Abstract The Global Initiative for Chronic Lung Disease (GOLD) was formed in the late 1990s to spread awareness of chronic obstructive pulmonary disease (COPD) as a major public health problem and facilitate its prevention and treatment. GOLD has since become internationally recognized for the development of evidence-based strategy documents, most notably the annual GOLD Reports, for COPD diagnosis, management, and prevention. The GOLD Reports incorporate the latest evidence and...
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Related ArticlesLexical Selectivity of 2-Year-Old Children With and Without Repaired Cleft Palate Based on Parent Report. Cleft Palate Craniofac J. 2020 Apr 02;:1055665620915060 Authors: Baylis A, Vallino LD, Powell J, Zajac DJ Abstract OBJECTIVE: To determine vocabulary and lexical selectivity characteristics of children with and without repaired cleft palate at 24 months of age, based on parent report. PARTICIPANTS: Forty-nine children with...
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Related ArticlesAnalysis of the Intrinsic Predictors of Oronasal Fistula in Primary Cleft Palate Repair Using Intravelar Veloplasty. Cleft Palate Craniofac J. 2020 Apr 01;:1055665620915056 Authors: Yi CR, Kang MK, Oh TS Abstract INTRODUCTION: The purpose of the present study was to investigate various factors of cleft palate and to analyze their effect on fistula occurrence following palatal muscle repair using intravelar veloplasty. METHODS:...
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Abstract Newcastle disease (ND) is considered as one of the most devastating infectious diseases targeting domestic birds and has considerable threat to the commercial poultry production. Two surface glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F), act as antigens in the virus structure and also play important roles in infecting host cells. In the current study, the expression of the chimeric HN-F protein in canola seeds and its immunogenicity in chickens were investigated....
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Abstract Deinstitutionalization is often described as an organizational shift of moving care from the psychiatric hospital towards the community. This paper analyses deinstitutionalization as a daily care practice by adopting an empirical ethics approach instead. Deinstitutionalization of mental healthcare is seen as an important way of improving the quality of lives of people suffering from severe mental illness. But how is this done in practice and which different goods are strived...
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Abstract Background Careful post-operative monitoring of free flaps is important in flap survival; immediate action increases flap salvage rate. Although various methods are available, room for improvement remains. Thermal cameras have proven their value in medicine and are nowadays readily available at low costs. The objective of this study was to evaluate the potential of an affordable infrared thermal camera and software in the detection...
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Abstract Background The gluteal region is one of the many alternative donor sites for autologous breast reconstruction. However, the harvest of the gluteal flap is rather difficult, and the major drawback of gluteal flaps has been the need for position changes for flap harvest and inset. A new approach of a gluteal flap is introduced, based on the septocutaneous perforators of the superior gluteal artery: the septocutaneous gluteal artery...
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Abstract Background The idea of this study stemmed to understand if sexuality can be a factor that affects the perception of one’s body and can be a feature that makes the subject more inclined to undergo esthetic surgery. Methods A total of 51 male subjects participated in this study by filling out the Italian version of the DAS59 consisting of 59 items,...
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Abstract Hanging ala is one of the alar-columellar discrepancies encountered in a rhinoplasty procedure among the Asian population. The principle of lifting both the ala effectively while keeping its symmetry remains a challenge. The arrow tip technique is designed to address the bilateral hanging ala which allows greater alar mobility and lifting effect, producing a desirable outcome of the overall nasal feature. This retrospective review is aimed to analyse the effectiveness...
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Publication date: Available online 2 April 2020Source: Biochimica et Biophysica Acta (BBA) - Proteins and ProteomicsAuthor(s): Lena Hölzen, Maria Alejandra Parigiani, Thomas Reinheckel
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Background: Glioblastoma (GBM) is a dismal disease. Recurrence is inevitable despite initial surgery and postoperative temozolomide (TMZ) and radiotherapy. Salvage surgery is the standard treatment in selected patients. Chemotherapy, biological agents, and re-irradiation are other treatment approaches available. Stereotactic radiotherapy (SRT) is nowadays a common treatment as a salvage treatment option. Materials and Methods: We reviewed the files of 132 GBM cases treated between 2010 and 2018....
