bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating bioinformatics into K‐12 Outreach activities (720.8)
Authors: Toby Inimary , Widmer Jonah 
Published: June 2021

The use of biological databases has emerged as an exciting part of most research laboratories and programs. Until the turn of the decade, tasks such as searching genomes for differences between genes or transcription factors would have seemed daunting and perhaps laborious. However nowadays in the post‐genomic era, researchers all over the world can have easily access these various types of information. Many have suggested that we must find ways to continue inspiring our nation’s young people to develop a love or appreciation for science.We wanted to exploit the availability of these databases to develop research projects aimed at students in grades 9th‐ 12th. This population of students can be challenging to teach because they are always looking for some practical applications to the subject learned and often have misapprehensions about how science is done. Our goal for the students research projects was to use Bioinformatics tools such as computer programming and database mining as a way to extract physiological information about microbial organisms. We utilized Pfam, signalp, CDART, and TmmHmm databases for analysis. Students were provided with protein sequences from various microorganisms for comparative analysis.We found that these computer‐based projects provided a unique opportunity for the student to engage in research while testing their knowledge from basic biology such as examining differences amongst genes, proteins, and genomes. Students were also able to learn skills, including programming, statistical analysis, and MySQL database management. Upon completion of their projects, we reviewed the students’ responses from surveys and final reports. These enabled us to ascertain what the students gained from the internship, what they enjoyed and what if any, improvements were necessary as we offer this to more students. In the future, we would like to track the progress of these students as they return to high school and go on to pursue further studies in postsecondary institutions.Grant Funding Source: NIH INBRE grant
Alzheimer’s is associated with neuropathological changes in olfactory bulb that are related to APOE genotype (728.1)
Authors: Parcon Paul , Aboud Orwa , Biedermann JoAnn , Mrak Robert , Griffin W. Sue 
Published: June 2021

Alzheimer patients (AD) may experience changes in olfaction before clinical or neuropathological manifestations. Neuroinflammation, in particular interleukin‐1 (IL‐1), is known to induce each of the precursors of these manifestations.We studied anatomical and pathological features in frozen and paraffin‐embedded tissue sections of olfactory bulbs resected from autopsy tissue of 15 patients (5 APOE ε3,3 neurologically normal, 5 APOE ε3,3 and 5 APOE ε4,4 AD patients) with an age range from 68 to 85 yrs, using fluorescent and western immunochemistry.Compared to control, patients with AD had greater expression of hyper‐phosphorylated tau, particularly in those of APOE ε4,4 genotype compared to ε3,3. These findings were associated with increased expression of IL‐1, and the number of activated microglia was elevated. Furthermore, hyperphosphorylated tau expression was high in neuron cell bodies compared to that in axons in the olfactory tract. Although corpora amylacea were abundant, there was no disease‐related difference in distribution, number, or size.Our findings are consistent with the idea that changes in expression of disease‐associated precursor proteins in olfactory structures and the cytokines that drive their expression are related to APOE genotype and are important elements in the neuroanatomical spread of the neuropathological changes in AD.Grant Funding Source: Supported by NIH/NIA AG12411 and the Windgate Foundation
Fkbp5 and its interaction in fear extinction (728.15)
Authors: Criado‐Marrero Marangelie , Porter James 
Published: June 2021

