By SAURABH JHA, MD Despite an area under the ROC curve of 1, Cassandra’s prophesies were never believed. She neither hedged nor relied on retrospective data – her predictions, such as the Trojan war, were prospectively validated. In medicine, a new type of Cassandra has emerged – one who speaks in probabilistic tongue, forked unevenly between the probability of being right and the possibility of being wrong. One who, by conceding that she may be categorically wrong, is technically...
Mon Oct 07, 2019 18:12
Andrographolide (Andr) is a major component isolated from the plant Andrographis paniculata. Inflammation, apoptosis, and impaired angiogenesis are implicated in the pathogenesis of high glucose (HG)-induced injury of vascular endotheliocytes. Our study is aimed at evaluating the effect of Andr on HG-induced HUVEC injury and the underlying mechanism. HUVECs were exposed to HG levels (33 mM) and treated with Andr (0, 12.5, 25, and 50 μM). Western blot analysis, real-time PCR, immunofluorescence staining,...
Mon Oct 07, 2019 17:05
Background. T-helper type 1 (Th1) cells and Th1-produced cytokines play essential roles in the immune response to foreign pathogens, such as Brucella spp. The aim of this study was to evaluate the dynamic changes of Th1 cells and Th1-produced cytokines in patients with acute brucellosis and their impact on clinical decision-making. Methods. Fifty-one individuals with acute brucellosis and 17 healthy subjects were enrolled in this study. The brucellosis patients were diagnosed based on clinical symptoms,...
Mon Oct 07, 2019 13:05
Abstract Purpose To evaluate the progression of demineralization during orthodontic treatment, the assessment of lesion activity is important in addition to the detection of lesion extent. This study aimed to evaluate the ability of laser fluorescence measurements to differentiate between active and inactive initial lesions in vitro. Methods In all, 63 extracted,...
Mon Oct 07, 2019 03:00
Abstract Purpose Orthodontic treatment is based on the principle of force application to teeth and subsequently to the surrounding tissues and periodontal cells. Sequestosome 1 (SQSTM1) is a well-known marker for autophagy, which is an important cellular mechanism of adaptation to stress. The aim of this study was to analyze whether biomechanical loading conditions regulate SQSTM1 in periodontal cells and tissues, thereby providing further...
Mon Oct 07, 2019 03:00
ABSTRACT Objective Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose‐response relationship between duration of football played and CTE risk and severity. Methods In a convenience sample of 266 deceased American football players from the Veterans Affairs‐Boston University‐Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association...
Mon Oct 07, 2019 17:00
Relationships in which a woman is significantly older than her male partner have always attracted a lot of attention and scrutiny. Case in point: remember what big news it was when Demi Moore and Ashton Kutcher were together? Or the international media obsession that followed French president Emmanuel Macron and his spouse, Brigitte, who happens to be 24 years his senior? This same scrutiny isn’t usually applied to relationships in which men are significantly older than their female partners. For...
Mon Oct 07, 2019 17:00
Key points •The main cause of death from opioid overdose is respiratory depression due to the activation of mu opioid receptors (MORs). •We conditionally deleted MORs from neurons in two key areas of the brainstem respiratory circuitry (the Kölliker‐Fuse nucleus (KF) or pre‐Bötzinger complex (preBötC)) to determine their role in opioid‐induced respiratory disturbances in adult, awake mice. •Deletion of MORs from KF neurons attenuated respiratory rate depression at all doses of morphine. •Deletion...
Mon Oct 07, 2019 15:56
Antioxidants, Vol. 8, Pages 458: Phenolics and Carotenoid Contents in the Leaves of Different Organic and Conventional Raspberry (Rubus idaeus L.) Cultivars and Their In Vitro Activity Antioxidants doi: 10.3390/antiox8100458 Authors: Ponder Hallmann : Raspberry leaves are a source of carotenoids and polyphenols, including ellagic acid and salicylic acid. The results of scientific research suggest that they have potential pro-health properties that contribute to human health. The...
