The Common Cell Types of Cerebrospinal Fluid

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeremy A Miller ◽  
Nathan W Gouwens ◽  
Bosiljka Tasic ◽  
Forrest Collman ◽  
Cindy TJ van Velthoven ◽  
...  

The advancement of single-cell RNA-sequencing technologies has led to an explosion of cell type definitions across multiple organs and organisms. While standards for data and metadata intake are arising, organization of cell types has largely been left to individual investigators, resulting in widely varying nomenclature and limited alignment between taxonomies. To facilitate cross-dataset comparison, the Allen Institute created the common cell type nomenclature (CCN) for matching and tracking cell types across studies that is qualitatively similar to gene transcript management across different genome builds. The CCN can be readily applied to new or established taxonomies and was applied herein to diverse cell type datasets derived from multiple quantifiable modalities. The CCN facilitates assigning accurate yet flexible cell type names in the mammalian cortex as a step toward community-wide efforts to organize multi-source, data-driven information related to cell type taxonomies from any organism.


2020 ◽  
Vol 11 ◽  
Author(s):  
Dimitris G. Placantonakis ◽  
Maria Aguero-Rosenfeld ◽  
Abdallah Flaifel ◽  
John Colavito ◽  
Kenneth Inglima ◽  
...  

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.


Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev180612
Author(s):  
Filip J. Wymeersch ◽  
Valerie Wilson ◽  
Anestis Tsakiridis

ABSTRACTThe generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by the coordinated production of various cell types from a pool of posteriorly-located axial progenitors. Here, we review the key features of this process and the biology of axial progenitors, including neuromesodermal progenitors, the common precursors of the spinal cord and trunk musculature. We discuss recent developments in the in vitro production of axial progenitors and their potential implications in disease modelling and regenerative medicine.


2004 ◽  
Vol 6 (14) ◽  
pp. 1-14 ◽  
Author(s):  
Anne Corbett ◽  
Rachel Exley ◽  
Sandrine Bourdoulous ◽  
Christoph M. Tang

Neisseria meningitidis is the leading cause of bacterial meningitis, a potentially fatal condition that particularly affects children. Multiple steps are involved during the pathogenesis of infection, including the colonisation of healthy individuals and invasion of the bacterium into the cerebrospinal fluid. The bacterium is capable of adhering to, and entering into, a range of human cell types, which facilitates its ability to cause disease. This article summarises the molecular basis of host–pathogen interactions at the cellular level during meningococcal carriage and disease.


Author(s):  
Kenneth Douglas

Abstract: This book describes how bioprinting emerged from 3D printing and details the accomplishments and challenges in bioprinting tissues of cartilage, skin, bone, muscle, neuromuscular junctions, liver, heart, lung, and kidney. It explains how scientists are attempting to provide these bioprinted tissues with a blood supply and the ability to carry nerve signals so that the tissues might be used for transplantation into persons with diseased or damaged organs. The book presents all the common terms in the bioprinting field and clarifies their meaning using plain language. Readers will learn about bioink—a bioprinting material containing living cells and supportive biomaterials. In addition, readers will become at ease with concepts such as fugitive inks (sacrificial inks used to make channels for blood flow), extracellular matrices (the biological environment surrounding cells), decellularization (the process of isolating cells from their native environment), hydrogels (water-based substances that can substitute for the extracellular matrix), rheology (the flow properties of a bioink), and bioreactors (containers to provide the environment cells need to thrive and multiply). Further vocabulary that will become familiar includes diffusion (passive movement of oxygen and nutrients from regions of high concentration to regions of low concentration), stem cells (cells with the potential to develop into different bodily cell types), progenitor cells (early descendants of stem cells), gene expression (the process by which proteins develop from instructions in our DNA), and growth factors (substances—often proteins—that stimulate cell growth, proliferation, and differentiation). The book contains an extensive glossary for quick reference.