Introduction: The hypothalamic‐pituitary‐adrenal (HPA) axis and the limbic system are involved in the response to stressful situations. Disruption of this negative feedback loop has been related to depression and anxiety like behaviors such as Post‐traumatic Stress Disorders (PTSD). To prevent an excessive (pathological) stress response, the neuronal effects induced by the stress hormone corticosterone (or cortisol in humans) are modulated by negative feedback through the glucocorticoid receptors (GR) in neurons. Two key regulators of this negative intracellular feedback are the FK506‐binding protein 4 (Fkbp4) and the FK506‐binding protein 5 (Fkbp5). Deletion of the Fkbp5 gene is associated with less anxiety and variants of the Fkbp5 gene are associated with PTSD. The objective of this study is to examine the role of Fkbp5 during fear extinction learning. Hypothesis: Signaling via Fkpb5 and its interaction with glucocorticoid receptors in the prefrontal cortex plays an important role in fear extinction by modulating the neuronal effects of corticosterone. Methodology: Young and adult male rats were subjected to habituation, conditioning, and extinction learning phases. They were sacrificed and their prelimbic (PL) and infralimbic (IL) cortical tissue was extracted. Microarrays and RT‐ PCR were used to determine the expression of Fkbp4 and Fkbp5 mRNA during the different behavioral phases. Results: Fkbp5 mRNA expression, but not Fkbp4, in IL is reduced 5 hrs after cued fear extinction in rats. However, no changes were observed in PL. Conclusion: These results suggest that a reduction in Fkbp5 activity is necessary for consolidation of fear extinction and that fear extinction could be enhanced by reducing Fkbp5 expression in IL. Future Projections: By further examining the role of Fkbp5 in fear conditioning and extinction, we could identify novel targets for enhancing the treatment of PTSD patients.Grant Funding Source: Supported by RISE grant R25GM082406, Molecular Biology Core Lab (Grant RR003050/MD007579),
Laminin‐coated filaments co‐grafted with Schwann cells and GDNF direct axonal growth following rat thoracic spinal cord injury (729.2)
Authors: Deng Lingxiao , Walker Chandler , Wen Xuejun , Xu Xiao‐Ming 
Published: June 2021

Biomaterials are ideal for promoting directional axon growth after spinal cord injury (SCI). We assessed effects of unidirectional polypropylene filaments of varying densities combined with laminin, glial cell line‐derived neurotrophic factor (GDNF) and Schwann cells (SCs) on axon regrowth after T10 spinal hemisection in adult rats. Filaments reduced lesion cavity ~90% compared with non‐filament group and attenuated astrogliosis and inflammation (p < 0.001). Low density filaments promoted more axons (324.4±36.5) and vascular growth (226±49.3) over no filament, middle and high density filament grafting (p < 0.05). Laminin pre‐coated filaments were optimal for axon and vascular regrowth compared with matrigel and hydrogel. To evaluate axon orientation, axons randomly selected at the graft interface were traced by ‘best fit’ lines. The angle between axon lines and filaments parallel to the rostral‐caudal axis of the cord defined orientation (0° = parallel and 90° = perpendicular to the axis). Filament group axon angles were less than the non‐filament group (24.3±7.8° vs. 44.7°±8.3°; p < 0.01). This directional effect was enhanced by co‐grafting SCs and GDNF. Thus, combination of filaments, laminin, SCs and GDNF provided sub‐micron topographic cues for directional axon regrowth revealing new insight for large lesion gap repair and functional recovery after SCI.Grant Funding Source: NIH grants NS036350, NS052290, NS050243, NS059622, the Daniel Heumann Fund for Spinal Cord Research
Expression and distribution of the scavenger receptor CD36 suggests important roles in the pathophysiology of spinal cord injury (729.3)
Authors: Cordero‐Cabán Kathia , Licero‐Campbell Jennifer , Figueroa Johnny , De León Marino 
Published: June 2021

Spinal cord injury (SCI) remains a devastating cause of lifetime medical comorbidities in modern society. Unfortunately, only a few preventive strategies have been shown to prevent the profound pathophysiological mechanisms associated with this condition. In previous studies, our laboratory has shown that a diet enriched in polyunsaturated fatty acids (O3PUFAs), including docosahexaenoic acid (DHA), can reduce neurodegeneration, chronic pain, motor functional deficit, loss of sensitivity, and accelerates autonomic bladder function in a rat model of SCI. CD36 is a multifunctional protein that has been recently implicated as a scavenger receptor and lipid transporter. This membrane protein plays a major role in physiological and pathological inflammation. The purpose of this study was to investigate the expression and roles of CD36 in the context of SCI and dietary O3PUFAs. We hypothesized that trauma to the spinal cord result in a reduction in the protein levels of this protein. Further, we proposed that dietary O3PUFAs normalize the expression of CD36 in the injured spinal cord. Here we determined the protein expression of CD36 after SCI. In particular, we analyzed the temporal and spatial expression of CD36 after contusive injury to the rat spinal cord using immunoblotting and double‐labeling immunofluorescent experiments. Our data demonstrates that acute SCI results in a marked downregulation of CD36. This protein was predominantly observed in both neuronal and glial cells. Importantly, we found that dietary lipids may be implicated in the regulation of this important protein. Altogether, our data supports a potential molecular link between dietary O3PUFAs beneficial effects in the injured spinal cord. This protein may represent an important therapeutic target to reduce the burden of SCI in humans.Grant Funding Source: Supported by 5P20MD006988 and 2R25GM060507
Bridging the gap: a cell and molecular study of muscle after rotator cuff injury (731.12)
Authors: Gigliotti Deanna , Upadhaya Ritika , Macek Bryce , MacDonald Peter , Leiter Jeff , Anderson Judith 
Published: June 2021

