of childhood SV victimization perceived the hypothetical SV assault as being less severe, and victim more culpable, than respondents with no SV victimization. Results are discussed in the context of SV normalization. Methodological limitations and applications for current findings are also outlined

Hepatic autophagy contributes to the metabolic response to dietary protein restriction

© 2016 Elsevier Inc. All rights reserved. Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction

5′,11′-Dihydro­dispiro­[cyclo­hexane-1,6′-indolo[3,2-b]carbazole-12′,1′′-cyclo­hexa­ne]

The title compound, C28H30N2, is a symmetrical 2:2 product from the condensation of indole and cyclo­hexa­none. It is the only reported 5,11-dihydro­indolo[3,2-b]carbazole compound in which the spiro atoms are quaternary C atoms. Crystals were grown by vapor diffusion in a three-zone electric furnace. The mol­ecule resides on a crystallographic inversion center. The cyclo­hexyl rings are in a slightly distorted chair conformation, whereas the indole units and the spiro-carbons are coplanar within 0.014 Å

Low-Intensity Exercise Induces Acute Shifts In Liver And Skeletal Muscle Substrate Metabolism But Not Chronic Adaptations In Tissue Oxidative Capacity

Adaptations in hepatic and skeletal muscle substrate metabolism following acute and chronic (6 wk; 5 days/wk; 1 h/day) low-intensity treadmill exercise were tested in healthy male C57BL/6J mice. Low-intensity exercise maximizes lipid utilization; therefore, we hypothesized pathways involved in lipid metabolism would be most robustly affected. Acute exercise nearly depleted liver glycogen immediately postexercise (0 h), whereas hepatic triglyceride (TAG) stores increased in the early stages after exercise (0-3 h). Also, hepatic peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) gene expression and fat oxidation (mitochondrial and peroxisomal) increased immediately postexercise (0 h), whereas carbohydrate and amino acid oxidation in liver peaked 24-48 h later. Alternatively, skeletal muscle exhibited a less robust response to acute exercise as stored substrates (glycogen and TAG) remained unchanged, induction of PGC-1 alpha gene expression was delayed (up at 3 h), and mitochondrial substrate oxidation pathways (carbohydrate, amino acid, and lipid) were largely unaltered. Peroxisomal lipid oxidation exhibited the most dynamic changes in skeletal muscle substrate metabolism after acute exercise; however, this response was also delayed (peaked 3-24 h postexercise), and expression of peroxisomal genes remained unaffected. Interestingly, 6 wk of training at a similar intensity limited weight gain, increased muscle glycogen, and reduced TAG accrual in liver and muscle; however, substrate oxidation pathways remained unaltered in both tissues. Collectively, these results suggest changes in substrate metabolism induced by an acute low-intensity exercise bout in healthy mice are more rapid and robust in liver than in skeletal muscle; however, training at a similar intensity for 6 wk is insufficient to induce remodeling of substrate metabolism pathways in either tissue. NEW & NOTEWORTHY Effects of low-intensity exercise on substrate metabolism pathways were tested in liver and skeletal muscle of healthy mice. This is the first study to describe exercise-induced adaptations in peroxisomal lipid metabolism and also reports comprehensive adaptations in mitochondrial substrate metabolism pathways (carbohydrate, lipid, and amino acid). Acute low-intensity exercise induced shifts in mitochondrial and peroxisomal metabolism in both tissues, but training at this intensity did not induce adaptive remodeling of metabolic pathways in healthy mice

Liquid Sucrose Consumption Promotes Obesity and Impairs Glucose Tolerance Without Altering Circulating Insulin Levels

© 2018 The Obesity Society Objective: Multiple factors contribute to the rising rates of obesity and to difficulties in weight reduction that exist in the worldwide population. Caloric intake via sugar-sweetened beverages may be influential. This study tested the hypothesis that liquid sucrose intake promotes obesity by increasing serum insulin levels and tissue lipid accumulation. Methods: C57BL/6J mice were given 30% sucrose in liquid form. Changes in weight gain, body composition, energy expenditure (EE), and tissue lipid content were measured. Results: Mice drinking sucrose gained more total body mass (TBM), had greater fat mass, and displayed impaired glucose tolerance relative to control mice. These metabolic changes occurred without alterations in circulating insulin levels and despite increases in whole body EE. Lipid accrued in liver, but not skeletal muscle, of sucrose-consuming mice. Oxygen consumption (VO2) correlated with fat-free mass and moderately with TBM, but not with fat mass. ANCOVA for treatment effects on EE, with TBM, VO2, lean body mass, and fat-free mass taken as potential covariates for EE, revealed VO2 as the most significant correlation. Conclusions: Weight gain induced by intake of liquid sucrose in mice is associated with lipid accrual in liver, but not skeletal muscle, and occurs without an increase in circulating insulin

Thiobenzothiazole-modified hydrocortisones display anti-inflammatory activity with reduced impact on islet β-cell function

© 2015, American Society for Biochemistry and Molecular Biology Inc. All rights reserved. Glucocorticoids signal through the glucocorticoid receptor (GR) and are administered clinically for a variety of situations, including inflammatory disorders, specific cancers, rheumatoid arthritis, and organ/tissue transplantation. However, glucocorticoid therapy is also associated with additional complications, including steroid-induced diabetes. We hypothesized that modification of the steroid backbone is one strategy to enhance the therapeutic potential of GR activation. Toward this goal, two commercially unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent and human islets. We found that MS4 had transrepression properties but lacked transactivation ability, whereas MS6 retained both transactivation and transrepression activities. In addition, MS4 and MS6 both displayed anti-inflammatory activity. Furthermore, MS4 displayed reduced impact on islet β-cell function in both rodent and human islets. Similar to dexamethasone, MS6 promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We conclude that modification of the functional groups attached to the D-ring of the hydrocortisone steroid molecule produces compounds with altered structure-function GR agonist activity with decreased impact on insulin secretion and reduced adipogenic potential but with preservation of anti-inflammatory activity

Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice

© 2017 American Society for Investigative Pathology Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (\u3e250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+ cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease

Db / db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet

© 2017 Susan J. Burke et al. To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass