IGERT: Predoctoral Training in Functional Genomics of Model Organisms

The objective of this IGERT project is to initiate an interdisciplinary, inter-institutional degree program in Functional Genomics of Model Organisms supported by an interactive faculty from the University of Maine, the Jackson Laboratory, and the Maine Medical Center Research Institute. The major challenge for biological and biomedical research for the foreseeable future is to understand how the information encoded within a genome determines the development and functioning of a living organism. To move from the level of DNA sequence to an understanding of the molecular interplay producing the final traits of an individual will require a continuum of experimental approaches ranging from experimental genomics, molecular biology, and novel biophysical methodologies, to advanced data screening schemes and computational techniques. Traditional alignments of the biologically based disciplines will be insufficient to solve the complex problems associated with functional genomics. Genome projects, regardless of the organism, will rely increasingly on the physical and computational sciences. The increased need for interdisciplinary research will require scientists trained to work interactively in multiple disciplines. This program introduces a new educational paradigm, developed to train students to move freely among the disciplines needed to investigate genome function. Students receive training in the biological, physical and computational sciences through a combination of core and advanced courses, intensive workshops, and research seminars. Emphasis is placed on a high-quality research environment and a tutorial relationship between the student and her/his mentors and program committee. Central to the students\u27 training in interdisciplinary research will be the use of a paired mentoring system, a concept referred to as twinning. The primary mentor plays a role similar to the traditional graduate advisor and comes from the student\u27s primary area of research. The secondary mentor comes from a second discipline, and each student develops a research project dependent upon interdisciplinary collaborations.IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the multidisciplinary backgrounds and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries. In the fifth year of the program, awards are being made to twenty-one institutions for programs that collectively span the areas of science and engineering supported by NSF

Maintenance of a gluten free diet in coeliac disease: The roles of self-regulation, habit, psychological resources, motivation, support, and goal priority

Introduction: A strict lifelong gluten free diet (GFD) is the only treatment for coeliac disease (CD). Theory-based research has focused predominantly on initiation, rational, and motivational processes in predicting adherence. The aim of this study was to evaluate an expanded collection of theoretical constructs specifically relevant to the maintenance of behaviour change, in the understanding and prediction of GFD adherence. Methods: Respondents with CD (N = 5573) completed measures of GFD adherence, psychological distress, intentions, self-efficacy, and the maintenance-relevant constructs of self-regulation, habit, temptation and intentional and unintentional lapses (cognitive and behavioural consequences of lowered or fluctuating psychological resources and self-control), motivation, social and environmental support, and goal priority, conflict, and facilitation. Correlations and multiple regression were used to determine their influence on adherence, over and above intention and self-efficacy, and how relationships changed in the presence of distress. Results: Better adherence was associated with greater self-regulation, habit, self-efficacy, priority, facilitation, and support; and lower psychological distress, conflict, and fewer self-control lapses (e.g., when busy/stressed). Autonomous and wellbeing-based, but not controlled motivations, were related to adherence. In the presence of distress, the influence of self-regulation and intentional lapses on adherence were increased, while temptation and unintentional lapses were decreased. Discussion: The findings point to the importance of considering intentional, volitional, automatic, and emotional processes in the understanding and prediction of GFD adherence. Behaviour change interventions and psychological support are now needed so that theoretical knowledge can be translated into evidence-based care, including a role for psychologists within the multi-disciplinary treatment team

A Microfluidic Co-Flow Route for Human Serum Albumin-Drug-Nanoparticle Assembly.

Nanoparticles are widely studied as carrier vehicles in biological systems because their size readily allows access through cellular membranes. Moreover, they have the potential to carry cargo molecules and as such, these factors make them especially attractive for intravenous drug delivery purposes. Interest in protein-based nanoparticles has recently gained attraction due to particle biocompatibility and lack of toxicity. However, the production of homogeneous protein nanoparticles with high encapsulation efficiencies, without the need for additional cross-linking or further engineering of the molecule, remains challenging. Herein, we present a microfluidic 3D co-flow device to generate human serum albumin/celastrol nanoparticles by co-flowing an aqueous protein solution with celastrol in ethanol. This microscale co-flow method resulted in the formation of nanoparticles with a homogeneous size distribution and an average size, which could be tuned from ≈100 nm to 1 μm by modulating the flow rates used. We show that the high stability of the particles stems from the covalent cross-linking of the naturally present cysteine residues within the particles formed during the assembly step. By choosing optimal flow rates during synthesis an encapsulation efficiency of 75±24 % was achieved. Finally, we show that this approach achieves significantly enhanced solubility of celastrol in the aqueous phase and, crucially, reduced cellular toxicity

Analysis of Gene Expression in a Developmental Context Emphasizes Distinct Biological Leitmotifs in Human Cancers

A systematic analysis of the relationship between the neoplastic and developmental transcriptome provides an outline of global trends in cancer gene expression

In Vivo Airway Surface Liquid Cl− Analysis with Solid-State Electrodes

The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl−] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl−] in the “thin” ASL (∼30 μm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl−] in vivo. In initial experiments, the electrode measured [Cl−] in physiologic salt solutions, small volume (7.6 μl) test solutions, and in in vitro cell culture models, with ≥93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl− measurements were made in the following airway regions and species. First, ASL [Cl−] was measured in normal human nasal cavity and averaged 117.3 ± 11.2 mM (n = 6). Second, ASL [Cl−] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 ± 1.8 mM; (n = 6) and 126.9 ± 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 ± 4.2 mM (n = 13); and monkey bronchus = 112.3 ± 10.9 mM (n = 3). Third, Cl− measurements were made in small (1–2 mm) diameter airways of the rabbit (108.3 ± 7.1 mM, n = 5) and monkey (128.5 ± 6.8 mM, n = 3). The measured [Cl−], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology

Establishing Research Competitiveness in Biophysical Sciences in Maine

The Maine EPSCoR Research Infrastructure Improvement award is designed to enhance Maine\u27s competitiveness in molecular biophysical sciences through a partnership between the University of Maine and Maine\u27s non-profit research organizations. The proposed Biophysical Sciences Institute brings together University of Maine faculty in physics, chemistry, biology, mathematics, and spatial engineering, with biomedical researchers at the Jackson Laboratory and Maine Medical Center Research Institute. Maine EPSCoR proposes to hire additional tenure-track faculty in the fields of biophysics and advanced optics, biochemistry, structural biology, applied mathematics, computer science, image analysis and visualization, and material science. The new and existing investigators will form research teams to develop new measurement techniques, new sensors, and innovative approaches to data processing and interpretation in intracellular structures and dynamics, functional materials as a means to manipulate cellular reactions, and biocomputing. In addition to establishing the institute, Maine EPSCoR will integrate research and education through improvements to graduate training

Food consumption patterns in the Waterloo Region, Ontario, Canada: a cross-sectional telephone survey

BACKGROUND: The demographics and lifestyles of Canadians are changing, thereby influencing food choices and food preparation in the home. Although different dietary practices are associated with increased risk of foodborne illness, our ability to evaluate food consumption trends and assess risks associated with foodborne illness is limited by lack of data on current eating habits and consumer food safety practices. The objective of this study was to describe, for the first time, the food consumption patterns in a Canadian-based population from a food safety perspective, in order to establish baseline data on actual food intake of individuals. METHOD: A cross-sectional telephone survey of 2,332 randomly selected residents of Waterloo Region, Ontario, Canada (C-EnterNet pilot site) was conducted between November 2005 and March 2006. Food intake was assessed using a 7-day dietary recall method. RESULTS: Certain food items were consumed more than others among the same food groups, and consumption of many food items varied by gender and age. Specific foods considered high-risk for the transmission of certain enteric pathogens were significantly more likely to be consumed by males (i.e. unpasteurized juice, bean sprouts, and undercooked meat) and elderly individuals (i.e. undercooked eggs). The majority of households prepared and consumed most meals at home, allocating an average of 44 minutes to prepare a meal. CONCLUSION: Baseline data on actual food intake is useful to public health professionals and food safety risk assessors for developing communication messages to consumers and in foodborne outbreak investigations

The New Biomedicine: A Critical Appraisal

Mahidol University’s namesake, H.R.H. Prince Mahidol, stated the University’s universal view of higher education as follows: ‘True success is not in the learning, but in its application to the benefit of mankind’.1 It is thus fitting that the following commentary speaks to the University’s goal. The acquisition of basic scientific knowledge by scientists working in genetics, embryology, developmental biology, immunology and virology throughout the twentieth century led to its application to clinical problems in the twenty-first. The technology to repair genetically-deficient pluripotent stem cells, treating diseased adults or ensuring the birth of healthy babies now is almost within our power. However, the application of this knowledge to living organisms, using cells that can mutate and selectively evolve, makes clinical application tricky while social and ethical issues arising from the eventual use of these technologies requires thought. Future attention to trends in basic science research should make stem cell therapy applicable to all

Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation

© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Quaternized vinyl- and alkynyl-pyridine reagents were shown to react in an ultrafast and selective manner with several cysteine-tagged proteins at near-stoichiometric quantities. We have demonstrated that this method can effectively create a homogenous antibody-drug conjugate that features a precise drug-to-antibody ratio of 2, which was stable in human plasma and retained its specificity towards Her2+ cells. Finally, the developed warhead introduces a +1 charge to the overall net charge of the protein, which enabled us to show that the electrophoretic mobility of the protein may be tuned through the simple attachment of a quaternized vinyl pyridinium reagent at the cysteine residues. We anticipate the generalized use of quaternized vinyl- and alkynyl-pyridine reagents not only for bioconjugation, but also as warheads for covalent inhibition and as tools to profile cysteine reactivity.Funded under the EU Horizon 2020 Programme, Marie Skłodowska-Curie ITN GA No. 675007, the Royal Society (UF110046 and URF\R\180019 to G.J.L.B.), FCT Portugal (iFCT IF/00624/2015 to G.J.L.B. and PhD studentship SFRH/BD/115932/2016 to A.G.), Xunta de Galicia (Galician Plan of research, innovation and growth 2011–2015, ED481B 2014/086-0 and ED481B 2018/007 to M.J.M.), D.G.I. MINECO/FEDER (grants CTQ2015-70524-R and RYC-2013–14706 to G.J.-O. and C.D.N and CTQ2015-67727-R to F.C.), Universidad de la Rioja (FPI PhD studentship to I.C.), FAPESP (BEPE 2015/07509-1 and 2017/13168-8 to B.B.), and by an ERC StG (GA No. 676832).info:eu-repo/semantics/publishedVersio