scholarly journals TRIOBP promotes bidirectional radial stiffness gradients within the organ of Corti

2021 ◽  
Author(s):  
Hesam Babahosseini ◽  
Inna Belyantseva ◽  
Rizwan Yousaf ◽  
Risa Tona ◽  
Shadan Hadi ◽  
...  
Keyword(s):  
Organ Of Corti ◽  
Cell Types ◽  
Supporting Cell ◽  
Sensory Epithelium ◽  
Apical Surface ◽  
Wild Type ◽  
Radial Stiffness ◽  
Genes Encoding ◽  
Individual Contributions ◽  
The Individual

Hearing depends on complex mechanical properties of the inner ear sensory epithelium. Yet, the individual contributions of different cell types to the stiffness spectrum of the sensory epithelium have not been thoroughly investigated. Using sub-100 nanometer spatial resolution PeakForce Tapping Atomic Force Microscopy (PFT-AFM), we mapped the Youngs modulus (stiffness) of the apical surface of different cells of freshly-dissected cochlear epithelium from wild-type mice and mice lacking the F-actin bundling protein TRIOBP-5 or TRIOBP-4 and TRIOBP-5. Variants of the genes encoding human and mouse TRIOBP are associated with deafness. We show that TRIOBP deficiency affects formation of supporting cell apical phalangeal microfilaments and bundled cortical F-actin of hair cell cuticular plates, softening the apical surface of the sensory epithelium. Unexpectedly, high-resolution PFT-AFM-mapping also revealed previously unrecognized reticular lamina radial stiffness gradients of opposite orientations in wild-type supporting and hair cells. Deafness-associated TRIOBP deficiencies significantly modified these bidirectional radial stiffness gradients.

scholarly journals Multiphoton NAD(P)H FLIM reveals metabolic changes in individual cell types of the intact cochlea upon sensorineural hearing loss

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Paromita Majumder ◽  
Thomas S. Blacker ◽  
Lisa S. Nolan ◽  
Michael R. Duchen ◽  
Jonathan E. Gale
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Cell Model ◽  
Organ Of Corti ◽  
Cell Types ◽  
Fluorescence Lifetime Imaging ◽  
Noise Induced Hearing Loss ◽  
Label Free ◽  
Age Related ◽  
The Individual

AbstractAn increasing volume of data suggests that changes in cellular metabolism have a major impact on the health of tissues and organs, including in the auditory system where metabolic alterations are implicated in both age-related and noise-induced hearing loss. However, the difficulty of access and the complex cyto-architecture of the organ of Corti has made interrogating the individual metabolic states of the diverse cell types present a major challenge. Multiphoton fluorescence lifetime imaging microscopy (FLIM) allows label-free measurements of the biochemical status of the intrinsically fluorescent metabolic cofactors NADH and NADPH with subcellular spatial resolution. However, the interpretation of NAD(P)H FLIM measurements in terms of the metabolic state of the sample are not completely understood. We have used this technique to explore changes in metabolism associated with hearing onset and with acquired (age-related and noise-induced) hearing loss. We show that these conditions are associated with altered NAD(P)H fluorescence lifetimes, use a simple cell model to confirm an inverse relationship between τbound and oxidative stress, and propose such changes as a potential index of oxidative stress applicable to all mammalian cell types.

scholarly journals Additive Attenuation of Virulence ofStreptococcus pneumoniae by Mutation of the Genes Encoding Pneumolysin and Other Putative Pneumococcal Virulence Proteins

2000 ◽  
Vol 68 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Anne M. Berry ◽  
James C. Paton
Keyword(s):  
Protein A ◽  
Surface Protein ◽  
The Other ◽  
Virulence Proteins ◽  
Vaccine Antigens ◽  
Genes Encoding ◽  
Individual Contributions ◽  
The Individual ◽  
The Impact

ABSTRACT Although the polysaccharide capsule of Streptococcus pneumoniae has been recognized as a sine qua non of virulence, much recent attention has focused on the role of pneumococcal proteins in pathogenesis, particularly in view of their potential as vaccine antigens. The individual contributions of pneumolysin (Ply), the major neuraminidase (NanA), autolysin (LytA), hyaluronidase (Hyl), pneumococcal surface protein A (PspA), and choline-binding protein A (CbpA) have been examined by specifically mutagenizing the respective genes in the pneumococcal chromosome and comparing the impact on virulence in a mouse intraperitoneal challenge model. Mutagenesis of either the ply, lytA, or pspA gene in S. pneumoniae D39 significantly reduced virulence, relative to that of the wild-type strain, indicating that the respective gene products contribute to pathogenesis. On the other hand, mutations in nanA, hyl, or cbpA had no significant impact. The virulence of D39 derivatives carrying aply deletion mutation as well as an insertion-duplication mutation in one of the other genes was also examined. Mutagenesis of either nanA or lytA did not result in an additional attenuation of virulence in the ply deletion background. However, significant additive attenuation in virulence was observed for the strains with ply-hyl,ply-pspA, and ply-cbpA double mutations.

scholarly journals Immune regulation by glucocorticoids can be linked to cell type–dependent transcriptional responses

2019 ◽  
Vol 216 (2) ◽  
pp. 384-406 ◽  
Author(s):  
Luis M. Franco ◽  
Manasi Gadkari ◽  
Katherine N. Howe ◽  
Jing Sun ◽  
Lela Kardava ◽  
...  
Keyword(s):  
Cell Types ◽  
Cell Receptor ◽  
Cell Type ◽  
Transcriptional Responses ◽  
Functional Studies ◽  
Specific Effects ◽  
Genes Encoding ◽  
Inflammatory Drugs ◽  
The Individual ◽  
Transcriptional Output

Glucocorticoids remain the most widely used immunosuppressive and anti-inflammatory drugs, yet substantial gaps exist in our understanding of glucocorticoid-mediated immunoregulation. To address this, we generated a pathway-level map of the transcriptional effects of glucocorticoids on nine primary human cell types. This analysis revealed that the response to glucocorticoids is highly cell type dependent, in terms of the individual genes and pathways affected, as well as the magnitude and direction of transcriptional regulation. Based on these data and given their importance in autoimmunity, we conducted functional studies with B cells. We found that glucocorticoids impair upstream B cell receptor and Toll-like receptor 7 signaling, reduce transcriptional output from the three immunoglobulin loci, and promote significant up-regulation of the genes encoding the immunomodulatory cytokine IL-10 and the terminal-differentiation factor BLIMP-1. These findings provide new mechanistic understanding of glucocorticoid action and emphasize the multifactorial, cell-specific effects of these drugs, with potential implications for designing more selective immunoregulatory therapies.

scholarly journals Co-released Norepinephrine and Galanin Act on Different Timescales to Promote Stress-Induced Anxiety-Like Behavior

2020 ◽  
Author(s):  
Rachel P. Tillage ◽  
Stephanie L. Foster ◽  
Daniel Lustberg ◽  
L. Cameron Liles ◽  
David Weinshenker
Keyword(s):  
Stress Responses ◽  
Acute Stress ◽  
Noradrenergic Neurons ◽  
Wild Type ◽  
Functional Roles ◽  
Behavioral Stress ◽  
Normal Expression ◽  
Individual Contributions ◽  
The Individual ◽  
Deficient Mice

ABSTRACTBackgroundBoth the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC); however, the individual contributions of LC-derived norepinephrine (NE) and galanin to behavioral stress responses are unclear. Here we aimed to disentangle the functional roles of co-released NE and galanin in stress-induced behavior.MethodsWe used foot shock, optogenetics, and behavioral pharmacology in wild-type (WT) mice and mice lacking either NE (Dbh-/-) or galanin (GalcKO-Dbh) specifically in noradrenergic neurons to isolate the roles of these co-transmitters in regulating anxiety-like behavior in the elevated zero maze (EZM) either immediately or 24 h following stress.ResultsFoot shock and optogenetic LC stimulation produced immediate anxiety-like behavior in WT mice, and the effects of foot shock persisted for 24 h. NE-deficient mice were resistant to the anxiogenic effects of acute stress and optogenetic LC stimulation, while mice lacking noradrenergic-derived galanin displayed typical increases in anxiety-like behavior. However, when tested 24 h after foot shock, both Dbh-/- and GalcKO-Dbh mice lacked normal expression of anxiety-like behavior. Pharmacological rescue of NE, but not galanin, in knockout mice during EZM testing was anxiogenic. In contrast, restoring galanin, but not NE, signaling during foot shock normalized stress-induced anxiety-like behavior 24 h later.ConclusionsThese results indicate that NE and noradrenergic-derived galanin play complementary, but distinguishable roles in behavioral responses to stress. NE is required for the expression of acute stress-induced anxiety, while noradrenergic-derived galanin mediates more persistent responses following a stressor.

