bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hip center edge angle and alpha angle correlate with gait variables in femoroacetabular impingement morphology (919.11)
Authors: Farkas Gary , Haro Marc , Lee Simon , Espinoza Orias Alejandro , Nho Shane 
Published: June 2021

Gait deviations have been observed in symptomatic femoroacetabular impingement (FAI) and other disorders of hip morphology1‐2. However the nature of the relationship between hip morphology and gait is still unclear. We hypothesize that when FAI is diagnosed via the alpha or center edge angles, significant associations with kinematic and kinetic gait variables will be present. This IRB approved study recruited 20 preoperative patients scheduled for FAI hip arthroscopy. Subjects with back or lower extremity pathologies were excluded. Gait testing was performed using published methods3. Radiographs measured by a single observer were compared to range of motion and peak external moments (%body weight x height) about the surgical side hip and knee. Significant correlations were found between the center edge angle and minimum knee flexion angle (R=0.460, p=0.041) as well as peak external knee extension moment (R=0.547, p=0.013). Alpha angle significantly correlated with peak external hip extension moment (R=0.447, p=0.048). A moderate correlation was found between the alpha angle and minimum hip flexion angle (R=0.414, p=0.069) and the center edge angle and peak external hip flexion moment (R=‐0.399, p=0.081).The relationships seen with this preliminary data are encouraging and support the association between hip morphological abnormalities and gait variables.1.Hunt MA, Gunether JR, Gilbart MK. Kinematic and kinetic differences during walking in patients with and without symptomatic femoroacetabular impingement. Clin Biom. 2013: 28(5): 519‐523.2.Rylander JH, Shu B, Favre J, et al. Functional testing provides unique insights into the pathomechanics of femoroacetabular impingement and an objective basis for evaluating treatment outcome. J Ortho Research. 2013: 31(9): 1461‐1468.3.Andriacchi TP, Natarajan RN, Hurwitz DE. Musculoskeletal dynamic locomotion and clinical applications. Mow VC, Huiskes R. Basic Ortho. Biom and MechanoBiology. 3 Ed. PA: Lippincott; 2005. 91‐121.Grant Funding Source: Sponsored by the American Association of Anatomists/Anatomy and Rush University Medical Center
Deconstructing the dogma of fore and hindlimb serial homology: evidence from regenerative, developmental, comparative, paleontological and evolutionary studies (919.3)
Authors: Diogo Rui , Ziermann Janine , Johnston Peter 
Published: June 2021

Most textbooks and papers state that the structures of the tetrapod fore‐ and hindlimb are serial homologues. We provide an updated discussion of this subject based on a literature review and on our regenerative studies of axolotls, developmental studies of tetrapods, and comparative and evolutionary studies of all major vertebrate groups, including recent re‐analyses of the appendicular muscles of chondrichthyans, dipnoans and coelacanths. The integrative analysis of the data available strongly supports the idea that the similarity of muscles and bones of the fore and hindlimbs of tetrapods such as salamanders and modern humans is not due to serial homology, but is instead the result of independent evolutionary changes (homoplasy) due to a complex interplay between developmental, functional, topological and phylogenetic constraints. It also offers new insights about the ancestral Bauplan and morphogenetic gradients of tetrapod limbs, including the striking similarity of the zeugopodial (forearm/leg) and autopodial (hand/foot) muscles of the two limbs and ventro‐dorsal symmetry of the zeugopodial muscles of a same limb, about the marked differences between pelvic and pectoral girdle structures, about homeotic transformations related to the number/identity of the digits and associated soft tissue changes, about limb birth defects, and about the differences between limb ontogeny and regeneration.Grant Funding Source: Faculty Start‐Up Package, Howard University College of Medicine
Is evolutionary biology becoming too politically correct? A reflection on the scala naturae, phylogenetically basal clades, anatomically plesiomorphic taxa, and “lower” animals (919.4)
Authors: Diogo Rui , Ziermann Janine , Linde‐Medina Marta 
Published: June 2021

The notion of scala naturae dates back to thinkers such as Aristotle, who ranked animals along a graded scale of complexity from “lower” to “higher” animals, such as humans. In the last decades, evolutionary biologists have tended to move from this extreme to the opposite extreme, i.e. to avoid using terms such as “phylogenetically basal” and “anatomically plesiomorphic” taxa, which are seen as “politically incorrect” vestiges of old teleological theories. Recently there has been a renewed interest on these topics, but most discussions on the scala naturae and related issues continue to be based on hard tissue and molecular data. Here we provide the first discussion of these topics based on empirical data obtained from comparative, developmental and phylogenetic myological studies of all the major vertebrate clades, including primates. We specifically 1) contradict the notions of a scala naturae or evolutionary progressive trends leading to more complexity and culminating in Homo sapiens; and 2) stress that the refutation of these old notions does necessarily not mean that one should not keep using the terms “phylogenetically basal” and particularly “anatomically plesiomorphic” to refer to groups such as the urodeles within the Tetrapoda, or the strepsirrhines and lemurs within the Primates, for instance. Grant Funding Source: Faculty Start‐Up Package, Howard University College of Medicine
Parallelism between ontogeny and phylogeny ő a case study in amphibians (921.10)
Authors: Ziermann Janine , Diogo Rui 
Published: June 2021

Ernst Haeckel’s idea of “ontogeny is a fast recapitulation of adult phylogenetic stages” was discussed extensively since its publication in 1866 and has been refuted. Authors such as Stephen Jay Gould have re‐defined a theory that stresses that there is a parallelism between ontogeny and phylogeny, but no ontogenetic recapitulation of ancestral adult stages. To test this theory, we studied amphibian cranial muscle development by undertaking dissections, using whole‐mount antibody staining, and doing serial sectioning. The order in which muscles appear during amphibian ontogeny was analyzed with Parsimov. We found 1) general patterns in cranial muscle development, e.g. the differentiation of muscles from anterior to posterior, from lateral to medial, and from origin to insertion; 2) that there is effectively a similarity between the order in which muscles appear in ontogeny and in phylogeny; 3) that there are some heterochronic events but these events cannot be related to a particular lifestyle; and 4) that contrary to the commonly accepted view that ontogeny tends to lead to the differentiation of new muscles, several amphibian larval cranial muscles actually become indistinct during metamorphosis. This latter point can lead to confusion about the homology of several cranial muscles in salamanders, frogs and other vertebrates, which should be resolved in order to understand vertebrate evolutionary history. Grant Funding Source: Faculty Start‐Up Package, Howard University College of Medicine
Subnasale to gnathion distance and nasal index of children with homozygous sickle cell disease in Port Harcourt, Nigeria (922.1)
Authors: Ligha Aloysius , Fawehinmi Hakeem 
Published: June 2021

Aim: This study is designed to determine changes in some of craniofacial parameters such as subnasale to gnathion distance and nasal index in sickle cell anaemia in comparison to the healthy children in Port‐Harcourt.Method: In this research which span over a two year period, measurements were taken of the facial indices (nasal and the subnasale to gnathion distances) of 100 confirmed homozygous (SS) children who attended the Sickle cell clinic of the University of Port Harcourt teaching Hospital and 500 normal growing children, drawn from the University of Port Harcourt Day Care Centre and Demonstration Nursery, Primary and Secondary Schools.Result: Results from the study showed that mean values for nasal index were lower, though, not statistically significant, showing tendency towards more platyrrhine noses which is most prominent between ages 2‐5 years when skull growth is at its peak. Mean values of subnasale to gnathion distance were higher but also not statistically significant among age groups for sickle cell anaemia.Conclusion: These features were put forward to explain the possible facial dysmorphology associated with the long term effect of haemolytic anaemia at the different stages of postnatal skull growth.Key words: Normal growth, Sickle cell disease, subnasale to gnathion distance, nasal index.
Cissus quadrangularis has anti‐oxidant and anti‐inflammatory properties: in vitro and in vivo studies (922.15)
Authors: Navarro Jorge , Espinosa Joanna , Das Kishore , Faraji Bahram , Innis‐Whitehouse Wendy , Wei Sun‐Gen , Banu Jameela 
Published: June 2021

Oxidative stress in cells increases the level of reactive oxygen species (ROS), causing cellular damage and inflammation, leading to apoptosis of cells. It plays a major role in different diseases including obesity and diabetes. One of the complications that results from obesity and diabetes is osteoporosis, a disease that makes bones fragile and increases the risk of fractures. ROS inhibits osteoblast differentiation, decreasing bone formation leading to bone loss. Cissus quadrangularis (CQ), a herb used in Ayurvedic medicine, has bone protective properties and is reported to decrease oxidative damages induced by obesity. We used mouse osteoblastic cells (MC3T3) to determine the anti‐oxidative effects of CQ. The cells were assessed for ROS production after determining the optimal concentration and time period of treatment with CQ. Increased ROS production can cause inflammation and activate the apoptotic pathway leading to cell death. We also completed an in vivo study using rats and measured the pro‐inflammatory cytokines in the serum after 4 months of feeding diet containing CQ. Results demonstrate significant inhibition of ROS and caspase 12 in CQ treated cells. We also found that caspase 12 levels are decreased in the presence of CQ. In vivo results showed decreased levels of IL‐1α and IL‐6 in the serum. These results suggest that CQ can protect bone as an anti‐oxidatant and anti‐inflammatory agent.Grant Funding Source: Undergraduate research Inititiative, NSF ADVANCE
The role of TGFβ1 and HTRA1 in the pathogenesis of TMJ osteoarthritis (922.8)
Authors: Wong Phillip , Reece Daniel , Hepworth Jared , Wilhelm Spencer , Mecham David , Kooyman David , Seegmiller Robert 
Published: June 2021

The objective of this study is to understand the pathogenesis of osteoarthritis (OA) in the temporomandibular joint (TMJ) by testing for the presence of established biomarkers present in OA of the knee.Six wild‐type mice (M. musculus) and six mice heterozygous for the chondrodysplasia gene mutation (cho/+) were used in this study. The mice were euthanized at three months of age, and their TMJs were isolated, fixed, decalcified, embedded in paraffin, and sectioned at 6µ thickness. Fifteen sections of each mouse were stained with Safranin O and Fast Green to determine the extent of OA. Fifteen additional sections of each mouse were immunohistochemically stained for the presence of TGFß1 and HTRA1.Using the Modified Mankin and OARSI scoring systems, it was determined that OA is present in the TMJ of cho/+ mice but not in the wild type. Also, staining for TGFß1 and HTRA1 was positive in cho/+ TMJs and absent in the wild type.We have established that at three months of age, i.e., when early signs of OA histopathology are detectable, TGFß1 and HTRA1 are upregulated in the TMJ articular cartilage of cho/+ mice. We propose that TGFß1 is a biomarker for OA and can be used as an early diagnostic tool of TMJ OA. This finding is of clinical significance in light of the current practice to use TGFß1 as a therapeutic agent of TMJ OA. Despite the lack of type II collagen in TMJ articular cartilage relative to that of the knee joint, the presence of HTRA1 here suggests that the degenerative changes involve the same pathogenetic mechanism as in the knee joint.Grant Funding Source: NIH grant 1‐R15‐AR056861‐01A1
Real‐time in vitro monitoring of impedance in rat bone‐like cells (UMR 106‐01 BSP) (923.10)
Authors: Joseph Eugene , Joshi Neil , Kim Kevin 
Published: June 2021

Cultured mammalian cells have been exhaustively studied by biological and biochemical means. Such studies have been effective, but limited in providing real‐time cellular data in vitro. The purpose of this study was to validate electric cell‐substrate impedance sensing (ECIS) to assess and monitor spreading and attachment of bone‐like cells (UMR cells) under varying initial cell plating concentrations and under treatment of the cells with camptothecin, an inducer of oxidative stress. UMR cells were routinely passaged, counted, then plated at 250 X 10³, 125 X 10³ and 62.5 X 10³ cells/mL in eight‐well ECIS array culture plates equipped with gold electrodes. Designated cells were treated with 6.0 μM camptothecin. The array culture plates were placed on the ECIS array holder of the ECIS instrument, then incubated at 37 degrees Celsius under 5% carbon dioxide infusion. Impedance measurements of the cells were monitored for 48 hours. The results showed that the total impedance, attachment and rate of spreading were affected in a cell concentration‐dependent manner. The higher the concentration of cells, the higher the impedance measurements as well as the rate of spreading. Cells treated with 6.0 μM camptothecin exhibited significantly lower impedance values and a slower rate of spreading as compared to controls. F test ANOVA was used to compare variances and all values in the results were expressed as means ±SD. The results validate the use of ECIS technology as a reliable approach for real‐time monitoring of UMR cells in culture. Moreover, ECIS provides data regarding the physical properties of cells that can be used to corroborate the outcomes of biological and biochemical studies of UMR cells.Grant Funding Source: Supported by La Sierra University, CAS Dean
Protein acetylation contributes to higher genome fidelity during replication and repair (925.5)
Authors: Balakrishnan Lata , Bambara Robert 
Published: June 2021

In eukaryotic nuclear DNA replication, one strand of DNA is synthesized continuously, but the other must be made as short Okazaki fragments that are later joined. The discontinuous process is inherently more complex and the steps involving fragmented intermediates create risks for disruptions of genomic integrity. Our recent observations suggest that the cell uses specific lysine (K) acetylation to alter the enzymatic properties of DNA replication and LP‐BER proteins. Adding to the knowledge that acetylation partially inhibits human FEN1, we found that it also stimulates human Dna2 nuclease/helicase activities and promotes strand displacement synthesis by human pol δ and human pol β. These observations led us to hypothesize that acetylation increases the extent of RNA‐DNA primer removal during Okazaki fragment synthesis. Acetylation would also increase the patch size made by pol β during BER. The likely reason for regulation by acetylation is to fully excise the error‐prone primer region made by pol α and the damaged region needing repair. Involvement of p300, a histone acetyltransferase an epigenetic regulator, suggests that there are times when it is advantageous to the cell to switch between efficient and high fidelity DNA synthesis. Differential regulation of the activities of replication/repair by p300 indicates a mechanism in which the acetylase promotes formation of longer flaps in the cell at the same time as insuring correct processing. Such intentional formation of longer flaps mediated by p300 in an active chromatin environment would increase the re‐synthesis patch size, providing increased opportunity for incorrect nucleotide removal during DNA replication and damaged nucleotide removal during DNA repair. Thus we propose acetylation to be a regulatory mechanism that promotes higher fidelity of DNA transactions, ensuring genome stability. Possibly this depends on development, nutritional state, or the region of the chromatin that is being duplicated.Grant Funding Source: Supported by National Institutes of Health grants GM098328 (to L.B.) and GM24441 (to R.A.B.)
Mutation in the PPARG ligand binding domain impairs PPARG‐mediated turnover of the p65 subunit of NF‐κB (930.2)
Authors: Mukoda Masashi , Stump Madeliene , Ketsawatsomkron Pimonrat , Quelle Federick , Sigmund Curt 
Published: June 2021

PPARG is a ligand activated transcriptional factor known to regulate metabolism. A recent study suggests that PPARG may elicit its anti‐inflammatory activity by promoting the degradation of the p65 subunit of nuclear factor kappa B (NF‐kB). We previously demonstrated that transgenic mice expressing dominant negative PPARG in vascular muscle (S‐P467L) exacerbates atherosclerosis in ApoE knockout mice. However, the mechanism remains unknown. We hypothesize that mutant PPARG promotes inflammation because its stimulation of p65 degradation is impaired. To test this, we co‐transfected HEK293T cells with vectors encoding p65 and either empty vector, wild type (WT) PPARG, or different PPARG mutants (P467L, V290M, R165T, S273A, K268R and K293R). We showed that the level of p65 protein expression was significantly decreased in WT‐PPARG‐transfected cells compared to empty vector. Compared with WT‐PPARG, there was an increase in p65 in P467L transfected cells. Using immunoprecipitation, we also demonstrated that WT‐PPARG directly interacts with p65 and induces p65 of ubiquitination. However, this interaction is impaired with P467L PPARG.We conclude that p65 turnover may be regulated, at least in part by PPARG and its mutation can result in impaired p65 degradation. Loss of PPARG‐mediated p65 degradation may contribute to the increased inflammation and formation of atherosclerotic lesions found in S‐P467L mice.Grant Funding Source: Supported by NIH
Dysfunction of polyubiquitin binding by ABIN1 as a basis for lupus nephritis (930.3)
Authors: Korte Erik , G'Sell Rachel , Sheehan Ryan , Caster Dawn , Powell David 
Published: June 2021

