bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Sinus Surgery Increase the Risk of Orbital Fractures in Patients?
Authors: Joshi Rootu , Johnson Marjorie , Willmore Katherine , Galil Khadry , Jenkyn Thomas , Sowerby Leigh , Moore Corey 
Published: November 2023

IntroductionThe orbit is bounded by thin bony walls that are prone to fracture in facial trauma. Despite its thin nature, the medial orbital wall, or lamina papyracea, is less likely to fracture than the orbital floor. This may be due to the uncinate process of the ethmoid bone, as well as the ethmoid bulla, acting as buttresses for the medial orbital wall. What is not understood is how functional endoscopic sinus surgery (FESS), and its associated uncinectomy and ethmoidectomy, affect the fragility of the bony orbit. Resection of the uncinate process and ethmoid bulla, as well as skeletonization of the lamina papyracea, may predispose a patient to post‐surgical fractures. We hypothesize that FESS will decrease the force required to induce a fracture in the medial orbital wall.Objectives/MethodsThe objective of this study was to establish the force required to induce orbital fractures in cadaveric specimens, while evaluating the occurrence, severity and pattern of post‐surgery fractures. Using fixed (n=4) cadaveric heads, a pilot study was conducted to test the protocol and narrow the range of force required to produce orbital fractures. Subsequent studies will be performed using fresh‐frozen (n=8) cadaveric heads. FESS has been performed on one side of the head for each fresh‐frozen specimen, while the other side serves as control. Pre‐operative CT scans have been performed on all heads. Heads will be potted in 4″ PVC pipes, with dental cement, for stability during testing. Globes will be reinflated with a viscous sodium hyaluronate injectable for standardization of pressure, confirmed with a tonometer. An impactor mass of 1.356 kg will be dropped from varying heights onto the orbit to induce fractures. The force of impact will be measured, via accelerometer, to compare operated and non‐operated sides. Post‐operative fractures within the orbital wall will be detected via cone‐beam CT.ResultsPilot study results indicate that the force required to fracture the orbital floor is lower than the force required to fracture the medial orbital wall and these forces are in line with published values (orbital floor: ≥ 2.08 J; medial wall: ≥ 4.90 J). The post‐surgical force testing and scanning has not been completed at this time.Discussion/Future DirectionsThis is the first study to look at the effect of sinus surgery on orbital fracture risk in patients. Subsequent studies will analyze whether FESS decreases the force required to induce fractures of the medial orbital wall. As the prevalence of post‐FESS patients increases, it is important to understand how the bony alterations of sinus surgery affect the stability of the orbit in order to counsel patients appropriately and obtain informed consent.
an Animal Series of Embryological Models in Plaster by Meusel in Germany, circa 1900, probably Representing the Amphioxus
Authors: Le Floch‐Prigent Patrice P. 
Published: November 2023

Twenty (20 cm high) models in plaster represented the beginning of the animal embryology. They were mounted on a wooden basis by a metallic wire. All the early models had a polar globule. The first stages of the segmentation were represented with successively : one, two, four, eight, and so on cells, then was a morula and a blastula stage with a cyst and then the gastrulation. At least, three models in a large size represented two hemi‐sections : one (33cm long) was probably an amphioxus larva with three layers dorsally and two ones ventrally ; the other one with ten big somites could be a drosophila sample ; and a frontal cross‐section with the beginning of the organogenesis. A label (L M M) on the basis corresponded to Meusel, a german craftsman which was active during two or three decades after 1900.These models could be the representation of the first embryological stages in the amphioxus or in a sea urchin which were largely studied in these times. Unfortunately the embryology even for its morphological aspects has made so much progress that these models have now only an historical interest and no more a teaching one.Support or Funding InformationBrieux‐Gillot Scientific Library, 48 rue Jacob, Paris 6th. France
Expression of myostatin in postnatal mouse head and leg muscles
Authors: Miwa Yoko , Takada Hiroshi , Sato Iwao , Sunohara Masataka 
Published: November 2023