scholarly journals Brg1 controls neurosensory cell fate commitment and differentiation in the mammalian inner ear

2018 ◽  
Author(s):  
Jinshu Xu ◽  
Jun Li ◽  
Yong-Hwee Eddie Loh ◽  
Ting Zhang ◽  
Huihui Jiang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Inner Ear ◽  
Cell Fate ◽  
Chromatin Remodeling ◽  
Cell Types ◽  
Supporting Cell ◽  
Regulatory Elements ◽  
Sensory Epithelium ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Almost All

AbstractOtic ectoderm gives rise to almost all cell types of the inner ear; however, the mechanisms that link transcription factors, chromatin, lineage commitment and differentiation capacity are largely unknown. Here we show that Brg1 chromatin-remodeling factor is required for specifying neurosensory lineage in the otocyst and for inducing hair and supporting cell fates in the cochlear sensory epithelium. Brg1 interacts with the critical neurosensory-specific transcription factors Eya1/Six1, both of which simultaneously interact with BAF60a or BAF60c. Chromatin immunoprecipitation-sequencing (ChIP-seq) and ChIP assays demonstrate Brg1 association with discrete regulatory elements at the Eya1 and Six1 loci. Brg1-deficiency leads to markedly decreased Brg1 binding at these elements and loss of Eya1 and Six1 expression. Furthermore, ChIP-seq reveals Brg1-bound promoter-proximal and distal regions near genes essential for inner ear morphogenesis and cochlear sensory epithelium development. These findings uncover essential functions for chromatin-remodeling in the activation of neurosensory fates during inner ear development.

A technique for protecting delicate specimens during processing

1989 ◽  
Vol 47 ◽  
pp. 982-983
Author(s):  
R.J. Mount ◽  
R.V. Harrison
Keyword(s):  
Basilar Membrane ◽  
Low Cost ◽  
Organ Of Corti ◽  
Region Of Interest ◽  
Sensory Epithelium ◽  
Physical Damage ◽  
Air Drying ◽  
Specimen Handling ◽  
Two Component

The sensory end organ of the ear, the organ of Corti, rests on a thin basilar membrane which lies between the bone of the central modiolus and the bony wall of the cochlea. In vivo, the organ of Corti is protected by the bony wall which totally surrounds it. In order to examine the sensory epithelium by scanning electron microscopy it is necessary to dissect away the protective bone and expose the region of interest (Fig. 1). This leaves the fragile organ of Corti susceptible to physical damage during subsequent handling. In our laboratory cochlear specimens, after dissection, are routinely prepared by the O-T- O-T-O technique, critical point dried and then lightly sputter coated with gold. This processing involves considerable specimen handling including several hours on a rotator during which the organ of Corti is at risk of being physically damaged. The following procedure uses low cost, readily available materials to hold the specimen during processing ,preventing physical damage while allowing an unhindered exchange of fluids.Following fixation, the cochlea is dehydrated to 70% ethanol then dissected under ethanol to prevent air drying. The holder is prepared by punching a hole in the flexible snap cap of a Wheaton vial with a paper hole punch. A small amount of two component epoxy putty is well mixed then pushed through the hole in the cap. The putty on the inner cap is formed into a “cup” to hold the specimen (Fig. 2), the putty on the outside is smoothed into a “button” to give good attachment even when the cap is flexed during handling (Fig. 3). The cap is submerged in the 70% ethanol, the bone at the base of the cochlea is seated into the cup and the sides of the cup squeezed with forceps to grip it (Fig.4). Several types of epoxy putty have been tried, most are either soluble in ethanol to some degree or do not set in ethanol. The only putty we find successful is “DUROtm MASTERMENDtm Epoxy Extra Strength Ribbon” (Loctite Corp., Cleveland, Ohio), this is a blue and yellow ribbon which is kneaded to form a green putty, it is available at many hardware stores.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

A Handbook to Eddic Poetry: Myths and Legends of Early Scandinavia, ed. Carolyne Larrington, Judy Quinn, and Brittany Schorn. Cambridge: Cambridge University Press, 2016, xii, 413 pp., 12 b/w ill.

