Enhancement of Antimicrobial Function by L/D-Lysine Substitution on a Novel Broad-Spectrum Antimicrobial Peptide, Phylloseptin-TO2: A Structure-Related Activity Research Study.

Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from frogs, have been proven to have antimicrobial activity via membrane interaction.

Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic.

Mucolytic treatment of chronic rhinosinusitis in a murine model of primary ciliary dyskinesia.

Genetic defects in motile cilia cause primary ciliary dyskinesia (PCD), a rare disease with no specific therapeutics. Individuals with PCD often have impaired fertility and laterality defects and universally suffer from upper and lower airway diseases. Chronic rhinosinusitis is a universal feature of PCD, and mucus accumulation and subsequent infections of the sinonasal cavity cause significant morbidity in individuals with PCD.

Conjugation of a Cationic Cell-Penetrating Peptide with a Novel Kunitzin-like Trypsin Inhibitor: New Insights for Enhancement of Peptide Bioactivities.

Cationic cell-penetrating peptides (CPPs), such as transactivator of transcription (TAT) peptide, have been proposed as effective drug carriers to improve intracellular delivery of biological macromolecules. Amphibian skin-derived Kunitz-type trypsin inhibitors (KTIs), short counterparts of KTIs from plant sources, were found to possess potent serine protease inhibitory activity. However, poor transmembrane permeability of these molecules has largely hindered the study of the full spectrum of their biological actions.

The role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia.

Mutations in SPAG1, a dynein axonemal assembly factor (DNAAF) that facilitates the assembly of dynein arms in the cytoplasm before their transport into the cilium, result in primary ciliary dyskinesia (PCD), a genetically heterogenous disorder characterized by chronic oto-sino-pulmonary disease, infertility and laterality defects. To further elucidate the role of SPAG1 in dynein assembly, we examined its expression, interactions and ciliary defects in control and PCD human airway epithelia. Immunoprecipitations showed that SPAG1 interacts with multiple DNAAFs, dynein chains and canonical components of the R2TP complex.

Expression of a Truncated Form of Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype.

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the function of motile cilia, resulting in chronic upper and lower respiratory disease, reduced fertility, and a high prevalence of situs abnormalities. The disease is genetically and phenotypically heterogeneous, with causative mutations in > 50 genes identified, and clinical phenotypes ranging from mild to severe. Absence of (), a component of the outer dynein arm docking complex, results in a failure to assemble outer dynein arms (ODAs), mostly immotile cilia, and a typical PCD phenotype.

Structural insights into the cause of human primary ciliary dyskinesia.

Cilia and flagella are evolutionarily conserved eukaryotic organelles involved in cell motility and signaling. In humans, mutations in Radial Spoke Head Component 4A () can lead to primary ciliary dyskinesia (PCD), a life-shortening disease characterized by chronic respiratory tract infections, abnormal organ positioning, and infertility. Despite its importance for human health, the location of RSPH4A in human cilia has not been resolved, and the structural basis of PCD remains elusive.

Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia.

Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full characterization of CFTR expression in normal human airway epithelia is missing. To identify the cell types that contribute to expression and function within the proximal-distal axis of the normal human lung.

Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, reduced fertility, and randomization of the left/right body axis. It is caused by defects of motile cilia and sperm flagella. We screened a cohort of affected individuals that lack an obvious axonemal defect for pathogenic variants using whole exome capture, next generation sequencing, and bioinformatic analysis assuming an autosomal recessive trait.

Mice with a Deletion of Exhibit a Low Level of Mucociliary Clearance and Develop a Primary Ciliary Dyskinesia Phenotype.

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disease caused by mutations in over 40 different genes. Individuals with PCD caused by mutations in (radial spoke head 1 homolog) have been reported to have a milder phenotype than other individuals with PCD, as evidenced by a lower incidence of neonatal respiratory distress, higher nasal nitric oxide concentrations, and better lung function. To better understand genotype-phenotype relationships in PCD, we have characterized a mutant mouse model with a deletion of .

Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary Clearance.

Primary ciliary dyskinesia (PCD) is a genetic disorder in which impaired ciliary function leads to chronic airway disease. Exome sequencing of a PCD subject identified an apparent homozygous frameshift variant, c.887_890delTAAG (p.

Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance.

Cilia are essential to many diverse cellular processes. Although many major axonemal components have been identified and studied, how they interact to form a functional axoneme is not completely understood. To further our understanding of the protein composition of human airway cilia, we performed a semiquantitative analysis of ciliary axonemes using label-free LC/MS, which identified over 400 proteins with high confidence.

Reduced mucociliary clearance in old mice is associated with a decrease in Muc5b mucin.

Respiratory infections are a major cause of morbidity and mortality in the elderly. Previous reports have suggested that mucociliary clearance (MCC) is impaired in older individuals, but the cause is unclear. To unravel the mechanisms responsible for the age-associated decline in MCC, we investigated the MCC system in young (3 mo) and old (2 yr) C57BL/6 mice.

Continuous mucociliary transport by primary human airway epithelial cells in vitro.

Mucociliary clearance (MCC) is an important innate defense mechanism that continuously removes inhaled pathogens and particulates from the airways. Normal MCC is essential for maintaining a healthy respiratory system, and impaired MCC is a feature of many airway diseases, including both genetic (cystic fibrosis, primary ciliary dyskinesia) and acquired (chronic obstructive pulmonary disease, bronchiectasis) disorders. Research into the fundamental processes controlling MCC, therefore, has direct clinical application, but has been limited in part due to the difficulty of studying this complex multicomponent system in vitro.

Microsurgical anatomy of perforated arteries in the hypothalamic area.

Aim: This study aimed to investigate the microsurgical anatomy of perforating arteries in the hypothalamic area, which are associated with diabetes insipidus.

Material And Methods: A total of 20 adult cadaver heads soaked in formalin were infused with red latex through the carotid artery and vertebral artery, and supplementary perfusion was performed after 1 day.

Results: The perforating arteries in the hypothalamic area could be divided into three groups according to their origins, namely, the former, below and outside groups.

Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia.

Cilia play essential roles in normal human development and health; cilia dysfunction results in diseases such as primary ciliary dyskinesia (PCD). Despite their importance, the native structure of human cilia is unknown, and structural defects in the cilia of patients are often undetectable or remain elusive because of heterogeneity. Here we develop an approach that enables visualization of human (patient) cilia at high-resolution using cryo-electron tomography of samples obtained noninvasively by nasal scrape biopsy.

Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype.

Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD.

Objectives: To identify disease-causing mutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD.

Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing.

[Guiding values of facial nerve 3D-TOF-MRA and 3D-FIESTA scan for primary hemifacial spasm operation].

Objective: To explore the operative guiding values of facial nerve three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and three-dimensional fast imaging employing steady state acquisition three-dimensional fast imaging employing steady state acquisition (3D-FIESTA) scan.

Methods: A total of 125 cases of primary hemifacial spasm was treated at our hospital from 2004 to 2012. Among them, 80 cases received preoperative facial nerve MRA scan.

Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 20 genes, but collectively they account for only ∼65% of all PCDs. To identify mutations in additional genes that cause PCD, we performed exome sequencing on three unrelated probands with ciliary outer and inner dynein arm (ODA+IDA) defects.

Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ~60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects.

[Recognition and management of hidden related vessel during the operation of microvascular decompression for hemifacial spasm].

Objective: To investigate the recognition and approach of the hidden related vascular in hemifacial spasm patients during the operation of microvascular decompression.

Methods: The clinical records of 85 patients of hemifacial spasm were analyzed at our hospital. The hidden related vessel was found in 7 patients.

Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage.

Background: Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-kappaB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kappaB) signaling in the rat brain after early SAH.

WITHDRAWN: Activation of TLR4/NF-kappaB signaling pathway in early brain injury after subarachnoid hemorrhage.

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