bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular Matrix Protection Factor‐1, a Novel Osteoarthritis Therapeutic, Decreases Expression of Interleukin‐1 beta by Primary Cultures of Human Osteoarthritic Chondrocytes
Authors: Belogorodsky Dimitry , Buckley Andrea Lynn , Milton LaBraya , Popper Hannah Ruth , Mattioli Patrisia , Miller Lawrence , Behling Kathryn , Selim Abdulhafez , D'Angelo Marina 
Published: June 2021

Osteoarthritis (OA) is characterized by an imbalance of cartilage extracellular matrix (ECM) production and degradation, due, in part, to increased cytokine production. It has been demonstrated that the cytokine, Interleukin‐1 beta (IL‐1β), is produced by OA articular chondrocytes and plays a prominent role in altering ECM metabolism by targeting the matrix metalloproteases (MMPs) that degrade the ECM. We are developing a novel, OA therapeutic, Extracellular Matrix Protection Factor‐1 (ECPF‐1) that targets MMP interaction with its ECM substrate. We have demonstrated a reduction in ECM degradation when primary, human OA chondrocyte (HOAC) cultures are treated with ECPF‐1. In this study, HOACs isolated from total knee arthroplasty were reared in three‐dimensional, serum‐free, alginate cultures. The sides of least and greatest pathology of the femoral condyles and tibial plateaus were determined by gross inspection and cells isolated were cultured separately (LP and GP). Chondrocytes were plated at 2.5×106 cells per milliliter of alginate and incubated in serum‐free medium for five days. Cells were released from the alginate and the RNA extracted from the pellet, reverse‐transcribed into cDNA and quantitative, real time PCR (qRT‐PCR) was performed with TaqMan Gene Expression assays for IL‐1β, collagen type I, collagen type II and 18s rRNA. In a previous study, IL‐1β production was detected in the conditioned media of HOAC cultures with the highest concentration of this cytokine present in the cultures established from the region of greatest pathology (GP). In this study, IL‐1β expression was detectable in mRNA produced by LP and GP HOAC cultures. The expression was reduced 2‐fold in LP cultures treated 24 hours with 2.5 uM ECPF‐1 and 1.4 fold in GP cultures. These results demonstrate the ability of ECPF‐1 to alter expression of a molecule involved in the feedback loop of ECM destruction. ECPF‐1 provides a tool with which to further define the cellular mechanisms responsible for OA chondrocyte pathology.Support or Funding InformationNew Jersey Health Foundation, Center for Chronic Disorders of Aging Small Grant, PCOM's Division of ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating the Triceps Surae in Chronic Inflammatory Demyelinating Polyneuropathy Patients using Magnetic Resonance Imaging
Authors: Fanous Jacob , Gilmore Kevin J. , Kimpinski Kurt , Rice Charles L. 
Published: June 2021

IntroductionChronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease, primarily characterized by peripheral nerve demyelination. Patients present with sensory and motor deficits, including but not limited to symmetrical diffused muscle weakness. Studies to date have mainly focused on the neuropathic aspects of CIDP and its involvement in paresis. Impairments in skeletal muscle quality and quantity may be a consequence of motor nerve deficits, but these aspects have not been investigated comprehensively. Thus, the purpose of this study was to use magnetic resonance imaging (MRI) to explore anatomical and functional differences in the triceps surae muscle complex in a group with CIDP with a healthy control group.MethodsTo date, five patients with CIDP and six healthy control subjects were matched on anthropomorphic characteristics. Both groups underwent isometric plantar flexion strength measurements on a custom dynamometer. On separate days, MRI (T1 and T2) of the leg musculature was acquired via serial axial plane scans in a 3.0‐Tesla magnet. All MRI scans were analyzed using OsiriX imaging processing software. Total muscle volume was computed using the T1 weighted anatomical images with a 3D FLASH sequence: (0.9mm slice thickness with slice separation of 1mm ranging from 280 to 400 slices). T2 weighted relaxation times were determined from images with a spin‐echo sequence (5.0mm slice thickness; 16 echoes between 13.2–211.2ms). Both total volume (T1) and relaxation times (T2) were calculated separately for the three components of the triceps surae: soleus, medial gastrocnemius (MG), and lateral gastrocnemius (LG).ResultsCIDP patients had ~34% less plantar flexion strength compared with controls. CIDP patients had ~14%, ~28% and ~38% smaller muscle total volumes in the soleus, MG and LG, respectively, compared to controls. When strength was normalized to total triceps surae volume it was ~26% lower in CIDP. T2 relaxation times were significantly longer in CIDP with the soleus, MG and LG showing ~37%, ~31% and ~29% longer relaxation times, respectively.ConclusionCIDP patients were significantly weaker compared to control subjects. When strength was normalized to total triceps surae volume the difference remained indicating CIDP patients have lower intrinsic muscle contractile quality. This is further reinforced by the significantly longer T2 relaxation times, which likely reflects an increase in intramuscular fat infiltration in the CIDP group. The results indicate that muscle quantity and quality are affected by alterations in axonal function due to CIDP.Support or Funding InformationSupported by NSERCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscle‐intensive and High‐Impact Exercises Differentially Influence Whole Bone 3D Morphology in Young Outbred Male Mice
Authors: Smolinsky Amanda N. , Aldridge Kristina , Middleton Kevin M. 
Published: June 2021

Skeletal morphology is predominantly dictated by the genetic background and the habitual loading environment of individual bones. Mechanical loads placed on bones are derived from intracorporeal contractions of muscles and from extracorporeal ground reaction forces generated by bearing weight and by substrate reaction forces during locomotion. We investigated the relative effects of these two sources of load on the growing skeleton using an outbred mouse model system. The 3D shape of the femur was compared across groups of mice following discrete exercise regimens designed to emphasize specific loading environments. Hsd:ICR (CD‐1) mice (N=80; 20 per group) were randomly assigned to one of four treatment groups at four weeks old: swimming which emphasizes muscle forces, dropping which emphasizes impact forces, wheel running which results in a combination of muscle and impact forces, and non‐exercised controls which were free to move about their cages. Durations of swimming, running, and impact loading were matched so that mice received approximately the same intensity. After 20 days mice were euthanized and right hind limbs were micro‐CT scanned (~20 μm3 voxel size). Femoral shape was defined by digitizing 23 landmarks on each scan. To adjust for size, each individual femur was scaled to the geometric mean of all possible linear distances among landmarks. Group differences were analyzed using Euclidean Distance Matrix Analysis (EDMA), and differences >5% were considered substantial. In all three activity groups, we find decreased robusticity of the femoral diaphysis and increased distal condylar breadth compared to non‐exercised controls. Additionally, each group displays unique femoral morphologies when compared to controls. The swimming treatment group shows increased length of the femoral neck. The wheel running treatment group shows a narrower femoral neck with a larger femoral head. The impact loading group shows a lengthened and reoriented distal diaphysis. Overall, the running and swimming groups show similar patterns of morphology that diverge from the non‐exercised mice, suggesting muscle forces differentially affect the loading environment during running in mice compared to impact forces. Further, these results indicate the regional sensitivity of femoral morphology to muscle‐ and impact‐derived loads, and emphasize how activity patterns during adolescence can lead to distinct morphologies in the limb skeleton.Support or Funding InformationResearch support: University of Missouri School of MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Morphological Variants of The Pes Anserinus of Tibia in South Indian Population
Authors: Chettiar Ganesh Kumar , Murlimanju B.V. 
Published: June 2021

