bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ADAM17 on EMMPRIN Expression after Vesicant Injury to the Cornea
Authors: Gordon Marion K , DeSantis‐Rodrigues Andrea , Chang Yokechen , Hahn Rita A , Zhou Peihong , Heindel Ned D , Gerecke Donald R , Svoboda Kathy K. H. 
Published: November 2023

In a cancer cell line expressing EMMPRIN and ADAM17, it has been shown that inhibiting EMMPRIN expression has no effect on ADAM17 levels, but inhibiting ADAM17 expression significantly inhibits EMMPRIN expression (Xu et al. Tumour Biol. 35:7575‐75‐86, 2014). To verify that this sequence of events was not a phenomenon peculiar to cancer cells, but instead represented a cell's normal response to injury, we examined whether ADAM17 was activated quickly in corneas injured by nitrogen mustard (NM), and whether inhibiting ADAM17 activation had any effect on EMMPRIN expression. Rabbit corneal organ cultures were exposed to topical NM for 0 min (i.e., immediately washed off), or 5 min, or 10 min. NM was washed off at the appointed times and the corneal proteins extracted for ADAM17 activity assays using the Innozyme TACE activity assay kit. This revealed that ADAM17 activity was turned on immediately by NM exposure. We then looked at EMMPRIN in exposed corneas, as well as in exposed corneas where ADAM17 activity was inhibited by hydroxamate NDH4417 (N‐octyl‐N‐hydroxy‐2‐[4‐hydroxy‐3‐methoxyphenyl acetamide). Western analyses showed that inhibiting ADAM17 in exposed corneas reduced EMMPRIN levels by 10 fold, as compared to NM‐exposed corneas not treated with the hydroxamate. Furthermore, reducing EMMPRIN resulted in reduced MMP‐9 activity. These data support the idea that, upon injury, ADAM17 activation impacts EMMPRIN expression, and thereby plays a key role in the downstream activation of matrix metalloproteinase, such as MMP9.Support or Funding InformationNIAMD U54AR055073 Counter ACT award and NIEHS P30ES005022 Center for Environmental Exposures and Disease
The Non‐Receptor Tyrosine Kinase, Src, and its Regulator PTP1B are Present at Tubulobulbar Complexes
Authors: Ho Clement Dallas , Lyon Kevin RP , Vogl A Wayne 
Published: November 2023

During spermiation, the intercellular junctions between Sertoli cells and the spermatids must be internalized before the spermatid can be released into the lumen of the seminiferous tubule. Prior to release from the epithelium, the spermatids are engulfed in protrusions of Sertoli cell cytoplasm which are referred to as apical processes. Unique endocytic structures termed, tubulobulbar complexes (TBCs), internalize these intercellular junctions during sperm release. TBCs have three regions: a proximal tubule, a bulbar region and a distal tubule ending in a clathrin‐coated pit. At sites of intercellular junctions between Sertoli and sperm cells, TBCs form by invaginating into the Sertoli cell and dragging the spermatid's membrane along with it through its intercellular attachments. This results in the entire structure consisting of a double membrane. The tubular regions are surrounded by a dendritic actin network, which is absent at the bulbar region. The bulbar region is a swelling in the distal third part of the TBC and is closely associated with a cisterna of endoplasmic reticulum. Eventually the bulb region of the TBC vesiculates and enters the endosomal pathway of the Sertoli cell. It has been shown by immunoprecipitation that Src, a non‐receptor tyrosine kinase, associates with components of the intercellular junctions between Sertoli cells and spermatids. One of the substrates that Src is able to phosphorylate is cortactin, a component of the dendritic actin networks at TBCs. We suspect that Src is involved in regulating the actin network at TBCs. In this study, we used immunofluorescence to evaluate whether or not Src and its phosphatase regulator, protein tyrosine phosphatase 1b (PTP1B), are associated with TBCs. Rat testes were perfusion‐fixed and cryosectioned or fragmented to get epithelial fragments. Sections and fragments were probed with antibodies against Src or PTP1B and an appropriate fluorescent secondary antibody. The Src antibody labels linear tracts in apical processes that could represent the tubular regions of TBCs. In cryosections, the PTP1B antibody has a Sertoli cell‐labeling pattern that extends from the base of the seminiferous epithelium to the apex. In fragments and cryosections, the PTP1B antibody labels regions of the Sertoli cell where TBCs would be expected to form. This evidence suggests that Src and its regulator PTP1B are present at TBCs.Support or Funding InformationSupported by the Natural Sciences and Engineering Research Council of Canada Discovery Grants program.
Sarco/Endoplasmic Reticulum Ca2+‐ATPase 2 (SERCA2) is Present at Tubulobulbar Complexes
Authors: Lyon Kevin RP , Vogl A Wayne 
Published: November 2023

