bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical Anatomy of the occipital condyle and its relation to hypoglossal canal
Authors: Chentanez Vilai , Thintharua Pakpoom 
Published: May 2022

Occipital condyles (OC) are two bony structures located laterally to the foramen magnum (FM) on the inferior surface of the occipital bone. It is commonly described as an ovoid structure. Craniovertebral junction (CVJ) is an area that connects the cranium to the upper cervical spine. It is bounded laterally by the jugular foramen (JF), hypoglossal canal (HC), and OC. Lesions at CVJ are difficult to manage because of their location and complex anatomic relations. Stability of CVJ after surgery in depends mainly on the resection of OC. HC has been used as a landmark for the extent of OC resection. It was claimed to locate in the middle part of OC. OC resection should not extend beyond HC to prevent CVJ instability. However, previous study showed that the HC was not always located at the middle part of OC. This study aimed to focus on the measurement of OC and its relation to HC in dry skull collected from Thailand for improving the successful surgical outcome.One hundred dry skulls of equal number of both sex were examined for the shape and dimension of each OC. The location of intra and extra cranial orifice of HC (iHc and eHC) related to OC length and the distance to the posterior edge of OC (OCPE‐iHC, OCPE‐eHC) were determined. The results showed that the most prevalence of OC shape was oval‐like (33%) and the least was ring like (1%). Symmetrical OC shape was found in 46% of cases. The mean OC length was 22.13+2.51mm in male and 20.50+ 2.08 mm in female with a significant difference between sex (p=000). The OC width and height were 10.41+1.48 and 7.45+ 1.14 mm in male, 10.62+ 1.34 and 7.34+ 1.13 mm in female. No statistical significant difference of OC width and OC height between sex was found. The dimension of OC did not show any significant difference between sides. The location of iHC was mostly related to middle 1/3 of OC in 54% on the left side and located at the junction between anterior and middle 1/3 of OC in 36% on the right side. In contrast, eHC was located at anterior 1/3 of OC in 81% and 67% on the left and right side, respectively. None was related to posterior 1/3 of OC. Symmetrical location of iHC and eHC was found in 36% and 64% of cases, respectively. The distance OCPE‐iHC, OCPE‐eHC was 9.16+ 1.56, 14.1.0 + 1.98 mm in male and 8.83+ 1.62, 13.30+ 2.4 mm in female. Statistical significant difference between sex was found in OCPE‐eHC (p=0.011). In conclusion, the OC length is longer in male, the eHC located more anteriorly than iHC, therefore resection of the OC should not beyond posterior 1/3 of the OC length or about 7 mm from the posterior edge of OC. These morphometric data might be a benefit for surgical planning on resection of the occipital condyle to avoid injury to neurovascular structure and reserve the stability of craniovertebral junction.
Autophagic State Confers Facultative Stem Cell Capacity in The Intestinal Epithelium
Authors: Parham Louis R. , Johnson Nicolette , Na Jeeyoon , Klochkova Alena , Williams Patrick , Li Ning , Whelan Kelly A. , Lengner Christopher J. , Hamilton Kathryn E. 
Published: May 2022

