Providing Access to Content using Technology to Engage All Learners

The purpose of this module is to provide access to research and tools which can be used to differentiate lessons in a classroom for all types of learners. First, the module helps educators understand TPACK as well as why using technology with students is effective. Next, the module delineates the research and tools into 4 categories of learning, which allows educators to learn/ teach using tools specific for different learners. The module concludes by encouraging educators to practice using the tools with a group of learners and a content specific standard. View professional learning module.https://digitalcommons.gardner-webb.edu/improve/1017/thumbnail.jp

Understanding potentials and restrictions of solvent-free enzymatic polycondensation of itaconic acid: an experimental and computational analysis

6siItaconic acid is a chemically versatile unsaturated diacid that can be produced by fermentation and potentially it can replace petrol based monomers such as maleic and fumaric acids in the production of curable polyesters or new biocompatible functionalized materials. Unfortunately, due to the presence of the unsaturated C=C bond, polycondensation of itaconic acid is hampered by cross reactivity and isomerization. Therefore, enzymatic polycondensations would respond to the need of mild and selective synthetic routes for the production of novel bio-based polymers. The present work analyses the feasibility of enzymatic polycondensation of diethyl itaconate and, for the first time, provides comprehensive solutions embracing both the formulation of the biocatalyst, the reaction conditions and the choice of the co-monomers. Computational docking was used to disclose the structural factors responsible for the low reactivity of dimethyl itaconate and to identify possible solutions. Surprisingly, experimental and computational analysis revealed that 1,4-butanediol is an unsuitable co-monomer for the polycondensation of dimethyl itaconate whereas the cyclic and rigid 1,4-cyclohexanedimethanol promotes the elongation of the oligomers.partially_openembargoed_20160430Corici, Livia; Pellis, Alessandro; Ferrario, Valerio; Ebert, Cynthia; Cantone, Sara; Gardossi, LuciaCorici, Livia; Pellis, Alessandro; Ferrario, Valerio; Ebert, Cynthia; Cantone, Sara; Gardossi, Luci

Towards feasible and scalable solvent-free enzymatic polycondensations: integrating robust biocatalysts with thin film reactions

There is an enormous potential for synthesizing novel bio-based functionalized polyesters under environmentally benign conditions by exploiting the catalytic efficiency and selectivity of enzymes. Despite the wide number of studies addressing in vitro enzymatic polycondensation, insufficient progress has been documented in the last two decades towards the preparative and industrial application of this methodology. The present study analyses bottlenecks hampering the practical applicability of enzymatic polycondensation that have been most often neglected in the past, with a specific focus on solvent-free processes. Data here presented elucidate how classical approaches for enzyme immobilization combined with batch reactor configuration translate into insufficient mass transfer as well as limited recyclability of the biocatalyst. In order to overcome such bottlenecks, the present study proposes thin-film processes employing robust covalently immobilized lipases. The strategy was validated experimentally by carrying out the solvent-free polycondensation of esters of adipic and itaconic acids. The results open new perspectives for enlarging the applicability of biocatalysts in other viscous and solvent-free syntheses

Functionalization of Enzymatically Synthesized Rigid Poly(itaconate)s via Post-Polymerization aza-Michael Addition of Primary Amines

8The bulky 1,4-cyclohexanedimethanol was used as co-monomer for introducing rigidity in lipase synthetized poly(itaconates). Poly(1,4-cyclohexanedimethanol itaconate) was synthetized on a 14 g scale at 50°C, under solvent-free conditions and 70 mbar using only 135 Units of lipase B from Candida antarctica per gram of monomer. The mild conditions preserved the labile vinyl group of itaconic acid and avoided the decomposition of 1,4-cyclohexanedimethanol observed in chemical polycondensation. Experimental and computational data show that the enzymatic polycondensation proceeds despite the low reactivity of C1 of itaconic acid. The rigid poly(1,4-cyclohexanedimethanol itaconate) was investigated in the context of aza-Michael addition of hexamethylenediamine and 2-phenylethylamine to the vinyl moiety. The enzymatically synthesized linear poly(1,4-butylene itaconate) was studied as a comparison. The two oligoesters (Molecular Weights ranging from 720 to 2859 g mol-1) reacted on a gram scale, at 40-50°C, at atmospheric pressure and in solvent-free conditions. The addition of primary amines led to amine-functionalized oligoesters but also to chain degradation, and the reactivity of the poly(itaconate)s was influenced by the rigidity of the polymer chain. Upon the formation of the secondary amine adduct, the linear poly(1,4-butylene itaconate) undergoes fast intramolecular cyclization and subsequent degradation via pyrrolidone formation, especially in the presence of hexamethylenediamine. On the contrary, the bulky 1,4-cyclohexanedimethanol confers rigidity to poly(1,4-cyclohexanedimethanol itaconate), which hampers the intramolecular cyclization. Also the bulkiness of the amine and the use of solvent emerged as factors that affect the reactivity of poly(itaconate)s. Therefore, the possibility to insert discrete units of itaconic acid in oligoesters using biocatalysts under solvent-free mild conditions opens new routes for the generation of bio-based functional polymers or amine-triggered degradable materials, as a function of the rigidity of the polyester chain.partially_openopenAlice Guarneri, Viola Cutifani, Marco Cespugli, Alessandro Pellis, Roberta Vassallo, Fioretta Asaro, Cynthia Ebert, Lucia GardossiGuarneri, Alice; Viola, Cutifani; Cespugli, Marco; Alessandro, Pellis; Roberta, Vassallo; Asaro, Fioretta; Ebert, Cynthia; Gardossi, Luci