Endocytic structures known as tubulobulbar complexes (TBCs) internalize intact intercellular junction proteins at sites of intercellular attachment between spermatids and Sertoli cells prior to sperm release. TBCs are highly specialized clathrin‐based endocytosis machines. They also resemble podosomes which have an elongated membrane tube and an associated dendritic actin network. However, unlike podosomes that have a membrane core of a single plasma membrane, the core of TBCs consists of two plasma membranes: the membrane of the Sertoli cell which the structure is invaginated into and the membrane of a spermatid. TBCs have a bulb region in the distal third part of the complex which does not have the cuff of actin but is closely associated with a cisterna of endoplasmic reticulum (ER). We hypothesize that the plasma membrane/ER junction is involved in Ca2+ signaling. If this is true then we would expect to find molecular machinery involved in calcium signaling mechanisms in other systems. In this study, we used immunofluorescence to probe for the calcium pump, sarco/endoplasmic reticulum Ca2+ ‐ATPase 2 (SERCA2), which pumps Ca2+ into the ER. Cryosections and epithelial fragments from perfusion‐fixed rat testes were probed with antibodies against SERCA2 and an appropriate fluorescent secondary antibody. The SERCA2 antibody has a labeling pattern that extends from the base of the epithelium to the apex which is consistent with a Sertoli cell pattern. As seen in both epithelial fragments and cryosections, the SERCA2 antibody labels regions where we would expect TBCs to be. Our results show that one possible component of a calcium signaling mechanism is present in regions containing TBCs.Support or Funding InformationSupported by the Natural Sciences and Engineering Research Council of Canada Discovery Grants program.
Development of the Epaxial Muscles in the Human Embryo
Authors: Mekonen Hayelom Kebede , Hikspoors Jill P.J.M , Mommen Greet , Köhler S Eleonore , Lamers Wouter H 
Published: November 2023

BackgroundThe appearance of the true muscles of the back is dominated by three muscle columns, but a division into a lateral sacrospinal compartment with longissimus (medial) and iliocostal (lateral) divisions, and a medial compartment with transversospinal muscles is presently more often used. Although back muscles are defined by their embryological origin and innervation pattern, no detailed study on their development is available.MethodsHuman embryos (5–10 weeks development) were studied, using Amira® and Cinema4D® remodeling software for visualization.ResultsAt Carnegie Stage (CS)15, the epaxial portions of the myotomes became identifiable laterally to the developing vertebrae. At CS16, these portions fused to form a longitudinal muscle column, which became innervated by the dorsal branch of the spinal nerve. At CS17, the longitudinal muscle mass segregated into medial and lateral columns (completed at CS18). At CS18, the medial column segregated again into intermediate and medial columns (completed at CS20). Between CS20 and CS23, the cervical portions of the three columns segregated again form lateral to medial resulting ventrolaterally in rod‐like continuations of the caudal portions of the columns and dorsomedially in spade‐like portions. The lateral and intermediate columns did not separate in the lower lumbar and sacral region. The observed topography identifies the iliocostalis and splenius as belonging to the lateral column, the longissimus to the intermediate column, and the multifidus and (semi‐)spinalis to the medial column. The medial group acquired its transverso‐spinal course during closure of the vertebral arches in the early fetal period.ConclusionEpaxial muscle growth is characterized by cranio‐caudal and latero‐medial gradients in development. Our ontogenetic approach shows that all back muscles can be classified as components of the erector spinae.Support or Funding InformationNFP (Netherlands Fellowship Programmes)
Thoracic Vertebral Morphology and Locomotor Adaptation in Anthropoid Primates
Authors: Sarrazin Blake D , Middleton Emily R , Ward Carol V 
Published: November 2023