2020 ◽  
Vol 13 (5) ◽  
pp. 281-288
Author(s):  
Mark Newton ◽  
Paraskevi Tsirevelou

The discharging ear, also known as otorrhoea, is a common ear, nose and throat symptom and defined as drainage or flow exiting the ear. The discharge can be wax, blood, pus, mucus, or cerebrospinal fluid. The underlying cause can usually be determined from the history and physical examination. Most patients with otorrhoea can be managed within primary care and do not require referral or hospital admission. This article considers the common causes of a discharging ear, appropriate management, guidance for referral of patients to secondary care and some key take home points.


1992 ◽  
Vol 71 (7) ◽  
pp. 311-313 ◽  
Author(s):  
David T. Daly ◽  
William M. Lydiatt ◽  
Frederic P. Ogren ◽  
Gary F. Moore

This paper presents a review of the extracranial evaluation and treatment of cerebrospinal fluid (CSF) rhinorrhea. Diagnosis with attention to a careful history and physical with maneuvers which exacerbate drainage and thorough physical exam along with imaging techniques are discussed. The common etiologies of CSF rhinorrhea including trauma, spontaneous leakage, tumor, and iatrogenic injury are included. Management consists of conservative measures including the avoidance of straining maneuvers which increases intracranial pressure. Periodic drainage of CSF via lumbar puncture or continuous drainage via flow-regulated systems may also be of benefit in attempts of conservative management. Failure of conservative management, constant leakage, pneumocephalus, and recurrent meningitis are indicators for surgical repairs. Ethmoid-cribiform plate region repairs are generally approached by external ethmoidectomy and the development of mucoperiosteal flaps from various donor sites which are then rotated to the leak area to seal the defect. Frontal sinus leaks are usually repaired via an osteoplastic flap technique with direct repair of the dural defect or the use of fascial graft tucked under the bony defect, then obliterated with abdominal fat. CSF rhinorrhea presents a diagnostic and surgical challenge to the otolaryngologist. After diagnosis and localization, operative repair using extracranial approaches is accepted as the initial method of intervention in these cases.


2012 ◽  
Vol 92 (4) ◽  
pp. 1915-1964 ◽  
Author(s):  
Haruo Kasai ◽  
Noriko Takahashi ◽  
Hiroshi Tokumaru

The dynamics of exocytosis are diverse and have been optimized for the functions of synapses and a wide variety of cell types. For example, the kinetics of exocytosis varies by more than five orders of magnitude between ultrafast exocytosis in synaptic vesicles and slow exocytosis in large dense-core vesicles. However, in all cases, exocytosis is mediated by the same fundamental mechanism, i.e., the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is often assumed that vesicles need to be docked at the plasma membrane and SNARE proteins must be preassembled before exocytosis is triggered. However, this model cannot account for the dynamics of exocytosis recently reported in synapses and other cells. For example, vesicles undergo exocytosis without prestimulus docking during tonic exocytosis of synaptic vesicles in the active zone. In addition, epithelial and hematopoietic cells utilize cAMP and kinases to trigger slow exocytosis of nondocked vesicles. In this review, we summarize the manner in which the diversity of exocytosis reflects the initial configurations of SNARE assembly, including trans-SNARE, binary-SNARE, unitary-SNARE, and cis-SNARE configurations. The initial SNARE configurations depend on the particular SNARE subtype (syntaxin, SNAP25, or VAMP), priming proteins (Munc18, Munc13, CAPS, complexin, or snapin), triggering proteins (synaptotagmins, Doc2, and various protein kinases), and the submembraneous cytomatrix, and they are the key to determining the kinetics of subsequent exocytosis. These distinct initial configurations will help us clarify the common SNARE assembly processes underlying exocytosis and membrane trafficking in eukaryotic cells.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1424-1424
Author(s):  
Bjoern Schneider ◽  
Stefan Nagel ◽  
Maren Kaufmann ◽  
Hilmar Quentmeier ◽  
Yoshinobu Matsuo ◽  
...  