Mon Oct 07, 2019 03:00
Antioxidants, Vol. 8, Pages 457: Nitric Oxide and Hydrogen Sulfide in Higher Plants under Physiological and Stress Conditions Antioxidants doi: 10.3390/antiox8100457 Authors: Corpas n/a
Mon Oct 07, 2019 03:00
Antioxidants, Vol. 8, Pages 456: Benefits of Magnesium Supplementation to Broiler Subjected to Dietary and Heat Stress: Improved Redox Status, Breast Quality and Decreased Myopathy Incidence Antioxidants doi: 10.3390/antiox8100456 Authors: Estevez Petracci Poultry is highly sensitive to oxidative reactions. Oxidative reactions have attracted considerable attention from animal and food scientists because of the adverse effects of these reactions on animal welfare, performance and...
Mon Oct 07, 2019 03:00
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectivesThis study is designed to investigate the effects of obstructive sleep apnea/hypopnea syndrome (OSA) surgery on serum leptin levels and metabolic disturbances, both of which contribute to the risk of cardiovascular diseases.Study DesignCase series with planned data collection.SettingTertiary referral medical center.Subjects and MethodsA retrospective chart review of 101 consecutive patients with OSA who refused or failed conservative...
Tue Oct 01, 2019 11:59
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectiveTo identify clinical variables associated with the decision to surgically discontinue bone-anchored hearing device function.Study DesignRetrospective chart review.SettingTertiary neurotology referral center.Subjects and MethodsThis study examines surgical interventions performed on existing bone-anchored hearing devices at a single institution from 2008 to 2018. Patient characteristics, indications for implantation, and complications...
Tue Oct 01, 2019 11:18
Otolaryngology–Head and Neck Surgery, Ahead of Print. With increasing emphasis on patient safety/quality improvement, health care systems are mirroring industry in the implementation of root cause analysis (RCA) for the identification and mitigation of errors. RCA uses a team approach with emphasis on the system, as opposed to the individual, to accrue empirical data on what happened and why. While many otolaryngologists have a broad understanding of RCA, practical experience is often lacking. Part...
Tue Oct 01, 2019 11:09
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectiveThe objective of this study was to provide a proof of concept and to assess the success and safety of stapes surgery for otosclerosis under local anesthesia in an office-based setting (OBS) as compared with a hospital operating room setting (ORS).Study DesignRetrospective cohort study.SettingWe reviewed all patients who underwent stapes surgery by the same surgeon from October 2014 to January 2017 at our tertiary care center (ORS, n =...
Tue Oct 01, 2019 11:06
Otolaryngology–Head and Neck Surgery, Ahead of Print. Objectives(1) To characterize changes in brainstem neural activity following unilateral deafening in an animal model. (2) To compare brainstem neural activity from unilaterally deafened animals with that of normal-hearing controls.Study DesignProspective controlled animal study.SettingVivarium and animal research facilities.Subjects and MethodsThe effect of single-sided deafness on brainstem activity was studied in Chinchilla lanigera. Animals...
Tue Oct 01, 2019 11:04
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectiveUnilateral vestibular weakness has considerable potential etiologies. One source is a vestibular schwannoma. This article evaluates, in the absence of other symptoms and signs, if unilateral vestibular weakness is an analogue to asymmetric sensorineural hearing loss and serves as an indication for lateral skull base imaging.Study DesignRetrospective chart review.SettingAcademic tertiary center.Subjects and MethodsAll patients undergoing...
Tue Oct 01, 2019 11:03
Accuracy of a Modern Intraoperative Navigation System for Temporal Bone Surgery in a Cadaveric Model
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectivesTo determine the accuracy of a modern navigation system in temporal bone surgery. While routine in other specialties, navigation has had limited use in the temporal bone due to issues of accuracy, perceived impracticality, and value.Study DesignProspective observational study.SettingTemporal bone laboratory.Subjects and MethodsEighteen cadaveric specimens were dissected after rigid fiducials were implanted and computed tomography scans...
Tue Sep 24, 2019 11:56
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectivesTo study optimal head position after intratympanic steroid injections to enhance drug bioavailability.Study DesignApplication of virtual and in vitro models of the intratympanic anatomy.SettingThe surgical 3-dimensional printing laboratory of a tertiary academic medical center.Subjects and MethodsA high-resolution computerized tomographic scan of healthy temporal bone and surrounding soft tissue was segmented and reconstructed to a 3-dimensional...
