bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Novel Serine Protease Inhibitors to Ameliorate Cockroach‐Induced Airway Inflammation and Cell Damage
Authors: Reihill James , Yang Zhixuan , Carroll Emma , McGarvey Lorcan , Lundy Fionnuala , Lockhart John , Sergeant Gerard , Martin Lorraine 
Published: June 2021

Exposure to cockroach can lead to allergic airway inflammation. Serine proteases in cockroach extract (CRE) have been demonstrated to affect airway epithelial cells via activation of PARs (protease‐activated receptors) and via release of inflammatory cytokines (GM‐CSF, IL‐8 and IL‐6). The serine protease inhibitor gabexate mesilate (GM) has been shown to attenuate both cockroach‐induced bronchial cell damage and the release of inflammatory cytokines.The aim of this study was to examine a number of natural peptides, derived from amphibian skin secretions, shown to be trypsin‐like protease inhibitors in an initial screen.Trypsin‐like protease activity present in German cockroach (Blattella germanica) extract was assayed in the presence or absence of candidate protease inhibitors using a fluorogenic substrate based assay. Cell viability was determined using the RealTime‐Glo assay (Promega). Inflammatory markers were assayed by ELISA.Four natural peptides were tested versus CRE tryptic activity. A pIC50 of −8.2, −9.1, −5.5 and −7.5 was calculated for QUB‐1812, QUB‐1813, QUB‐1913 and QUB‐2136 respectively. The two inhibitors that displayed greatest potency (QUB‐1813 and QUB‐1812) were further evaluated and shown to rescue CRE‐induced cytotoxicity and inflammation; to a greater extent than elicited by GM.We have identified two novel natural peptides that potently inhibit the abundant serine trypsin‐like protease activity present in cockroach preparations. Moreover, these peptides protect airway epithelial cells from the toxic and inflammatory effects normally induced by CRE. We will now proceed to test these peptides in advanced models to gain insight as to their potential clinical utility.Support or Funding InformationBREATH (Border and REgions Airways Training Hub) is funded by the EU's INTERREG Va programme managed by the Special EU Programmes Body (SEUPB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Secretory Profile of Inflammatory Mediators is Altered in Differentiated Primary COPD Samples at Air Liquid Interface Compared to Healthy Equivalents
Authors: Kelly Gillian A. , Douglas Lisa E.J. , Maye Jessica R. , Reihill James A. , McGarvey Lorcan P. , Lundy Fionnuala T. , Litherland Gary , Martin S. Lorraine 
Published: June 2021

In the UK, over 1 million people live with diagnosed chronic obstructive pulmonary disease (COPD) however, it is estimated that this is only 1/3 of the total COPD population. Diagnosis is based on patient airflow obstruction, a late developing symptom, by which time a significant amount of lung damage has already occurred (1). Investigation into a range of biomarkers to aid earlier identification of COPD is therefore essential.Apical and basolateral samples collected from differentiated primary healthy and COPD cells at air liquid interface (ALI) were screened for 35 proteases, 32 protease inhibitors and 37 other inflammatory mediators using R&D Systems Proteome Profiler Protease array and Anti‐Protease array and BioRad Bio‐Plex Pro Human Inflammation Panel 1, 37‐Plex Assay respectively, with the aim of identifying potential biomarkers.Both apical and basolateral secretory profiles were altered in COPD samples compared to their healthy counterparts. The majority of apically secreted proteases were up‐regulated whereas, protease inhibitors were down‐regulated. Basolateral secretion of inflammatory mediators was found to be both up‐ and down‐regulated depending on which mediator was being measured.These initial results highlight interesting targets which will be further investigated in clinical samples to assess their potential as biomarkers to aid the earlier diagnosis of COPD.Support or Funding InformationBREATH (Border and REgions Airways Training Hub) is funded by the EU's INTERREG Va programme managed by the Special EU Programmes Body (SEUPB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of muscle‐derived BAIBA on osteocytes with aging
Authors: Bonewald Lynda F. 
Published: June 2021

