Scalable Science Education via Online Cooperative Questioning.

A critical goal for science education is to design and implement learning activities that develop a deep conceptual understanding, are engaging for students, and are scalable for large classes or those with few resources. Approaches based on peer learning and online technologies show promise for scalability but often lack a grounding in cognitive learning principles relating to conceptual understanding. Here, we present a novel design for combining these elements in a principled way. The design centers on having students author multiple-choice questions for their peers using the online platform PeerWise, where beneficial forms of cognitive engagement are encouraged via a series of supporting activities. We evaluated an implementation of this design within a cohort of 632 students in an undergraduate biochemistry course. Our results show a robust relationship between the quality of question authoring and relevant learning outcomes, even after controlling for the confounding influence of prior grades. We conclude by discussing practical and theoretical implications.

Calcium-Sensing Receptors Control CYP27B1-Luciferase Expression: Transcriptional and Posttranscriptional Mechanisms.

25-hydroxyvitamin D 1α-hydroxylase (encoded by CYP27B1), which catalyzes the synthesis of 1,25-dihydroxyvitamin D3, is subject to negative or positive modulation by extracellular Ca2+ (Ca2+ o) depending on the tissue. However, the Ca2+ sensors and underlying mechanisms are unidentified. We tested whether calcium-sensing receptors (CaSRs) mediate Ca2+ o-dependent control of 1α-hydroxylase using HEK-293 cells stably expressing the CaSR (HEK-CaSR cells). In HEK-CaSR cells, but not control HEK-293 cells, cotransfected with reporter genes for CYP27B1-Photinus pyralis (firefly) luciferase and control Renilla luciferase, an increase in Ca2+ o from 0.5mM to 3.0mM induced a 2- to 3-fold increase in firefly luciferase activity as well as mRNA and protein levels. Surprisingly, firefly luciferase was specifically suppressed at Ca2+ o ≥ 5.0mM, demonstrating biphasic Ca2+ o control. Both phases were mediated by CaSRs as revealed by positive and negative modulators. However, Ca2+ o induced simple monotonic increases in firefly luciferase and endogenous CYP27B1 mRNA levels, indicating that the inhibitory effect of high Ca2+ o was posttranscriptional. Studies with inhibitors and the CaSR C-terminal mutant T888A identified roles for protein kinase C (PKC), phosphorylation of T888, and extracellular regulated protein kinase (ERK)1/2 in high Ca2+ o-dependent suppression of firefly luciferase. Blockade of both PKC and ERK1/2 abolished Ca2+ o-stimulated firefly luciferase, demonstrating that either PKC or ERK1/2 is sufficient to stimulate the CYP27B1 promoter. A key CCAAT box (-74 bp to -68 bp), which is regulated downstream of PKC and ERK1/2, was required for both basal transcription and Ca2+ o-mediated transcriptional upregulation. The CaSR mediates Ca2+ o-dependent transcriptional upregulation of 1α-hydroxylase and an additional CaSR-mediated mechanism is identified by which Ca2+ o can promote luciferase and possibly 1α-hydroxylase breakdown.

The importance of cognitive diversity for sustaining the commons.

Cognitive abilities underpin the capacity of individuals to build models of their environment and make decisions about how to govern resources. Here, we test the functional intelligences proposition that functionally diverse cognitive abilities within a group are critical to govern common pool resources. We assess the effect of two cognitive abilities, social and general intelligence, on group performance on a resource harvesting and management game involving either a negative or a positive disturbance to the resource base. Our results indicate that under improving conditions (positive disturbance) groups with higher general intelligence perform better. However, when conditions deteriorate (negative disturbance) groups with high competency in both general and social intelligence are less likely to deplete resources and harvest more. Thus, we propose that a functional diversity of cognitive abilities improves how effectively social groups govern common pool resources, especially when conditions deteriorate and groups need to re-evaluate and change their behaviors.

Protein Kinase C Epsilon Deletion in Adipose Tissue, but Not in Liver, Improves Glucose Tolerance.

Protein kinase C epsilon (PKCɛ) activation in the liver is proposed to inhibit insulin action through phosphorylation of the insulin receptor. Here, however, we demonstrated that global, but not liver-specific, deletion of PKCɛ in mice protected against diet-induced glucose intolerance and insulin resistance. Furthermore, PKCɛ-dependent alterations in insulin receptor phosphorylation were not detected. Adipose-tissue-specific knockout mice did exhibit improved glucose tolerance, but phosphoproteomics revealed no PKCɛ-dependent effect on the activation of insulin signaling pathways. Altered phosphorylation of adipocyte proteins associated with cell junctions and endosomes was associated with changes in hepatic expression of several genes linked to glucose homeostasis and lipid metabolism. The primary effect of PKCɛ on glucose homeostasis is, therefore, not exerted directly in the liver as currently posited, and PKCɛ activation in this tissue should be interpreted with caution. However, PKCɛ activity in adipose tissue modulates glucose tolerance and is involved in crosstalk with the liver.

The physiologic and phenotypic significance of variation in human amylase gene copy number.

Background: Salivary α-amylase gene (AMY1) copy number (CN) correlates with the amount of salivary α-amylase, but beyond this, the physiologic significance is uncertain. Objective: We hypothesized that individuals with higher AMY1 CN would digest starchy foods faster and show higher postprandial responses and lower breath hydrogen excretion compared with those with low CN. Design: Four linked studies were conducted. In Study 1, we genotyped 201 healthy subjects with the use of real-time quantitative polymerase chain reaction and determined glucose tolerance, insulin sensitivity, salivary α-amylase activity, body mass index (BMI), and macronutrient intake. In Study 2, a pool of 114 subjects tested 6 starchy foods, 3 sugary foods, 1 mixed meal, and 2 reference glucose solutions, containing either 50 or 25 g of available carbohydrate. In Study 3, we compared glycemic and insulin responses to starchy foods with responses to glucose in 40 individuals at extremes of high and low CN. In Study 4, we compared breath hydrogen and methane responses over 8 h in 30 individuals at extremes of CN. Results: AMY1 CN correlated positively with salivary α-amylase activity (r = 0.62, P < 0.0001, n = 201) but not with BMI, glucose tolerance, or insulin sensitivity. However, CN was strongly correlated with normalized glycemic responses to all starchy foods (explaining 26-61% of interindividual variation), but not to sucrose or fruit. Individuals in the highest compared with the lowest decile of CN produced modestly higher glycemia (+15%, P = 0.018), but not insulinemia, after consuming 2 starchy foods. Low-CN individuals displayed >6-fold higher breath methane levels in the fasting state and after starch ingestion than high-CN individuals (P = 0.001), whereas hydrogen excretion was similar. Conclusions: Starchy foods are digested faster and produce higher postprandial glycemia in individuals with high AMY1 CN. In contrast, having low CN is associated with colonic methane production. This trial was registered at www.anzctr.org.au as ACTRN12617000670370.

Improving large class performance and engagement through student-generated question banks.

Disciplines such as Biochemistry and Molecular Biology, which involve concepts not included in the high-school curriculum, are very challenging for many first year university students. These subjects are particularly difficult for students accustomed to surface learning strategies involving memorization and recall of facts, as a deeper understanding of the relationship between concepts is needed for successful transfer to related areas and subsequent study. In this article, we explore an activity in a very large first year Molecular Biology course, in which students create multiple-choice questions related to targeted learning outcomes, and then answer and evaluate one another's questions. This activity encompasses elements of both self- and peer-assessment and the generative tasks of creating questions and producing written feedback may contribute to a deeper understanding of the material. We make use of a free online platform to facilitate all aspects of the process and analyze the effect of student engagement with the task on overall course performance. When compared to previous semester's cohorts, we observe a pronounced improvement in class performance on exam questions targeting similar concepts to the student-generated questions. In addition, those students that engage to a greater extent with the activity perform significantly better on the targeted exam questions than those who are less active, yet all students perform similarly on a set of isolated control questions appearing on the same exam. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:306-317, 2018.

