bluuebunny/crossref_metadata_2025_split huggingface dataset:
The changing landscape of anatomical education: one opinion on how we might increase the value of our stock
Authors: Haines Duane E. 
Published: June 2021

Advances in medicine over the last 25 years have significantly improved the treatment of patients and, perhaps unwittingly, presented unique opportunities to the medical educator. While these advances were the product of medical exigency they have given medical educators unique innovations to embrace and use to their own advantage. The real question is, are we really integrating clinical concepts, information, or content in our courses?MRI and CT are unique and powerful educational tools that function in parallel with clinical terminology. During the time period in which these methods have become commonplace, there have been repeated efforts to reduce or diminish course content in the anatomical sciences. Have we, as medical educators, allowed this decease in emphasis to occur by our failure to embrace the very tools and concepts that show the absolute essential value of anatomy in medical education?There are several examples where MRI, CT, or clinical terminology, can be used to significant advantage in the basic science setting. First, CT and MRI show anatomy in vivo; such images should be an integral, if not dominate, part of gross anatomy. Second, when teaching cross‐sectional anatomy, "laterality" must be taken into account. A cross‐section in an "anatomical" orientation that does not match a corresponding MRI or CT is intrinsically flawed. Third, brainstem "anatomy" should be taught to match the "anatomy" in MRI; otherwise clinical correlations are difficult to make and time consuming to explain. Fourth, there are numerous examples where a clinical term can be used to designate an anatomical structure within its proper context.
Exercise induces Hsp70 in smooth muscle cells of the cerebral vasculature
Authors: Van Aarsen Marcus J , Noble Earl G 
Published: June 2021

Exercise (EX) is a complex physiological stressor of the cardiovascular system. EX is known to increase expression of the cytoprotective inducible isoform of the 70 kDa heat shock protein (Hsp70) in blood vessels of working muscle. The objective of this study was to determine whether EX induces a similar increase in Hsp70 content in the cerebral vasculature. Sprague‐Dawley rats (n=10) were randomly assigned to either an EX (60 min treadmill running, 30 m/min, 5 consecutive days) or control group. Brain was harvested 24 hours following the final EX bout and sectioned for immunohistological localization of Hsp70, vascular endothelium and smooth muscle. Results showed increased Hsp70 expression in the cerebral vasculature post‐EX versus controls. Post‐EX, Hsp70 was always observed in the vascular smooth muscle of large cerebral vessels adjacent to the midbrain, and was also infrequently present in the vascular endothelium of these vessels. No Hsp70 was detected in neural regions of the brain. Although unclear, increased expression of Hsp70 may be a response to the change in characteristics of blood and blood flow that occur due to EX, or due to increased autonomic outflow to the vascular smooth muscle. Regardless, the neuroprotective nature of EX may be in part due to the protection of cerebral blood vessels by Hsp70.Supported by NSERC #8170‐05Grant Funding SourceInternal
Characterization of Myogenic Factors in Normal Rat Mesenteric Veins
Authors: Enouri Saad Salama , Johnson Ron 
Published: June 2021

Vascular tone is maintained by the sympathetics, other neurohormones and myogenic factors. Myogenic factors have been characterized in arteries; however limited studies have been completed in veins. The objective of this study was to evaluate the contribution of myogenic factors to vascular tone in a large capacitance bed, the mesenteric veins, of normal male rats. Pressure myography was used to study isolated cannulated third order mesenteric venules (2‐12 mmHg) and arterioles (20‐140 mmHg). Arterioles showed myogenic contractions to pressure increases beginning at 60 mmHg, while venules showed evidence of myogenic tone (resistance to stretch) but not myogenic contractions. The contribution of endothelial dilators (N‐nitro‐L‐argentine, 100 µM) to net tone with increasing luminal pressure was minimal in both vessel types. The L‐type calcium channel blocker, Nifedipine (1 µM), abolished myogenic contributions to net tone in arterioles while only partially reducing responses in venules. The protein kinase C inhibitor (PKC), Chelerythrine (2.5 µM), also abolished myogenic contributions to net tone in arterioles; however, responses in venules were only substantially reduced. These findings suggest that in mesenteric venules (1) myogenic factors contribute to net venous tone and (2) myogenic tone is due in part to extracellular calcium and PKC activation and not altered by endothelial nitric oxide release.Grant Funding SourceNSERC
Variant Distribution of the Right Coronary Artery at the Crux of the Heart (Anatomical and Multislice CT Imaging Study)
Authors: El‐Maasarany Shirley Hilal , Aboul‐Enein Fatma Adel 
Published: June 2021