ObjectiveMyostatin (Mstn) is a member of the transforming growth factor‐β (TGF‐β) family that regulates muscle differentiation and growth. Thyroid hormone receptor alpha (TRα) effects to the producing the myogenic protein in muscle development. We aimed to identify the relationships between Mstn, TRα, and myosin heavy chain (MyHC) isoforms expression during postnatal mouse development.MethodsWe investigated the expression of Mstn, TRα, and MyHCs (embryonic, slow, IIa, IIb, and IIx) using quantitative real‐time RT‐PCR and ELISA (Mstn) in postnatal mouse muscles between day 0 and day 10. We also examined the correlations between Mstn, TR and MyHCs during early development of mouse masseter muscle (MM) and of the rectus femoris muscle (RFM).ResultsDistinct Mstn mRNA expression patterns were observed in the two muscles, despite nearly non‐significant changes in the Mstn protein abundance in MM. The expression pattern of the TRα mRNA in the MM differed from that observed in the RFM. The expression of the MyHC IIa, IIb and IIx mRNAs increased in the MM and decreased in the RFM from day 0 to day 10, while embryonic fiber MyHC mRNA expression was similar in both muscle types. Principal component analysis showed that the existence of correlation between; 1) TRα and MyHC, 2) Mstn and MyHC, and 3) TRα and Mstn. They were different according to two muscles. Cluster analyses identified the distinct clusters: cluster 1, days 0–4 for the MM and day 0 for the RFM; cluster 2, day 6 for the MM and day 2 for the RFM; and cluster 3, days 8–10 for the MM and days 4–10 for the RFM.ConclusionsThese data suggest that TRα potentially influences MyHC expression in both muscle types. In addition, Mstn has a limited effect in the MM related to the expression of individual MyHCs, as opposed to its role in the RFM, at early postnatal developmental stages. TRα could be involved in regulating both the temporal expression of MyHCs and Mstn at early postnatal stages in the mouse head and leg muscles.Support or Funding Informationnone
Human Hepatic Progenitor Cells in Hepatic Fibrosis of Elderly Cadavers: Lobular Distribution of Cytokeratin 7 and 19 Expressing Hepatic Progenitor Cells
Authors: Png Chien Yi M , Mark Ki M 
Published: November 2023

Human hepatic progenitor cells (HPCs) are small oval‐shaped cells with an ovoid nucleus and scant cytoplasm. Cytokeratin (CK) 7 and CK19 are strongly expressed by HPCs and have been widely used as phenotypic markers for HPCs. In normal liver, HPCs reside in a quiescent state in the canals of Hering that are located in the periportal parenchyma. When the liver is damaged, as in alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, and chronic cholestasis, the HPCs become activated. Since elderly cadavers with diverse causes of death demonstrated progressive stages of liver fibrosis (Mak et al., 2012, Anat Rec 295:40–50), we aimed to evaluate whether the cadaveric livers served as a model for fibrosis‐associated HPC activation in the aged liver. To that effect, consecutive paraffin liver sections from embalmed cadavers were immunoperoxidase stained using monoclonal CK7 and CK19 antibodies, in conjunction with EDTA‐based antigen unmasking. Sections were post‐stained with Sirius red stain for assessment of fibrosis. Positive CK7 and CK19 staining of intraportal bile ducts and ductules validated the specificity of the immunoreaction. HPCs were identified by the CK7 or CK19 immunostaining of the cytoplasm. In livers with minimal fibrotic changes, CK7 and CK19 positive HPCs were generally distributed in proximity to the portal tracts, as well as in the lobular parenchyma at variable distance from the portal tracts. These CK7 or CK19 immunoreactive cells appeared either as individual cells, small clusters of cells or strings of cuboidal cells. In septal fibrosis, CK7 positive HPCs, along with occasional CK19 stained HPCs, could be seen in proximity to the developing septa, bridging septa and parenchymal fibrotic foci. In cirrhosis, the matrix of fibrotic bands often revealed CK7 positive HPCs, while the parenchyma of the nodules contained variable numbers of CK7 stained HPCs. Strikingly, CK19 immunoreactive HPCs were either rare or undetectable in cirrhotic livers.ConclusionsThe deep intralobular distribution of HPCs likely resulted from their migration from the periportal area into the lobular parenchyma, possibly relating to hepatic regeneration consequent to liver damage caused by fibrosis. CK7 expressing HPCs were found in all stages of fibrosis, while CK19 HPCs were absent from cirrhosis, suggesting that CK7 serves as a more sensitive phenotypic marker for HPCs than CK19. Hence, embalmed livers from elderly cadavers provide a potentially useful model for assessing HPC activation in association with liver fibrosis progression in the aged liver.
A rare case of bilateral supra‐piriformis pelvic exit of the common fibular nerve and its clinical relevance
Authors: Vasan Cheryl , Goldman Evan , Vasan Nagaswami 
Published: November 2023

