Advanced organic chemistry laboratory curricula in Australian universities: Investigating the major topics and approaches to learning

A key goal of tertiary education is to prepare graduates with the training, skills, and knowledge necessary to thrive in the workforce. In chemistry, 50% of undergraduate students from Australia, New Zealand and the UK plan to pursue a career that uses chemistry (Ogunde et al., 2017). However, it has also been noted that there is a mismatch in the skills desired by industry when compared with what is taught to undergraduates (Martin et al., 2011; Yasin & Yueying, 2017). Laboratory work is an essential part of undergraduate programs with the objective of developing practical and interpersonal skills with ‘real world’ engagement in chemistry. It is therefore concerning to note the perception among industry stakeholders that the laboratory skills of high-achieving chemistry graduates do not meet the desired standard (Kirton et al., 2014). To extend our understanding regarding the importance and value of undergraduate laboratory skills, techniques, and equipment usage; semi-structured interviews were conducted with key external stakeholders, academics, and post-graduate teaching staff. This presentation will discuss the key findings from our perspectives analysis interviews with various organic chemistry experts across the country from both industry and academia. Key findings include the belief: the purpose of second-year laboratory courses is to teach and developing competency with laboratory skills, whilst third-year laboratory courses should build on this with student application of learned skills whether through lab project design or problem-solving tasks/challenges. REFERENCES Kirton, S. B., Al-Ahmad, A., & Fergus, S. (2014). Using Structured Chemistry Examinations (SChemEs) As an Assessment Method To Improve Undergraduate Students’ Generic, Practical, and Laboratory-Based Skills. Journal of Chemical Education, 91(5), 648-654. Martin, C. B., Schmidt, M., & Soniat, M. (2011). A Survey of the Practices, Procedures, and Techniques in Undergraduate Organic Chemistry Teaching Laboratories. Journal of Chemical Education, 88(12), 1630-1638. Ogunde, J. C., Overton, T. L., Thompson, C. D., Mewis, R., & Boniface, S. (2017). Beyond graduation: motivations and career aspirations of undergraduate chemistry students [10.1039/C6RP00248J]. Chemistry Education Research and Practice, 18(3), 457-471. Yasin, N. Y. B. M., & Yueying, O. (2017). Evaluating the Relevance of the Chemistry Curriculum to the Workplace: Keeping Tertiary Education Relevant. Journal of Chemical Education, 94(10), 1443-1449

Advanced Organic Chemistry laboratory curricula in Australian universities: Investigating the major topics and approaches to learning

A key goal of tertiary education is to prepare graduates with the training, skills, and knowledge necessary to thrive in the workforce. In chemistry, 50% of undergraduate students from Australia, New Zealand and the UK plan to pursue a career that uses chemistry (Ogunde et al., 2017). However, it has also been noted that there is a mismatch in the skills desired by industry when compared with what is taught to undergraduates (Martin et al., 2011; Yasin & Yueying, 2017). Laboratory work is an essential part of undergraduate programs with the objective of developing practical and interpersonal skills with ‘real world’ engagement in chemistry. It is therefore concerning to note the perception among industry stakeholders that the laboratory skills of high-achieving chemistry graduates do not meet the desired standard (Kirton et al., 2014). This project aims to investigate how we can better develop higher level undergraduate chemistry laboratory programs to improve training and competency with industrially relevant skills. This research will undertake an initial investigation into the current organic chemistry laboratory curricula of second- and third-year courses in Australian universities through content analysis of laboratory manuals and unit outlines. To extend our understanding, semi-structured interviews will be conducted with key external stakeholders, academics, and post-graduate teaching staff. This presentation will introduce the initial stages of this project and expand on our intentions to utilise these data to develop an intervention and set of recommendations for undergraduate laboratories. REFERENCES Kirton, S. B., Al-Ahmad, A., & Fergus, S. (2014). Using Structured Chemistry Examinations (SChemEs) as an assessment method to improve undergraduate students’ generic, practical, and laboratory-based skills. Journal of Chemical Education, 91(5), 648-654. Martin, C. B., Schmidt, M., & Soniat, M. (2011). A survey of the practices, procedures, and techniques in undergraduate organic chemistry teaching laboratories. Journal of Chemical Education, 88(12), 1630-1638. Ogunde, J. C., Overton, T. L., Thompson, C. D., Mewis, R., & Boniface, S. (2017). Beyond graduation: Motivations and career aspirations of undergraduate chemistry students. Chemistry Education Research and Practice, 18(3), 457-471. Yasin, N. Y. B. M., & Yueying, O. (2017). Evaluating the relevance of the chemistry curriculum to the workplace: Keeping tertiary education relevant. Journal of Chemical Education, 94(10), 1443-1449