Tue Sep 24, 2019 11:45
Otolaryngology–Head and Neck Surgery, Ahead of Print. ObjectiveTo compare the evaluation of vocal fold mobility between flexible nasal laryngoscopy (FNL) and a handheld application-based translaryngeal ultrasound (TLUS) platform.Study DesignProspective analysis included patients with unknown vocal fold mobility status who underwent FNL and TLUS.SettingTertiary referral center.Subjects and MethodsTLUS was performed on 23 consecutive children (<18 years old) presenting for laryngoscopy due to unknown...
Tue Sep 24, 2019 11:09
The process of phagophore closure requires the endosomal sorting complex required for transport III (ESCRT-III) subunit CHMP2A and the AAA ATPase VPS4, but their regulatory mechanisms remain unknown. Here, we establish a FACS-based HaloTag-LC3 autophagosome completion assay to screen a genome-wide CRISPR library and identify the ESCRT-I subunit VPS37A as a critical component for phagophore closure. VPS37A localizes on the phagophore through the N-terminal putative ubiquitin E2 variant domain, which...
Mon Oct 07, 2019 16:00
Recent research shows that potentially cancerous, somatic mutations can reside in normal cells. Pineda et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201907178) report on a unique management technique by hair follicle stem cells to evade tumorigenesis.
Mon Oct 07, 2019 16:00
Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum...
Mon Oct 07, 2019 16:00
Macrophages and other cell types can form podosomes, highly dynamic adhesive structures that mediate the interaction of these cells with the surrounding matrix. In this issue, Klapproth et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201903109) find that kindlin-3 regulates podosome stability by recruiting leupaxin, with concomitant effects on PTP-PEST phosphatase activity and paxillin phosphorylation.
Mon Oct 07, 2019 16:00
Focal adhesion (FA) turnover depends on microtubules and actin. Microtubule ends are captured at FAs, where they induce rapid FA disassembly. However, actin’s roles are less clear. Here, we use polarization-resolved microscopy, FRAP, live cell imaging, and a mutant of Adenomatous polyposis coli (APC-m4) defective in actin nucleation to investigate the role of actin assembly in FA turnover. We show that APC-mediated actin assembly is critical for maintaining normal F-actin levels, organization, and...
Mon Oct 07, 2019 16:00
Eph receptors bind ephrins on neighboring cells, oligomerizing into adhesive complexes that recruit signaling molecules. Execution of their signature repulsive program then generates pulling forces, enabling a cell to engulf a piece of another cell. New mechanistic insights by Gong et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201901032) define this process as a form of "cellular cannibalism."
Mon Oct 07, 2019 16:00
Molecular recognition features (MoRFs) provide interaction motifs in intrinsically disordered protein regions to mediate diverse cellular functions. Here we report that a MoRF element, located in the disordered linker domain of the mammalian signal recognition particle (SRP) receptor and conserved among eukaryotes, plays an essential role in sensing the ribosome during cotranslational protein targeting to the endoplasmic reticulum. Loss of the MoRF in the SRP receptor (SR) largely abolishes the ability...
Mon Oct 07, 2019 16:00
Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even with an elaborate network of molecular chaperones and protein folding facilitators, misfolding can occur quite frequently. To maintain protein homeostasis, eukaryotes have evolved a series of protein quality-control checkpoints. When secretory pathway quality-control pathways fail, stress response pathways, such as the unfolded protein response (UPR), are induced. In addition, the ER, which is the initial...
Mon Oct 07, 2019 16:00
Tight junctions (TJs) establish the epithelial barrier and are thought to form a membrane fence to regulate epithelial polarity, although the roles of TJs in epithelial polarity remain controversial. Claudins constitute TJ strands in conjunction with the cytoplasmic scaffolds ZO-1 and ZO-2 and play pivotal roles in epithelial barrier formation. However, how claudins and other TJ membrane proteins cooperate to organize TJs remains unclear. Here, we systematically knocked out TJ components by genome...