Bilateral supra‐piriformis pelvic exit of the common fibular nerve (CFN) was observed during dissection of the pelvis and gluteal region. The donor was a 70‐year old Caucasian female who died of coronary vascular disease. The sciatic nerve (SN) is an integrated lumbosacral plexus of nerves that exits the pelvis through the greater sciatic foramen inferior to the piriformis muscle and later divides into the tibial nerve (TN) and CFN. In the present case, the right and left CPN exited the pelvis superior to the piriformis muscle while the TN exited inferior to the muscle. Further pelvic dissection showed that TN and CFN followed an independent course and did not unite to form the SN prior to pelvic exit. The TN exited inferior to piriformis and descended in the middle of the thigh whereas the CFN pursued a lateral course through the gluteal region, posterior thigh and popliteal fossa. Variations in the pelvic exit of the TN, CFN and the SN have been observed and classified. Knowledge of the potential alterations in the course of the sciatic, TN and/or the CFN are of clinical importance when performing such procedures as hip arthroplasty, piriformis tendon release for treatment of piriformis syndrome or, sciatic anesthesia in the popliteal fossa for foot and ankle surgery. This poster will depict a number of actual images of the variation and its’ classification based on previously established classification systems.Support or Funding InformationThis study was supported by the Department of Biomedical Sciences.
A genome wide screen to identify genes that prevent the accumulation of mutations
Authors: Hombauer Hans Wolfgang , Schmidt Tobias , Cava Gloria Ximena Reyes , Ceylan Umran , Gries Kerstin , Meurer Matthias , Knop Michael 
Published: November 2023

Synthesis of eukaryotic genomes requires the function of DNA replicative polymerases Polα (Pol1), Polɛ (Pol2) and Polδ (Pol3). Biochemical evidence supports the idea that Polα initiates DNA synthesis at replication origins as well as at every Okazaki fragment. This initial DNA synthesis is further extended by the proofreading proficient DNA polymerases Polɛ and Polδ.The DNA lagging strand is synthesized by Polδ in a discontinuous manner, as 200–300 bases‐long Okazaki fragments. On the other hand, the leading strand is synthesized in a continuous manner; however, it is less clear if Polɛ, Polδ or a combination of both, are mainly required during this process.In order to identify unrecognized genes that might affect DNA replication fidelity, we performed a genome‐wide screen in S. cerevisiae searching for synergistic mutator interactions with DNA polymerase mutants. We modified the Synthetic Genetic Array protocol to cross low‐fidelity DNA polymerase mutants pol1‐L868M, pol2‐M644G and pol3‐L612M (or wild‐type) against the non‐essential yeast gene deletion collection. Single and double mutants were tested for an increased mutator phenotype with in vivo mutator assays (lys2‐10A and CAN1 inactivation). Analysis of the single mutants identified ~45 genes, with well‐known functions in different DNA repair pathways, which prevented the accumulation of mutations. Moreover, we identified one additional gene deletion that has not been previously linked to a mutator phenotype. This mutant not only resulted in elevated mutation rates, but also increased gross chromosomal rearrangements.Analysis of the double mutants identified a small number of gene deletions (including exo1Δ) that resulted in a strong synergistic mutator interaction with pol1‐L868M and pol3‐L612M, but not with pol2‐M644G. This unpredicted bias supports the hypothesis that leading and lagging strand are mainly synthesized by Polδ. Furthermore, we have identified a small number of genes whose roles become increasingly important under conditions of impaired DNA replication fidelity.Support or Funding InformationDeutsches Krebsforschungszentrum (DKFZ). Marie Curie CIG grant “iMMR”.
Implications for 4‐Oxo‐2‐nonenal‐Derived Histone Adducts in Mediating Gene Expression
Authors: Camarillo Jeannie Marie , Galligan James J , Marnett Lawrence J 
Published: November 2023