IntroductionThe tendons inserting at the antero medial surface of the tibia are called ‘pes anserinus' because of the resemblance to the ‘goose foot’. The tendons radiate during the insertion and it has been reported that the variations exist in the tendons. In this context, the objective of the present study was to study the morphological variations of the pes anserinus of the tibia in South Indian population.MethodsThe present study included 53 formalin fixed human lower limbs. The tendons inserting into the antero medial surface of the tibia were carefully dissected. The morphological variants were observed and the pictures were taken. The variants were tabulated and analysed.ResultsIt was observed that, 48 lower limbs (90.6%) had convergent type of the pes anserinus in which the gracilis tendon was in between the semitendinosus and semimembranosus tendons and all joined together. The semitendinosus was giving an extra slip, which was attaching to the medial condyle of tibia in 7 cases (13.2%). The pes anserinus was inserting into the fascia cruris in 8 specimens (15.1%). The remaining 5 lower limbs (9.4%) were having variant pattern. Semimembranosus muscle was taking in the formation of pes anserinus in 3 lower limbs (5.7%). The gracilis and sartorius were absent in one lower limb each (1.9%).ConclusionThe present study has provided the morphological knowledge about the variations of pes anserinus of the tibia in South Indian population. We believe that this information is enlightening to the orthopaedic and plastic surgeons.Support or Funding InformationNILThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MYOFASCIAL PLANTAR PAIN AND THE RELATIONSHIP BETWEEN THE INNERVATION OF ABDUCTOR HALLUCIS MUSCLE. NEW PHYSIOPATHOLOGICAL APPROACH
Authors: Wada Juliano , Akamatsu Flávia Emi , Itezerote Ana Maria , Hojaij Flávio , Andrade Mauro , Jacomo Alfredo Luiz 
Published: June 2021

The plantar myofascial pain syndrome is a common cause of chronic pain and dysfunction of the abductor hallucis muscle has been reported as a possible factor implicated in its physiopathology. We decided to investigate the anatomical correspondence of the muscle innervations to the clinical evaluation of patients with chronic foot pain.MethodsWe dissected 30 feet from fixed cadavers (ADG) and identified the entry points of nerve branches into each of four quadrants determined for the abductor hallucis muscle belly. The clinical group (OPG) consisted of 30 patients evaluated by digital algometer (Force Ten FDX, Wagner Instruments, Greenwich, CT) and the pression which triggered painful sensation in each of the quadrants of the muscle were obtained. We analyzed anatomical data with Poisson distribution and logarithm link function followed by Bonferroni multiple comparisons. For the patient's group, the same methods for normal distribution were employed.ResultsBranches of the medial plantar nerve were predominantly found in the posterolateral quadrant (Q1) and there was a match to the area of the muscle in which lower pressures were necessary to produce painConclusionAnatomical distribution of the branching of the medial plantar nerve into the abductor hallucis muscle is topographically similar to the muscle areas where patients with chronic foot pain referred higher sensitivity to external pressure. These findings suggest that the nervous supply to the muscle may be implicated in the physiopathology of the myofascial plantar pain.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
LOW LEVEL LASER THERAPY INCREASES MESENCHYMAL CELL PROLIFERATION AND COLLAGEN II AFTER EXPERIMENTAL INJURY
Authors: Akamatsu Flávia Emi , Teodoro Walcy R. , Itezerote Ana Maria , Saleh Samir , Martinez Carlos Augusto Real , Ribeiro Marcelo Lima , Pereira José Aires , Hojaij Flávio , Andrade Mauro , Jacomo Alfredo Luiz 
Published: June 2021