BackgroundIn case of dominance of the right coronary artery RCA (80%‐90%), the later reaches the crux to give the posterior interventricular artery (posterior descending artery PDA) , the atrio‐ventricular nodal artery AVNA and continues to give postero‐lateral branches that supply the inferior surface of the left ventricle.AimThe aim of the present work was to study the course, relations and distribution of the right coronary artery at the crux of the heart and its variations.Material and methodsTwenty embalmed human hearts showing no gross pathological lesions in the walls of the chambers were used. The crux of the heart was dissected to study the arteries in this region, their origin, relations and their destinations.Multi‐slice Computed Tomography MSCT of twenty healthy individual, with no obstructed lesions were studied retrospectively.ResultsAt the crux the RCA forms a loop upwards which gives the PDA of a considerable size and smaller AVNA. Double and triple PDAs were seen in two specimens. AVNA, in the majority of specimens, took origin from the loop of the RCA. It coursed upwards and forwards in the inferior septal space ISS to reach the AVN. Variant origin of the AVNA was seen in three of the specimens, where it took origin from the PDA or from its first septal perforator. Double AVNA was encountered in 4 of the 20 specimens. In MSCT the AVNA was recognized by its vertical course off the distal RCA.ConclusionsThese variant anatomical findings should be considered during various interventional and surgical procedures encountering the crux of the heart.
Dynamic Analysis of Blood Vessel Formation in Transgenic Quail Embryos
Authors: Sato Yuki , Huss David , Poynter Greg , Fraser Scott E , Lansford Rusty 
Published: June 2021

Blood vessels help to establish the circulatory system essential for gas, nutrient, and waste exchange. Blood vessels also play a vital role in formation of the nervous system and visceral organs during development. Although numerous molecules required for blood vessel formation have been identified, a detailed understanding of normal blood vessel formation and direct effects of the gene defects is lacking due to the difficulty of imaging living embryos. To take advantage of the easy accessibility to the developing embryos, we generated Tie1.H2B‐EYFP transgenic quail that express H2B‐eYFP in endothelial cells. The Tie1.H2B‐EYFP transgenic quail enable us to image nucleus of every blood vessel endothelial cell in living embryo by EYFP signals under the confocal laser microscopes. We are studying aorta formation to better understand various types of dynamic morphogenetic events including cell migration/sprouting, cell division, mesenchymal‐to‐epithelial transition, and rearrangement of luminal structure. We dynamically track individual endothelial cells to determine their individual behavior and their collective morphometric changes during the dorsal aorta formation. By combining dynamic imaging with DNA electroporation technique, we are trying to visualize the functional role of Shh signaling for the endothelial cell in angiogenesis and cardiogenesis.Grant Funding SourceNIH, Center of Excellence in Genomic Science (CEGS), Japan Society for Promotion of Science (JSPS)
Protocol to assess growth plate kinetics during long‐term in vivo multiphoton imaging using BrdU as a physiological marker
Authors: Liu Wenhua , Williams Rebecca M. , Farnum Cornelia E. 
Published: June 2021

With the ability to collect optical images deep into biological tissues, multiphoton microscopy (MPM) is a powerful tool to study growth plate kinetics in real time, but the act of imaging introduces variables with the potential to alter chondrocytic kinetics. This study is to develop a procedure to assess chondrocytic viability during in vivo MPM imaging on the proximal tibial growth plate of 4‐wk‐old mice. The BrdU labeling index is used as a physiological marker to assess imaging variables, following IACUC procedures. Isoflurane anesthesia was used at 1L/min (no ventilation) to maintain breathing at ~1.5/sec. Fluorescein was injected IP for a vascular concentration of ~1mM. After 2 hrs, a second dye injection was given with ~200 ul of isotonic fluids to avoid hydropenia. Body temperature was maintained at ~350C. The surgical limb was bathed in warm Ringer's. BrdU was given IP 0.5 hr before euthanasia. Fixation and plastic embedment followed, with analysis of BrdU LI by standard protocols. Maintenance of core and limb temperature, hydration, reinjection of the dye after 2 hrs, and limiting imaging to 3.5 hrs proved to be key to successful long‐term imaging. This standard protocol for BrdU‐based analysis of proliferative capacity will allow comparative assessment of multiple vital dyes for monitoring chondrocytic dynamics during multi‐hour MPM imaging. Supported by NIH‐R01AR052003.Grant Funding SourceNIH
Lymphotoxin‐alpha Concentrations at Sites of Periodontitis and Gingival Overgrowth
Authors: Johnson Roger B , Lester S. Reid , Bain Jennifer L , Serio Francis G 
Published: June 2021