Beta‐aminoisobutyric acid, BAIBA, is a metabolite released into the circulation by contracted muscle. It has been shown to have beneficial effects on metabolism, glucose tolerance, the browning of white fat, and recently on osteocyte viability and function. BAIBA prevents both bone and muscle loss due to unloading and synergizes with anabolic loading to promote bone formation. Combining BAIBA with voluntary wheel running of 12 mo old female mice for 6 mo until 18 mo of age preserved the capacity of the extensor digitorum longus and soleus muscles to produce factors that maintain osteocyte viability. This capacity is normally lost with aging. Ex vivo contraction of isolated murine muscle from both young (5 mo) and old (22mo) mice induces secretion of BAIBA, showing that with age muscle can still produce this factor with contraction. However, with aging, osteocytes appear to lose expression of the Mas related G protein receptor type D, the receptor in osteocytes that responds to BAIBA. Efforts are underway to identify means to either maintain or overexpress this receptor with aging.Support or Funding InformationNIH NIA PO1AG039355This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
How the Formation of the Turing Pattern Could Be Used in a Bio‐Mechano‐Chemical Framework for Describing Development of Bones and Joints
Authors: Alvarado Diego Alexander Garzón 
Published: June 2021

In this conference, we will show our mathematical models for interpreting different biological, biomechanical, and biochemical processes that are fundamental on bone and joints formation. In order to do this description, we use a set of reaction‐diffusion equations that are widely used in morphogenesis, in which biochemical factors are assumed to be secreted by precursor cells, mesenchymal cells, chondrocytes, and osteoblasts, in endochondral and intramembranous ossification, respectively. The solution leads to the so‐called Turing patterns, which represent these processes of ossification approximately. Besides, it has been included the mechanical effects on the growth and form in the development of joints, primary and secondary ossification centers, and bones. Those models have the property of describing the development and shape of bones and joints accurately. In this presentation, we will show the model and hypotheses used for describing the development of the skull, clavicle, patella, and finger joints. Also, we will present some of the research that we are doing around experimental and mathematical problems in biomedical engineering at Universidad Nacional de Colombia.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mind the Gap: How Reference Samples Impact Skeletal Age Estimation in Forensic Casework
Authors: Langley Natalie R. 
Published: June 2021

Forensic anthropologists are often tasked with determining skeletal age‐at‐death to assist law enforcement in identifying skeletal remains. If the remains are skeletally mature, degenerative changes in articular surfaces are typically assessed to determine age. If the skeleton is immature tooth eruption, dental development, and/or epiphyseal union are used to estimate age. Forensic anthropologists derive an age‐at‐death estimate by comparing our assessment of skeletal age indicator(s) to standards derived from skeletal collections of known age‐at‐death. Prior to the establishment of modern skeletal collections such at the William M. Bass Donated Collection at the University of Tennessee, anthropologists developed age estimation techniques using late 19th and early 20th century anatomical collections (e.g. the Hamann‐Todd Osteology Collection at the Cleveland Museum of Natural History and Terry Anatomical Collection at the Smithsonian Institution). However, research on Bass Collection skeletons has demonstrated remarkable changes in skeletal morphology in modern Americans compared to early 19th century birth cohorts, illustrating that standards derived from modern populations are imperative for forensic casework; anatomical collections and archaeological samples are not appropriate reference samples. Age estimation in forensic casework is further complicated by the age distribution of the forensic case population. Forensic cases often involve accidental deaths, homicides, and suicides of individuals from a younger age demographic than natural deaths which comprise many of the reference samples used to derive age estimates. This difference between the age distribution of the reference sample and that of the “target” population leads to ‘age mimicry’, whereby skeletal age‐at‐death may be under‐estimated. This presentation will highlight research that illustrates the impact of secular change and reference sample composition on the accuracy and precision of forensic skeletal age‐at‐death estimation. The documentation of significant changes in skeletal morphology illustrates what evolutionary biologists already know—phenotype is dynamic, not static. These short‐term evolutionary changes in skeletal form have implications for anatomical research beyond the hard tissues.Support or Funding InformationNational Institute of JusticeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CRISPR‐based functional evaluation of common SZ risk variants
Authors: Schrode Nadine , Ho Seok‐Man , Brennand Kristen 
Published: June 2021