BACKGROUNDTendon is a mechanosensitive tissue which transmits muscle derived forces to bones. Photobiomodulation (PBM) also known as low‐level laser (or light) therapy (LLLT), has been used in therapeutic approaches in tendon lesions but uncertainties about its mechanisms of action have prevented its widespread use so far. We investigated the response of LLLT therapy in experimental lesions of the calcaneous tendon in rats.METHODS AND MATERIALThirty adult male Wistar rats weighing 250 to 300 g were surgically submitted to bilateral partial transverse section of the calcaneous tendon. The right tendon was treated with LLLT whereas the left tendon served as control. On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each which were treated with LLLT (Konf, Aculas – HB 750), 780 nm and 80 mW for 20 seconds, three times/week for 7, 14 and 28 days. The Sca‐1 was examined by immunohistochemistry and histomorphometry and COLA1, COLA2 and COLA3 gene expression by qRT‐PCR.RESULTSCOLA2 gene expression was higher in LLLT treated rats as compared to the control group. Interestingly, the histomorphometric analysis coincided with increased number of mesenchymal cells, characterized by Sca‐1 expression in the lesion region (p<0.001).CONCLUSIONLLLT effectively interferes in tendon tissue repair after injury by stimulating mesenchymal cells proliferation and synthesis of collagen type II, which could provide structural support to the interstitial tissues during the healing process of the calcaneous tendon. Further studies are needed to confirm LLLT role in tendon healing.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Probing the role of distal residues in DinB and Pol Kappa in the extension step of DNA damage bypass
Authors: Stern Hannah R. , Mills Caitlyn L. , Ondrechen Mary Jo , Beuning Penny 
Published: June 2021

DNA is constantly subjected to damage from endogenous and exogenous sources. Replicative DNA polymerases are typically unable to replicate damaged DNA, but specialized DNA polymerases in the Y family possess this ability. Escherichia coli has two Y family polymerases that are specialized to bypass damage when copying DNA in a process called translesion synthesis (TLS). DinB is one of these polymerases and is involved in bypassing deoxyguanosine adducts at the N2 position. Humans have four Y family polymerases, including DNA polymerase kappa. E. coli DinB and human pol kappa both bypass minor groove adducts and are inhibited by major groove adducts. However, pol kappa is more efficient in copying past DNA damage in the extension step of translesion synthesis. In order to probe the importance of particular residues in the extension step of TLS, the computational tool POOL was utilized. This method identified active site residues and residues previously observed to be important for activity. POOL also predicted more distant residues that do not have direct contact with substrates that may have catalytic importance, but the residues are in different regions of DinB and pol kappa. To study the contribution of these distal residues on the extension step of TLS, DinB and pol kappa variants with mutations at the predicted distal positions were constructed and are being assayed for bypass of damage. We have identified variants with a range of activity on undamaged and damaged DNA; in particular several mutations in the DinB little finger domain severely reduce activity.Support or Funding InformationSupport from NSF‐MCB‐1517290, American Cancer Society RSG‐12‐161‐01‐DMC, and the PhRMA Foundation (predoctoral fellowship in informatics awarded to CLM)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Wavelength of light impacts circadian regulation in Rdl mutant Drosophila melanogaster
Authors: Walters Benjamin Patricia , MacDonald Stephanie Patricia , Rogers Ryan Patricia 
Published: June 2021

Drosophila melanogaster are a useful human analog for circadian rhythm research. They have a short life cycle, similar genetic loci to humans with respect to spatial and temporal gene expression and easily traceable mutant phenotypes. This study analyzes the impact of specific photon wavelength on circadian rhythm in Drosophila melanogaster. In flies, Resistant to Dieldrin (Rdl) encodes a subunit of the GABA receptor, which is upregulated by the circadian oscillator, WAKE. This interaction induces RDL localization to the plasma membrane to modulate sleep; however, the specific function of RDL and its downstream interactions to facilitate sleep/wake switching, are yet to be characterized. The Drosophila Activity Monitor TriKinetics System and a custom‐built light controlling apparatus were used to characterize the impact of varied light wavelengths on locomotion in control, RdlMD‐RR mutant flies and flies overexpressing Rdl in a subset of circadian neurons. Preliminary data suggests RdlMD‐RR flies show less activity during daylight hours, and severely diminished locomotion in darkness compared to controls; thus, it is the intent to characterize the specific wavelength associated with induction of this phenotype. These data will provide information related to sleep latency and quality of sleep as different wavelengths of light would amplify or diminish sleep onset and duration.Support or Funding InformationThis work was supported by funds from the Department of Sciences at Wentworth Institute of Technology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Direct pharmacologic regulation of the ETS transcription factor PU.1
Authors: Lee Sangchoon , Poon Gregory M. K. 
Published: June 2021