Rotator cuff injury is a debilitating condition that surgical intervention often fails to resolve; failure rates range between 30 ‐ 94%. Muscle from 13 patients (4 females, 9 males; 49 ‐ 65 yrs) with rotator cuff injury was studied at a cellular and molecular level to test the notion that it shows signs of atrophy, with or without features related to denervation with the hope of highlighting possible explanations for surgical failures. Satellite cell response to activation via a nitric oxide donor drug called isosorbide dinitrate (ISDN) was also investigated with the idea that satellite cells could be activated during the conservative management phase to promote muscle growth and repair. Supraspinatus and deltoid muscle biopsies taken during arthroscopic rotator cuff repair were analyzed in pairs for histology and showed muscle atrophy in the affected supraspinatus muscle. There were more small diameter fibres (p<0.005) and a smaller mean fibre diameter (17.9 ± 0.3μm) in supraspinatus vs. control deltoid muscle (21.8 ± 0.3μm & p<0.003). Alpha‐bungarotoxin staining of acetylcholine receptors and western blotting for their gamma and epsilon subunits showed tendencies (p=0.13) to a linear arrangement and increased gamma to epsilon ratio respectively; both are signs of denervation. Response to ISDN showed more mitotically active Pax7+ satellite cells in supraspinatus muscle cultured with ISDN than in untreated supraspinatus or in the deltoid (p<0.03). Results are consistent with the notion that supraspinatus muscle of the injured rotator cuff is atrophic with possible denervation; together these features may increase susceptibility to muscle injury and surgical failure. Results also suggest the potential for the using ISDN to promote muscle growth and increase surgical success.Grant Funding Source: Supported by Canadian Orthopedic Foundation, Pan Am Clinic Foundation & Department of Surgery
Effect of exercise on limb muscle fiber architecture in a Pompe mouse model (731.4)
Authors: Daly Shane , Case Laura , Pastva Amy , Kishnani Priya , Koeberl Dwight , Taylor Andrea 
Published: June 2021

Pompe disease, a glycogen storage disease causing muscle weakness, is treated by enzyme replacement (ERT). As part of a larger study of exercise effects, we studied the impact of exercise on limb muscle fiber architecture using a mouse knockout model (GAA‐KO) on ERT via gene therapy. Thirty‐seven mice were assigned to 1 of 3 exercise groups: high treadmill (HT), low treadmill (LT), voluntary wheel (WL) vs. sedentary control (SED) and sacrificed after eight weeks. Muscle weight, fiber length (Lf) and in situ sarcomere length were measured and physiologic cross‐sectional area computed for tibialis anterior (TA), gastrocnemius (GA) and soleus (SOL). Initial results: The nonparametric Kruskal‐Wallis revealed significant group differences in Lf for TA (p=.030) and GA (p=.049). Post‐hoc Mann‐Whitney U tests showed significantly longer TA fibers in WL and HT vs. LT (p=.034) and a trend toward longer fibers in WL vs. SED (p=.059). GA fibers were significantly shorter (p=.034) in HT and WL vs. LT. We observed a trend toward shorter GA fibers in HT vs. all other groups and in WL vs. SED (p=.083). Lengthened TA fibers and correspondingly shorter GA fibers may indicate dorsiflexion weakness, as in human infantile onset Pompe disease on ERT, supporting prior concerns about potential negative effect of more strenuous exercise regimens. Further data analysis will continue to explore effects of exercise on muscle strength and function.Grant Funding Source: Supported by R24 HD050837‐01 and NSF BCS 0962677
An increase in microRNA‐23 prevents muscle wasting in mice with chronic kidney disease in resistance exercise (731.8)
Authors: Wang Xiaonan 
Published: June 2021

