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1. Utilizing a case-based approach, participants will self-report an understanding of the historical context of cardiopulmonary resuscitation, do-not-attempt-resuscitation (DNAR) orders, and unilateral do-not-attempt-resuscitation (UDNAR) orders. 2. Utilizing a case-based approach, participants will self report a knowledge of the ethical principles involved with UDNAR orders as well as concerns for unequal utilization of UDNAR orders for underserved populations. The principle of non-maleficence calls upon providers to not offer treatments we believe to be futile or non-beneficial. In recent years, this concept has led to the rise of so-called Unilateral Do-Not-Attempt-Resuscitation (UDNAR) orders. However, emerging evidence suggests that UDNAR orders may be disproportionately affecting underserved communities and may drive distrust between these communities and medical organizations. In serious illness communication, discussions around code status are common and typically occur in the context of end of life care. Traditionally, an individual's default code status has been understood to be "Full Code" and that cardiopulmonary resuscitation could only be withheld at the explicit request of a patient or their surrogate decision maker. However, providing full code measures for a patient dying of an irreversible process can cause a great deal of moral distress to clinicians. In the last 10-15 years the idea of a unilateral do-not-attempt resuscitation (UDNAR) order has gained increasing acceptance, recognizing that clinicians can identify when the aggressive treatment of a cardiopulmonary arrest provides little to no benefit to the terminally ill. More recently, however, controversies about when and how to invoke UNDAR orders have arisen. During the COVID pandemic, concerns were raised about inappropriate blanket DNAR orders for patient's severely ill with COVID, and recent studies have suggested that vulnerable populations may be inordinately subject to UDNAR orders in the hospital. In this case-based discussion, we will review the historical context of both cardiopulmonary resuscitation and do-not-attempt resuscitation (DNAR) orders; discuss the rise of UDNAR orders; outline the ethical argument for and against UDNAR orders; and explore recent work involving disparities in its application to patients at the end of life. Ethical / Legal Aspects of Care; Diversity, Equity, Inclusion, Belonging, Justice [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to explore student perceptions of recycling and explore whether one university's strategy helped or hindered student recycling in their university's halls of residence. There is near-universal acknowledgement of the urgency of the climate crisis, yet household recycling rates remain low at 45.2%. Student-recycling rates have been suggested to be even lower. After a brief consideration of the recent history of sustainability and recycling, this paper identifies the actions required to increase student recycling, including peer influence, education and information, physical structures and attitudes and motivations. Design/methodology/approach: Twelve in-depth, semi-structured interviews were undertaken at one Southern English university. The rich, qualitative data obtained were then analysed thematically. The theory of environmentally significant behaviour provided a framework for understanding perceptions and behaviours in that site. Findings: Confirming aspects of existing literature, students' recycling behaviours were found to be limited through lack of perceived ability, lack of facilities and unconfident knowledge. Students were also found to be limiting their own actions. A holistic approach including peer influence, education and information, physical structures and attitudes and motivations was recommended. Originality/value: There is little research into student recycling behaviours and limited literature concerning halls of residence, especially in the UK. This paper draws on one case to add to nascent understandings. While limited to one site and by sample size, a number of recommendations are made, covering university facilities, student empowerment and individual responsibility to increase future recycling. [ABSTRACT FROM AUTHOR]