ObjectiveThere are no studies available comparing lymphotoxin‐alpha (LT‐alpha) gingival concentrations between sites of periodontal disease and gingival overgrowth (OG).MethodsGingiva was obtained from human donors prior to extraction of the adjacent teeth. The tissue was grouped based on adjacent pocket depth and bleeding on probing (BOP). Gingiva adjacent to a = 3 mm sulcus without BOP were classified as "normal" (N; n=26); Gingiva adjacent to a 4‐6 mm sulcus featuring BOP were classified as "diseased, moderate" (DM; n=23) and gingiva adjacent to > 6 mm sulci were classified as "diseased, severe" (DSev; n=28). OG gingiva was obtained following gingivectomy from patients receiving nifedipine/cyclosporine treatment (n=24). Tissues were solubilized and IL‐6, IL‐1‐β and LT‐alpha concentrations were assessed by ELISA. Data were compared by factorial ANOVA and a post‐hoc Tukey test. Groups were defined as significantly different when p<0.05.ResultsGingival concentrations of IL‐6 were significantly greater at DSev than at N sites (p<0.001) and significantly greater within OG than within gingiva adjacent to N, DM, and DSev sites (p<0.001). In contrast, IL‐1‐β concentrations within OG tissues were significantly lower than within gingiva adjacent to N, DM, and DSev sites (p<0.001). LT‐alpha concentrations were significantly greater within OG than within gingiva adjacent to N, DM, and DSev sites (p<0.001) and at DM compared to N and DSev sites (p<0.05).ConclusionOur data suggest that LT‐alpha may have an important role in the etiology of OG gingival inflammation and could be a target for therapeutic intervention for OG.
EXPRESSION OF PROINFLAMMATORY CHEMOKINES AS BIOCOMPATIBILITY MARKERS OF DENTAL SEALERS
Authors: SOLIS‐SOTO JUAN MANUEL , SOUSA‐MORENO VANESSA 
Published: June 2021

Biocompatibility of new dental sealers should be evaluated before their clinical application.ObjectiveWe studied the in situ production of chemokines in order to evaluate the biocompatibility of five endodontic sealers of different composition (Sealer 26, Tubli‐Seal, MTA, Silverfree AH 26, and Endorez).MethodsBALB/c mice were subcutaneously implanted with the different dental sealers. Then the tissue was prepared for histopathological and immunohistochemical analysis.ResultsThe proinflammatory chemokines CCL3 and CCL4 participated in both, acute and chronic inflammatory response induced by each dental sealer studied. Immunoreactive cells to both chemokines, were observed abundantly in the dermis, especially in the inflamed tissue around the dental sealers. Higher amounts were observed in the acute inflammatory response. According to morphometrical analysis, the order from more to less biocompatible was: MTA, Sealer 26, Tubli‐Seal, Endorez, Silverfree AH26. There were more immunoreactive cells to CCL4 than CCL3 in response to dental sealers (p<0.05).ConclusionsExpression of the proinflammatory chemokines CCL3 and CCL4 is an excellent in vivo model to study the biocompatibility of dental materials. MTA and Sealer 26 are the most biocompatible dental sealers.
Investigating Molecular Chaperone Activity Associated with Human TorsinA
Authors: Burdette Alexander Justin , Churchill Perry F. , Caldwell Guy A , Caldwell Kim A 
Published: June 2021

TorsinA is a member of the AAA+ ATPase family of proteins and, interestingly, is the only such ATPase localized to the ER lumen. TorsinA has been suggested to act as a molecular chaperone while a deletion mutant form associated with early‐onset torsion dystonia, a dominantly inherited movement disorder, appears to result in a net loss‐of‐function in vivo. Thus far, no studies have examined the chaperone activity of torsinA in vitro. Here we expressed and purified both WT and mutant torsinA fusion proteins (to maltose binding protein) in bacteria and examined their ability to function as molecular chaperones by monitoring suppression of luciferase and citrate synthase aggregation, as well as luciferase reactivation. As measured by light scattering, both WT and mutant torsin effectively and similarly suppressed protein aggregation compared to controls. Further, both forms of torsinA demonstrated the capacity to hold luciferase in an intermediate state for refolding and reactivation by other chaperones. These data not only provide conclusive evidence that torsinA acts as a molecular chaperone in vitro, but also suggest that dystonia is likely not a consequence of a loss in torsinA chaperone activity.Research support: Dystonia Medical Research Foundation
Using Next Generation Solexa Sequencing to Identify Genes that Regulate Stem Cell Proliferation in the Caenorhabditis elegans Germline
Authors: Jones Vovanti , Fox Paul , Mardis Elaine , Schedl Tim 
Published: June 2021