Histone modifications play a critical role in the maintenance of chromatin structure and the regulation of gene expression. For example, Lys acetylation to histone tails results in chromatin remodeling to allow transcriptional activation of targeted genes. Recent work has identified core histones as targets for adduction by the oxidative stress‐derived lipid electrophile, 4‐oxo‐2‐nonenal (4‐ONE). Here, we investigate the potential implications of these modifications on gene expression. Using an alkyne analog of 4‐ONE, a4‐ONE, we employed click chemistry to selectively tag modified proteins from RKO cells treated with electrophile. Our data reveal that a4‐ONE is a long‐lived histone modification, present up to 24 hours after treatment. Using pharmacological inhibitors of histone acetylation and deacetylation, we observe alterations in the acetylation of core histones when cells are co‐treated with a4‐ONE. These data suggest that a4‐ONE modifications occur at physiologically relevant sites that regulate chromatin structure and gene expression. Further, utilizing a combination of chromatin immunoprecipitation and click chemistry, we can selectively pull out DNA associated with adducted histones, further suggesting a putative role for these modifications in the regulation of gene expression. Together, our data suggest that histone adducts may play a role in chromatin structure and the mediation of gene expression.Support or Funding InformationNCI F31 CA192861 (JMC) and NCI R37 CA087819 (LJM)
Reduced Expression of MicroRNA‐200 Family Members Lead to Epithelial‐Mesenchymal Transition of a Chemoresistant Colorectal Cancer Cell Line
Authors: San KayKay , Martino Alice , Ezekiel Uthayashanker 
Published: November 2023

After a patient's tumor is removed, he/she undergoes adjuvant chemotherapy and/or radiotherapy. Both of these treatments lead to formation of resistant cells that become metastatic cancer cells. The cellular program responsible for the change of epithelial tumors (such as breast, colorectal, pancreatic, and ovarian) into metastatic mesenchymal cell types is Epithelial‐Mesenchymal Transition (EMT). EMT is a normal process during embryogenesis, where epithelial cells lose their characteristics and become motile mesenchymal cells. Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. During EMT, the primary tumor cells lose cell‐cell adhesion, normally mediated by E‐cadherin, and attain mesenchymal markers. The cells exhibit increased intercellular separation and elongated shape with pseudopodia. We developed a chemoresistant colorectal cancer cell line (DLD‐1 OxR) by exposing DLD‐1 colorectal cancer cells to increasing concentrations of oxaliplatin (a chemotherapy drug used for colorectal cancer). DLD‐1 OxR cells exhibit increased intercellular separation, increased motility, and elongated spindle shape with pseudopodia. MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression postranscriptionally. MiRNA, with silencing complexes, bind 3′ untranslated regions which lead to degradation of RNA or translation repression. Recent studies show that miRNA‐200 family members regulate the EMT process and metastasis. Decreased expression of miRNA‐200 family members leads to metastatic transformation of cancer cells. One of the miRNA‐200 family members is miRNA‐200c. Our hypothesis is that miRNA‐200c expression is decreased in DLD‐1 OxR cells. Loss of miRNA‐200c leads to expression of several regulatory genes involved in EMT, such as, Suz12 (one of the polycomb repressive complex proteins) and claudin‐1 (an integral membrane protein). We have found that miRNA‐200c expression is lower in DLD‐1 OxR cells compared to the parental DLD‐1 cells. Also, the miRNA‐200c targets are upregulated in DLD‐1 OxR. In conclusion, our study suggests that miRNA‐200c is involved in the EMT process in colorectal cancer cells.Support or Funding InformationKS and AM are supported by the DeNardo Education and Research Foundation.
Untethering glucocorticoid receptor‐mediated transcriptional repression
Authors: Weikum Emily Rye , Hudson William , Ortlund Eric 
Published: November 2023