Type I interferon-regulated gene expression and signaling in murine mixed glial cells lacking signal transducers and activators of transcription 1 or 2 or interferon regulatory factor 9.

Type I interferons (IFN-I) are critical in antimicrobial and antitumor defense. Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2, and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways. For example, the absence of STAT1, STAT2, or IRF9 exacerbates neurological disease in transgenic mice with CNS production of IFN-I. Here we determined the role of IFN-I-driven, ISGF3-independent signaling in regulating global gene expression in STAT1-, STAT2-, or IRF9-deficient murine mixed glial cell cultures (MGCs). Compared with WT, the expression of IFN-α-stimulated genes (ISGs) was reduced in number and magnitude in MGCs that lacked STAT1, STAT2, or IRF9. There were significantly fewer ISGs in the absence of STAT1 or STAT2 versus in the absence of IRF9. The majority of ISGs regulated in the STAT1-, STAT2-, or IRF9-deficient MGCs individually were shared with WT. However, only a minor number of ISGs were common to WT and STAT1-, STAT2-, and IRF9-deficient MGCs. Whereas signal pathway activation in response to IFN-α was rapid and transient in WT MGCs, this was delayed and prolonged and correlated with increased numbers of ISGs expressed at 12 h versus 4 h of IFN-α exposure in all three IFN-I signaling-deficient MGCs. In conclusion, 1) IFN-I can mediate ISG expression in MGCs via ISGF3-independent signaling pathways but with reduced efficiency, with delayed and prolonged kinetics, and is more dependent on STAT1 and STAT2 than IRF9; and 2) signaling pathways not involving STAT1, STAT2, or IRF9 play a minor role only in mediating ISG expression in MGCs.

Interrelationships among mediators of cellular zinc homeostasis in healthy and type 2 diabetes mellitus populations.

SCOPE: The involvement of zinc in multiple physiological systems requires tight control of cellular zinc concentration. This study aims to explore the relationships among selected mediators of cellular zinc homeostasis in an apparently healthy (AH) population and a cohort with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Baseline data of three trials forming two cohorts, AH (n = 70) and T2DM (n = 42), were used for multivariate analyses to identify groupings within ten zinc transporter and metallothionein (MT) gene expressions, stratified by health status. Multiple regression models were used to explore relationships among zinc transporter/MT groupings and plasma zinc. Gene expression of zinc transporters and MTs, with the exception of ZnT6, were significantly lower in the T2DM cohort (p < 0.01). Cluster analysis showed that the groupings of zinc transporters and MTs were largely similar between the two cohorts, with the exception for ZnT1 and ZIP7. Zinc transporters and MTs were significant determinants of plasma zinc (r2 = 0.48, p = 0.001) in the AH cohort, but not in the T2DM cohort. CONCLUSION: The current study suggests altered cellular zinc homeostasis in T2DM and supports the use of multiple zinc transporters and MTs groupings to further understand zinc homeostasis in health and T2DM.

Cognitive Capitalism: Economic Freedom Moderates the Effects of Intellectual and Average Classes on Economic Productivity.

Cognitive ability stimulates economic productivity. However, the effects of cognitive ability may be stronger in free and open economies, where competition rewards merit and achievement. To test this hypothesis, ability levels of intellectual classes (top 5%) and average classes (country averages) were estimated using international student assessments (Programme for International Student Assessment; Trends in International Mathematics and Science Study; and Progress in International Reading Literacy Study) (N = 99 countries). The ability levels were correlated with indicators of economic freedom (Fraser Institute), scientific achievement (patent rates), innovation (Global Innovation Index), competitiveness (Global Competitiveness Index), and wealth (gross domestic product). Ability levels of intellectual and average classes strongly predicted all economic criteria. In addition, economic freedom moderated the effects of cognitive ability (for both classes), with stronger effects at higher levels of freedom. Effects were particularly robust for scientific achievements when the full range of freedom was analyzed. The results support cognitive capitalism theory: cognitive ability stimulates economic productivity, and its effects are enhanced by economic freedom.

