3,693 research outputs found
Discovery of selective saccharide receptors via Dynamic Combinatorial Chemistry
The diagnosis of various diseases and pathological conditions can be accomplished by screening and detecting glycans in cells. Certain glycans serve as excellent biomarkers, being related to cell malfunctioning, while other structurally similar glycans perform completely different functions and are naturally present in healthy cells. Despite the theoretical feasibility of using glycans as biomarkers for early disease detection, our current inability to discriminate between them limits their use.
One promising approach to distinguishing between glycans is targeting their dissimilarities in saccharide chains. However, designing selective receptors for saccharides is challenging due to the complexity of these molecules. Their vast diversity, the fact that they exist in many interconvertible forms, their lack of recognisable functional groups, or the fact that they are normally heavily solvated in aqueous environments have made the design of receptors for saccharides a challenge that has kept the scientific community busy for the last 35 years. Although there have been ground-breaking discoveries in the field, improvements are needed to enhance our disease detection and risk stratification tools.
To address this challenge, we employed a technique known as Dynamic Combinatorial Chemistry (DCC). DCC enables the self-formation and self-selection of the best possible receptor for a given target from a pool or library of potentially good ligands. DCC has been effective for creating receptors for biomolecules such as DNA, RNA, and proteins, but its use for discovering sugar receptors is less explored. In this work, we filled this gap by implementing DCC for screening common saccharides (glucose, galactose, mannose, and fructose) using small, simple, and inexpensive building blocks. Our results indicated that molecule 2DD, which consists of a benzene ring with 2 units of amino acid aspartic acid derivatives connected in positions 1 and 3, is the best receptor in a library of very similar structures for the saccharides glucose, galactose, and mannose. For fructose, molecule 1P, a benzene ring linked to just one unit of the amino acid phenylaldehyde, was appointed as the best receptor. The differential behaviour of fructose can provide insight into the relatively unknown processes behind molecular recognition of sugars.
Molecules 2DD and 1P, as well as some other library members as negative controls, were then synthesised for further testing and DCC results were then validated by Isothermal Titration Calorimetry (ITC) and NMR techniques, proving the effectiveness of DCC as a molecular recognition tool for the creation of receptors for saccharides. Moreover, molecule 1P was found to have a high binding constant (K = 1762 M) and selectivity (50-100 times over other sugars) for fructose, which is surprisingly good considering the simplicity of the receptor.
A much more challenging approach was attempted by employing short peptides as scaffolds in DCC experiments. The benefits of using peptides are numerous but can be summarised in three bullet points: customisability, flexibility, and easiness in their synthesis. Unfortunately, we encountered many difficulties for the complete functionalisation of the peptides within the Dynamic Combinatorial Library (DCL) and this approach did not yield the desired results before the research project came to an end. However, we believe in its potential and the knowledge that we gained on the topic helped to stablish the foundations on which new research will be carried out in the near future within the research group.
In summary, this thesis reports the development of a rapid methodology for the discovery of selective receptors for monosaccharides, employing a library of simple and inexpensive starting building blocks. While this was a proof-of-concept study, it can be scalable to larger library sizes and to target more complex biomolecules, becoming a useful tool that could accelerate the discovery of new molecules with biomedical applications
Archaeological palaeoenvironmental archives: challenges and potential
This Arts and Humanities Research Council (AHRC) sponsored collaborative doctoral project represents one of
the most significant efforts to collate quantitative and qualitative data that can elucidate practices related to
archaeological palaeoenvironmental archiving in England. The research has revealed that archived
palaeoenvironmental remains are valuable resources for archaeological research and can clarify subjects that
include the adoption and importation of exotic species, plant and insect invasion, human health and diet, and
plant and animal husbandry practices. In addition to scientific research, archived palaeoenvironmental remains
can provide evidence-based narratives of human resilience and climate change and offer evidence of the
scientific process, making them ideal resources for public science engagement. These areas of potential have
been realised at an imperative time; given that waterlogged palaeoenvironmental remains at significant sites
such as Star Carr, Must Farm, and Flag Fen, archaeological deposits in towns and cities are at risk of decay due
to climate change-related factors, and unsustainable agricultural practices. Innovative approaches to collecting
and archiving palaeoenvironmental remains and maintaining existing archives will permit the creation of an
accessible and thorough national resource that can service archaeologists and researchers in the related fields
of biology and natural history. Furthermore, a concerted effort to recognise absences in archaeological
archives, matched by an effort to supply these deficiencies, can produce a resource that can contribute to an
enduring geographical and temporal record of England's biodiversity, which can be used in perpetuity in the
face of diminishing archaeological and contemporary natural resources.