Abstract: We provide novel insights into the function(s) of β-carotene-15,15′-oxygenase (CMOI) during embryogenesis. By performing in vivo and in vitro experiments, we showed that CMOI influences not only lecithin:retinol acyltransferase but also acyl CoA:retinol acyltransferase reaction in the developing tissues at mid-gestation. In addition, LC/MS lipidomics analysis of the CMOI−/− embryos showed reduced levels of four phosphatidylcholine and three phosphatidylethanolamine acyl chain species, and of eight triacylglycerol species with four or more unsaturations and fifty-two or more carbons in the acyl chains. Cholesteryl esters of arachidonate, palmitate, linoleate, and DHA were also reduced to less than 30% of control. Analysis of the fatty acyl CoA species ruled out a loss in fatty acyl CoA synthetase capability. Comparison of acyl species suggested significantly decreased 18:2, 18:3, 20:1, 20:4, or 22:6 acyl chains within the above lipids in CMOI-null embryos. Furthermore, LCAT, ACAT1 and DGAT2 mRNA levels were also downregulated in CMOI−/− embryos. These data strongly support the notion that, in addition to cleaving β-carotene to generate retinoids, CMOI serves an additional function(s) in retinoid and lipid metabolism and point to its role in the formation of specific lipids, possibly for use in nervous system tissue. [Copyright &y& Elsevier]

Adequate roost sites for hibernacula are an important factor in the distribution and abundance of temperate bat species and knowledge of specific hibernacula is necessary to make sound management decisions. Caves are recognized as one of the most important roosting sites for bats, yet surveys in caves are uncommon in North America. This paper presents data on the distribution and abundance of bats hibernating in Iowa (U.S.A.) caves and includes new hibernacula records. These are the first published records of bats in Iowa caves in almost 25 years. [ABSTRACT FROM AUTHOR]

Studies were conducted to examine the in vivo transfer of chylomicron (dietary) retinoid from rat liver parenchymal to stellate cells. We specifically addressed the question of whether chylomicron retinyl ester is transferred directly from hepatic parenchymal to stellate cells without first undergoing hydrolysis. [14C]Retinyl palmitate and its non-hydrolyzable ether analog, retinyl [3H]hexadecyl ether, were utilized to answer this question. Chylomicrons labeled with these retinoids were injected intravenously into rats. Liver cell fractions, highly enriched in parenchymal or in stellate cells, were isolated 0.5 h, 4.5 h and 24 h after chylomicron injection. The ratio of 3H: 14C found in parenchymal cell preparations 4.5 h after injection was 1.8 times the ratio for the injected chylomicrons, and 24 h postinjection the ratio had increased to 2.5 times that of the chyloimcrons. In the stellate-cell-enriched preparations the 3H: 14C ratio was found to be 0.39, 0.29, and 0.23 times the ratio found in the injected labeled chylomicrons at 0.5 h, 4.5 h and 24 h after injection respectively. From the levels of 14C observed in the isolated stellate cells, it is estimated that 0.5 h postinjection the stellate cells contained approximately 34% of the 14C (i.e. the retinol injected as chylomicron retinyl ester) present in the liver. By 4.5 h the 14C present in isolated stellate cells had risen to approximately 41% of that present in the total liver, and 24 h after injection approximately 55% of hepatic total 14C was found in the stellate cells. These findings suggest that chylomicron retinyl ester is not transferred dircetly from the parenehymal to stellate cells without first undergoing hydrolysis to retinol. [ABSTRACT FROM AUTHOR]

The article discusses the predation of meadow fritillary or Boloria bellona, a common butterfly in the family of nymphalidae by predator ambush bugs or phymata. Topics discussed include the group mortality of meadow fritillary found at the remnant fen located in Muscatine County in Iowa, the incomplete inspection of inflorescence to limit the disturbance of the ambush bugs, and the effect of the predation on the populations of the pollinators.