Enlarging the tools for efficient enzymatic polycondensation: structural and catalytic features of cutinase 1 from Thermobifida cellulosilytica

9siCutinase 1 from Thermobifida cellulosilytica is reported for the first time as an efficient biocatalyst in polycondensation reactions. Under thin film conditions the covalently immobilized enzyme catalyzes the synthesis of oligoesters of dimetil adipate with different polyols leading to higher Mw (~1900) and Mn (~1000) if compared to lipase B from Candida antarctica or cutinase from Humicola insolens. Computational analysis discloses the structural features that make this enzyme readily accessible to substrates and optimally suited for covalent immobilization. As lipases and other cutinase enzymes, it presents hydrophobic superficial regions around the active site. However, molecular dynamics simulations indicate the absence of interfacial activation, similarly to what already documented for lipase B from Candida antarctica. Notably, cutinase from Humicola insolens displays a “breathing like” conformational movement, which modifies the accessibility of the active site. These observations stimulate wider experimental and bioinformatics studies aiming at a systematic comparison of functional differences between cutinases and lipases.partially_openembargoed_20161210Pellis, Alessandro; Ferrario, Valerio; Zartl, Barbara; Brandauer, Martin; Gamerith, Caroline; Herrero-Acero, Enrique; Ebert, Cynthia; Gardossi, Lucia; Guebitz, GeorgPellis, Alessandro; Ferrario, Valerio; Zartl, Barbara; Brandauer, Martin; Gamerith, Caroline; Herrero Acero, Enrique; Ebert, Cynthia; Gardossi, Lucia; Guebitz, Geor

The CARSO (Computer Aided Response Surface Optimization) Procedure in Optimization Studies

The paper illustrates innovative ways of using the CARSO (Computer Aided Response Surface Optimization) procedure for response surfaces analyses derived by DCM4 experimental designs in multivariate spaces. Within this method, we show a new feature for optimization studies: the results of comparing their quadratic and linear models for discussing the best way to compute the most reliable predictions of future compound

Fully renewable polyesters via polycondensation catalyzed by Thermobifida cellulosilytica cutinase 1: an integrated approach

The present study addresses comprehensively the problem of producing polyesters through sustainable processes while using fully renewable raw materials and biocatalysts. Polycondensation of bio-based dimethyl adipate with different diols was catalyzed by cutinase 1 from Thermobifida cellulosilytica (Thc_cut1) under solvent free and thin-film conditions. The biocatalyst was immobilized efficiently on a fully renewable cheap carrier based on milled rice husk. A multivariate factorial design demonstrated that Thc_cut1 is less sensitive to the presence of water in the system and it works efficiently under milder conditions (50 \ub0C; 535 mbar) when compared to lipase B from Candida antarctica (CaLB), thus enabling energy savings. Experimental and computational investigations of cutinase 1 from Thermobifida cellulosilytica (Thc_cut1) disclosed structural and functional features that make this serine-hydrolase efficient in polycondensation reactions. Bioinformatic analysis performed with the BioGPS tool pointed out functional similarities with CaLB and provided guidelines for future engineering studies aiming, for instance, at introducing different promiscuous activities in the Thc_cut1 scaffold. The results set robust premises for a full exploitation of enzymes in environmentally and economically sustainable enzymatic polycondensation reactions

Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

Evolving biocatalysis to meet bioeconomy challenges and opportunities

4siThe unique selectivity of enzymes, along with their remarkable catalytic activity, constitute powerful tools for transforming renewable feedstock and also for adding value to an array of building blocks and monomers produced by the emerging bio-based chemistry sector. Although some relevant biotransformations run at the ton scale demonstrate the success of biocatalysis in industry, there is still a huge untapped potential of catalytic activities available for targeted valorization of new raw materials, such as waste streams and CO2. For decades, the needs of the pharmaceutical and fine chemistry sectors have driven scientific research in the field of biocatalysis. Nowadays, such consolidated advances have the potential to translate into effective innovation for the benefit of bio-based chemistry. However, the new scenario of bioeconomy requires a stringent integration between scientific advances and economics, and environmental as well as technological constraints. Computational methods and tools for effective big-data analysis are expected to boost the use of enzymes for the transformation of a new array of renewable feedstock and, ultimately, to enlarge the scope of biocatalysis.partially_openopenPellis, Alessandro; Cantone, Sara; Ebert, Cynthia; Gardossi, LuciaPellis, Alessandro; Cantone, Sara; Ebert, Cynthia; Gardossi, Luci

Alliance of Genome Resources Portal: unified model organism research platform

The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource