bluuebunny/crossref_metadata_2025_split huggingface dataset:
MICROANATOMY OF THE MANDIBULAR SYMPHYSIS IN LIZARDS
Authors: Holliday Casey , Gardner Nicholas , Paesani Sylvia , Douthitt Mallory , Ratliff Jack 
Published: June 2021

Although the mandibular symphysis is a functionally and evolutionarily important feature of the vertebrate skull, little is known about the soft‐tissue morphology of the joint in squamate reptiles. Lizards evolved a diversity of skull shapes and feeding behaviors, thus it is expected that the morphology of the symphysis will correspond with functional patterns. Here we present new histological data illustrating the morphology of the joint in a number of lizard taxa. The symphyses of all taxa exhibit dorsal and ventral fibrous portions of the joints that possess an array of parallel and woven collagen fibers. The middle and ventral portions of the joints are complemented by contributions of Meckel's cartilage. Kinetic taxa have more loosely‐built symphyses with large domains of parallel‐oriented fibers whereas hard biting and akinetic taxa have symphyses primarily composed of dense, woven fibers. Whereas most taxa maintain unfused Meckel's cartilages, iguanids and geckos independently evolved fused Meckel's cartilages however the joint's morphologies suggest different developmental mechanisms. Fused Meckel's cartilages may be associated with the apomorphic lingual behaviors exhibited by iguanids (tongue translation) and geckoes (eye wiping). These morphological data shed new light on the functional, developmental, and evolutionary patterns displayed by the heads of lizards.Grant Funding Source: West Virgina NASA Space Grant Consortium
Long faces and small eyes: Papionin models for the relationship between orbit size and facial prognathism
Authors: Yang David , Pagano Anthony Santino , Laitman Jeffrey T 
Published: June 2021

The papionins are unique among anthropoid primates for their long faces and large canines. The genera Papio and Mandrillus are here used as natural experiments for facial elongation among microsmatic primates. It is hypothesized that the bony orbits of long faced papionins take on smaller dimensions so as not to encroach upon the elongated nasal cavity. Long faced Papio and Mandrillus are contrasted against relatively orthognathic Macaca, Cercocebus, and Lophocebus via 3D geometric morphometrics. Only adult males were used since marked sexual dimorphism was present among all species. 3D landmark coordinates were collected around the face and upper respiratory tract. Landmark coordinate data between individuals was optimally superimposed and scaled using the Procrustes method, allowing direct comparison of linear measures, areas, and volume. It was found that Papio and Mandrillus are distinguished from Macaca, Cercocebus, and Lophocebus in palate length, area of the piriform aperture, orbital volume, and width of the orbital rim (p<.05). There is a strong negative correlation (−.78, p<.0001) between orbital volume and palate length and a weaker correlation between orbital volume and palate width (.57601; p<.0001). The data supports a functional relationship between orbit size and nasal cavity length.Grant Funding Source: Mount Sinai CAFM Student Research Support
Molecular Regulation of Osteoactivin Expression in Osteoblasts
Authors: Singh Maneet , Del Carpio‐Cano Fabiola , Monroy Alexandra , Popoff Steven N 
Published: June 2021

Osteoblast (OB) commitment, proliferation and differentiation from mesenchymal stem cells are regulated by Bone Morphogenetic Protein2 (BMP2). BMP2 mediates these osteoinductive effects by recruiting Transcription Factors (TFs), namely Runx2, Homeodomain (HD), Smad1 and Smad4 proteins to the promoter of OB specific genes and induces their transcription. Our laboratory has previously shown that Osteoactivin (OA), OB‐related glycoprotein acts as a downstream mediator of BMP2 effects on OB differentiation and function. Furthermore, we showed that Smad1 signaling regulates BMP2 induced OA expression. The goal of our study is to characterize OB specific TFs that regulate BMP2 induced OA promoter activity. In order to study the effects of BMP2 on OA promoter activity, we cloned 1kb upstream of rat OA gene into a luciferase expression vector and have shown that BMP2 stimulates OA promoter activity in a time and dose‐dependent manner. Secondly, knockdown of Runx2, HD, Smad1 and Smad4 using specific siRNAs decreased BMP2 induced OA promoter activity. Similarly, loss of consensus binding sites of these TFs from OA promoter decreased OA promoter activity. Furthermore, ChiP assays at various stages of OB differentiation indicated that Runx2, Smad1, Smad4 and HD proteins associate differentially with OA promoter. Collectively, our results suggest that Runx2, Smad1, Smad4 and HD TFs differentially regulate BMP2 induced OA promoter activity during OB differentiation.Grant Funding Source: NIAMS
Honokiol Regulates Phosphorylation of Tau via Inhibition of GSK3β
Authors: Le Nguyen Mai Khoa , Kim So‐Yeon , Lee Dalim , Kim Sung‐Soo , Suh‐Kim Haeyoung , Ryu Jae‐Ha , Lee Young‐Don 
Published: June 2021

Abnormal phosphorylation of tau plays an important role in neurodegeneration and subsequent dementia in Alzheimer's desease (AD). Much effort has been dedicated to treat AD, including inhibits GSK3β which is major kinase responsible for hyperphosphorylated tau. Honokiol, one of the major components isolated from Magnolia obovata, has been reported to have variety of pharmacological activities including anti‐inflammation and neuroprotection.In this study, the main objective was to determine whether Honokiol has inhibitory effects on phosphorylation of tau via modulation of GSK3β activities. Honokiol suppressed phosphorylation of tau in a dose‐dependent manner and inhibited GSK3β in 293T cells. Cholinergic neuroblastoma cell lines, LA‐N‐2 or SN56.B5.G4 were differentiated by CNTF and the cells were treated with oligomeric Aβ for an AD‐like pathogenic condition. The cells showed morphological changes such as long processes and branches, cell death and aggregation in the presence of CNTF or Aβ. Treatment with Honokiol not only recovered morphological changes but also decreased the phosphorylation of tau and the activity of GSK3β in vitro.Although further experiments about CDK5 which is known as the other cause for tau phosphorylation are required, our results implies that Honokiol regulates the phosphorylation of tau and the phosphorylation of GSK3β.
Neuroinflammation in a Forceps Compression Model of Spinal Cord Injury
Authors: Vaughn Chloe N. , Henley Jessica B. , Iafrate Julia , Stevenson Edward , Jones T. Bucky 
Published: June 2021

We sought to evaluate the neuroinflammatory response in a compression model of spinal cord injury (SCI). Because compression is a common mechanism of injury in human spinal cord trauma, such a model has clinical relevance. In this study we used forceps to induce lateral compression injury to the spinal cord, producing a moderate degree of injury as previously described in the contusion model (Basso et al., 1996).Post‐injury inflammation has been implicated in secondary degeneration but has not been characterized in this model. We evaluated the inflammatory response in the injured spinal cord using immunohistochemistry. We found that neutrophils are present within the lesion site by 1 day post injury (dpi) but do not persist past 3 dpi. T‐cells were present by 1 dpi, mainly in gray matter at the epicenter. They peaked in number at 7 dpi, but persisted to 42 dpi. A similar time course was observed for macrophage activation, although the response was more widespread at the impact site and extended further rostrocaudally. Overall, we confirm that forceps compression of the spinal cord produces a neuroinflammatory response similar to what has been described in human spinal cord trauma and in contusion models of experimental spinal cord trauma. Thus, forceps compression represents a clinically relevant experimental model for evaluating secondary injury.Grant Funding Source: MWU Biomedical Sciences program
Histological validation of the diffusion tensor: feasibility in human brain tissue
Authors: Ortiz Jake , Hageman Nathan , Salin Ashley , Salin Megan , Dong Hong‐wei , Stark M. Elena , Vinters Harry V. , Toga Arthur W. , Wisco Jonathan J. 
Published: June 2021

