Single-cell, spatial, and fate-mapping analyses uncover niche dependent diversity of cochlear myeloid cells.

Recent advances in fate mapping and single-cell technologies have revealed how the dynamics and function of tissue-resident macrophages are shaped by their environment. However, macrophages in sensory organs such as the cochlea where the central nervous system and peripheral nervous system meet remain understudied. Combining single-cell transcriptomics, fate mapping, and parabiosis experiments, we show that five types of myeloid cells including three tissue-resident macrophage subpopulations, coexist in the mouse cochlea.

Cardiac Amyloidosis: A Contemporary Review of Medical and Surgical Therapy.

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis.

Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.

Although an increased risk of the skin cancer melanoma in people with Parkinson's Disease (PD) has been shown in multiple studies, the mechanisms involved are poorly understood, but increased expression of the PD-associated protein alpha-synuclein (αSyn) in melanoma cells may be important. Our previous work suggests that αSyn can facilitate DNA double-strand break (DSB) repair, promoting genomic stability. We now show that αSyn is preferentially enriched within the nucleolus in the SK-MEL28 melanoma cell line, where it colocalizes with DNA damage markers and DSBs.

Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target.

Amyotrophic lateral sclerosis (ALS) is a fatal disease affecting upper and lower motor neurons. Microglia directly interact with motor neurons and participate in the progression of ALS. Single-cell mass cytometry (CyTOF) analysis revealed prominent expression of α5 integrin in microglia and macrophages in a superoxide dismutase-1 G93A mouse model of ALS (SOD1).

Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial.

Background: Topical anti-inflammatory therapy is a cornerstone of treatment for atopic dermatitis (AD). However, many unmet needs remain with existing therapies. B244 is a live topical biotherapeutic being tested for the reduction of pruritus and improvement of eczema signs in patients with AD.

Tissue Engineering for Gastrointestinal and Genitourinary Tracts.

The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated.

Tissue Engineering in Gynecology.

Female gynecological organ dysfunction can cause infertility and psychological distress, decreasing the quality of life of affected women. Incidence is constantly increasing due to growing rates of cancer and increase of childbearing age in the developed world. Current treatments are often unable to restore organ function, and occasionally are the cause of female infertility.

Genitourinary Tissue Engineering: Reconstruction and Research Models.

Tissue engineering is an emerging field of research that initially aimed to produce 3D tissues to bypass the lack of adequate tissues for the repair or replacement of deficient organs. The basis of tissue engineering protocols is to create scaffolds, which can have a synthetic or natural origin, seeded or not with cells. At the same time, more and more studies have indicated the low clinic translation rate of research realised using standard cell culture conditions, i.

Engineering Bacteriophage-Based Biosensors.

Bacteriophages have been used for diagnostic purposes in the past, but a lack of parallelizable engineering methods had limited their applicability to a narrow subset of diagnostic settings. More recently, however, advances in DNA sequencing and the introduction of more sensitive reporter systems have enabled novel engineering methods, which in turn have broadened the scope of modern phage diagnostics. Here we describe advanced methods to engineer the genomes of bacteriophages in a modular and rapid fashion.

Validation of Workflow Changes, Phage Concentration and Reformatted Detection Threshold for the Sample6 DETECT/L™ Test: Level 3 Modification.

The AOAC Research Institute Program certified Sample6 DETECT/L™ in April 2014 (Certification No. 041401) for the detection of species () on stainless steel environmental surfaces. A modification was approved in January 2016, increasing the concentration of sanitizer-neutralizing reagents in detection reagents, increasing the number of phage in the detection solution, and increasing the sample test volume.

The Validation of the Sample6 DETECT HT/L for AOAC Research Institute.

Background: Listeria spp. are an important foodborne human pathogen because of their ability to cause disease and high mortality in individuals, particularly pregnant women, neonates, the elderly, immunocompromised individuals, and children. The Sample6 DETECTTM HT/L Kit is a semi-automated qualitative pathogen detection system designed to detect Listeria spp.

Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways.