Schizophrenia (SZ) is a highly heritable neuropsychiatric disorder. Nevertheless, the functional mechanisms through which the large contribution of common genetic variation underlies this disorder remain unclear. GWAS and eQTL analyses have previously identified candidate genes, whose expression is affected by common SZ risk variants (SZ‐eQTL genes). We established a genetics‐driven hiPSC‐based approach for the prioritization and functional validation of common variants and genes associated with SZ.Using this strategy, we prioritized one putative causal SZ‐eQTL SNP and five SZ‐eQTL genes for functional evaluation. By integrating CRISPR‐mediated gene editing, activation and repression technologies, our isogenic hiPSC‐based neuronal platform recapitulated genotype‐dependent gene expression differences from post‐mortem brains in SNP‐edited hiPSC‐neurons, identified evidence of molecular convergence downstream of common variant perturbations and uncovered specific pre‐ and post‐synaptic neuronal deficits associated with the SZ‐eQTL gene SNAP91.We demonstrate a systematic and comprehensive strategy to interpret and evaluate the growing number of SZ‐associated variants and genes across neural cell types and genetic backgrounds, which will be applicable to other complex genetic disorders driven in large part by common variation.Ultimately, our objective is to understand the cell‐type specific contributions of SZ risk variants to disease predisposition.Support or Funding InformationThis work was partially supported by National Institute of Health (NIH) grants R01 MH101454 (K.J.B.), R01 MH106056 (K.J.B.) and R01 MH109897 (P.S. and K.J.B.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AP‐2α and AP‐2β Cooperatively Regulate Gene Expression of Ectodermal WNT Ligands to Drive Craniofacial Patterning
Authors: Van Otterloo Eric , Milanda Isaac , Li Hong , Williams Trevor 
Published: June 2021

Tissue‐tissue interactions are central to proper embryogenesis and are often disrupted in developmental disorders—providing an impetus to further understand their regulation. These interactions require coordinated molecular crosstalk (i.e., signaling molecules) between tissues, thus, providing the instructional cues necessary to generate complex anatomical structures. A prototypical example includes epithelial:mesenchymal interactions—necessary to pattern the craniofacial complex as well as central to the development of a variety of ectodermal appendages. While a great deal of information exists on both the molecules involved in crosstalk and their immediate transcriptional response in adjacent tissues, much less is known regarding how such signals are established. Here, through the use of conditional loss‐of‐function models of AP‐2 transcription factors (AP‐2α and AP‐2β) in mice, we reveal an essential, cooperative role for AP‐2α/β in driving expression of the genes encoding a variety of WNT ligands. Focusing on craniofacial development, loss of AP‐2α/β from the ectoderm results in major dysregulation of the WNT‐signaling pathway, dysregulation of downstream WNT target genes in adjacent tissues, and finally a profound impact on facial form. Importantly, genetic reduction of a WNT‐pathway inhibitor in AP‐2α/β ectoderm mutants can partially mitigate some of these defects. In addition, highlighting a broader role for AP‐2 in regulating WNT signaling, we find numerous WNT‐dependent ectodermal appendages are disrupted in AP‐2α/β ectoderm mutants. Ongoing work is being conducted to identify the molecular nature by which AP‐2 regulates Wnt ligand expression in the face as well as additional structures. Given WNT‐signaling components are often mutated in a variety of human craniofacial disorders and are key components of vertebrate facial evolution, these findings suggest that ectodermal AP‐2 regulation of WNT‐signaling is likely a key axis in these processes.Support or Funding InformationEVO NIH NIDCR K99 DE026823TW NIH NIDCR 2R01 DE012728 and 1R01 DE019843This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anatomy as a Science Worth Seeing: Killing Many Birds of Our Academic Role with One Stone
Authors: Chapman Jamie 
Published: June 2021