Associations between CD36 gene polymorphisms and metabolic response to a short-term endurance-training program in a young-adult population.

Recent studies have shown that CD36 gene variants are associated with an increased prevalence of chronic disease. Although a genetic component to trainability has been proven, no data are available specifically on the influence of CD36 on training response. Two single nucleotide polymorphisms (SNPs) (rs1527479 and rs1984112) were assessed for associations with whole-body substrate oxidation, response to a 75-g dextrose oral glucose tolerance test, fasting plasma lipids, and cardiovascular disease risk factors in a young healthy cohort, both using cross-sectional analysis and following a 4-week endurance-exercise training program. Genotyping was performed using real-time polymerase chain reaction. Cross-sectional data were collected in 34 individuals (age, 22.7 ± 3.5 years), with 17 completing the training program. At baseline, TT SNP carriers at rs1527479 and wild-type GG carriers at rs1984112 were associated with significantly greater whole-body rate of fat oxidation (Fatox) during submaximal exercise (P < 0.05), whilst AA carriers at the same position were associated with elevated triglyceride (TG) levels. A significant genotype × time interaction in Fatox at SNP rs1984112 was identified at rest. Significant genotype × time interactions were present at rs1527479, with TT carriers exhibiting a favourable response to training when compared with C-allele carriers for fasting TG, diastolic blood pressure (DBP), and mean arterial pressure (MAP). In conclusion, cross-sectional assessment identified associations with Fatox and TG. Training response at both SNPs identified "at-risk" genotypes responding favourably to the training stimulus in Fatox, TG, DBP, and MAP. Although these data show potential pleiotropic influence of CD36 SNPs, assessment in a larger cohort is warranted.

Interactions Between Fatty Acid Transport Proteins, Genes That Encode for Them, and Exercise: A Systematic Review.

Long-chain fatty acid (LCFA) movement into skeletal muscle involves a highly mediated process in which lipid rafts are utilized in the cellular membrane, involving numerous putative plasma membrane-associated LCFA transport proteins. The process of LCFA uptake and oxidation is of particular metabolic significance both at rest and during light to moderate exercise. A comprehensive systematic search of electronic databases was conducted to investigate whether exercise alters protein and/or gene expression of putative LCFA transport proteins. There were 31 studies meeting all eligibility criteria, of these 13 utilized an acute exercise protocol and 18 examined chronic exercise adaptations. Seventeen involved a study design incorporating an exercise stimulus, while the remaining 14 incorporated a combined exercise and diet stimulus. Divergent data relating to acute exercise, as well as prolonged exercise training (≥3 weeks), on protein content (PC) response was identified for proteins CD36, FABPpm and CAV1. Messenger ribonucleic acid (mRNA) data did not always correspond to functional PC, supporting previous suggestions of a disconnect due to potentially limiting factors post gene expression. The large array of study designs, cohorts, and primary dependent variables within the studies included in the present review elucidate the complexity of the interaction between exercise and LCFA transport proteins. Summary of the results in the present review validate the need for further targeted investigation within this topic, and provide an important information base for such research. J. Cell. Physiol. 231: 1671-1687, 2016. © 2015 Wiley Periodicals, Inc.

Zinc-induced upregulation of metallothionein (MT)-2A is predicted by gene expression of zinc transporters in healthy adults.

The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults (n = 39) were randomised to zinc treatment (ZT), receiving 22 mg Zn/day (n = 19), or no treatment (NT) (n = 20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT-2A gene expression and fold change were found to be higher in the ZT group (P = 0.025 and P = 0.016, respectively) compared to the NT group, specifically at Day 2 (40 ± 18 % increase from baseline, P = 0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT-2A gene expression was correlated with changes in all zinc transporter expressions (r (2) = 0.54, P = 0.029); the change in ZIP1 expression emerged as a univariate predictor (P = 0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions (P = 0.030). Physical activity level was positively correlated with baseline ZIP7 expression (r = 0.36, P = 0.029). The present study shows that MT-2A expression is related to changing expression of zinc transporter genes, specifically ZIP1, in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.

Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system.

Interleukin-6 (IL-6) participates in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch homolog 2 (Sbno2) as an IL-6-stimulated gene in murine astrocytes. Sbno2 is a mouse homolog of the sno gene in Drosophila but little is known about the regulation or function of the mammalian gene. Here we examined the regulation of the Sbno2 gene in astrocytes in vitro and in the murine CNS following systemic endotoxin administration. In murine and human cultured astrocytes, Sbno2 gene expression was significantly upregulated in a dose- and time-dependent fashion by hyper-IL-6 (IL-6 + soluble IL-6 receptor). The level of Sbno2 mRNA was also upregulated significantly in murine astrocytes by other glycoprotein130 cytokine-family members and the pro-inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha. These changes were reflected by corresponding alterations in the level of the SBNO2 protein. Inhibiting protein synthesis resulted in higher Sbno2 mRNA and did not abolish the upregulation of Sbno2 mRNA mediated by hyper-IL-6. Inhibition of transcription led to a rapid reduction in hyper-IL-6-induced Sbno2 mRNA in astrocytes suggesting that the Sbno2 mRNA is quite unstable. Following intra-peritoneal lipopolysaccharide injection in mice, Sbno2 mRNA levels in the brain were significantly increased. Cellular localization studies revealed that this increase in Sbno2 mRNA occurred predominantly in astrocytes and in the choroid plexus and in some microglia, endothelial cells, and neurons. These findings are consistent with SBNO2 functioning as an acute inflammatory response gene in astrocytes as well as other cells in the CNS.

TNF-α gene expression is increased following zinc supplementation in type 2 diabetes mellitus.

Chronic low-grade inflammation in type 2 diabetes mellitus (DM) can elicit changes in whole-body zinc metabolism. The interaction among the expression of inflammatory cytokines, zinc transporter and metallothionein (MT) genes in peripheral blood mononuclear cells in type 2 DM remains unclear. In a 12-week randomized controlled trial, the effects of zinc (40 mg/day) supplementation on the gene expression of cytokines, zinc transporters and MT in women with type 2 DM were examined. In the zinc-supplemented group, gene expression of tumour necrosis factor (TNF)-α tended to be upregulated by 27 ± 10 % at week 12 compared to baseline (P = 0.053). TNF-α fold change in the zinc-treated group was higher than in those without zinc supplementation (P < 0.05). No significant changes were observed in the expression or fold change of interleukin (IL)-1ß or IL-6. Numerous bivariate relationships were observed between the fold changes of cytokines and zinc transporters, including ZnT7 with IL-1ß (P < 0.01), IL-6 (P < 0.01) and TNF-α (P < 0.01). In multiple regression analysis, IL-1ß expression was predicted by the expression of all zinc transporters and MT measured at baseline (r (2) = 0.495, P < 0.05) and at week 12 (r (2) = 0.532, P < 0.03). The current study presents preliminary evidence that zinc supplementation increases cytokine gene expression in type 2 DM. The relationships found among zinc transporters, MT and cytokines suggest close  interactions between zinc homeostasis and inflammation.

The associations between polymorphisms in the CD36 gene, fat oxidation and cardiovascular disease risk factors in a young adult Australian population: a pilot study.

Our pilot study in a young adult Australian cohort aimed to investigate potential associations between CD36 polymorphisms (rs1527479 and rs1984112), fat oxidation and cardiovascular disease risk. CD36 genotype was associated with fat oxidation during sub-maximal exercise, resting heart rate and blood pressure, indicating increased chronic disease risk in this otherwise healthy cohort.

Using an ePortfolio system as an electronic laboratory notebook in undergraduate biochemistry and molecular biology practical classes.