BackgroundThe intestinal epithelium is a highly proliferative tissue that undergoes complete turnover in 3 to 5 days. The presence of intestinal stem cells expressing the canonical Wnt target gene Lgr5, known as active intestinal stem cells (a‐ISCs), are responsible for generating daughter cells that differentiate into specialized epithelial cells to carryout various functions in the intestine. The proliferative nature of the intestinal epithelium renders it susceptible to DNA damage‐inducing injury, such as high‐dose irradiation and chemotherapy. Although a‐ISCs and early daughter cells are killed by these insults, a radio‐resistant population of facultative intestinal stem cells (f‐ISCs) can regenerate lost a‐ISCs to restore homeostasis following injury. The functional characteristics of f‐ISCs are becoming increasingly understood, however, whether any epithelial cell can act as an f‐ISC is less clear. One reason for this ambiguity is a heavy reliance on Cre‐driven reporter mouse models with low recombination efficiency. Our objective was to find a functional marker to identify f‐ISCs based on cellular state rather than gene expression. The autophagy pathway has been shown to protect against DNA damage and irradiation‐induced apoptosis in the intestinal epithelium. Furthermore, recent studies demonstrate a requirement for the autophagy pathway during cellular de‐differentiation in both gastric chief and pancreatic acinar cells following metaplasia‐inducing injury. Given that autophagy plays roles in both radio‐resistance and cellular plasticity, two integral features of f‐ISCs, we hypothesized that autophagic activity could serve to identify cells with f‐ISC capacity.Methods and ResultsUsing the autophagic vesicle tracer dye CytoID combined with fluorescence‐activated cell sorting, we demonstrate that intestinal epithelial cells with high levels of CytoID exhibit increased organoid‐formation efficiency (OFE) compared to CytoID ‘low’ cells. Single cell sequencing reveals that the CytoID high population is largely composed of secretory cells including Paneth, Goblet, Tuft, and Enteroendocrine cells, whereas the CytoID low population consisted mainly of a‐ISCs and absorptive Enterocytes. Using reporter mice and antibodies against cell surface receptors, we observe that CytoID can identify cells with high OFE within Enteroendocrine, Paneth, and Goblet cell lineages. Finally, we demonstrate that autophagy is required for the enhanced organoid‐formation observed in CytoID high cells by plating these cells in the presence of the lysosomal inhibitor Bafilomycin A1.ConclusionsOur new data support the notion that epithelial cells in a high autophagic state are biased to secretory lineages and that autophagy status functions as a lineage agnostic marker of f‐ISCs. Furthermore, our data suggests that autophagy is required for organoid formation in these lineages.
Expression Status of Proton Sensing Receptor GPR68 in Various Breast Cancer Molecular Subtypes
Authors: Elemam Noha M. , Youness Rana , Talaat Iman M. , Maghazachi Azzam A. 
Published: May 2022

Background and aimBreast cancer has become the most diagnosed cancer and the leading cause of global cancer incidence in 2020. It is quite known that highly malignant and invasive cancers have disrupted metabolism that leads to the creation of an acidic milieu of the tumor microenvironment (TME). Among the acid sensing G protein‐coupled receptors is GPR68/OGR1. In this study, we aimed to investigate the expression of GPR68 in breast cancer patients and cell lines in order to understand its role in the breast cancer TME.Patients, Materials and MethodsIn silico tools such as TNMplot and UALCAN were used to assess the expression of GPR68 in breast cancer patients. The expression pattern was validated in fresh and formalin‐fixed paraffin‐embedded tissues obtained from breast cancer patients using qPCR and immunohistochemistry (IHC), respectively. Also, in silico tool EMBEL‐EBI was used to assess GPR68 expression in different breast cancer cell lines. Validation of GPR68 expression was done on the mRNA and protein levels using qPCR and immunofluorescence techniques in four different breast cancer cell lines (MCF‐7, MDA‐MB‐231, BT‐549 and SkBr3).ResultsGPR68 expression was found to be significantly increased in breast cancer patients using the in silico tools and upon validation using qPCR and IHC (figure 1). Additionally, upon classification according to molecular subtypes, the luminal subtype showed highest GPR68 expression followed by triple negative and HER2 enriched classes. Also, in silicoanalysis revealed that the triple negative breast cancer cell line MDA‐MB‐231 showed the highest expression of GPR68, followed by the luminal A, MCF‐7 and Her2+ SkBr3, and lastly BT‐549. Quantitative PCR and immunofluorescence were used to validate this pattern of expression (figure 2), where all four cell lines showed cytoplasmic and membranous expression indicating possible internalization of GPR68 receptor that might be due to its excessive activation.ConclusionGPR68 plays a critical role in the TME of breast cancer and its different molecular subtypes. Such a marker could be a potential diagnostic marker and therapeutic target in breast cancer.
An Introduction to Anatomic Knowledge in Pre‐Hispanic Mesoamerica
Authors: Kruskie Megan 
Published: May 2022