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Abstract Aims To identify image quality criteria that can be applied to assess breast implant (BI) mammograms according to radiologists and radiographers’ perspectives and to explore the level of agreement about criteria priority. Methods A two-round Delphi method using a questionnaire was applied to identify the level of agreement between experts,...
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Palmitoylethanolamide is an endogenous lipid that exerts complex vascular effects, enhances the effects of endocannabinoids and induces a direct hypotension, but the mechanisms involved have been poorly explored. Hence, this study investigated in Wistar pithed rats the role of CB1, CB2, TRPV1 and GPR55 receptors in the inhibition by palmitoylethanolamide of the vasopressor responses produced by sympathetic stimulation or exogenous noradrenaline. Frequency- and dose-dependent vasopressor responses...
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Microtubules are cytoskeletal structures critical for mitosis, cell motility, and protein and organelle transport and are a validated target for anticancer drugs. However, how tubulins are regulated and recruited to support these distinct cellular processes is incompletely understood. Posttranslational modifications of tubulins are proposed to regulate microtubule function and dynamics. Although many of these modifications have been investigated, only one prior study reports tubulin methylation and...
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Vascular endothelial growth factor (VEGF) contributes to blood-retinal barrier (BRB) dysfunction in several blinding eye diseases, including diabetic retinopathy. Signaling via the secreted protein norrin through the frizzled class receptor 4 (FZD4)/LDL receptor–related protein 5–6 (LRP5–6)/tetraspanin 12 (TSPAN12) receptor complex is required for developmental vascularization and BRB formation. Here, we tested the hypothesis that norrin restores BRB properties after VEGF-induced vascular permeability...
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The PD-1 ligands PD-L1 and PD-L2 are commonly expressed on the surface of cells, where they regulate immune system activation. However, the specific role played by each ligand has been unclear. Using site-directed mutagenesis, surface plasmon resonance, and crystallography, Philips et al. explore the distinct features of PD-L2 and identify a specific evolutionary event linked to its appearance. This work provides a deeper understanding of how the immune system adapted to mammalian placental gestation...
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As a branch of the unfolded protein response, protein kinase R-like endoplasmic reticulum kinase (PERK) represses global translation in response to endoplasmic reticulum (ER) stress. This pathophysiological condition is associated with the tumor microenvironment in cancer. Previous findings in our lab have suggested that PERK selectively represses translation of some mRNAs, but this possibility awaits additional investigation. In this study, we show that a stem-cell marker protein, leucine-rich repeat-containing...
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Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca2+). Current models assume that cytosolic Ca2+ regulates workload and that mitochondrial Ca2+ uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS. This implies that...
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Cell senescence is one of the most important processes determining cell fate and is involved in many pathophysiological conditions, including cancer, neurodegenerative diseases, and other aging-associated diseases. It has recently been discovered that the E3 ubiquitin ligase STIP1 homology and U-box–containing protein 1 (STUB1 or CHIP) is up-regulated during the senescence of human fibroblasts and modulates cell senescence. However, the molecular mechanism underlying STUB1-controlled senescence is...
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Heart muscle contractility and performance are controlled by posttranslational modifications of sarcomeric proteins. Although myosin regulatory light chain (RLC) phosphorylation has been studied extensively in vitro and in vivo, the precise role of cardiac myosin light chain kinase (cMLCK), the primary kinase acting upon RLC, in the regulation of cardiomyocyte contractility remains poorly understood. In this study, using recombinantly expressed and purified proteins, various analytical methods, in...