Despite many apparent advantages, including security, back-up, remote access, workflow, and data management, the use of electronic laboratory notebooks (ELNs) in the modern research laboratory is still developing. This presents a challenge to instructors who want to give undergraduate students an introduction to the kinds of data curation and notebook keeping skills that will inevitably be required as ELNs penetrate normal laboratory practice. An additional problem for the teacher is that ELNs do not generally have student-administrative functions and are prohibitively expensive. In this report, we describe the use and impact of an ePortfolio system as a surrogate ELN. Introduction of the system led to several pedagogic outcomes, namely: increased preparedness of students for class, encouragement of creativity and reflection with respect to experimental methods, greatly enhanced engagement between students and tutors, and it gave instructors the ability to scrutinize original data files and monitor student-tutor feedback cycles. However, implementation led to a disruption of tutor workloads and incurred new levels of accountability that threatened to undermine the initiative. Through course evaluations and other reflective processes, we reached an appreciation of how an ELN should be introduced into practical class teaching so that it not only becomes an appropriate aid for teaching the laboratory experience, but also becomes a life-long resource for students.

Effects of dietary protein to carbohydrate balance on energy intake, fat storage, and heat production in mice.

OBJECTIVE: Protein leverage plays a role in driving increased energy intakes that may promote weight gain. The influence of the protein to carbohydrate ratio (P:C) in diets of C57BL/6J mice on total energy intake, fat storage, and thermogenesis was investigated. DESIGN AND METHODS: Male mice (9 weeks old) were provided ad libitum access to one of five isocaloric diets that differed in P:C. Food intake was recorded for 12 weeks. After 16 weeks, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were dissected, weighed, and the expression levels of key metabolic regulators were determined in BAT. In a separate cohort, body surface temperature was measured in response to 25 diets differing in protein, fat, and carbohydrate content. RESULTS: Mice on low P:C diets (9:72 and 17:64) had greater total energy intake and increased WAT and BAT stores. Body surface temperature increased with total energy intake and with protein, fat, and carbohydrate, making similar contributions per kJ ingested. Expression of three key regulators of thermogenesis were downregulated in BAT in mice on the lowest P:C diet. CONCLUSIONS: Low-protein diets induced sustained hyperphagia and a generalized expansion of fat stores. Increased body surface temperature on low P:C diets was consistent with diet-induced thermogenesis (DIT) as a means to dissipate excess ingested energy on such diets, although this was not sufficient to prevent development of increased adiposity. Whether BAT was involved in DIT is not clear. Increased BAT mass on low P:C diets might suggest so, but patterns of thermogenic gene expression do not support a role for BAT in DIT, although they might reflect failure of thermogenic function with prolonged exposure to a low P:C diet.

Effect of ensilation of potato on viability of Taenia hydatigena eggs.

A Taenia hydatigena model was used to assess the effect 0, 7, 14, 21, and 28 days of ensilation of minced potato on viability of tapeworm eggs. For infection of lambs, 2,000 T. hydatigena eggs were ensiled for 0, 7, 14, 21 and 28 days in minced potato at 22°C and fed to recently weaned lambs (29.9±0.76 kg). At slaughter, no cysticerci were recovered from lambs infected with eggs ensiled for 28 days while a mean of 5.0±5.0 cysticerci (0.25% of the initial egg dose) were recovered from lambs infected with eggs ensiled for 21 days. For lambs fed eggs ensiled for 0 days (control), 359.3±55.6 cysticerci were recovered (18.0% of the initial egg dose). Regression analysis revealed that a 99.9% reduction in viability was attained after 18.59 days of ensilation.

Effect of heat treatment on viability of Taenia hydatigena eggs.

Effects of heat treatments on activation and infectivity of Taenia hydatigena eggs were assessed. Eggs containing oncospheres were used for in vitro and in vivo studies to determine the response to 5min of heat treatment, ranging from room temperature (22°C) to 60°C. The study demonstrated 99.47% and 100% reduction in oncosphere activation or infectivity after 5min of heat treatment at 60°C and 57.38°C under in vitro and in vivo conditions, respectively. Similar results between the two approaches indicted the appropriateness of the in vitro methods to identify oncosphericidal treatments of practical significance. Similar heat treatments may also be effective against Taenia saginata and help to reduce occurrence of beef cysticercosis.