Regulation of liver mitochondrial metabolism during hibernation by post-translational modification

Hibernation, characterized by a seasonal reduction in metabolism and body temperature, allows animals to conserve energy when environmental conditions (e.g. temperature, food availability) are unfavourable. During hibernation, small mammals such as the 13-lined ground squirrel (Ictidomys tridecemlineatus) cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by \u3e95% and body temperature falls to ~5 °C, and interbout euthermia (IBE), where metabolic rate and body temperature rapidly increase and are maintained at euthermic levels several hours. Suppression of metabolism during entrance into torpor is paralleled by rapid suppression of liver mitochondrial metabolism. In my thesis, I aimed to characterize the regulatory mechanisms that underlie this rapid and reversible mitochondrial suppression. Using high resolution respirometry and enzymatic assays, I determined that this suppression between IBE and torpor occurs at electron transport system (ETS) complexes I and II. Flux through complexes I and II is suppressed during torpor by 40% and 60%, respectively, despite no differences in protein content between the two hibernation states. I used two-dimensional differential gel electrophoresis and Blue-Native PAGE to determine if differences in post-translational modification of mitochondrial proteins parallels these metabolic changes. I found that the 75 kDa subunit of complex I is significantly more phosphorylated in torpor than IBE, and that the complex II flavoprotein subunit is significantly more phosphorylated in IBE than torpor. To investigate the potential that this differential phosphorylation mediates the observed differences in enzyme activity and mitochondrial metabolism between torpor and IBE, I attempted to manipulate phosphorylation state of complexes I and II as well as stimulate the endogenous protein kinase A (PKA) pathway within intact liver mitochondria. I found that dephosphorylation of complex I reversed suppression of its activity during torpor, and that dephosphorylation of complex II induced suppression of its activity in IBE. I was unable to stimulate the endogenous PKA within intact mitochondria, and suggest that another pathway is responsible for mediating changes in phosphorylation in vivo. Together, my results point to novel ETS phosphorylation sites that may contribute to metabolic regulation in general and, in particular, suppression of mitochondrial metabolism during hibernation

Student learning gains in higher education: A longitudinal analysis with faculty discussion

Student learning is the primary desired outcome of a college education. To understand how educational programming and curricula affect students, colleges and universities must collect evidence of student learning gain. In this study, a longitudinal design was employed to investigate how a math and science general education curriculum impacted college students’ quantitative and scientific reasoning. Quantitative and scientific reasoning gain scores were computed and predicted from personal (i.e., prior knowledge, gender) and curriculum (i.e., number of completed courses in the domain) characteristics to uncover what factors relate to learning gain. Collapsing across personal and curriculum variables, gain scores were moderate (average of 3.72 out of 66 points) with little variation and were not predicted by personal or curriculum characteristics. Disaggregating gain scores by coursework revealed that students had modest learning gains after completing one course but did not gain with additional coursework. Given performance on the quantitative reasoning test has no personal consequence for the students (i.e., low-stakes test), low examinee effort could attenuate student learning gain estimates. Therefore, gain scores and gain score predictions were estimated again after data from unmotivated students were removed (i.e., motivation filtering). Test-specific and test-session specific motivation measures were used to filter unmotivated students; results were compared to determine if they are measure-dependent. The learning gain estimates derived from using the two motivation measures were not different from each other or the unfiltered estimates. Faculty expectations of learning gain estimates were assessed. Faculty overestimated the learning gains of students with quantitative and scientific reasoning coursework. Findings imply that students are not learning as much as expected or desired from their coursework and further investigation is necessary to explain why

Saponin-Permeabilization is Not a Viable Alternative to Isolated Mitochondria for Assessing Oxidative Metabolism in Hibernation

Saponin permeabilization of tissue slices is increasingly popular for characterizing mitochondrial function largely because it is fast, easy, requires little tissue and leaves much of the cell intact. This technique is well described for mammalian muscle and brain, but not for liver. We sought to evaluate how saponin permeabilization reflects aspects of liver energy metabolism typically assessed in isolated mitochondria. We studied the ground squirrel (Ictidomys tridecemlineatus Mitchell), a hibernating mammal that shows profound and acute whole-animal metabolic suppression in the transition from winter euthermia to torpor. This reversible metabolic suppression is also reflected in the metabolism of isolated liver mitochondria. In this study we compared euthermic and torpid animals using saponin permeabilized tissue and mitochondria isolated from the same livers. As previously demonstrated, isolated mitochondria have state 3 respiration rates, fueled by succinate, that are suppressed by 60-70% during torpor. This result holds whether respiration is standardized to mitochondrial protein, cytochrome a content or citrate synthase activity. In contrast, saponin-permeabilized liver tissue, show no such suppression in torpor. Neither citrate synthase activity nor VDAC content differ between torpor and euthermia, indicating that mitochondrial content remains constant in both permeabilized tissue and isolated mitochondria. In contrast succinate dehydrogenase activity is suppressed during torpor in isolated mitochondria, but not in permeabilized tissue. Mechanisms underlying metabolic suppression in torpor may have been reversed by the permeabilization process. As a result we cannot recommend saponin permeabilization for assessing liver mitochondrial function under conditions where acute changes in metabolism are known to occur