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Aminoacyl-tRNA synthetases (aaRSs) are ancient enzymes that play a fundamental role in protein synthesis. They catalyze the esterification of specific amino acids to the 3′-end of their cognate tRNAs and therefore play a pivotal role in protein synthesis. Although previous studies suggest that aaRS-dependent errors in protein synthesis can be beneficial to some microbial species, evidence that reduced aaRS fidelity can be adaptive is limited. Using bioinformatics analyses, we identified two distinct...
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The skin-colonizing commensal bacterium Staphylococcus epidermidis is a leading cause of hospital-acquired and device-related infections. Its pathogenicity in humans is largely due to its propensity to form biofilms, surface-adherent bacterial accumulations that are remarkably resistant to chemical and physical stresses. Accumulation-associated protein (Aap) from S. epidermidis has been shown to be necessary and sufficient for mature biofilm formation and catheter infection. Aap contains up to 17...
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Specificity protein 1 (Sp1) is an important transcription factor implicated in numerous cellular processes. However, whether Sp1 is involved in the regulation of RNA polymerase III (Pol III)-directed gene transcription in human cells remains unknown. Here, we first show that filamin A (FLNA) represses Sp1 expression as well as expression of TFIIB-related factor 1 (BRF1) and general transcription factor III C subunit 2 (GTF3C2) in HeLa, 293T, and SaOS2 cell lines stably expressing FLNA-silencing shRNAs....
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Formation of a single new centriole from a pre-existing centriole is strictly controlled to maintain correct centrosome number and spindle polarity in cells. However, the mechanisms that govern this process are incompletely understood. Here, using several human cell lines, immunofluorescence and structured illumination microscopy methods, and ubiquitination assays, we show that the E3 ubiquitin ligase F-box and WD repeat domain–containing 7 (FBXW7), a subunit of the SCF ubiquitin ligase, down-regulates...
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We previously reported that the transcription factor Wilms tumor 1 (WT1) regulates the expression of insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) during decidualization of human endometrial stromal cells (ESCs). However, other roles of WT1 in decidualization remain to be fully clarified. Here, we investigated how WT1 regulates the physiological functions of human ESCs during decidualization. We incubated ESCs isolated from proliferative-phase endometrium with cAMP to...
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Animal cells use pattern-recognition receptors (PRRs) to detect specific pathogens. Pathogen detection mounts an appropriate immune response, including interferon and cytokine induction. The intracellular PRR-signaling pathways that detect DNA viruses have been characterized, particularly in myeloid cells. In these pathways, cGMP-AMP synthase (cGAS) and the pyrin and HIN domain family member (PYHIN) protein interferon-γ–inducible protein 16 (IFI16) detect DNA and signal via stimulator of interferon...
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The voltage-gated potassium channel Kv1.5 plays important roles in atrial repolarization and regulation of vascular tone. In the present study, we investigated the effects of mechanical stretch on Kv1.5 channels. We induced mechanical stretch by centrifuging or culturing Kv1.5-expressing HEK 293 cells and neonatal rat ventricular myocytes in low osmolarity (LO) medium and then recorded Kv1.5 current (IKv1.5) in a normal, isotonic solution. We observed that mechanical stretch increased IKv1.5, and...
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Oxidative stress-induced DNA damage, the senescence-associated secretory phenotype (SASP), and impaired autophagy all are general features of senescent cells. However, the cross-talk among these events and processes is not fully understood. Here, using NIH3T3 cells exposed to hydrogen peroxide stress, we show that stress-induced DNA damage provokes the SASP largely via cytosolic chromatin fragment (CCF) formation, which activates a cascade comprising cGMP-AMP synthase (cGAS), stimulator of interferon...
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Programmed cell death protein 1 (PD-1) is an inhibitory receptor on T lymphocytes that is critical for modulating adaptive immunity. As such, it has been successfully exploited for cancer immunotherapy. Programmed death ligand 1 (PD-L1) and PD-L2 are ligands for PD-1; the former is ubiquitously expressed in inflamed tissues, whereas the latter is restricted to antigen-presenting cells. PD-L2 binds to PD-1 with 3-fold stronger affinity compared with PD-L1. To date, this affinity discrepancy has been...
