Meteorin regulates mesendoderm development by enhancing nodal expression

During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu

Far-Ultraviolet Cooling Features of the Antlia Supernova Remnant

We present far-ultraviolet observations of the Antlia supernova remnant obtained with Far-ultraviolet IMaging Spectrograph (FIMS, also called SPEAR). The strongest lines observed are C IV 1548,1551 and C III 977. The C IV emission of this mixed-morphology supernova remnant shows a clumpy distribution, and the line intensity is nearly constant with radius. The C III 977 line, though too weak to be mapped over the whole remnant, is shown to vary radially. The line intensity peaks at about half the radius, and drops at the edge of the remnant. Both the clumpy distribution of C IV and the rise in the C IV to C III ratio towards the edge suggest that central emission is from evaporating cloudlets rather than thermal conduction in a more uniform, dense medium.Comment: 9 pages, 4 figures, will be published in ApJ December 1, 2007, v670n2 issue. see http://astro.snu.ac.kr/~jhshinn/ms.pd

The Effect of Ca-P Coated Bovine Bone Mineral on Bone Regeneration around Dental Implant in Dogs

There are many obstacles to overcome in implant dentistry. The bony defect around implant can be seen in immediate installation procedures. Following tooth extraction, however, a socket often presents dimensions that may be considerably greater than the dimensions of a conventional implant

FAK Promotes Early Osteoprogenitor Cell Proliferation by Enhancing mTORC1 Signaling

Focal adhesion kinase (FAK) has important functions in bone homeostasis but its role in early osteoprogenitor cells is unknown. We show herein that mice lacking FAK in Dermo1- expressing cells exhibited low bone mass and decreased osteoblast number. Mechanistically, FAK- deficient early osteoprogenitor cells had decreased proliferation and significantly reduced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, a central regulator of cell growth and proliferation. Furthermore, our data showed that the pharmacological inhibition of FAK kinase- dependent function alone was sufficient to decrease the proliferation and compromise the mineralization of early osteoprogenitor cells. In contrast to the Fak deletion in early osteoprogenitor cells, FAK loss in Col3.6 Cre- targeted osteoblasts did not cause bone loss, and Fak deletion in osteoblasts did not affect proliferation, differentiation, and mTORC1 signaling but increased the level of active proline- rich tyrosine kinase 2 (PYK2), which belongs to the same non- receptor tyrosine kinase family as FAK. Importantly, mTORC1 signaling in bone marrow stromal cells (BMSCs) was reduced if FAK kinase was inhibited at the early osteogenic differentiation stage. In contrast, mTORC1 signaling in BMSCs was not affected if FAK kinase was inhibited at a later osteogenic differentiation stage, in which, however, the concomitant inhibition of both FAK kinase and PYK2 kinase reduced mTORC1 signaling. In summary, our data suggest that FAK promotes early osteoprogenitor cell proliferation by enhancing mTORC1 signaling via its kinase- dependent function and the loss of FAK in osteoblasts can be compensated by the upregulated active PYK2. © 2020 American Society for Bone and Mineral Research.Schematic model of the differential roles of FAK in the cells of osteoblast lineage. The model depicts the mechanisms of FAK action at three distinct stages of osteoblast lineage in which the roles of FAK have been addressed by genetic and pharmacological approaches as well as the respective Cre transgenes used to target Fak, including Dermo1- Cre (this study), Osterix- Cre,(10) Col3.6- Cre (this study), and Col2.3- Cre.(9) Red - indicates that the loss of FAK in osteoblasts can be compensated by the upregulated active PYK2.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162813/3/jbmr4029-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162813/2/jbmr4029_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162813/1/jbmr4029.pd

Cell density-dependent differential proliferation of neural stem cells on omnidirectional nanopore-arrayed surface