SAGA1 and SAGA2 promote starch formation around proto-pyrenoids in Arabidopsis chloroplasts

The pyrenoid is a chloroplastic microcompartment in which most algae and some terrestrial plants condense the primary carboxylase, Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) as part of a CO2-concentrating mechanism that improves the efficiency of CO2 capture. Engineering a pyrenoid-based CO2-concentrating mechanism (pCCM) into C3 crop plants is a promising strategy to enhance yield capacities and resilience to the changing climate. Many pyrenoids are characterized by a sheath of starch plates that is proposed to act as a barrier to limit CO2 diffusion. Recently, we have reconstituted a phase-separated “proto-pyrenoid” Rubisco matrix in the model C3 plant Arabidopsis thaliana using proteins from the alga with the most well-studied pyrenoid, Chlamydomonas reinhardtii [N. Atkinson, Y. Mao, K. X. Chan, A. J. McCormick, Nat. Commun.11, 6303 (2020)]. Here, we describe the impact of introducing the Chlamydomonas proteins StArch Granules Abnormal 1 (SAGA1) and SAGA2, which are associated with the regulation of pyrenoid starch biogenesis and morphology. We show that SAGA1 localizes to the proto-pyrenoid in engineered Arabidopsis plants, which results in the formation of atypical spherical starch granules enclosed within the proto-pyrenoid condensate and adjacent plate-like granules that partially cover the condensate, but without modifying the total amount of chloroplastic starch accrued. Additional expression of SAGA2 further increases the proportion of starch synthesized as adjacent plate-like granules that fully encircle the proto-pyrenoid. Our findings pave the way to assembling a diffusion barrier as part of a functional pCCM in vascular plants, while also advancing our understanding of the roles of SAGA1 and SAGA2 in starch sheath formation and broadening the avenues for engineering starch morphology

Adenovirus 36 DNA in Adipose Tissue of Patient with Unusual Visceral Obesity

Massive adipose tissue depositions in the abdomen and thorax sufficient to interfere with respiration developed in a patient with multiple medical problems. Biopsy of adipose tissue identified human adenovirus 36 (Adv 36) DNA. Adv 36 causes adipogenesis in animals and humans. Development of massive lipomatosis may be caused by Adv 36

Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

RNA sequencing in livers; TGFβ1; Epigenetic driversSeqüenciació d’ARN en el fetge; TGFβ1; Controladors epigenèticsSecuenciación de ARN en el hígado; TGFβ1; Controladores epigenéticosAlcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.This work was mainly supported by NIH/NIAAA funded Consortia "Integrated approaches for identifying molecular targets in alcoholic hepatitis" InTEAM (U01AA021908) (R.B., P.M., P.S-B., I.R., J.Cbl). This work was supported in part by: NIH/NIAAA (R01AA023781), USA (C.W.); Hepacare Project, Fundacion La Caixa, Spain (M.A.A., C.B. and M.U.L); Fond national de la recherche scientifique (FNRS J.0146.17) and Fond de la recherche scientifique medicale (FRSM T.0217.18), Belgium (P.S.); NIH/NCATS (UH3TR000503) and EPA (STAR 83573601), USA (D.L.V. and L.A.T.); MRC, UK (MK/K001949/1) and NIH/NIAAA, USA (UO1AA018663) (J.M.); NIH/NIAAA (1U01AA021908-01-33490), Instituto de Salud Carlos III (PI17/00673) and Miguel Servet (CPII16/00041) and "Una manera de hacer Europa" program, European Regional Development Fund (ERDF), EU (P.S-B.); National Institute for Health Research Imperial Biomedical Research Centre and NIHR Health Technology Assessment Grant 08-14-44 (M.R.T.); NIH T32, DK007052, USA (L.R.E.); NIH/NIAAA (1U01AA021908) and AFEF (P.M., L.D., A. L.)