Taking advantage of anisotropic water movement caused by cytoarchitectural properties of brain tissue, Diffusion Tensor Imaging (DTI) is capable of representing approximate true nerve fiber orientations as a diffusion tensor at each voxel. The interpretation of DT images remains hampered in part by the error inherent in tensor calculations. This pilot study demonstrates the feasibility of histological validation of DTI in post‐mortem human brain tissue, with the eventual goal of constructing a probabilistic, ground‐truth atlas of fiber orientations specifically designed to reduce the uncertainty of tensor calculations. As a first step, we mapped nerve fibers of the corpus callosum, cingulum bundle and the intersecting region from images of histological sections nonlinearly registered to tensor maps. We confirmed that tensors accurately represented homogeneous but not necessarily heterogeneous fiber populations. Histological validation can provide a priori constraints for tensor calculations and will have a direct impact on the reconstruction of fiber tracts and help clinicians to identify and manage diseases involving white matter pathologies with greater sensitivity and specificity. This work was supported in part by NIH grants U54 RR021813, P41 RR013642, P50 AG16570, R21 MH083180, R90 DA023419‐01, T90 DA023419‐01 and GM08042.Grant Funding Source: U54 RR021813, P41 RR013642, P50 AG16570, R21 MH083180, R90 DA023419‐01, T90 DA023419‐01 and GM08042
Phrenic nerve morphometry in male and female spontaneously hypertensive rats
Authors: Rodrigues Anaceres Ribeiro , Ferreira Renata Silva , Salgado Helio Cesar , Fazan Valeria Paula 
Published: June 2021

Histological examination of the diaphragm showed gender differences in fiber composition but gender differences on phrenic nerve morphometry were not thoroughly addressed. Ventilatory differences were described between male and female rats, as well as among different rat strains. However, the morphology of the phrenic nerve was not investigated in spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) rats. After arterial pressure and heart rate recordings, phrenic nerves of 20 week‐old male and female SHR and WKY were prepared for epoxy resin embedding and light microscopy. Morphometry was performed with the aid of computer software. Our results showed for male and female SHR remarkable longitudinal asymmetry on both sides and an asymmetry between sides on distal segments, which were not present on WKY nerves. Phrenic nerves were generally larger in males compared to females on both strains but larger on WKY compared to SHR for both genders. Myelinated fiber number and density were significantly larger on females of both groups and remarkably larger on WKY compared to SHR in both genders. Strain and gender differences on phrenic nerve myelinated fiber number is described for the first time in this experimental model of hypertension, pointing to the need for thorough functional studies of this nerve on male and female SHR.Grant Funding Source: FAPESP
Alterations in atypical PKC expression and activity near the phrenic motor nucleus following cervical spinal injury
Authors: Guenther Courtney H. , Tubon Thomas C. , Windelborn James A. , Yin Jerry C.P. , Mitchell Gordon S. 
Published: June 2021

Atypical protein kinase C (aPKC) is a kinase family critical for maintenance of hippocampal synaptic plasticity (Pastalkova and Serrano, et. al., 2006). aPKCs are expressed in phrenic motor neurons (Guenther and Mitchell, unpublished), a key site of respiratory plasticity (Mitchell, et. al., 2001), particularly following C2 cervical hemisection (C2HS). We tested the hypothesis that C2HS increases the expression and activity of atypical PKCs near the phrenic motor nucleus suggesting a contribution to injury‐induced respiratory plasticity. C2 laminectomy (sham) or C2HS were performed on adult, male Lewis rats. Ventral spinal segments C3‐5 were harvested 1, 3 or 28 days post‐surgery and prepared for enzyme activity assays and immunoblots to assess changes in aPKC activity and expression. Ventral cervical aPKC activity increased at 1 and 28 days (not 3) post‐C2HS (1 day: 63% vs shams ipsilateral to injury; p<0.05; 28 day: increased activity vs sham, but without difference ipsilateral and contralateral to injury; p<0.05). Total PKCζ protein expression was unchanged by C2HS, but total PKMζ (constitutively active PKCζ isoform) was increased vs shams ipsilateral to injury at 28 days post‐C2HS. Changes in aPKC expression near the phrenic motor nucleus following a C2HS suggest the possibility that aPKCs contribute to spinal respiratory plasticity following cervical spinal injury (NIH HL 80209 and HL69064).Grant Funding Source: NIH
Bifunctional protein for improved stent performance and endothelial regeneration
Authors: Baumer Yvonne , Leder Christoph , Schoenberger Tanja , Ziegler Melanie , Filzmayer Christina , Buehring Hans‐Joerg , Gawaz Mainrad , Schlosshauer Burkhard 
Published: June 2021