As anatomy academics, formal parts of our role are to engage the community, provide service to our university and to our discipline of anatomy. With increasing demands and workloads, it can be difficult to fulfill all of these different roles. However, it is possible to meet many of these different roles at the same time through anatomy outreach.To many, the general public and others in the scientific community, anatomy is often seen as a dead science (or simply a science of studying the dead). Our role, in providing service to the discipline of anatomy, is to dispel this misconception and demonstrate that anatomy is very much for the living. As anatomists, we're also lucky in that, compared with many of the other sciences, anatomy has the added bonus of being highly visual – something which is also highly coveted by people interested in marketing and the media. Now, while we cannot typically use cadaveric anatomy to engage the public, there are a number of other activities which we can use – anatomical body painting, for example.Anatomical body painting (ABP) was introduced to our level 1 introductory Human Biology unit as a means to increase student engagement with the musculoskeletal system. While ABP is not new to anatomy education, it was new to this specific context and to this institution. Through the engagement of the university's marketing team, local media were invited to film the practical and perform interviews. Soon after, cascading invitations to bring ABP to public engagements began to flow and the level of anatomy engagement with the community increased.ABP was used at the university's Open Days. With the help of a life‐model and a number of volunteer students, over the course of five hours, Anatomy‐Man was painted. Also introduced was the ABP of the hand skeleton on the general public, an anatomical‐themed variation of face‐painting often seen at fairs and birthday parties, which proved extremely popular with younger audiences.Anatomy was subsequently included in “Science Worth Seeing”, a public science engagement event supported by the Federal Government's Inspiring Australia grant. Anatomy was promoted through ABP, ABP of hand skeletons for children and the use of plastic anatomical models as jigsaws, all of which enabled multiple meaningful interactions and discussions about the human body with children and the general public. ABP also made an appearance at a pop‐up science bar during Australia's National Science Week, which featured on a national news bulletin.Embracing the power of the visual nature of anatomy through activities such as ABP, anatomists can provide service to the discipline, to their institutions and provide outreach to the community.Support or Funding InformationPartly funded through The University of Tasmania's School of Medicine Staff Research Conference Support.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pharmacogenomics in Indigenous Populations
Authors: Claw Katrina G. , Henderson Lindsay M. , Burke Wylie , Thummel Kenneth E. 
Published: June 2021

The integration of genomic technology into healthcare settings has the potential to transform health care through increased personalization of medical decisions. In particular, pharmacogenomic research on drug disposition and response can tailor and improve medication regimens for all patients by informing tests of function altering variation in drug metabolism and transport genes. Unfortunately, Indigenous peoples remain underrepresented in genomic and health research despite having a higher prevalence of heart disease, cancer, diabetes and stroke than any other population. Effective strategies to create research partnerships between tribal communities and genomic researchers are often lacking, yet such partnerships are needed for trustworthy research. As such, Indigenous populations are less likely to benefit from personalized medicine if they are not represented in studies that ascertain genotype‐phenotype relationships that can lead to improved drug treatment efficacy.We review what is currently known about pharmacogenetic variation in Indigenous populations and evaluate three case studies in which pharmacogenetic research with Indigenous populations were conducted. We highlight the importance of including Indigenous populations in future pharmacogenetic studies and discuss strategies for ethical engagement and collaboration in genomic research with Indigenous communities. The inclusion of Indigenous and other underrepresented communities in genomic research has the potential to expand our understanding of genomic influences on health and improve clinical approaches for all populations.Support or Funding InformationNIGMS F32 GM119237This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dynamic Control of Gene Expression during mRNA Export and Translation
Authors: Wente Susan R. , Dawson T. Renee , Adams Rebecca L. , Galoda Aditi , Glass Laura , Mason Aaron C. , Sharma Manisha 
Published: June 2021