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Crystallization of recombinant proteins has been fundamental to our understanding of protein function, dysfunction, and molecular recognition. However, this information has often been gleaned under extremely nonphysiological protein, salt, and H+ concentrations. Here, we describe the development of a robust Inka1-Box (iBox)–PAK4cat system that spontaneously crystallizes in several mammalian cell types. The semi-quantitative assay described here allows the measurement of in vivo protein-protein interactions...
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Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel activated by protein kinase A (PKA) phosphorylation on the regulatory (R) domain. Phosphorylation at several R domain residues stimulates ATP-dependent channel openings and closings, termed channel gating. To explore the protein segment responsible for channel potentiation and PKA-dependent activation, deletion mutations were constructed by removing one to three protein segments of the R domain including residues 708–759...
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Family 45 glycoside hydrolases (GH45) are endoglucanases that are integral to cellulolytic secretomes, and their ability to break down cellulose has been successfully exploited in textile and detergent industries. In addition to their industrial relevance, understanding the molecular mechanism of GH45-catalyzed hydrolysis is of fundamental importance because of their structural similarity to cell wall–modifying enzymes such as bacterial lytic transglycosylases (LTs) and expansins present in bacteria,...
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The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing...
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The ileal apical sodium-dependent bile acid transporter (ASBT) is crucial for the enterohepatic circulation of bile acids. ASBT function is rapidly regulated by several posttranslational modifications. One reversible posttranslational modification is S-acylation, involving the covalent attachment of fatty acids to cysteine residues in proteins. However, whether S-acylation affects ASBT function and membrane expression has not been determined. Using the acyl resin-assisted capture method, we found...
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Increasing hepatic mitochondrial activity through pyruvate dehydrogenase and elevating enterohepatic bile acid recirculation are promising new approaches for metabolic disease therapy, but neither approach alone can completely ameliorate disease phenotype in high-fat diet–fed mice. This study showed that diet-induced hepatosteatosis, hyperlipidemia, and insulin resistance can be completely prevented in mice with liver-specific HCLS1-associated protein X-1 (HAX-1) inactivation. Mechanistically, we...
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The small GTPase cell division cycle 42 (CDC42) plays essential roles in neurogenesis and brain development. Previously, using murine embryonic P19 cells as a model system, we showed that CDC42 stimulates mTOR complex 1 (mTORC1) activity and thereby up-regulates transcription factors required for the formation of neural progenitor cells. However, paradoxically, although endogenous CDC42 is required for both the initial transition of undifferentiated P19 cells to neural progenitors and their ultimate...
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The necrosome is a protein complex required for signaling in cells that results in necroptosis, which is also dependent on tumor necrosis factor receptor (TNF-R) signaling. TNFα promotes necroptosis, and its expression is facilitated by mitogen-activated protein (MAP) kinase–activated protein kinase 2 (MK2) but is inhibited by the RNA-binding protein tristetraprolin (TTP, encoded by the Zfp36 gene). We have stimulated murine macrophages from WT, MyD88−/−, Trif−/−, MyD88−/−Trif−/−, MK2−/−, and Zfp36−/−...
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Formins direct the elongation of unbranched actin filaments by binding their barbed ends and processively stepping onto incoming actin monomers to incorporate them into the filament. Binding of profilin to actin monomers creates profilin–actin complexes, which then bind polyproline tracts located in formin homology 1 (FH1) domains. Diffusion of these natively disordered domains enables direct delivery of profilin–actin to the barbed end, speeding the rate of filament elongation. In this study, we...
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R-loop structures are a prevalent class of alternative non-B DNA structures that form during transcription upon invasion of the DNA template by the nascent RNA. R-loops form universally in the genomes of organisms ranging from bacteriophages, bacteria, and yeasts to plants and animals, including mammals. A growing body of work has linked these structures to both physiological and pathological processes, in particular to genome instability. The rising interest in R-loops is placing new emphasis on...
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