Thoracic shape is related to locomotor adaptation in anthropoid primates. Pronograde quadrupeds tend to have narrow, deep rib cages, whereas those of hominoids tend to be broader mediolaterally. Further, hominoids, especially humans, have the thoracic vertebral column invaginated into the rib cage to support orthograde posture. Humans, and to a lesser extent apes, also exhibit declination of the sternal ends of the ribs. Although the ribs may be the best indicator of overall thoracic shape, they are not well preserved as fossils and are not found in articulation with the vertebral column. However, thoracic form and vertebral invagination should be reflected in orientation of the transverse processes of the thoracic vertebrae, as they articulate with the ribs.To test this hypothesis, we examined the fifth and ninth thoracic (T5, T9) vertebrae from 168 anthropoids. Landmark data were collected using a Microscribe G2X digitizer and analyzed using Polyworks software (Innovmetric, Inc.). Using this program, planes were fit to the superior surface of the vertebral body and to the median plane. A vector was fit between costovertebral and costotransverse articular facets, and used to measure the angles of dorsal and inferior inclination of the transverse process orientation. Statistical analysis of the data was performed using the R statistical software package.As predicted, hominoids, in particular humans, have more dorsally inclined transverse processes than monkeys. However, the semisuspensory atelines are similar to hominoids in regards to this feature, suggesting a relationship between suspension and invagination of the thoracic column into the rib cage. Differences are greater in T9 than at T5. Hominoids, including humans, were found to have more horizontally projecting T5 transverse processes than monkeys. At T9, humans are even more horizontal than apes, and all hominoids have more horizontally projecting transverse processes than do monkeys. These patterns reflect variation in rib declination among taxa and show that a relatively more superior position of the costotransverse joints contributes to declination of the sternal end of the ribs. Comparing these relationships using in silico models of thoracic shape will further refine our understanding of the geometry of all of these elements together. Overall, our results support our hypothesis that the thoracic transverse processes are able to reflect ventral invagination of the vertebral column into the rib cage and variation in rib declination, and so are a useful indicator of thoracic form in fossil anthropoids.
Ontogenetic Shape Change in the Human Cranial Base and its Relationship to Positional Behavior
Authors: McGechie Faye R 
Published: November 2023

The cranial base is frequently used to make inferences about upright posture in the hominin fossil record, particularly as it relates to the earliest evidence of bipedalism. There is contention, however, regarding which aspects of cranial base morphology best reflect upright posture. The goal of this study is to evaluate how changes in cranial base morphology may relate to changes in positional behavior throughout human ontogeny. A close relationship between positional behavior and cranial base morphology would support the use of similar morphological features to reconstruct posture in fossil hominins. The study sample included an ontogenetic series of crania (n=33) ranging in age from neonate to adult. Crania were grouped based on ages at which humans undergo changes in positional behavior. Three dimensional landmark data were acquired either from computed tomography scans or digitized from an archaeological collection. Data were analyzed using Morphologika2 and MorphoJ software. Specifically, Principal Components Analysis was used to determine differences in cranial base shape among age groups. Results demonstrate age‐related changes in nuchal plane length, anterior cranial base length, and occipital condyle position congruent with the acquisition of upright posture in human infants. This analysis supports the use of features such as cranial base length and occipital condyle position as a tool to reconstruct posture in fossil hominins and identifies future avenues of study.Support or Funding InformationFunding for analysis provided by Barrett, the Honors College at Arizona State University
Factors affecting craniofacial development in a mouse model of Crouzon Syndrome
Authors: Brakora Katherine , Percival Christopher J , Green Rebecca , Gong Siew‐Ging , Hallgrimsson Benedikt , Marcucio Ralph 
Published: November 2023

Crouzon Syndrome (CS) is characterized by premature fusion of calvarial bones (craniosynostosis) as well facial malformations including midfacial hypoplasia and hypertelorism. The phenotype is variable, even when caused by the same mutation within the same family. The cause(s) of this variability remain unknown. Using a mouse model of CS, caused by a missense mutation in FGF Receptor 2, we investigate the role of age, sex, and parental genotype in the development of the craniofacial phenotype. Specimens were collected at E10.5–13.5, E17.5, P0, and at 12 weeks or more, andgenotyped. Specimens younger than 3 weeks were sexed using PCR for the SRY gene. 2D and 3D geometric morphometrics was used to compare craniofacial size and shape, using surface landmarks for embryos, and bones after birth. Wildtype and heterozygous groups were compared at each age, controlling for all other variables, to create a detailed picture of the ontogenetic progression of the CS phenotype caused by this mutation. Then, specimens were grouped by genotype and tested for differences in size and shape based on sex or parental genotypes. We identify when in development homozygous mutants, heterozygous mutants, and wildtype phenotyeps diverge in size and shape, and to what degree sex and parental genotypes affect the timing, severity, or variability of heterozygous and wildtype phenotypes at each age.Support or Funding InformationSupported by NIH‐NIDCR grants F32DE024939 to KB and 2R01DE018234‐05A1 to RM and BH.
Effects of zoledronate regimen on the induction of BRONJ in rats
Authors: Elsalanty Mohammed , Daoudi Asma , Howie Nicole , Panos Anastasia , Kurago Zoya 
Published: November 2023