Mediaevistik ◽  
2018 ◽  
Vol 31 (1) ◽  
pp. 366-366
Author(s):  
Albrecht Classen
Keyword(s):  
Old Norse ◽  
Entire Volume ◽  
Cambridge University ◽  
Critical Studies ◽  
Individual Contributions ◽  
The Many ◽  
The Individual ◽  
Made In ◽  
Scandinavian Literature

Eddic poetry constitutes one of the most important genres in Old Norse or Scandinavian literature and has been studied since the earliest time of modern-day philology. The progress we have made in that field is impressive, considering the many excellent editions and translations, not to mention the countless critical studies in monographs and articles. Nevertheless, there is always a great need to revisit, to summarize, to review, and to digest the knowledge gained so far. The present handbook intends to address all those goals and does so, to spell it out right away, exceedingly well. But in contrast to traditional concepts, the individual contributions constitute fully developed critical article, each with a specialized topic elucidating it as comprehensively as possible, and concluding with a section of notes. Those are kept very brief, but the volume rounds it all off with an inclusive, comprehensive bibliography. And there is also a very useful index at the end. At the beginning, we find, following the table of contents, a list of the contributors, unfortunately without emails, a list of translations and abbreviations of the titles of Eddic poems in the Codex Regius and then elsewhere, and a very insightful and pleasant introduction by Carolyne Larrington. She briefly introduces the genre and then summarizes the essential points made by the individual authors. The entire volume is based on the Eddic Network established by the three editors in 2012, and on two workshops held at St. John’s College, Oxford in 2013 and 2014.

Employee Surveys and Sensing

2020 ◽  
Keyword(s):  
Organizational Performance ◽  
Employee Engagement ◽  
Computational Linguistics ◽  
Full Range ◽  
Organization Culture ◽  
Employee Survey ◽  
Passive Data ◽  
Individual Contributions ◽  
Action Taking ◽  
The Individual

This volume comprises 27 chapters focused on the design and execution of employee survey programs. These chapters reflect the latest advances in technology and analytics and a pervasive emphasis on driving organizational performance and effectiveness. The individual chapters represent the full range of survey-related topics, including design, administration, analysis, feedback, and action-taking. The latest methodological trends and capabilities are discussed including computational linguistics, applications of artificial intelligence, and the use of qualitative methods such as focus groups. Extending beyond traditional employee surveys, contributions include the role of passive data collection as an alternative or supplement in a comprehensive employee listening system. Unique contextual factors are discussed including the use of surveys in a unionized environment. Individual contributions also reflect increasing stakeholder concerns for the protection of privacy among other ethical considerations. Finally, significant clarifications to the literature are provided on the use of surveys for measuring organization culture, strategic climate, and employee engagement.

Knowledge First

2017 ◽  
Author(s):  
J. Adam Carter ◽  
Emma C. Gordon ◽  
Benjamin W. Jarvis
Keyword(s):  
Philosophy Of Mind ◽  
Theoretical Background ◽  
Contemporary Research ◽  
Timothy Williamson ◽  
Research Themes ◽  
New Directions ◽  
Individual Contributions ◽  
The Individual

In this introductory chapter, the volume’s editors provide a theoretical background to the volume’s topic and a brief overview of the papers included. The chapter is divided into five parts: Section 1 explains the main contours of the knowledge-first approach, as it was initially advanced by Timothy Williamson in Knowledge and its Limits. In Sections 2–3, some of the key philosophical motivations for the knowledge-first approach are reviewed, and several key contemporary research themes associated with this approach in epistemology, the philosophy of mind and elsewhere are outlined and briefly discussed. The volume’s papers are divided into two broad categories: foundational issues and applications and new directions. Section 4 discusses briefly the scope and aim of the volume as the editors have conceived it, and Section 5 offers an overview of each of the individual contributions in the volume.

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