It is estimated that at least five million people worldwide have a form of systemic lupus erythematosus (SLE). Lupus Nephritis (LN) occurs in about 50% of SLE patients and represents a major source of morbidity and mortality. Recent genome‐wide association studies have linked mutations in the A20‐binding inhibitor of NF‐κB (ABIN1) gene to increased risk of developing LN. The molecular signalling events involved in the pathogenesis of LN in SLE patients are not well defined, but ABIN1 has been shown to have a role. We aim to describe the specific role for ABIN1 in the development of SLE and LN using ubiquitin binding deficient mutants in both humans (ABIN1[D472N]) and the orthologous mutation in transgenic mice (ABIN1[D485N]). Urinary protein loss measured by ELISA and gross pathological findings in sectioned kidneys of transgenic animals expressing ABIN1[D485N] mutation depict progressive nephritis which is apparent at 3 months and severe at 5‐6 months of age. Immune deposits in the kidneys were detected via immunofluorescence in the ABIN1[D485N] mice but were not seen in wild type mice. These data dramatically exhibit the importance of ABIN1 function in the maintenance of normal immune activity relative to the kidney. Furthermore, we illustrate the immunoprotective function of ABIN1 in kidney cells themselves. RT‐PCR, western blot and ELISA depict exaggerated immunostimulatory and inflammatory responses of cultured kidney cells expressing ABIN1[D472N] (including podocytes, tubular cells and mesangial cells) to TNF‐α and IL‐1β when compared to wild type ABIN1. Increased production of cytokines and chemokines suggests an increased propensity to recruit immune cells to target tissue which may lead to the inflammatory states characteristic of LN. Collectively, we have shown in both in vivo and in vitro models that ABIN1‐mediated inhibition of NF‐κB signalling is required in the kidney for the prevention of LN.Grant Funding Source: National Institutes of Health
Identifying transcriptional changes in an oligodendrocyte‐specific conditional knockout mouse (934.6)
Authors: Stefanik Taylor , Yu Gang , Dries Daniel 
Published: June 2021

gamma‐secretase is a proteolytic complex involved in development and implicated in the etiology of Alzheimer’s disease. We recently developed a conditional knockout mouse in which gamma‐secretase was specifically deleted from oligodendrocytes, the myelinating cells of the brain. The conditional knockout mouse had a profound neurological phenotype, including hyperactivity and decreased prepulse inhibition. Here, we use RNA‐seq to compare the transcriptional profiles of conditional knockout and control mice in an effort to identify a set of candidate genes that may explain the complex neurological phenotype of our conditional knockout mouse.Grant Funding Source: Supported by National Institute of Neurological Disorders and Stroke grant 1R01NS079796
Investigating the DNA binding and transactivation activity of rdyCRX as a molecular basis for retinal dysplasia in Felis catus (943.1)
Authors: Paszek Miles , Lipsett Koren 
Published: June 2021

In a pedigree developed from affected Abyssinian cats, an early onset rod‐cone dysplasia (Rdy) was identified and demonstrates an autosomal dominant inheritance. This is an excellent model for inherited retinal disorders such as retinitis pigmentosa (RP), cone‐rod dystrophy (CoRD), and Leber’s congenital amaurosis (LCA) because these lead to early developmental blindness via rod and cone photoreceptor dysfunction. The putative mutation for the Rdy phenotype is a single nucleotide deletion in the cone rod homeobox (CRX) protein, causing a frame shift that introduces a premature stop codon. Both normal CRX and rdyCRX proteins are expressed in vivo, suggesting a competitive interaction as the mechanism of pathology. The premature stop codon causes the truncation of the last third of the CRX protein containing the transactivational domains required for functional activity, while retaining the DNA binding domains allowing the rdyCRX to potentially compete with the normal CRX protein for binding to promoter regions. This could result in disrupting transcription initiation of genes necessary for the development and maintenance of the eye. EMSA analysis demonstrates competitive binding to Bat‐1 promoter oligonucleotide. Wild type CRX, rdyCRX, NRL, and NR2E3 have been successfully cloned in preparation of the development of a transcriptional activity assay.Grant Funding Source: Supported by HHMI