Background and ObjectiveThe study of the history of anatomy has primarily focused on contributions from Asia and the Mediterranean, while other civilizations are only briefly mentioned. The purpose of this study was to explore the anatomic knowledge of three Mesoamerican civilizations ‐ the Olmecs, Maya, and Aztecs ‐ based on available literature, as well as identify barriers to research on this subject.ResultsIn order to understand the anatomic knowledge of these civilizations, medical researchers have turned to other fields such as archaeology and linguistics. The Olmec heart effigy portrayed a four chambered heart and the great vessels, making it the earliest accurate depiction of the organ. Other Olmec sculptures record observations about human gestation, recognizable stages of fetal development, and congenital abnormalities. Analysis of Mayan dictionaries and other works show that their understanding of anatomy, physiology, and pathology compared to that of pre‐Vesalian Europe. The Aztecs demonstrated their knowledge of anatomy and physiology that was gained through the practice of sacrificial rituals in large ceramic figures and collections of medical texts. Identified barriers to this research include destruction of primary sources by the Spanish during the conquest, substantial linguistic and archaeologic differences across regions, as well as a general lack of investigation.ConclusionWith the reinterpretation of sculpted figures and by taking a second look at their written works, researchers have begun to reveal that the Olmec, Maya, and Aztec peoples had a much better understanding of anatomy than they have previously been credited. Their knowledge of anatomy and medicine in general should be recognized and discussed in the same regard as that of the Mediterranean and Asia.
Repair of the Murine Tympanic Membrane Displays Hallmarks of Regeneration
Authors: Scaria Sonia , Frumm Stacey , Sheth Amar H. , Tward Aaron 
Published: May 2022

BackgroundThe tympanic membrane (TM) has a remarkable ability to repair itself, with perforations typically closing in days to weeks in all mammalian species studied. The cellular and molecular mechanisms underlying TM repair remain largely unknown, however. This study looked to thoroughly characterize the repair process of the injured TM and uncover mechanisms of repair to inform future treatments for TM disorders. We hypothesized that the TM does not undergo canonical “wound healing” but regenerates in response to injury.MethodsCells from TMs injured on adult mice 14, 7, 3, and 1 day prior to sacrifice were submitted for single‐cell RNA sequencing using the 10x Genomics scRNA‐seq platform. Using Seurat clustering and the CellFindR algorithm, unbiased cell clusters were generated with matrices of differentially expressed genes for each cluster. Protein detection via immunofluorescence (IF) and RNA detection via RNAscope were used to biologically validate and define the anatomic locations of distinct cellular populations. The K5Cre‐ERT2 promoter was utilized in mouse models to genetically manipulate and fluorescently label keratinocyte (KC) populations. The mTmG and Confetti reporters were utilized as fluorescent labels.ResultsRNA expression data from all timepoints of perforation were merged and analyzed, revealing 8 distinct major populations of cells and revealing time‐dependent transcriptional shifts in each layer of the TM. From both cross‐sectional and whole‐mount views, the TM shows a rapid, proliferative response to injury by 18 hours post‐injury, predominantly in the KCs. 3 days after perforation, there are large transcriptional shifts in the immune, mesenchymal, and mucosal populations. The multi‐layered tissue shows a large volumetric increase by day 7 but quickly remodels and restores the original volume of the TM by day 14. At slightly longer timepoints, the radial and circular collagen patterning of the TM is also restored, creating a scar‐free structure. We identified a regeneration‐induced “wounded epithelial” population, characterized by a combination of distinct marker genes. A K5Cre‐ERT2;Confetti mouse model shows that the population migrates from known stem cell regions of the organ to the site of injury. Based on expression values and immunostaining, EGFR signaling is upregulated during regeneration, corresponding with increased expression of EGFR ligands and processing co‐factors. When EGFR is deleted in vivo, using a K5‐CreERT2;Egfrfl/fl; R26mTmG/mTmG mouse model, TMs no longer display proliferation post‐injury and cannot repair perforations.ConclusionsTM perforation healing displays a complex and coordinated series of transcriptional, morphological, and patterning events, ultimately culminating in the restoration of normal tissue architecture to the TM. These characteristics are more typical of epimorphic regeneration, rather than more typical scar induced mammalian wound healing.
The Effect of Mutations on Protein‐Protein and Protein‐Ligand Interactions for a 17β‐Hydroxysteroid Dehydrogenase
Authors: Roman David , Boldyrev Mary K. , Yang Song‐Yu , Philipp Manfred 
Published: May 2022