BackgroundBisphosphonate‐Related Osteonecrosis of the Jaw (BRONJ) has been reported in patients undergoing long‐term bisphosphonate treatement. So far, no biological mechanism has been shown to explain the condition. This study compared the induction of the clinical features of BRONJ between two zoledronic acid (ZA) regimens. We hypothesized that duration of treatment would be more important than the dose of ZA for the induction of BRONJ.MethodsWe included 80 female Sprague‐Dawley rats in four groups (20 rats‐each): Group 1 received 80μg/kg of intravenous ZA weekly for 13 weeks, group 2 received 150μg/kg ZA daily for 16 consecutive days, while groups 3 and 4 received corresponding injections of saline for the same durations. At the end of the treatment period, the first and second mandibular molars were extracted. Animals were sacrificed at 1, 2, 4, and 8 weeks. The study analyzed the therapeutic effect of treatment on vertebral bone quality, the features of BRONJ, and the toxic effects on the liver and kidneys.ResultsThere was an increase in the cortical thickness and area fraction of the vertebra in the ZA‐treated animals at 1 and 8 weeks post extraction compared to the controls. This “therapeutic” effect was more pronounced in the lower ZA dose. On the other hand, All ZA‐treated animals manifested the clinical, histological, and radiographic features of BRONJ. There was a significant decline in osteoclast activity in the treatment groups at 1‐week. The higher dose had a more persistent decline in osteoclast recruitment at 8 weeks.ConclusionsBoth doses induced BRONJ in all treated animals. The shorter, high‐dose course of ZA had less therapeutic effect and induced features of organ toxicity. The longer, lower dose of ZA provides a superior translational model for BRONJ.Support or Funding InformationThis study was supported by NIA 1P01AG036675, a Georgia Regents University Extramural Success Award (ESA), the Fort Gordon Periodontology Command, the Center for Undergraduate Research and Scholarship and the Honors Program at Georgia Regents University.
Determination of Palatal Bone Density to Aid in Oral Mini‐Implant Surgical Success
Authors: Flores Alicia , Reed James Christopher 
Published: November 2023

Mini‐implants are titanium alloy rods implanted in the bone of the hard palate to help secure dental prostheses like dentures, fixed crowns, and bridge installations. Recent research suggests presurgical determination of bone density quality provides increased mini‐implant surgical success rates. In replication of these methods, we evaluated 19 tomographic scans of crania using Osirix 8.5 imaging software. Bone density was recorded at 90 separate coordinates using Hounsfield units, measured at three millimeter intervals (mediolaterally and anteroposteriorly starting at the incisive foramen.) The data was then analyzed for age differences and average bone density throughout different regions of the hard palate including intra‐ and interobserver analysis. Sex differences were closely investigated in this study because prior research has indicated that women may have a higher palatal bone density than men.Support or Funding InformationStudent Summer Scholars Grant, Office of Undergraduate Research, Grand Valley State University
Extracellular Matrix Protection Factor 1 (ECPF‐1), A Novel Inhibitor of Matrix Metalloprotease 13 (MMP‐13) Is Chondroprotective In A Serum‐Free Culture Model Of Primary Human Articular Chondrocytes
Authors: Buckley Andrea Lynn , George‐Weinstein Mindy , Milton LaBraya , Datillo Victoria , Goswami Soumendro , Lozano‐Torres Xiomara , Behling Kathryn , Cho Ellen , Chmielewski Sarah , Selim Abdulhafez , Miller Lawrence , D'Angelo Marina 
Published: November 2023