The PAH1-encoded phosphatidate (PA) phosphatase in Saccharomyces cerevisiae is a pivotal enzyme that produces diacylglycerol for the synthesis of triacylglycerol (TAG) and simultaneously controls the level of PA used for phospholipid synthesis. Quantitative lipid analysis showed that the pah1Δ mutation caused a reduction in TAG mass and an elevation in the mass of phospholipids and free fatty acids, changes that were more pronounced in the stationary phase. The levels of unsaturated fatty acids in the pah1Δ mutant were unaltered, although the ratio of palmitoleic acid to oleic acid was increased with a similar change in the fatty acid composition of phospholipids. The pah1Δ mutant exhibited classic hallmarks of apoptosis in stationary phase and a marked reduction in the quantity of cytoplasmic lipid droplets. Cells lacking PA phosphatase were sensitive to exogenous fatty acids in the order of toxicity palmitoleic acid > oleic acid > palmitic acid. In contrast, the growth of wild type cells was not inhibited by fatty acid supplementation. In addition, wild type cells supplemented with palmitoleic acid exhibited an induction in PA phosphatase activity and an increase in TAG synthesis. Deletion of the DGK1-encoded diacylglycerol kinase, which counteracts PA phosphatase in controlling PA content, suppressed the defect in lipid droplet formation in the pah1Δ mutant. However, the sensitivity of the pah1Δ mutant to palmitoleic acid was not rescued by the dgk1Δ mutation. Overall, these findings indicate a key role of PA phosphatase in TAG synthesis for protection against fatty acid-induced toxicity. [ABSTRACT FROM AUTHOR]

Intestinal monoacylglycerol (MG) metabolism is well known to involve its anabolic reesterification to triacylglycerol (TG). We recently provided evidence for enterocyte MG hydrolysis and demonstrated expression of the monoacylglycerol lipase (MGL) gene in human intestinal Caco-2 cells and rodent small intestinal mucosa. Despite the large quantities of MG derived from dietary TG, the regulation of MG metabolism in the intestine has not been previously explored. In the present studies, we examined the mRNA expression, protein expression, and activities of the two known MG-metabolizing enzymes, MGL and MGAT2, in C57BL/6 mouse small intestine, as well as liver and adipose tissues, during development and under nutritional modifications. Results demonstrate that MG metabolism undergoes tissue-specific changes during development. Marked induction of small intestinal MGAT2 protein expression and activity were found during suckling. Moreover, while substantial levels of MGL protein and activity were detected in adult intestine, its regulation during ontogeny was complex, suggesting post-transcriptional regulation of expression. In addition, during the suckling period MG hydrolytic activity is likely to derive from carboxyl ester lipase rather than MGL. In contrast to intestinal MGL, liver MGL mRNA, protein and activity all increased 5-10-fold during development, suggesting that transcriptional regulation is the primary mechanism for hepatic MGL expression. Three weeks of high fat feeding (40% kcal) significantly induced MGL expression and activity in small intestine relative to low fat feeding (10% kcal), but little change was observed upon starvation, suggesting a role for MGL in dietary lipid assimilation following a high fat intake. [ABSTRACT FROM AUTHOR]

No studies exist concerning the ability of the plasma membrane Ca2+ pump (PMCA), sarcoplasmic reticulum Ca2+ pump (SERCA) and Na+–Ca2+ exchanger (NCX) to regulate myoplasmic Ca2+ (Cam) in vascular smooth muscle cells from diabetic individuals with dyslipidemia. We tested the hypothesis that diabetic dyslipidemia would increase vascular smooth muscle cells to buffer Cam. Cells were isolated from the coronary artery of male Yucatan pigs treated for 20 weeks with: (1) a low fat diet (control group); (2) a high fat/cholesterol diet (F group); or (3) alloxan-induced diabetic pigs fed the high fat diet (DF group). The maximum Cam response to a depolarizing 80 mM KCl (80 K) solution was evaluated in the absence and presence of thapsigargin (TSG; inhibits SERCA) and low Na (inhibits NCX). In response to 80 K alone, there was no difference in the Cam response between groups. In the presence of TSG, the 80 K response decreased by 43% in the DF group; TSG did not affect the 80 K response in the control and F groups. When exposed to both TSG and low Na, the 80 K response also decreased by 55% in the DF group. This suggests increased Cam buffering by the PMCA and/or mitochondria in the DF group when SERCA and NCX are inhibited. Compared to the control and F groups, low Na alone elicited a 50% lower Cam amplitude in the DF group, which was reversed with TSG treatment; this suggests that SERCA activity is increased in DF pigs. Western blots also indicated a 7-fold increase in the ≈115 kDa band density of an anti-SERCA2 antibody in DF compared to control pigs. This is the first report to demonstrate increased Ca2+ buffering, specifically by SERCA, in vascular smooth muscle cells from diabetic individuals with dyslipidemia. [Copyright &y& Elsevier]

Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway. [ABSTRACT FROM AUTHOR]

The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis. [ABSTRACT FROM AUTHOR]

Background:Aberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO) is assessed as a therapy for mesothelioma. Methods:Mesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment. Results:eIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number. Conclusion:4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity. [ABSTRACT FROM AUTHOR]

One approach to achieve continuous overproduction of lipids in microalgal 'cell factories' relies upon depletion or removal of nutrients that act as competing electron sinks (e.g., nitrate and sulfate). However, this strategy can only be effective for bioenergy applications if lipid is synthesized primarily de novo (from CO fixation) rather than from the breakdown and interconversion of essential cellular components. In the marine diatom, Phaeodactylum tricornutum, it was determined, using C-bicarbonate, that cell growth in nitrate (NO)-deprived cultures resulted predominantly in de novo lipid synthesis (60 % over 3 days), and this new lipid consisted primarily of triacylglycerides (TAGs). Nearly complete preservation of C occurred in all previously existing TAGs in NO-deprived cultures and thus, further TAG accumulation would not be expected from inhibition of TAG lipolysis. In contrast, both high turnover and depletion of membrane lipids, phosphatidylcholines (PCs), were observed in NO-deprived cultures (both the headgroups and fatty acid chains), while less turnover was observed in NO replete cultures. Liquid chromatography-tandem mass spectrometry mass spectra and C labeling patterns of PC headgroups provided insight into lipid synthesis in marine diatoms, including suggestion of an internal pool of glycine betaine that feeds choline synthesis. It was also observed that 16C fatty acid chains incorporated into TAGs and PCs contained an average of 14 C carbons, indicating substantial incorporation of C-bicarbonate into fatty acid chains under both nutrient states. [ABSTRACT FROM AUTHOR]

The function of small intestinal monoacylglycerol lipase (MGL) is unknown. Its expression in this tissue is surprising because one of the primary functions of the small intestine is to convert diet-derived MGs to triacylglycerol (TG), and not to degrade them. To elucidate the function of intestinal MGL, we generated transgenic mice that over-express MGL specifically in small intestine (iMGL mice). After only 3 weeks of high fat feeding, iMGL mice showed an obese phenotype; body weight gain and body fat mass were markedly higher in iMGL mice, along with increased hepatic and plasma TG levels compared to wild type littermates. The iMGL mice were hyperphagic and displayed reduced energy expenditure despite unchanged lean body mass, suggesting that the increased adiposity was due to both increased caloric intake and systemic effects resulting in a hypometabolic rate. The presence of the transgene resulted in lower levels of most MG species in intestinal mucosa, including the endocannabinoid 2-arachidonoyl glycerol (2-AG). The results therefore suggest a role for intestinal MGL, and intestinal 2-AG and perhaps other MG species, in whole body energy balance via regulation of food intake as well as metabolic rate. [ABSTRACT FROM AUTHOR]

When grown for energy production instead for smoking, tobacco can generate a large amount of inexpensive biomass more efficiently than almost any other agricultural crop. Tobacco possesses potent oil biosynthesis machinery and can accumulate up to 40% of seed weight in oil. In this work, we explored two metabolic engineering approaches to enhance the oil content in tobacco green tissues for potential biofuel production. First, an Arabidopsis thaliana gene diacylglycerol acyltransferase ( DGAT) coding for a key enzyme in triacylglycerol (TAG) biosynthesis, was expressed in tobacco under the control of a strong ribulose-biphosphate carboxylase small subunit promoter. This modification led to up to a 20-fold increase in TAG accumulation in tobacco leaves and translated into an overall of about a twofold increase in extracted fatty acids (FA) up to 5.8% of dry biomass in Nicotiana tabacum cv Wisconsin, and up to 6% in high-sugar tobacco variety NC-55. Modified tobacco plants also contained elevated amounts of phospholipids. This increase in lipids was accompanied by a shift in the FA composition favourable for their utilization as biodiesel. Second, we expressed in tobacco Arabidopsis gene LEAFY COTYLEDON 2 ( LEC2), a master regulator of seed maturation and seed oil storage under the control of an inducible Alc promoter. Stimulation of LEC2 expression in mature tobacco plants by acetaldehyde led to the accumulation of up to 6.8% per dry weight of total extracted FA. The obtained data reveal the potential of metabolically modified plant biomass for the production of biofuel. [ABSTRACT FROM AUTHOR]