Abstract Genomic amplifications of the 11q23 region occur in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) where MLL and a few neighboring genes, notably DDX6, are deemed salient targets. However, the extent to which amp(lified)-MLL and translocated MLL share effector targets remains to be established. Even less is known about the target(s) of deletions affecting the long arm of chromosome 5 (5q-) which reportedly partner amp-MLL. We analyzed three AML/MDS cell lines by cytogenetics (conventional and FISH) in parallel with real time q(uantitative)-PCR at both 11q23 and 5q2 to measure copy number and expression of salient target genes together with putative downstream targets. The cell lines comprised: MOLM-17 (transforming-MDS), SAML-2 (therapy-related AML), and UOC-M1 (AML-M1). All three cell lines exhibited approximately four-fold genomic amplification of 11q23 including MLL and DDX6, while the amplicon extended telomerically to include FLI1 (11q24) and HNT (11q25) in MOLM-17 and UOC-M1 only. Expression, quantified relative to AML/MDS cell lines without MLL rearrangement, revealed that of the genomically amplified genes only MLL was generally overexpressed, namely by 9.5x (MOLM-17), 5.1x (UOC-M1), and 4.6x (SAML-2). In addition to the highest MLL expression, in MOLM-17 FLI1 (3.8x) and DDX6 (2.8x) were significantly upregulated. Expression was also quantified among reputed MLL target genes, and showed that in the three cell lines MEIS1 was upregulated in MOLM-17 only (by 6x), and CDKN2C in all cell lines (by about 2x), while HOXA9 and CDKN1B showed near-normal levels of expression. All three cell lines carried 5q- with a common deleted region at 5q31 extending from 134.2–137.5 Mbp. Of a panel of genes recently identified as 5q- deletion targets (centromere-TIGA1, CAMLG, C5orf15, C5orf14, BRD8, HARS, KIAA0141, CSNK1A1, RBM22-telomere), only C5orf15 (function unknown) and BRD8 (a component of the nua4 histone acetyltransferase complex involved in transcriptional activation) were generally downregulated - to about 0.25x, and about 0.4x normalized expression levels, respectively. Both genes lie within the common deleted region. In summary, we have characterized amp-MLL and 5q- in MOLM-17, the first MDS cell line to be described with these rearrangements, together with two AML cell lines with similar cytogenetic profiles. Our data suggest that MLL is the only clear object of 11q23 amplification hitherto identified and CDKN2C its sole unequivocal target in AML/MDS cell lines. It is possible that MEIS1 is also targeted for activation in specific cell types or disease phases in MDS. These findings also highlight C5orf15 and/or BRD8 as possible leukemogenic accomplices targeted for downregulation in accompanying 5q-. These findings may point to differences in signalling pathways targeted by amp-MLL in AML and MDS.


2005 ◽  
Vol 119 (1) ◽  
pp. 12-15 ◽  
Author(s):  
C J Dunn ◽  
A Alaani ◽  
A P Johnson

The aim of this study was to identify the common features in a study group of patients with spontaneous cerebrospinal fluid (CSF) rhinorrhoea, to develop a hypothesis to explain the cause of this condition and to investigate the outcome of surgical techniques adopted to repair the leak. In this retrospective study the authors have reviewed all the cases of spontaneous CSF leaks attending and receiving treatment from the otolaryngology department of Queen Elizabeth Hospital, Birmingham, from 1992 to 2002.Of 34 patients with CSF leaks, 15 were spontaneous in nature and formed the study group. Of these 15 patients, 14 were female; with ages ranging from 37 to 70 years and a median age of 50 years. All the female patients were overweight with a body mass index (BMI) >24.9 and, of these, nine were considered obese with a BMI >30. It was attempted to identify common factors in the study group and it was evident that female sex, obesity and age played a key role in this condition.The follow-up period ranged from two to 98 months. Thirteen patients were asymptomatic but two patients remained symptomatic, one of these despite repeated surgical intervention.


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