Messenger (m)RNA‐binding proteins (RBPs) are key arbiters in coordinating gene expression from transcription through translation. The specific RBP complement is repeatedly remodeled across the mRNA lifecycle through the activation of distinct RNA‐dependent DEAD‐box ATPases (Dbps in yeast/DDXs in humans). In this manner, the dynamic interactions of mRNA‐RBP complexes (mRNPs) with cellular machinery are controlled in a spatial and temporal manner to direct an mRNA's progression and ultimate fate. For mRNA export through the nuclear pore complex (NPC), an mRNP at the nuclear face must contain the proper complement of adaptor proteins and export receptor to initiate and mediate export, and the removal of key proteins by remodeling at the cytoplasmic NPC face is critical for export directionality. This mRNP remodeling is achieved through localized activation of human DDX19B (S. cerevisiae Dbp5) by Gle1, a multifunctional regulator of distinct Dbps/DDXs, and inositol hexakisphosphate (IP6). At least two Gle1 isoforms are expressed in human cells, with Gle1B required at the NPC and Gle1A in the cytoplasm. We recently uncovered the role for the Nup42 carboxy‐terminal domain (CTD) in mRNA export during the stress response. Altering the minimal Nup42 binding site on Gle1B revealed that mRNA export in HeLa cells requires the Nup42‐Gle1B interaction. In vitro assays with purified, recombinant proteins for both yeast and human systems demonstrated that the Nup42 CTD enhanced the Gle1/Gle1B‐stimulated, RNA‐dependent Dbp5/DDX19B ATPase activity independently of IP6. Of note, the Gle1B‐IP6 stimulatory effect also required purification of DDX19B from a baculovirus insect cell expression system. In contrast to Gle1B at the NPC, Gle1A lacks the Nup42 binding domain, is primarily cytoplasm at steady state, and is not capable of supporting mRNA export. We found that Gle1A is required for translation activity and stress granule dynamics. Furthermore, ERK1/2, JNK and GSK3 targeted Gle1A for stress‐induced sequential phosphorylation. Analysis of gle1A mutants mimicking phospho‐deficient or hyperphosphorylated states revealed roles for its phosphorylation in stress granule dynamics, Gle1 oligomerization, and Gle1‐mediated stimulation of DDX3 activity. Overall, multifactorial control of Gle1 functions by Nup42, IP6, and phosphorylation allows for regulation of gene expression from mRNA export through translation, and provides potential new insights into gle1 dysfunction underlying disease pathologies.Support or Funding InformationNIH 5R37 GM051219This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of Mass Spectrometry in the Advancement of HLA Epitope Prediction
Authors: Abelin Jennifer G. 
Published: June 2021

A challenge in developing personalized cancer immunotherapies is the prediction of putative cancer‐specific antigens. Currently, predictive algorithms are used to infer binding of peptides to human leukocyte antigen (HLA) heterodimers to aid in the selection of putative epitope targets. One drawback of current epitope prediction algorithms is that they are trained on datasets containing biochemical HLA‐peptide binding data that may not completely capture the rules associated with endogenous processing and presentation. The field of MS has made great improvements in instrumentation speed and sensitivity, chromatographic resolution, and proteogenomic database search strategies to facilitate the identification of HLA‐ligands from a variety of cell types and tumor tissues. As such, these advances have enabled MS profiling of HLA‐binding peptides to be a tractable, orthogonal approach to lower throughput biochemical assays for generating comprehensive datasets to train epitope prediction algorithms. Today, we will highlight recent progress made in the field of HLA‐ligand profiling enabled by MS and its impact on epitope prediction strategies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.