The pathogenic process that defines osteoarthritis (OA) is the imbalance between excess degradation of the extracellular matrix in articular cartilage and a decreased ability of chondrocytes to remodel the matrix. There are many factors that contribute to this disease including unchecked actions of matrix metalloproteinase 13 (MMP‐13), an enzyme specific for the breakdown of collagen type II which is the main component of cartilage extracellular matrix. We have developed a three‐dimensional, serum‐free culture system to rear primary, human articular chondrocytes. In this study, we tested the effects of a member of the novel class of MMP inhibitors, Extracellular Matrix Protection Factors, ECPF‐1.Primary human articular chondrocytes were isolated from patients who underwent surgery for total knee arthroplasty (TKA). The medial and lateral aspects of the joint samples were kept separated and labeled as greatest or least pathology. The number of lives cells were determined and plated at 2.5 × 106 cells per 35 mm well. Cells were either treated with 250nM ECPF‐1 at time of culture, day 0, and again on day 2 of culture or left untreated as serum‐free control. Day 2 and day 5 conditioned media and day 5 cell‐associated matrix was isolated, concentrated with centrifugation and immunoassays conducted to measure collagen type I degradation telopeptides. Treatment with 250nM ECPF‐1 resulted in statistically significant reduction in collagen type I degradation products present in the conditioned media and in the cell‐associated matrix of cells isolated from the side of greatest pathology when compared with untreated controls following five days in culture. Cells isolated from the side of least pathology produced significantly lower amounts of collagen degradation products when compared to the side of greatest pathology.This study demonstrates that human articular chondrocytes reared in serum‐free, primary culture are responsive to the novel therapeutic, ECPF‐1. Our culture model is a straightforward and cost effective system in which to test potential OA therapeutics.Support or Funding InformationCenter for Chronic Disorders of Aging Pilot Grant, PCOM Cooper Foundation Grant, Cooper Health System
Laterality of Pancreatic Metastases from Renal Cell Carcinoma: An Anatomical Perspective from the Left Kidney and Tail of the Pancreas
Authors: Raffoul Adam J , Hartley Christopher Kirk , Johnson Marjorie , Gomez Jose A , Pautler Stephen , McAlister Vivian 
Published: November 2023

IntroductionSurgical findings have shown left kidney renal cell carcinoma (RCC) spreads to the pancreas in an isolated fashion. The pancreas is not a common metastatic site for cancers known to spread via the systemic circulation or lymphatics so no anatomical explanation for these findings has been described. Current literature dictates that rapidly growing neoplasms can transgress renal fascial planes. We hypothesize that there is both a lymphatic and vascular track traversing and within Gerota's fascia which provides local communication between the left kidney and tail of the pancreas. The lymphatic and vascular systems in the perirenal and pararenal spaces are undocumented.ObjectivesThe objective of this study is to propose an anatomical explanation for the spread of RCC from the left kidney to the proximal tail of the pancreas and establish its laterality in regards to preferential metastatic spread.MethodsFour fresh‐frozen cadaveric specimens and 20 fixed cadaveric specimens are in the process of retroperitoneal dissection. Left sided perirenal and pararenal lymphatic vessels and lymph nodes will be identified using GEWF (glacial acetic acid, ethanol, distilled water, and formaldehyde) and immunohistochemistry; monoclonal antibody D2–30 (a lymphatic endothelial marker). Vasculature will be identified under a surgical microscope and further characterized using immunohistochemistry; polyclonal antibody CD31(a pan‐endothelial marker). A chart review of patients with RCC metastasis (from the London Health Sciences Centre, London Ontario) is currently being developed into a retrospective case‐control study to determine frequency of RCC metastasis to the pancreas.ResultsDissection of fresh‐frozen cadavers has revealed vascular bundles that emerge from the fibrous kidney capsule to enter the fat‐filled perirenal space. These bundles contain arteries, veins and lymphatics. Microdissection has revealed a high concentration of these vascular networks in the superior pole of the left kidney, converging on the left adrenal gland. These networks are also seen to traverse the perirenal space, contained within Gerota's fascia. Small venules are seen piercing Gerota's fascia and running within this multilaminar connective tissue. We predict that the chart review will show left kidney tumours metastasizing more often to the tail of the pancreas possibly by means of these described networks.ConclusionsUnderstanding the vascular and lymphatic pathways between the left kidney and the tail of the pancreas will help determine dissection planes and the extent of radical resection surgery with a curative intent. The anatomical description of existing pathways between these structures and the perirenal and pararenal spaces may aid in the anatomical understanding of the spread of RCC. It may also have implications where local resection of tumours is considered.