17beta‐hydroxysteroid dehydrogenase type 10, also known as 3‐hydroxyacyl CoA dehydrogenase type 2, is variously abbreviated as HSD10, ABAD, ERAB, SDR5C1 or HADH2. The gene for this homotetrameric mitochondrial enzyme, designated as HSD17B10, is found on the X chromosome. Mutations in this protein are associated with neurodegenerative disorders.In addition to its enzymatic activities, HSD10 is a structural component of human ribonuclease P (7ONU.pdb) and is bound to beta‐amyloid during Alzheimer's disease (1SO8.pdb).This study examines single nucleotide polymorphisms found in HSD17B10 for their possible effects on protein structure, protein‐protein interactions, and protein‐ligand interactions, concentrating on the NAD+ binding site. This study compares the mutations that result from these polymorphisms to the sequence differences between rat and human HSD10.References: Kissinger et al, JMB, 342, 943 (2004); Powell et al. JMB 303, 311 (2000); Yang et al. J. Steroid Biochem. Mol. Biol. 143, 460 (2013)
Junction adhesion molecule‐A is involved in asthma through JNK and ERK pathway
Authors: Jang Ansoo , An Min‐Hyeok 
Published: May 2022

BackgroundJunctional adhesion molecule (JAM)‐A is an immunoglobulin‐like molecule that colocalizes with tight junctions (TJs) in endothelium and epithelium and is also found on blood leukocytes and platelets.ObjectiveWe aimed to elucidate the role of JAM‐A on airway hyperresponsiveness and inflammation in asthma using a murine asthma model, and to check blood level of JAM‐A in asthmatic patients.Methods;Using mice sensitized and challenged with OVA, as well as mice sensitized and challenged with saline, we investigated whether Jam‐a be involved in the pathogenesis of bronchial asthma. The level of JAM‐A was checked in the plasma of asthmatic patients and control subjects. The relation of JAM‐A with clinical variables in patients with asthma was searched.ResultsJAM‐A level had higher concentrations in plasma from patients with asthma (n = 19) than that of healthy controls (n = 12). JAM‐A level was correlated with FVC%, FEV1%, FEV1/FVC, total IgE, and blood lymphocyte proportion in patients with asthma. Jam‐a protein expression in lung tissue was significantly increased in OVA/OVA mice compared with control mice. Phospho‐JNK and phosphor‐ERK protein expression in lung tissue was significantly increased in OVA/OVA mice compared with control mice. A western blotting was used NHBE cells treated with HDM extracts for 4, 8 and 24 h. NHBE cells showed that HDM extracts resulted in increased JAM‐A, phospho‐JNK, phospho‐ERK expression.Conclusion;These data suggest that JAM‐A be elevated in plasma of patients with asthma, which raise the possibility that JAM‐A be involved in asthma through JNK and ERK pathway.
The Minichromosome Maintainance Complex is Up‐regulated in the Placentas of Low‐Insulin Sensitive Mothers in the First Trimester of Pregnancy
Authors: Bandres‐Meriz Julia , Hurtado Irene , Majali‐Martinez Alejandro , Hoch Denise , Honeder Sophie , Birner‐Grünberger Ruth , Dalgaard Louise T. , Desoye Gernot 
Published: May 2022

IntroductionObesity in women at reproductive age is increasing worldwide and is a risk factor for pregnancy complications. In the first trimester of pregnancy the human placenta is rapidly growing making it sensitive to environmental influences. Therefore, we hypothesized that the altered intrauterine milieu associated with maternal obesity modifies placental proteome and function.MethodsMaternal BMI was calculated and leptin, glucose, C‐peptide and insulin sensitivity (ISHOMA) quantified in maternal serum. To identify obesity‐associated changes in the placental proteome we run untargeted proteomics (LC‐MS/MS) in placentas from lean (n=10) and obese (n=10) women (gestational age 5+0‐ 6+6 weeks). The results were validated using westernblotting and immunohistochemistry. The first trimester trophoblast cell line ACH‐3P was used to perform functional assays in vitro.The cells were challenged with insulin (10nM) or palmitoleoyl ethanolamide (100nM), a metabolite found in higher concentrations in women with low insulin sensitivity (untargeted metabolomics) for 24h at physiological oxygen tension (6.5% O2) in a hypoxia bench. Changes in the concentration of the top identified proteins under exposure to the different stimuli was quantified by qPCR and westernblotting.ResultsPlacental proteome differed between lean and obese women with a stronger separation between those with low vs high insulin sensitivity (Principal Component Analysis). Proteins (n=89) enriched (p<0.05, FDR<0.05) in the low insulin sensitive mothers were selected for pathway analysis (KEEG). The top enriched pathways were related to DNA replication and cell cycle (FDR<0.001). Six members of the Minichromosome Maintenance Complex (MCM), involved in DNA damage response and cell cycle arrest, were associated with low maternal insulin sensitivity. There was a significant correlation (R2=0.45 p<0.001) between MCM6 and γH2AX (DNA damage marker) concentration in total tissue. Furthermore, MCM6 co‐localized with γH2AX in the nuclei of cytotrophoblast cells, suggesting increased DNA‐damage in this specific cell type, which was indeed found by semiquantitative γH2AX immmunohistochemistry. Challenging ACH‐3P cells with palmitoleoyl ethanolamide resulted in increased (p<0.05; n=4) MCM6 gene expression after 24h treatment.ConclusionLow insulin sensitivity of pregnant women in in the early first trimester of pregnancy associated with obesity induced changes in the placental proteome related to DNA replication and cell cycle. This may reflect trophoblast response to increased DNA damage in these placentas.
EU‐OPENSCREEN: Discovery and development of novel chemical probes through an international, collaborative model
Authors: Stechmann Bahne 
Published: May 2022