Mon Oct 07, 2019 16:00
During mitosis, the formation of microtubule–kinetochore attachments is monitored by the serine/threonine kinase monopolar spindle 1 (MPS1). MPS1 is recruited to unattached kinetochores where it phosphorylates KNL1, BUB1, and MAD1 to initiate the spindle assembly checkpoint. This arrests the cell cycle until all kinetochores have been stably captured by microtubules. MPS1 also contributes to the error correction process rectifying incorrect kinetochore attachments. MPS1 activity at kinetochores requires...
Mon Oct 07, 2019 16:00
Trogocytosis, in which cells nibble away parts of neighboring cells, is an intercellular cannibalism process conserved from protozoa to mammals. Its underlying molecular mechanisms are not well understood and are likely distinct from phagocytosis, a process that clears entire cells. Bi-directional contact repulsion induced by Eph/ephrin signaling involves transfer of membrane patches and full-length Eph/ephrin protein complexes between opposing cells, resembling trogocytosis. Here, we show that the...
Mon Oct 07, 2019 16:00
Clathrin-mediated endocytosis depends on the formation of functional clathrin-coated pits that recruit cargos and mediate the uptake of those cargos into the cell. However, it remains unclear whether the cargos in the growing clathrin-coated pits are actively monitored by the coat assembly machinery. Using a cell-free reconstitution system, we report that clathrin coat formation and cargo sorting can be uncoupled, indicating that a checkpoint is required for functional cargo incorporation. We demonstrate...
Mon Oct 07, 2019 16:00
Tripathi investigates how the tumor suppressor DLC1 is regulated by oncogenic kinases.
Mon Oct 07, 2019 16:00
Mutations associated with tumor development in certain tissues can be nontumorigenic in others, yet the mechanisms underlying these different outcomes remains poorly understood. To address this, we targeted an activating Hras mutation to hair follicle stem cells and discovered that Hras mutant cells outcompete wild-type neighbors yet are integrated into clinically normal skin hair follicles. In contrast, targeting the Hras mutation to the upper noncycling region of the skin epithelium leads to benign...
Mon Oct 07, 2019 16:00
Lipid droplet (LD) catabolism in hepatocytes is mediated by a combination of lipolysis and a selective autophagic mechanism called lipophagy, but the relative contributions of these seemingly distinct pathways remain unclear. We find that inhibition of lipolysis, lipophagy, or both resulted in similar overall LD content but dramatic differences in LD morphology. Inhibition of the lipolysis enzyme adipose triglyceride lipase (ATGL) resulted in large cytoplasmic LDs, whereas lysosomal inhibition caused...
Mon Oct 07, 2019 16:00
The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore–microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imbalanced phosphoregulation leads to error-prone chromosome segregation and aneuploidy, a hallmark of cancer cells. However, little is known about the molecular events that control the balance of phosphorylation...
Mon Oct 07, 2019 16:00
Metastasis is a major cause of cancer-related death. Membrane type 1–matrix metalloproteinase (MT1-MMP) is a critical protease for local invasion and metastasis. MT1-MMP is synthesized in the endoplasmic reticulum (ER) and transported in vesicles to invadopodia, specialized subdomains of the plasma membrane, through secretory and endocytic recycling pathways. The molecular mechanism underlying intracellular transport of MT1-MMP has been extensively studied, but is not fully understood. We show that...
Mon Oct 07, 2019 16:00
Outer kinetochore assembly enables chromosome attachment to microtubules and spindle assembly checkpoint (SAC) signaling in mitosis. Aurora B kinase controls kinetochore assembly by phosphorylating the Mis12 complex (Mis12C) subunit Dsn1. Current models propose Dsn1 phosphorylation relieves autoinhibition, allowing Mis12C binding to inner kinetochore component CENP-C. Using Xenopus laevis egg extracts and biochemical reconstitution, we found that autoinhibition of the Mis12C by Dsn1 impedes its phosphorylation...
Mon Oct 07, 2019 16:00
The spatio-temporal regulation of small Rho GTPases is crucial for the dynamic stability of epithelial tissues. However, how RhoGTPase activity is controlled during development remains largely unknown. To explore the regulation of Rho GTPases in vivo, we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the Drosophila orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13. Loss of Cysts causes a phenotype that closely resembles the mutant phenotype of the apical...
Mon Oct 07, 2019 16:00
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