Multicellular organisms depend on cell‐cell interactions to coordinate their development. In C. elegans, germline stem cell fate depends on the activity of the Notch receptor homolog, glp‐1. The loss of glp‐1 function prevents germ cell proliferation and produces sterile hermaphrodites. To identify new genes that regulate germline proliferation, suppressors of the temperature sensitive allele glp‐1(q231) have been isolated. These mutants, sog (suppressor of glp‐1), rescue sterility of q231 at 20°C. The sog‐1 gene was previously mapped to a 2 Mbp region on chrI. To [LL1]identify the gene responsible for the sog‐1 phenotype, we used Solexa sequencing to re‐sequence the entire genome of two independently isolated sog‐1 mutants. In the critical region, we identified 62 SNPs between the two strains and the reference genome. We performed RNAi screens of candidate genes to test whether they phenocopy sog‐1 suppression of glp‐1. RNAi screens of pbrm‐1 displayed an embryonic lethal phenotype for all strains, while unc‐14 and F57B10.3 potentially phenocopy the germline suppression of q231 by sog‐1. [LL2]Screens of other potential candidates were negative. These results may help identify new genes in germline proliferation and determine if Solexa sequencing will be useful in identifying genes defined by mutation.This work was funded by NIH/HIGMS MARC U*STAR T34 08663 National Research Service Award to UMBC, HHMI and BioMedRAP.
Understanding the effects of chronic cadmium exposure on breast cancer
Authors: Vegas Esera , Louie Maggie C. 
Published: June 2021

Cadmium is a heavy metal that is found in the environment and enters our body through either dietary sources or cigarette smoke. Heavy metals, like cadmium tend to bioaccumulate and induce toxicities by interacting with organic compounds inside the cell. Recent studies have suggested that cadmium may play a role in breast cancer by activating the estrogen receptor (ER) (Antila1996, Stoica et al. 2000, Martin et al. 2003, Johnson et al. 2003). Data from our lab also suggest that acute exposure of cadmium promotes ER‐dependent cell proliferation and induced ER target gene expression (i.e. cyclin D1, Cathepsin D, and c‐myc). However the effects of chronic cadmium exposure are unclear and require further investigation. The current focus of this project is to understand how chronic exposure of cadmium affects breast cancer cell growth. To accomplish this, we have established a cadmium‐breast cancer cell line (MCF‐7 Cd) by maintaining parental ER+ MCF‐7 cells in 10‐7 M cadmium for over 3 months. By comparing the growth and gene expression patterns of MCF7‐Cd and MCF7 cells, we hope to establish an understanding of how chronic cadmium exposure may contribute to the development of breast cancer.This project is supported by NIH R15 CA121983‐01A1
Phosphorylation and protein expression and dynamics at synapses in the central nervous system
Authors: Trinidad Jonathan C , Thalhammer Agnes , Schoepfer Ralf , Burlingame Alma L 
Published: June 2021

The neurotransmitter glutamate is detected by ligand‐gated ion channels at synapses in the brain. These ion channels reside within a complex protein network known as the postsynaptic density (PSD), which contains kinases/phosphatases, scaffolding molecules, and structural molecules. Activation of these ion channels results in cellular excitation and initiates signal‐transduction networks regulating PSD structure.We used mass spectrometry to identify 1700 proteins and 1500 sites of phosphorylation from PSD preparations. These were then quantified with stable isotope labeling using iTRAQ. We examined differential protein and phosphorylation patterns across synapses isolated from the cortex, midbrain, cerebellum, and hippocampus. NMDA‐type glutamate receptors had higher levels of phosphorylation compared to AMPA‐type receptors. We also examined temporal dynamics of synaptic changes resulting from chemically induced seizures. We observed multiple patterns of phosphorylation dynamics, presumably mediated by distinct kinase/phosphatase pathways.Funding by the Wellcome Trust and BBSRC (to RS) and NIH grant RR 01614 (to ALB).
Relaxin activation of PPAR[gamma] is ligand independent
Authors: Singh Sudhir , Bennett Robert G 
Published: June 2021