The majority of molecular biologists does not have ready access to suitable drug screening platforms and compound collections, which are generally expensive to purchase, operate and maintain. This represents a major limitation in the field to advance innovative drug discovery projects and chemical probe discovery projects in academia.With the aim to address this need, researchers from >20 institutions have joined forces to launch ‘EU‐OPENSCREEN’ (www.eu‐openscreen.eu), which offers international scientists access to a wide range of state‐of‐the‐art technology platforms, resources and expertise. This publicly funded initiative integrates high‐throughput screening (HTS) platforms and medicinal chemistry groups throughout Europe on a not‐for‐profit basis.The aim of EU‐OPENSCREEN is to collaboratively develop novel chemical probes together with external biologists and to support researchers seeking a better understanding on cellular phenomena by using chemical probes.Molecular biologists and biochemists who have a robust and HTS amenable assay, and are interested in developing novel potent chemical probes for their target of interest, can access EU‐OPENSCREEN's screening platforms on a collaborative basis and screen comprehensive, rationally designed screening collections with >100,000 compounds. After the primary screening, EU‐OPENSCREEN's medicinal chemists optimise the identified ‘hit’ compounds during the hit‐to‐probe program.I will explain how international biologists can access and collaborate with EU‐OPENSCREEN to advance their research projects, and highlight some recent collaborative research projects.
The Pronator Quadratus Muscle – its Morphology and Functions
Authors: van Schaardenburgh Michel , Poliacu‐Prose Lucian 
Published: May 2022

Knowledge of the architecture and nerve supply of the human pronator quadratus muscle (MPQ) appears to be rather scarce and is insufficient for a surgical approach of the muscle. In older French and more recent clinical studies it is stated that the MPQ consists of two or even three parts, each of them with an individual nerve supply and function. Former studies have described a superficial part that is active during pronation, and a deeper part which acts during supination. Furthermore, other authors described that the MPQ regulates the tension of the capsular complex at the distal radio‐ulnar joint.We studied the existence of subdivisions of the MPQ and their pattern of nerve supply from the anterior interosseous nerve in 15 cadaver forearms (8 M, 7 F, mean age 80 years). The dissection was carried out using a surgical microscope. In all 15 forearms the MPQ consisted of three parts: a superficial (pars superficialis; PQs), a deep proximal (pars profunda proximalis; PQpp) and a deep distal part (pars profunda distalis; PQpd).Three primary nerve branches were identified (ramus proximalis, ramus intermedius and ramus distalis) as they originated from the anterior interosseous nerve and at entry of the individual parts of the MPQ.We have not been able to conclude whether the ramus proximalis or the ramus intermedius supplies the superficial (PQs) or the deep proximal (PQpp) part of the MPQ. However, it could be established that the ramus distalis goes to the deep distal (PQpd) part of the MPQ. We could also confirm that only fibers of the deep distal part insert into the distal radio‐ulnar joint.On the basis of the existing division of the MPQ in three different parts, functional considerations can be made with regard to the complex functions of MPQ, i.e. pronation by the superficial part of the MPQ, fine‐tuning of motion of the radius during pronation and supination by the deep proximal part and capsular tension (stabilization) of the distal radio‐ulnar joint by the deep distal part of the MPQ.