The glucocorticoid receptor (GR), a ligand regulated transcription factor that controls the expression of thousands of genes driving both up‐ and down‐regulation at equal frequencies. The mechanism of gene activation is quite well understood and involves GR cooperatively dimerizing onto DNA at glucocorticoid response elements (GREs). However, the mechanism of repression is much more debated and is thought to occur though two possible mechanisms, DNA‐dependent and DNA‐independent. The DNA‐dependent mechanism involves direct binding of GR to the newly discovered negative glucocorticoid response elements (nGREs). The DNA‐independent mechanism involves GRs interaction with activator protein‐1 (AP‐1), which is a central transcription factor in immune systems that drives expression of inflammatory response genes. This mechanism, known as “tethering”, is the prevailing model for GR‐mediated repression at inflammatory genes. However, recent discovery of GR‐nGRE interactions lead us to wonder if DNA‐dependent repression was possible at AP‐1 response elements (TREs). We report that GR is able to repress inflammatory genes in the absence of AP‐1, GR binds to TRE sequences in vitro, and crystal structures of GR bound to novel recognition sites located within canonical TRE‐sequences. This data represents a paradigm shift in our understanding of GR‐mediated repression and represents an alternative mechanism to the tethering hypothesis.Support or Funding InformationF31 NRSA (1F31GM11397‐01A1)
Characterization of Mn(II) homeostasis within Bacillus subtilis
Authors: Baertlein Matt , Vos Cullen , Jeffries Will , Isaacson Erin , Gabriel Scott 
Published: November 2023

Metal ion homeostasis is a critical component of all cellular life. Metals act as cofactors for many essential enzymes; yet, in excess, metals can cause oxidative stress and cell death. In order to further understand metal ion homeostasis, investigation of pathways that regulate the corresponding intake and efflux of metal ions is needed. While many of the pathways which control metal ion intake and efflux within B. subtilis have been characterized, Mn(II) efflux still remains unknown. Zone of inhibition (ZOI) data from our lab shows a ydfM knockout decreases the survivability of B. subtilis in the presence of toxic Mn(II) levels, while there was no significant difference in toxic concentrations of Cu(II), Cd(II), and Zn(II). Additionally, Beta‐galactosidase assays have shown that ydfM transcription increases with increasing Mn(II) concentration but not increasing concentrations of Cd(II), Cu(II), Fe(III), Ni(II), or Zn(II). These results have led us to hypothesize that that YdfM acts as an Mn(II) efflux protein within B. subtilis.Concurrently, we also have aimed to identify the transcriptional regulator of YdfM. Interestingly, the gene immediately downstream of YdfM is predicted to be a metal efflux protein regulator. Initial bioinformatics work, shows that YdfL possesses a helix turn helix DNA binding motif as well as several conserved amino acid sequences which suggest it is similar to other metal ion influx and efflux regulators. ZOI data also shows there is a significant increase in survivability in the ydfL knockout when compared to wild type B. subtilis, further suggesting YdfL acts as a regulatory repressor of ydfM. Additional preliminary beta‐galactosidase, growth curve, and gel shift data currently ongoing will also be presented which aims to confirm YdfM's role in the efflux of Mn(II) as well as YdfL's role as a regulator of ydfM transcription.
Structure of the Bacterial Transcription Termination Factor Rho in Complex with the Regulatory Factor NusG
Authors: Lawson Michael , Berger James 
Published: November 2023

All eukaryotic and prokaryotic organisms utilize Spt5‐like proteins to regulate transcription. The bacterial Spt5 homolog NusG binds to RNA polymerase with its N‐terminal domain, and to transcription factors such as Rho with its C‐terminal domain. Rho is a hexameric helicase that utilizes energy from ATP hydrolysis to directionally translocate specific nascent transcripts through its central pore, which generates a force that disrupts transcription by RNA polymerase at distinct sites in bacterial genomes. For reasons that remain unclear, NusG is strictly required for a subset of transcripts at Rho‐dependent termination loci.In order to further elucidate the mechanism by which NusG aides Rho‐dependent transcription termination, we solved a 3.7 Å crystal structure of a complex of Rho, RNA, and the C‐terminal domain of NusG. The structure reveals that NusG binds to Rho in a fashion that orients Rho to translocate directly towards RNA polymerase, and positions the central pore of Rho near the RNA exit channel of the polymerase. We established both pulldown‐ and anisotropy‐based assays to track binding of NusG to Rho in vitro, and used the Rho/NusG complex structure to guide the engineering of point mutants that abrogate binding. We are using these mutants as tools to further probe the role of NusG in Rho‐dependent termination both in vitro and in vivo.Support or Funding InformationThis work was supported through funding from the G. Harold and Leila Y. Mathers Foundation and the NSF Graduate Research Fellowship Program.