To realise these opportunities, particular challenges must be overcome. The most prominent of these include
inconsistent collection policies resulting from pressures associated with shortages in storage capacity and
declining specialist knowledge in museums and repositories combined with variable curation practices. Many of
these challenges can be resolved by developing a dedicated storage facility that can focus on the ongoing
conservation and curation of palaeoenvironmental remains. Combined with an OASIS + module designed to
handle and disseminate data pertaining to palaeoenvironmental archives, remains would be findable,
accessible, and interoperable with biological archives and collections worldwide. Providing a national centre for
curating palaeoenvironmental remains and a dedicated digital repository will require significant funding.
Funding sources could be identified through collaboration with other disciplines. If sufficient funding cannot be
identified, options that would require less financial investment, such as high-level archive audits and the
production of guidance documents, will be able to assist all stakeholders with the improved curation,
management, and promotion of the archived resource
Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.
peer reviewe
Development of Corn Kernel-based Biocomposite Films for Food Packaging Applications
Most of the current and active food packaging resources and methods are nonbiodegradable and nonrenewable therefore harmful to the environment. Due to this, alternate sources of food packaging materials are in high demand. In this study, a bio-composite film has been developed, with Corn kernel powder as fiber reinforcement which is mixed with gelatin, and lignin two biopolymers as the matrix. The effect of Corn Kernel (CK) reinforcement on the Gelatin/Lignin (G/L) matrix on mechanical and barrier properties has been studied. CK has shown great potential as reinforcement to natural polymer, gelatin, and lignin (G/L) for food packaging applications as well as equating its unique attributes to biodegradability. Gelatin has significant limitations on barrier properties, hence choosing to crosslink polymer Lignin to minimize limitations. The higher particle size of CK affected the composite, hence it was further ground to a smaller size (Image analysis via. Digital Microscope). Four different mixtures at CK w% were used to prepare the composite film, CK (10%) – G/L (5%, 10%, 15%, 20%). Two G/L (5%, 10%) films without fiber were also produced to study performance comparison. The prepared composite films were subjected to morphological analysis, mechanical strength analysis, film thickness analysis, water vapor permeability analysis, and water uptake analysis. It has been observed that CK is well dispersed in the G/L matrix (Image analysis via. SEM). Mechanical properties of the CK composite film evaluated that with an increase of w% of CK the strength of the composite increases. A film with more matrix showed less absorption of water as well as less water vapor permeability. The WVP test and WU test revealed that film CK (10%) – G/L (20%) possesses the best barrier properties
ENGINEERING HIGH-RESOLUTION EXPERIMENTAL AND COMPUTATIONAL PIPELINES TO CHARACTERIZE HUMAN GASTROINTESTINAL TISSUES IN HEALTH AND DISEASE
In recent decades, new high-resolution technologies have transformed how scientists study complex cellular processes and the mechanisms responsible for maintaining homeostasis and the emergence and progression of gastrointestinal (GI) disease. These advances have paved the way for the use of primary human cells in experimental models which together can mimic specific aspects of the GI tract such as compartmentalized stem-cell zones, gradients of growth factors, and shear stress from fluid flow. The work presented in this dissertation has focused on integrating high-resolution bioinformatics with novel experimental models of the GI epithelium systems to describe the complexity of human pathophysiology of the human small intestines, colon, and stomach in homeostasis and disease. Here, I used three novel microphysiological systems and developed four computational pipelines to describe comprehensive gene expression patterns of the GI epithelium in various states of health and disease. First, I used single cell RNAseq (scRNAseq) to establish the transcriptomic landscape of the entire epithelium of the small intestine and colon from three human donors, describing cell-type specific gene expression patterns in high resolution. Second, I used single cell and bulk RNAseq to model intestinal absorption of fatty acids and show that fatty acid oxidation is a critical regulator of the flux of long- and medium-chain fatty acids across the epithelium. Third, I use bulk RNAseq and a machine learning model to describe how inflammatory cytokines can regulate proliferation of intestinal stem cells in an experimental model of inflammatory hypoxia. Finally, I developed a high throughput platform that can associate phenotype to gene expression in clonal organoids, providing unprecedented resolution into the relationship between comprehensive gene expression patterns and their accompanying phenotypic effects. Through these studies, I have demonstrated how the integration of computational and experimental approaches can measurably advance our understanding of human GI physiology.Doctor of Philosoph
2017 GREAT Day Program
SUNY Geneseo’s Eleventh Annual GREAT Day.https://knightscholar.geneseo.edu/program-2007/1011/thumbnail.jp
30th European Congress on Obesity (ECO 2023)
This is the abstract book of 30th European Congress on Obesity (ECO 2023
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