In our previous studies we found that exercise partially prevents chronic kidney disease (CKD)‐induced muscle atrophy. We also saw that microRNA‐23 (miR‐23) is decreased in muscles of CKD mice. In silico analysis suggested that miR‐23 targets several proteins associated with muscle atrophy. In this study, we evaluated whether exercise restores the level of miR‐23 in CKD mice. CKD was induced in 20‐25g mice by 5/6th nephrectomy. Muscle overloading, a resistance exercise model, was produced in both control and CKD mice by removing the gastrocnemius and soleus muscles from both hindlimbs. Overexpression of miR‐23 in cultured muscle cells inhibits the reporter luciferase activities of PTEN and YY1, suggesting that miR‐23 attenuates the expression of these predicted targets. Exercise significantly increased the level of miR‐23 in muscle of CKD mice vs. unexercised CKD mice. Consistent with this, exercise decreased PTEN protein and increased consequent Akt phosphorylation (2.3‐fold, P<0.001) which would limit muscle atrophy. In CKD mice, exercise increased MyoD, myogenin and eMyHC, proteins that are linked to the myogenic transcription factor, YY1. Conclusions: Resistance exercise can increase miR‐23 which leads to a suppression of multiple atrophy‐related target proteins that may contribute to the muscle‐sparing effects of exercise in CKD.Grant Funding Source: NIH AR060268 (XHW)
Low intensity laser irradiation in myogenic precursor cells: an in vitro study (732.4)
Authors: Amaral André , de Araújo Heloisa , Parizotto Nivaldo , Salvini Tânia 
Published: June 2021

The aim of this study was to analyze the influence of low intensity laser irradiation at wavelengths (λ) of 670, 685 and 830 nm on the mitochondrial activity and gene expression profile of myogenic precursor cells (MPCs) in vitro. Primary rat MPCs were sown in multiwell dishes of 96 and 6 wells. Six experimental groups were set up: a non‐irradiated control group and five groups ranged by differing doses of radiation (0.3; 0.6; 0.9; 1.2 and 1.5 J/cm2). After 24 hours of irradiation, the mitochondrial activity was quantified using the colorimetric technique MTT‐formazan and established in terms of percentage in relation to the control. The gene expression profile was established through the quantitative analysis of the related isoforms IIa and IIx of the myosin heavy chain (MHC) by RT‐PCR five days after irradiation. The results showed that irradiation at λ of 670, 685 and 830 nm promoted respective increase of 56.8, 70.6 and 84.8 % on mitochondrial activity. These values were achieved with the 1.2, 0.6 and 0.3 J/cm2. As far as concerns MHC isoforms expression, this showed that there was a significant decrease in the IIa isoform (685 nm) and an increase in the IIx isoform (685 and 830 nm) in comparison to the non‐irradiated cells. Laser radiation was characterized as being a wavelength and dose‐dependent effect on the intensity of mitochondrial activity and gene expression profile among MPCs in vitro.Grant Funding Source: Supported by: Fundação de Amparo à Pesquisa do Estado se São Paulo ‐ FAPESP
Interleukin‐6 and cyclooxygenase‐2 mediate myofibroblast‐induced polarization of alternatively activated macrophages (734.9)
Authors: Fernando Maria , McKay Derek 
Published: June 2021

Alternatively activated macrophages (AAMΦs) are a macrophage subset induced primarily by the Th2 cytokines IL‐4 and IL‐13. They are associated with anti‐inflammatory functions, such as wound healing and tissue repair and are also protective in animal models of diseases, such as inflammatory bowel disease and multiple sclerosis. In this study we showed that myofibroblasts, also associated with wound healing, may have a putative in vivo role in the induction and maintenance of AAMΦs. Macrophages and myofibroblasts (MFbs) were derived from murine bone marrow and dermal tissue (wild‐type and IL‐6‐/‐), respectively. MΦ were exposed to IL‐4+IL‐13 conditioned medium (CM) from control MFbs or MFbs treated with a non‐selective cyclooxygenase (COX)‐1 and ‐2 inhibitor (indomethacin) or a selective COX‐1 (SC‐560) or COX‐2 inhibitor (NS‐398). Exposure to control MFb CM enhanced markers of AAMΦ polarization and reduced LPS‐evoked nitric oxide release. These effects were partially reduced using MFbs from IL‐6‐/‐ mice, suggesting a role for IL‐6 in this process. CM from indomethacin‐ and NS‐398‐treated MFbs failed to enhance an AAMΦ phenotype ‐ SC‐560 did not have this same effect. Inhibition of EP4 on MΦ also eliminated the effect of MFb CM, implicating PGE2. These data indicate a role for IL‐6 and PGE2, two molecules commonly linked with pro‐inflammatory functions, in the differentiation of anti‐inflammatory AAMΦs.Grant Funding Source: CCFC, CIHR, CDHF, AIHS
Identification of novel aldosterone targets in mouse kidney cortical collecting duct cells (744.1)
Authors: Gumz Michelle , Richards Jacob , Solocinski Kristen 
Published: June 2021