In plants, animals, and fungi, members of the Dicer family of RNase III-related enzymes process double-stranded RNA (dsRNA) to initiate small-RNA-mediated gene-silencing mechanisms. To learn how C. elegans Dicer, DCR-1, functions in multiple distinct silencing mechanisms, we used a mass-spectrometry-based proteomics approach to identify DCR-1-interacting proteins.

Wnt signaling drives WRM-1/beta-catenin asymmetries in early C. elegans embryos.

beta-Catenin regulates cell adhesion and cellular differentiation during development, and misregulation of beta-catenin contributes to numerous forms of cancer in humans. Here we describe Caenorhabditis elegans conditional alleles of mom-2/Wnt, mom-4/Tak1, and wrm-1/beta-catenin. We use these reagents to examine the regulation of WRM-1/beta-catenin during a Wnt-signaling-induced asymmetric cell division.

A member of the polymerase beta nucleotidyltransferase superfamily is required for RNA interference in C. elegans.

RNA interference (RNAi) is an ancient, highly conserved mechanism in which small RNA molecules (siRNAs) guide the sequence-specific silencing of gene expression . Several silencing machinery protein components have been identified, including helicases, RNase-related proteins, double- and single-stranded RNA binding proteins, and RNA-dependent RNA polymerase-related proteins . Work on these factors has led to the revelation that RNAi mechanisms intersect with cellular pathways required for development and fertility .

A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus.

The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn.

Immunohistological diagnosis of primary brain lymphoma using monoclonal antibodies: confirmation of B-cell origin.

The antigenic characteristics of 20 primary cerebral lymphomas have been defined by their reactivity with a panel of monoclonal antibodies recognizing differentiation antigens of lymphocytes and other cell types. In 7 out of 20 cases (35%), immunohistological results were diagnostically crucial and this approach appeared almost to double the detection rate of brain lymphomas over a 10-year period. All 20 tumours were confirmed as B-cell neoplasms by the use of a monoclonal antibody (B-1) specific for B-lymphocytes, rather than by the demonstration of immunoglobulin production.

Immunohistological study of mononuclear cell infiltrate in malignant gliomas.

Sixty-five malignant gliomas (astrocytomas grade 3 and 4 and glioblastomas) were examined by means of immunoperoxidase staining on frozen tissue using various monoclonal antibodies directed against macrophages, lymphocytes and natural killer cells. Depending on the antibody used, the presence of macrophages in tumours ranged from 85%-100%. Many of the tumours contained substantial numbers of macrophages not only, as expected, in necrotic areas but also in intact tumour tissue.

Accuracy and indications of diagnostic studies for extracranial carotid disease.

We reviewed extracranial carotid studies in two groups of patients. The first group consisted of 200 patients who had been evaluated by both duplex scanning (DS) and direct arch-selective carotid arteriography (SCA). The second group consisted of 100 patients who had been evaluated by both intravenous digital subtraction angiography (IDSA) and conventional SCA.

Complications of renal dialysis access procedures.

The complications of 2,179 dialysis access procedures of various types have been reviewed in an effort to determine their possible prevention and management. Scribner arteriovenous shunts or central venous catheters were preferred for temporary dialysis. Infection was a common complication of central venous catheters, but responded well to removal of the catheter.

Newer developments of extra-anatomic bypass.

We have analyzed our eight year experience with more than 200 instances of extra-anatomic bypass and have made certain observations. Extra-anatomic bypass provides an acceptable alternative to extensive direct intra-abdominal and intrathoracic vascular reconstructive procedures. This is particularly true in high risk patients and in the presence of infection.

Aortoenteric fistula.

Because of the unacceptably high mortality rate associated with aortoenteric fistula, we have constantly re-evaluated our experience with this lesion. A study of 31 cases of aortoenteric fistula proven at operation has provided a better understanding of the prevention and management of aortoenteric fistula. Prevention remains the primary goal, as the treatment of this complication even with the adoption of recommendations made in our paper can be expected to continue to carry a significant late mortality rate.