Interaction of α-tocopherol with a polyunsaturated lipid studied by MD simulations

poster abstractPolyunsaturated phospholipids are essential components of neural membranes and their effect on membrane architecture is proposed to be the molecular origin of a myriad of health benefits. A downside of polyunsaturated phospholipids is that they are highly susceptible to oxidation due to the presence of multiple double bonds. α-Tocopherol is the most biologically active component in a family of phenolic compounds that comprise vitamin E, which is the major lipid soluble antioxidant in cell membranes. To investigate whether α-tocopherol preferentially interacts with polyunsaturated phospholipids to optimize protection against oxidation, we performed MD simulations on 1-stearoyl-2-docosahexaenoylphosphatiylcholine (SDPC, 18:0-22:6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) bilayers containing α-tocopherol. SDPC with a docosahexaenoyl sn-2 chain is polyunsaturated, while SOPC with an oleoyl sn-2 chain serves as a monounsaturated control. The simulations were run under constant pressure for 200 ns on a system that comprised 80 phospholipid molecules, 20 α-tocopherol molecules and 2165 water molecules. We discovered significant differences between the two systems. Analysis of the simulations indicates that the α-tocopherol has a strong interaction with the polyunsaturated fatty acid. The flip-flop of α-tocopherol across the bilayer is also much faster in SDPC than in SOPC. Solid state NMR, neutron scattering and complementary experiments are now underway to test the predictions from the MD simulations

α-Tocopherol is well designed to protect polyunsaturated fatty acids

poster abstractPolyunsaturated fatty acids (PUFA) are an influential constituent in cell membranes, but are extremely vulnerable to oxidation. The presumptive role for α-tocopherol (α-toc), the molecular form of vitamin E retained by the human body, is to protect PUFA-containing lipids from oxidation. To investigate whether α-toc preferentially interacts with PUFA in support of this function, we performed MD simulations on lipid bilayers composed of 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22-6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) in the presence of α-toc. SDPC with docosahexaenoic acid (DHA) for the sn-2 chain is polyunsaturated, while SOPC with oleic acid (OA) for the sn-2 chain serves as a monounsaturated control. The simulations were run at 37 °C under constant pressure for 200 ns on a system that comprised 80 phospholipid molecules, 20 α-toc molecules and 2165 water molecules. In qualitative agreement with our results from solid state 2H NMR and neutron scattering experiments, the simulations show that α-toc increases order inside the bilayer and that the chromanol headgroup sits near the surface in both SDPC and SOPC. Analyses of the density distribution of the lipid chains relative to α-toc show that the α-toc’s chromanol headgroup, the part of the molecule that protects against oxidation, would have more chance to interact with PUFA chains than saturated chains. A major prediction from our simulations is that α-toc undergoes flip-flop across the bilayer and that the rate is an order of magnitude greater in SDPC than SOPC. This is a remarkable finding that reveals a possible mechanism by which the chromanol group would not only wait at the membrane surface but would also patrol the membrane interior to meet lipid radicals and terminate the chain reaction by which lipid peroxidation proceeds

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

Climate reconstruction from paired oxygen-isotope analyses of chironomid larval head capsules and endogenic carbonate (Hawes Water, UK) - Potential and problems

Temperature and the oxygen isotopic composition (δ18O) of meteoric water are both important palaeoclimatic variables, but separating their influences on proxies such as the δ18O of lake carbonates is often problematic. The large temperature variations that are known to have occurred in the northern mid-latitudes during the Late Glacial make this interval an excellent test for a novel approach that combines oxygen-isotope analyses of chironomid larval head capsules with co-occurring endogenic carbonate. We apply this approach to a Late Glacial lake sediment sequence from Hawes Water (NW England). Oxygen-isotope values in chironomid head capsules show marked variations during the Late Glacial that are similar to the oxygen isotope record from endogenic carbonate. However, summer temperature reconstructions based on the paired isotope values and fractionation between chironomids and calcite yield values between −20 and −4 °C, which are unrealistic and far lower than reconstructions based on chironomid assemblages at the same site. The composition of a limited number of samples of fossil chironomid larval head capsules determined using Pyrolysis gas-chromatography mass spectrometry indicates the presence of aliphatic geopolymers, suggesting that diagenetic alteration of the head capsules has systematically biased the isotope-derived temperature estimates. However, a similar trend in the isotope records of the two sources suggests that a palaeoclimate signal is still preserved