Restenosis and thrombosis are undesired effects after stent implantation. Reduced or missing re‐endothelialization of injured coronary arteries shall be abolished by improving stem cell homing at the side of injury to support their differentiation into intact endothelium. We developed a bifunctional protein binding to collagen at the vessel lesion site and to stem/progenitor cells. ELISA studies demonstrated that this bifunctional protein binds to collagen type1 comparably strong as the control protein. Employing stem cell marker overexpressing cells and human CD34+ endothelial progenitor cells on a multi substrate array (MSA) spotted with 14 different extracellular matrix proteins demonstrated the bifunctionality and specificity of the protein. This specificity was substantiated in flow chamber adhesion experiments. Furthermore, we tested colony forming ability and by this endothelial like differentiation of CD34+‐cells on fusion protein coated surfaces. In conclusion, this bifunctional protein is a promising construct to support re‐endothelialization and therefore reducing restenosis and thrombosis risk after stent implantation.Supported by the German Ministry of Education and Research (BMBF) # 01GU0727 and 01GU0726.
Insights on Rad51 Function from the Structure and Properties of a Filament Interface Mutant
Authors: Morrical Scott Walker , Chen Jianhong , Villanueva Nicolas , Rould Mark A. 
Published: June 2021

Rad51 protein promotes homologous recombination in eukaryotes. Recombination activities are activated by Rad51 filament assembly on single‐stranded DNA. Previous studies of yeast Rad51 showed that His352 occupies an important position at the filament interface, where it could relay signals between subunits and active sites. Here we report the 2.5A X‐ray crystallographic structure of the H352Y mutant of yeast Rad51. Biochemical data indicate that H352Y is trapped in a high‐affinity ssDNA‐binding conformation with limited catalytic turnover. The structure of H352Y reveals a right‐handed helical filament in a high‐pitch (130Å) conformation with P61 symmetry. The H352Y structure closely resembles DNA‐bound structures of E. coli RecA protein. Tyrosine substitution at position 352 locks Phe187 from the adjacent subunit into a position that interferes with the gamma‐phosphate binding site of Walker A, potentially explaining the limited catalysis observed in H352Y. Comparison of Rad51 H352Y and other RecA/Rad51 structures reveals a correlation between DNA bound/unbound status and the trans/cis configuration of a conserved peptide bond near Walker B.Funded by NIH grant number P01 CA098993.
Binding of the DNA primase of bacteriophage T7 to its recognition sequence in DNA is modulated by the zinc‐binding domain
Authors: Lee Seung‐Joo , Zhu Bin , Akabayov Barak , Richardson Charles 
Published: June 2021

The zinc‐binding domains (ZBD) of prokaryotic DNA primases are critical for recognition of specific sequence in ssDNA at which primers are synthesized. ZBDs are structurally conserved in primases but they direct recognition of distinct trinucleotide sequences. In order to determine regions of the ZBD responsible for sequence‐specific recognition, we carried out homolog‐scanning mutagenesis on T7 DNA primase using a bacterial homolog from Bacillus stearothermophilus. Substitution of a five amino acid residue segment in the ZBD eliminates the ability of the primase to synthesize primers from a specific template sequence. The role of residues neighboring two cysteins (Cys17 and Cys20) in the primase was investigated by generating a library comprised of multiple amino acid substitutions at positions of Pro16, Asp18, and Asn19 followed by genetic screening for functional gene 4 protein. Examinations of the altered proteins reveal that substitutions at the three sites do not change the specific sequence recognized. However, the more positively charged residues in the region facilitates the better binding to a recognition site in a short template, leading to more efficient primer synthesis. Results from this study suggest that sophisticated architecture of ZBD determines recognition of specific sequence by DNA primase.This work was supported by Public Health Service Grant GM 54397.
The Interaction of N‐Acetylglutamate Synthase with Other Mitochondrial Urea Cycle Enzymes
Authors: Haskins Nantaporn , Tuchman Mendel , Morizono Hiroki , Caldovic Ljubica 
Published: June 2021