Peroxisome proliferator‐activated receptor gamma (PPARγ) has many antifibrotic effects similar to those of relaxin (Rlx), raising the possibility that Rlx's antifibrotic effects may involve activation of the PPARγ pathway. To test this possibility, the Rlx effect on PPAR activity was assessed using a luciferase reporter vector fused to the PPAR response element (PPRE). Rlx increased the PPRE activity in a dose dependent manner. The PPARγ agonists increased the PPRE activity. The combined effect of Rlx and PPARγ agonists on PPRE activity was more than additive. Rlx increased the expression of PPARγ target genes, and when Rlx was combined with PPARγ agonists the effect was synergistic. PPARγ knockdown reduced the Rlx effect on PPRE activity, suggesting that part of Rlx effect is mediated through PPARγ. A PPARγ ligand blocker reduced PPRE activation and PPARγ target genes expression in response to PPARγ agonists but not Rlx, suggesting that Rlx stimulates ligand‐independent PPAR activation. Moreover, Rlx further increased the PPRE activity in cells overexpressing PPARγ without exogenous PPARγ ligands. PPARγ has diverse biological implications in broad range of diseases and the synergistic effects of PPARγ agonist with Rlx and better understanding of the signaling pathway will help to develop new therapies targeting PPARγ.Funding: NIAAADepartment of Veterans Affairs
Phenolics from mango (Mangifera indica L.) suppress growth in different cancer cells, targeting pro‐apoptotic and cell cycle control proteins
Authors: Bertoldi Michele Correa , Noratto Giuliana D. , Talcott Steve Terel , Mertens‐Talcott Susanne U. 
Published: June 2021

Gallotannins are phenolics in mango which have shown anti‐cancer activity. The objective was to evaluate the anti‐prolioferative activity of mango phenolics in cancer cells. The cultivars Haden (Hd) and Ataulfo (At) were selected based on phenolic content and antioxidant activity. The anti‐proliferative and pro‐apoptotic activities of phenolics extracts were tested in human Molt‐4 leukemia, A‐549 lung, MDA‐MB‐231 breast, SW‐480 colon and LnCap prostate cancer cells. Additionally, gene expression was investigated by RT‐PCR and cell cycle kinetics by flow cytometry. Hd inhibited the growth of SW‐480, Molt‐4, LnCap, MDA‐MB‐231, and A‐549 cells (IC50 = 2, 2.5, 7, 8.3, and 10.5 mg gallic acid equiv./L, respectively) as determined by cell counting at 72h, with SW‐480 cells being most sensitive to the treatments. In general, At extracts were less effective than Hd. HPLC‐PDA analysis of extracts revealed that Hd and At mainly contained gallotannins, though Hd contained higher concentration of lower molecular weight phenolics. The growth inhibition of Hd polyphenolics (15mg/L) in MDA‐MB‐231 was associated with increased expression of pro‐apoptotic caspase‐8 and Bax by 1.2 and 1.5 fold, respectively. Furthermore, Hd (up to 15mg/L) induced cell cycle arrest in the S and G2/M phase. Overall, mango phenolics may possess chemopreventive activities by targeting pro‐apoptotic genes and inducing cell cycle arrest.Grant Funding SourceNational Mango Board
Anti‐Inflammatory Effects of Grape Powder Extract (GPE) in Human Macrophages
Authors: Overman Angel , Bumrungpert Akkarach , Kennedy Arion , Martinez Kristina , West Tiffany , Hopkins Robin , Chuang Chia‐Chi , McIntosh Michael 
Published: June 2021

Obesity‐associated inflammation is characterized by an increased abundance of macrophages in white adipose tissue (WAT), along with production of inflammatory cytokines, chemokines, and prostaglandins. Grape powder extract (GPE) is rich in phenolic phytochemicals that possess anti‐inflammatory properties. Thus, we examined the ability of GPE to prevent lipopolysaccharide (LPS)‐mediated activation of mitogen activated protein kinases (MAPK), nuclear factor kappa B (NF‐κB), and activator protein‐1 (AP‐1), and induction of inflammatory genes in human macrophages. Cultures of differentiated U937 cells were treated with LPS in the absence or presence of GPE. Pretreatment with GPE attenuated LPS‐induced expression of inflammatory cytokines (e.g., TNFα, IL‐6, IL‐1B,), chemokines (i.e., IL‐8, IP‐10), and a marker of prostaglandin production (COX‐2). GPE also attenuated LPS activation of MAPK, NFκB, and AP‐1 as evidenced by decreased 1) phosphorylation of c‐Jun NH2‐terminal kinase (JNK) and p38, 2) degradation of I?Bα, and 3) phosphorylation of c‐Jun. These data suggest that GPE attenuates LPS‐mediated inflammatory gene expression in human macrophages by decreasing the activation of MAPK, NFκB, and AP‐1. (Supported by the W.B. Kellogg Institute for Food and Nutrition Research)Grant Funding SourceW.B Kellogg Institute for Food and Nutrition Research