Abstract: Lipolysis of stored triacylglycerols provides lipid precursors for the assembly of apolipoprotein B (apoB) lipoproteins in hepatocytes. Abhydrolase domain containing 5 (ABHD5) is expressed in liver and facilitates the lipolysis of triacylglycerols. To study the function of ABHD5 in lipoprotein secretion, we silenced the expression of ABHD5 in McA RH7777 cells using RNA interference and studied the metabolism of lipids and secretion of apoB lipoproteins. McA RH7777 cells deficient in ABHD5 secreted reduced amounts of apoB, triacylglycerols, and cholesterol esters. Detailed analysis of liquid chromatography-mass spectrometry data for the molecular species of secreted triacylglycerols revealed that deficiency of ABHD5 significantly reduced secretion of triacylglycerols containing oleate, even when oleate was supplied in the culture medium; the ABHD5-deficient cells partially compensated by secreting higher levels of triacylglycerols containing saturated fatty acids. In experiments tracking the metabolism of [14C]oleate, silencing of ABHD5 reduced lipolysis of cellular triacylglycerols and incorporation of intermediates derived from stored lipids into secreted triacylglycerols and cholesterol esters. In contrast, the incorporation of exogenous oleate into secreted triacylglycerols and cholesterol esters was unaffected by deficiency of ABHD5. These findings suggest that ABHD5 facilitates the use of lipid intermediates derived from lipolysis of stored triacylglycerols for the assembly of lipoproteins. [Copyright &y& Elsevier]

The relative importance of each core lipid in the assembly and secretion of very low density lipoproteins (VLDL) has been of interest over the past decade. The isolation of genes encoding diacylglycerol acyltransferase (DGAT) and acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) provided the opportunity to investigate the effects of isolated increases in triglycerides (TG) or cholesteryl esters (CE) on apolipoprotein B (apoB) lipoprotein biogenesis. Overexpression of human DGAT1 in rat hepatoma McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of TG. These effects were associated with decreased intracellular degradation and increased secretion of newly synthesized apoB as VLDL. Similarly, overexpression of human ACAT1 or ACAT2 in McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of CE. This led to decreased intracellular degradation and increased secretion of VLDL apoB. Overexpression of ACAT2 had a significantly greater impact upon assembly and secretion of VLDL from liver cells than did overexpression of ACAT1. The addition of oleic acid (OA) to media resulted in a further increase in VLDL secretion from cells expressing DGAT1, ACAT1, or ACAT2. VLDL secreted from DGAT1-expressing cells incubated in OA had a higher TG:CE ratio than VLDL secreted from ACAT1- and ACAT2-expressing cells treated with OA. These studies indicate that increasing DGAT1, ACAT1, or ACAT2 expression in McA-RH7777 cells stimulates the assembly and secretion of VLDL from liver cells and that the core composition of the secreted VLDL reflects the enzymatic activity that is elevated. [ABSTRACT FROM AUTHOR]

Presents information pertaining to the apolipoprotein B 100 with reference to the plasma low density lipoprotein (LDL) particles within the endoplasmic reticulum membrane. Indication of the protease protection assays of apolipoprotein B 100 (apoB); Information on the lumenal epitopes on marker proteins in secretory pathway compartments; Suggestion of observations.