An Interactionist Approach to BTLG Pride

Within and beyond Symbolic Interactionism, sociological studies of bisexual, transgender, lesbian, and gay (BTLG) populations have expanded dramatically in the past two decades. Although such studies have invigorated our understanding of many aspects of BTLG life and experience, they have thus far left BTLG Pride relatively unexplored. How do BTLG populations experience Pride, and what insights might such efforts have for sociologically understanding such populations and events? We examine these questions through an interview study of bi+ people (i.e., sexually fluid people who identify as bisexual, pansexual, or otherwise outside of gay/straight binaries; Eisner, 2013). Specifically, we analyze how bi+ people negotiate both (1) experiencing Pride as “outsiders within” the broader BTLG population (Collins, 1986), and (2) framing who Pride is for and what it means in practice. In so doing, we demonstrate how Interactionist analyses of certain groups’ meaning making around and experiences of Pride can expand existing sociologies of BTLG populations, bisexual experience, and Pride

Sources of total, non-milk extrinsic, and intrinsic and milk sugars in the diets of older adults living in sheltered accommodation

The WHO recommends limiting non-milk extrinsic sugars (NMES) consumption to ≤ 10 % energy to reduce the risk of unhealthy weight gain and dental caries, and to restrict frequency of intake to ≤ 4 times/d to reduce risk of dental caries. Older adults, especially those from low-income backgrounds, are at increased risk of dental caries, yet there is little information on sugars intake (frequency of intake and food sources) in this age group. The aim of this report is to present baseline data from a community-based dietary intervention study of older adults from socially deprived areas of North East England, on the quantity and sources of total sugars, NMES, and intrinsic and milk sugars, and on frequency of NMES intake. Dietary intake was assessed using two 3-d estimated food diaries, completed by 201 participants (170 female, thirty-one male) aged 65–85 years (mean 76·7 (sd 5·5) years) recruited from sheltered housing schemes. Total sugars represented 19·6 %, NMES 9·3 %, and intrinsic and milk sugars 10·3 % of daily energy intake. Eighty-one (40·3 %) exceeded the NMES intake recommendation. Mean frequency of NMES intake was 3·4 times/d. The fifty-three participants (26·4 %) who exceeded the frequency recommendation ( ≤ 4 times/d) obtained a significantly greater percentage of energy from NMES compared with those participants who met the recommendation. The food groups ‘biscuits and cakes’ (18·9 %), ‘soft drinks’ (13·1 %) and ‘table sugar’ (11·1 %) made the greatest contributions to intakes of NMES. Interventions to reduce NMES intake should focus on limiting quantity and frequency of intake of these food groups

“Can’t Put my Finger on It”: A Research Report on the Non-Existence and Meaninglessness of Sin

This paper presents findings from an exploratory study of sin. Based on nine in-depth interviews with self-identified religious people, we demonstrate that respondents define sin as (1) nonconformity, (2) relative to other social realities, and (3) taught by moral authorities. In so doing, respondents’ definitions reveal that sin, despite its use to justify all types of social policies, is a social construction that has no established concrete meaning in daily life. In conclusion, we argue that social scientists would benefit greatly from systematic analyses of the meaning (lessness) and significance of sin in people’s lives as well as within existing social scientific literature, and propose avenues for research concerning this term

Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype

Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18–30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: ERCC5 Asp1104His (rs17655); XPC Lys939Gln (rs2228001); ERCC2 Lys751Gnl (rs13181); XPC PAT (an 83 bp poly A/T insertion–deletion polymorphism in the XPC gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene–gene interactions were observed between XPC Lys939Gln and ERCC5 Asp1104His and XPC Lys939Gln and ERCC2 Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the ERCC2 Lys751Gnl single nucleotide polymorphism

The effects of graded levels of calorie restriction XVIII : tissue specific changes in cell size and number in response to calorie restriction

Open Access via the OUP Agreement This work was supported by Biotechnology and Biological Sciences Research Council (Grant Number: “China Partnering Award BB/J020028/1” and “Standard Grant BB/G009953/1”).Peer reviewedPublisher PD

Screening for Language Difficulties in Disadvantaged Populations on Entry to Early Years Education: Challenges and Opportunities

Children aged 3–4 years (n = 876) were recruited from deprived areas in England, and a significant minority of the sample were second language learners. Oral language ability was assessed using child administered standardized measures, and parents reported on children’s language. We adapted the Language Use Inventory [LUI; (1)] to capture carer’s reports of the children’s structural language in the language of instruction and their home language (where appropriate). The final measure included six subscales from the original: use of simple words, requests for help, gaining attention, talking about activities/actions, interactions with others, and building sentences. Children’s language abilities and non-verbal abilities were below norms on all standardized tests administered except non-word repetition. Factor analysis indicated that all the six scales of the adapted parent completed measure loaded on one language factor. The revised total scale score correlated significantly (p < 0.0005) with child assessed language measures, specifically expressive vocabulary and grammar. Different patterns across gender, language status and parental education were examined. Sensitivity and specificity of the scale to identify children with the greatest delays were evaluated. These preliminary data indicated that parent-reported information on children’s language skills at 3 years of age has the potential to provide a reliable indicator to inform pedagogy and practice at the start of nursery school. Study limitations are examined and avenues for future development explored