The ETS‐family transcription factor PU.1 is essential for the self‐renewal of hematopoietic stem cells (HSC) as well as their differentiation to various lineage‐committed hematopoietic progenitors. Specific to the bone marrow niche, PU.1 regulates the expression of several key cytokines (e.g. CXCR4) and their receptors (e.g. GM‐CSF receptor, FLT3) involved in HSC mobilization. Extensive studies have shown that incomplete loss of PU.1 activity, to ~20% wildtype levels, leads to lineage arrest and aggressive leukemic disease. Conversely, lentiviral overexpression of PU.1 resolves the differentiation block in leukemic blasts, and suggests the activation of PU.1 as a potential therapeutic approach. To this end, we have identified by phage display technology a panel of selective PU.1‐binding oligopeptides. Several of these peptides promote PU.1 binding to cognate DNA sites in a dose‐dependent manner and confer resistance to PU.1 against inhibition by netropsin. To determine the essential residues responsible for their activity, we screened a targeted library of truncated hit peptides and found that as few as four residues were sufficient to enhance site‐specific DNA binding by PU.1. These peptide sequences represent leads for developing direct‐acting PU.1‐specific modulators with respect to target DNA binding and interactions with major binding partners. The resulting low‐MW reagents could significantly expand the pharmacology of transcription factors and help overcome barriers in hematopoietic research and therapy that are currently imposed by genetic approaches.Support or Funding InformationSupported by NIH HL129063.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of Sp1 and Sp3 Occupation of the Distal Manganese‐Superoxide Dismutase Promoter in the Presence of HIV‐1 Tat
Authors: Manes Terrin , Cota‐Gomez Adela 
Published: June 2021

The introduction of antiretroviral therapies (ART) is largely responsible for the development of chronic HIV infection, but long‐term exposure to viral proteins can contribute to oxidative stress and chronic inflammation which could promote the development of HIV‐Associated co‐morbidities such as pulmonary arterial hypertension (HA‐PAH). Previously, we have reported that the HIV transcriptional regulator, Tat, can induce oxidative responses by depleting cellular glutathione and repressing the mitochondrial manganese‐superoxide dismutase (MnSOD, sod2); there are Tat‐regulated elements within the proximal region of the human sod2 promoter, designated Tat‐sensitive Sp‐responsive elements (TSS). Tat alters the pattern of binding by the Sp1 and Sp3 transcription factors on the sod2 TSS, resulting in transcriptional repression. Recently, we observed evidence of Tat‐regulated regions containing predicted Sp‐binding sequences within more distal sections of the sod2 promoter, which we have termed the DTSS (Distal Tat‐sensitive Sp‐responsive elements). The previous discoveries that Tat regulates the proximal promoter by changing the pattern of Sp binding prompted us to investigate if Tat influences transcription from the distal elements via modulation of Sp1 and Sp3 ratios. In this study, we transiently transfected luciferase‐reporter plasmids containing varying regions of the sod2 promoter in the presence or absence of a Tat‐expressing plasmid into human pulmonary artery endothelial cells (HPAEC). To further investigate the DTSS and the occupancy of Sp1 and Sp3, we collected Sp1 and Sp3‐bound DNA via Chromatin Immunoprecipitation (ChIP). Our data shows that under basal conditions certain regions of this promoter are highly expressed while others are repressed by an already existing biological ratio of Sp1 and Sp3. However, in the presence of Tat, all of these regions are repressed. ChIP analysis shows that Tat changes the amounts of Sp1 and Sp3 bound at the predicted Sp‐binding clusters. With this data we conclude that Tat represses sod2 by altering the ratio of Sp1 and Sp3 at both proximal and distal regions thereby extending the known regulatory sequences of the sod2 gene that are responsive to HIV Tat.Support or Funding InformationNational Institutes of Health (NIH) 1RO1HL125050‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.