The urea cycle operates in the mammalian liver to protect the central nervous system from the neurotoxic effects of ammonia via the highly efficient conversion of ammonia into urea. Protein:protein interactions between urea cycle enzymes are thought to contribute to the high efficiency of ureagenesis. We examined the interactions of the three mitochondrial urea cycle enzymes: N‐acetylglutamate synthase (NAGS), carbamylphosphate synthetase I (CPSI), and ornithine transcarbamylase (OTC).There are two known isoforms of NAGS protein, NAGS‐M and NAGS‐C, which differ only in the presence (NAGS‐M) or absence (NAGS‐C) of a ~ 50 amino acid N‐terminal variable segment. The distribution of NAGS‐M and NAGS‐C within the mitochondria was examined using ultracentrifugation and western blotting. NAGS‐M was loosely associated with the inner mitochondrial membrane, while NAGS‐C interacted strongly with the inner mitochondrial membrane. Co‐immunoprecipitation (CO‐IP) was used to determine if NAGS, CPSI and OTC interact. The NAGS‐M, but not NAGS‐C co‐immunoprecipitated with CPSI and OTC. In addition, CO‐IP was used to examine if the variable segment of mouse NAGS could compete with NAGS for interaction with CPSI. Results indicate the variable segment is sufficient for the binding of NAGS to CPSI. These finding suggest localization and interaction of mitochondrial urea cycle enzymes are important for regulation of ureagenesis.
Biochemical and Histological Changes in the Kidney of Streptozotocin‐Induced Diabetic Rats: Effects of Garlic and Ginger Compared to Aspirin
Authors: Alhouli Mouna J , Thomson Martha , Al‐Qattan Khaled , Muslim Ali Divya J.S. 
Published: June 2021

This study was conducted to determine the biochemical and histological efficacies of garlic and ginger in comparison to aspirin in streptozotocin‐induced diabetic rats. One week diabetic rats (blood glucose > 300 mg/dl) were divided into four groups of which three groups were treated for 8 weeks with daily IP doses of fresh extracts of garlic and ginger (500 mg/kg each) or aspirin (10 mg/kg). Kidney malondialdehyde (MDA), lactate dehydrogenase (LDH), catalase (CAT), protein and total antioxidants were measured. The results showed that kidney MDA and LDH levels of diabetic non‐treated rats were significantly increased as compared to both the normal controls and the garlic‐, ginger‐ and aspirin‐treated animals. Total antioxidants levels of untreated diabetic rats were significantly lower than those of both the normal controls and the three treated groups. CAT and protein levels of untreated diabetic rats were significantly decreased as compared to the normal controls and the garlic‐ and ginger‐treated groups. Aspirin‐treated rats were not statistically different from the diabetic non‐treated rats in regard to CAT and protein and from the garlic‐ and ginger‐treated rats with respect to MDA and total antioxidants. Diabetic renal corpuscles showed general distortion, in particular deterioration in capsular membrane and reduction in capsular space. All treatments attenuated the renal corpuscle modulation with more potency exerted by garlic and ginger. Results suggest that the hypoglycaemic effects of garlic and ginger can help in ameliorating diabetic nephrology, and it is concluded that these two herbs can be administered as a supplementary precaution against diabetes.This work was partially supported by the College of Graduate Studies, Kuwait University.
Differences among white adipose tissue depots in mice
Authors: Sala Lucila Sackmann , Munn Rachel , Lubbers Ellen , Berryman Darlene E , Kopchick John J 
Published: June 2021

Excess white adipose tissue (WAT) is widely associated with insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD). In fact, intra‐abdominal fat is better correlated with insulin resistance than subcutaneous fat. However, the physiological impact of adipose depot location is not well understood. Our goal was to investigate cellular and molecular differences between WAT depots. Cell sizes and proteomic profiles from subcutaneous (inguinal) and intra‐abdominal (mesenteric, epididymal and retroperitoneal) fat pads from C57BL6/J mice were analyzed. Proteomes resolved by two‐dimensional gel electrophoresis followed by mass spectrometry showed significant differences in proteins involved in glycolysis, energy production, lipid transport, stress resistance, cytoskeleton structure, and others. Some of these proteins showed significant correlations to plasma insulin, leptin and/or adiponectin levels. Mean adipocyte cross‐sectional area was measured by digital image analysis of paraffin embedded tissue and was highest in epididymal and lowest in inguinal and mesenteric fat. Together, these results show marked differences among WAT depots, even within intra‐abdominal fat. This and further studies will help clarify the depot‐specific characteristics and their influence on insulin resistance in an effort to establish new diagnostic and/or therapeutic targets for T2D and CVD.Supported in part by the State of Ohio's Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by NIH Grants DK075436‐01, AG019899‐06, 1P01AG031736‐01A1, by the Diabetes Research Initiative and the BioMolecular Innovation and Technology Partnership at Ohio University, and by AMVETS.