The kidney is critical for the regulation of blood pressure by maintaining sodium and fluid homeostasis. The hormone aldosterone is critical for the regulation of these processes. Aldosterone acts on principal cells of the renal collecting duct to increase sodium reabsorption by increasing transcription of the epithelial sodium channel and SGK1; these effects are mediated by the mineralocorticoid receptor (MR). Recent work by others identified two novel factors that may play a role in sodium reabsorption in the kidney. FK506 binding protein 5 (FKBP5), a member of the immunophilin family, is a co‐chaperone for MR, and causes increased translocation of MR into the nucleus. Growth arrest‐specific 5 (Gas5) is a long noncoding RNA (lncRNA) that acts as a decoy to the hormone response element (HRE) of MR. Gas5 may compete for binding of MR to the HREs of aldosterone target genes. However, it is unknown if FKBP5 or Gas5 are aldosterone targets. Thus we treated mouse kidney collecting duct cells (mpkCCDc14), with aldosterone for 24 hours. Aldosterone treatment led to increases in FKBP5 and Gas5 RNA expression. These data demonstrate that FKBP5 and Gas5 are potential aldosterone targets in kidney cortical collecting duct cells. This may be the first report demonstrating aldosterone‐mediated regulation of a lncRNA.Grant Funding Source: Supported by NIH, ASN and AHA
Genetic variation affecting temporal patterns of gene expression and disease in human brain (776.1)
Authors: Fraser Hunter , Martin Trevor 
Published: June 2021

It is widely recognized that noncoding regions of the human genome, including those controlling the cis‐regulation of gene expression, harbor most disease‐associated genetic variants and most regions under selective constraint. Although the expression of many genes is a dynamic process that changes during an organism’s lifetime, most studies mapping genetic variants affecting gene expression have either ignored the variation in ages among individuals, or treated it as a confounding variable. Here we introduce a method for mapping genetic variants that affect the developmental timing of gene expression, which we call temporal expression quantitative trait loci (teQTL). Applying this approach to human prefrontal cortex, we found several thousand genes associated with teQTLs. These teQTLs are distinct from variants affecting expression levels throughout life, and are often associated with distal transcriptional enhancers or age‐related changes in DNA methylation. Moreover they coincide with dozens of SNPs previously implicated in neurological traits such as Alzheimer’s disease, Parkinson’s disease, and educational attainment. These results suggest that teQTLs are a widespread source of variation in human neurological phenotypes.Grant Funding Source: Supported by the Pew Foundation
Clocking regional chemotherapy of liver metastases (780.2)
Authors: Turebaev D. , Urazova S. 
Published: June 2021

Clocking regional chemotherapy ‐ is an effective treatment for neoplastic lesions of the liver at a new modern level.Clocking regional chemotherapy was held in 58 patients (25 men and 33 women) with liver metastases of primary source different localization. Clocking method of regional chemotherapy is a method of improved chemotherapy, where drugs are introduced by the digital dosers, taking into account the pharmacodynamics of drugs and simultaneous administration of supporting drugs. The new modern digital infusion pumps and micropumps have been used, that allowed to keep a constant dose administration of drugs, their dosage requirement directly by the patient.The results of clinical observations have shown that with adequate controlled introduction of drugs increases their therapeutic effect.Improved schemes for using domestic Erbisol more clearly disclose its hepatoprotective properties and reparative and selectivelyimmunomodulatory properties ‐ stimulator of T‐ lymphocytes and NK cells.One of the important achievements of the proposed method the clocking regional chemotherapy is an active participation of the patient in the conducting therapy. It is controlled analgesia during manipulation and treatment ‐ the amount of pain medication was reduced by 35‐50%, further patient‐controlled administration of antiemetic drugs ‐ the volume was reduced by 40‐65%.