112Ysciescopu

Practical role of preoperative echocardiography in low-risk non-cardiac surgery

BackgroundDue to increased needs to reduce non-fatal as well as fatal cardiac events, preoperative echocardiography remains part of routine clinical practice in many hospitals. Data on the role of preoperative echocardiography in low-risk non-cardiac surgery (NCS) other than ambulatory surgeries do not exist. We aimed to investigate the role of preoperative echocardiography in predicting postoperative adverse cardiovascular events (CVEs) in asymptomatic patients undergoing low-risk NCS.MethodsThe study population was derived from a retrospective cohort of 1,264 patients who underwent elective low-risk surgery at three tertiary hospitals from June 1, 2021, to June 30, 2021. Breast, distal bone, thyroid, and transurethral surgeries were included. Preoperative examination data including electrocardiography, chest radiography, and echocardiography were collected. The primary outcome was a composite of postoperative adverse CVEs including all-cause death, myocardial infarction, cerebrovascular events, newly diagnosed or acutely decompensated heart failure (HF), lethal arrhythmia such as sustained ventricular tachycardia/fibrillation, and new-onset atrial fibrillation within 30 days after the index surgery.ResultsPreoperative echocardiography was performed in 503 patients (39.8%), most frequently in patients with breast surgery (73.5%), followed by transurethral (37.7%), distal bone (21.6%), and thyroid surgeries (11.9%). Abnormal findings were observed in 5.0% of patients with preoperative echocardiography. Postoperative adverse CVEs occurred in 10 (0.79%) patients. Although a history of previous HF was an independent predictor of postoperative CVE occurrence (adjusted odds ratio, aOR: 17.98; 95% confidence interval, CI: 1.21–266.71, P = 0.036), preoperative echocardiography did not significantly predict CVE in multivariate analysis (P = 0.097). However, in patients who underwent preoperative echocardiography, the presence of abnormal echocardiographic findings was independently associated with development of CVE after NCS (aOR: 23.93; 95% CI: 1.2.28–250.76, P = 0.008). In particular, the presence of wall motion abnormality was a strong predictor of postoperative adverse CVE.ConclusionIn real-world clinical practice, preoperative echocardiography was performed in substantial number of patients with potential cardiac risk even in low-risk NCS, and abnormal findings were independently associated with postoperative CVE. Future studies should identify patients undergoing low-risk NCS for whom preoperative echocardiography would be helpful to predict adverse CVE

The effect of alpha lipoic acid in a porcine in-stent restenosis model

SummaryBackgroundThe aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model.MethodsIn protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting.ResultsProtocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2. On histopathologic analysis, the neointimal area (4.0±1.0mm2 vs. 1.5±0.7mm2, p<0.001) and histopathologic area of stenosis (66.7±10.7% vs. 24.2±9.7%, p<0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9±0.8mm2 vs. 1.0±0.4mm2, p<0.001), and the histopathologic area of stenosis (67.1±8.8% vs. 17.4±10.0%, p<0.001) were reduced in the α-LA coated stent group compared to the control stent group.Conclusionsα-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC

Comparison of lateral tunnel and extracardiac conduit Fontan procedure

The purpose of this study was to compare the outcomes of lateral tunnel (LT) and extracardiac conduit (ECC) Fontan procedures at a single institution. From April 1995 to December 2006, 165 Fontan procedures were performed (67 LT, 98 ECC). Pre-, intra- and postoperative variable values were compared between two different techniques. Operative mortality was 5 (3 LT, 2 ECC). Immediate postoperative transpulmonary gradient (LT 8.5+/-ECC 2.5 vs. 6.6+/-2.4 mmHg) and central venous pressure (LT 18.3+/-3.8 vs. ECC 15.6+/-2.4 mmHg) showed significant difference (P<0.001). The LT patients had a higher incidence of sinus node dysfunction in the postoperative period (22.4% vs. ECC 11.2%; P=0.05). Mean follow-up was 74.1+/-31.5 months in LT, and 31.7+/-28.1 months in ECC patients. There was one late death. Actuarial survival at 10 years is 92% for LT, and 89% for ECC patients (P=0.796). The LT and ECC, both, showed comparable early and mid-term outcomes in operative morbidity and mortality, postoperative hemodynamics, survival. Use of ECC for modified Fontan operation reduces the risk of sinus node dysfunction and shows better outcome of immediate postoperative hemodynamics

New prehospital scoring system for traumatic brain injury to predict mortality and severe disability using motor Glasgow Coma Scale, hypotension, and hypoxia: a nationwide observational study

Objective Assessing the severity of injury and predicting outcomes are essential in traumatic brain injury (TBI). However, the respiratory rate and Glasgow Coma Scale (GCS) of the Revised Trauma Score (RTS) are difficult to use in the prehospital setting. This investigation aimed to develop a new prehospital trauma score for TBI (NTS-TBI) to predict mortality and disability. Methods We used a nationwide trauma database on severe trauma cases transported by fire departments across Korea in 2013 and 2015. NTS-TBI model 1 used systolic blood pressure 65 years. We assessed discriminative power via area under the curve (AUC) value for in-hospital mortality and disability defined according to the Glasgow Outcome Scale with scores of 2 or 3. We then compared AUC values of NTS-TBI with those of RTS. Results In total, 3,642 patients were enrolled. AUC values of NTS-TBI models 1 and 2 for mortality were 0.833 (95% confidence interval [CI], 0.815 to 0.852) and 0.852 (95% CI, 0.835 to 0.869), respectively, while AUC values for disability were 0.772 (95% CI, 0.749 to 0.796) and 0.784 (95% CI, 0.761 to 0.807), respectively. AUC values of NTS-TBI model 2 for mortality and disability were higher than those of RTS (0.819 and 0.761, respectively) (P<0.01). Conclusion Our NTS-TBI model using systolic blood pressure, motor component of GCS, oxygen saturation, and age was feasible for prehospital care and showed outstanding discriminative power for mortality