Conformational rigidity of cytochrome c'-α from a thermophile is associated with slow NO binding.

Cytochromes c'-α are nitric oxide (NO)-binding heme proteins derived from bacteria that can thrive in a wide range of temperature environments. Studies of mesophilic Alcaligenes xylosoxidans cytochrome c'-α (AxCP-α) have revealed an unusual NO-binding mechanism involving both heme faces, in which NO first binds to form a distal hexa-coordinate Fe(II)-NO (6cNO) intermediate and then displaces the proximal His to form a proximal penta-coordinate Fe(II)-NO (5cNO) final product. Here, we characterize a thermally stable cytochrome c'-α from thermophilic Hydrogenophilus thermoluteolus (PhCP-α) to understand how protein thermal stability affects NO binding.

A heme pocket aromatic quadrupole modulates gas binding to cytochrome c'-β: Implications for NO sensors.

The structural basis by which gas-binding heme proteins control their interactions with NO, CO, and O is fundamental to enzymology, biotechnology, and human health. Cytochromes c' (cyts c') are a group of putative NO-binding heme proteins that fall into two families: the well-characterized four alpha helix bundle fold (cyts c'-α) and an unrelated family with a large beta-sheet fold (cyts c'-β) resembling that of cytochromes P460. A recent structure of cyt c'-β from Methylococcus capsulatus Bath revealed two heme pocket phenylalanine residues (Phe 32 and Phe 61) positioned near the distal gas-binding site.

Alarmins and innate lymphoid cells 2 activation: A common pathogenetic link connecting respiratory syncytial virus bronchiolitis and later wheezing/asthma?

Severe respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient antiviral immune response. The airway epithelium, the first target of RSV, normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part II. Inhaled corticosteroids alone or in combination with surfactants.

This paper is the second in a two-part State-of-the-Art series that reviews the latest relevant clinical trials investigating the short-term and long-term effects of corticosteroids in the prevention and treatment of bronchopulmonary dysplasia (BPD). Inhaled postnatal corticosteroids demonstrate low systemic bioavailability and rapid systemic clearance with high pulmonary deposition and were expected to reduce the incidence of BPD with reduced adverse effects, however, increased rate of mortality in the neonatal period and at the 18-24 months follow-up was observed. In a milestone study, intratracheal instillation of corticosteroids combined with surfactant decreased the incidence of BPD without increasing the mortality or the long-term neurodevelopmental adverse outcomes.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part I. systemic corticosteroids.

Bronchopulmonary dysplasia (BPD) is the most significant respiratory complication of prematurity, and its consequences last from birth into adulthood. Unfortunately, the dramatic improvements in the management of premature infants have not led to a decreased incidence of BPD, or to breakthroughs in treatments offered for this long-lasting chronic respiratory disorder. Over recent decades the pathological picture of BPD has changed from inflammation, interstitial fibrosis and emphysema attributed to volu-, barotrauma and oxygen toxicity to larger, simplified alveoli and dysmorphic vessels related to arrested alveolarization and vasculogenesis with inflammation maintaining a central role.

Pediatric Asthma Attack and Home Paint Exposure.

Although asthma mortality has been declining for the past several decades, asthma morbidity is on the rise, largely due to deteriorating indoor air quality and comorbidities, such as allergies. Consumer products and building materials including paints emit volatile organic compounds (VOCs), such as propylene glycol (PG), which is shown to dehydrate respiratory tracts and can contributor to airway remodeling. We hypothesize that paint exposure increases the risk of asthma attacks among children because high levels of VOCs persist indoors for many weeks after painting.

Allergies, Allergic Comorbidities and the Home Environment in Pediatric Asthma in Southern Florida.

Environmental exposure is critical in sensitization to environmental allergens and pediatric asthma morbidity, especially in tropical climates where children are perennially exposed to bioaerosols, such as pollen and mold spores, and endotoxins. : This cross-sectional study examines the association of allergies, associated allergic comorbidities, and the home environment separately and synergistically in pediatric asthma, including in asthma prevalence, severity of asthma, and undiagnosed asthma, in South Florida. An online survey was administered to the parents of children attending two of the University of Miami pediatric clinics from June to October 2016.

Respiratory syncytial virus and airway microbiota - A complex interplay and its reflection on morbidity.

The immunopathology of respiratory syncytial virus (RSV) infection varies considerably, severe disease occurring only in a minority of the affected children. The variability of the clinical presentation is in part explained by viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiologic immaturity of the innate and adaptive immune system. There is evidence that the maturation of the host immune response is positively influenced by the composition of the nasopharyngeal microbiome that, promoting an efficient reaction, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity.

Upregulation of neuropeptides and obstructive airway disorder in infancy: A review with focus on post-RSV wheezing and NEHI.

Obstructive airway disorders, common in infancy and early childhood, include some entities that are recognized to have neuro immune mediators as their underlying pathogenetic mechanisms. The best characterized example amongst post-viral wheezing phenotypes is the disorder that follows respiratory syncytial virus (RSV) infection and leads to intermittent, long-term wheezing. The underlying mechanisms of the airway reactivity related to RSV infection have been extensively studies and are associated with dysregulation of the nonadrenergic-noncholinergic (NANC) system, via upregulation of neurotransmitters, typically Substance P.

Hydroxylamine Complexes of Cytochrome : Influence of Heme Iron Redox State on Kinetic and Spectroscopic Properties.

Hydroxylamine (NHOH or HA) is a redox-active nitrogen oxide that occurs as a toxic intermediate in the oxidation of ammonium by nitrifying and methanotrophic bacteria. Within ammonium containing environments, HA is generated by ammonia monooxygenase (nitrifiers) or methane monooxygenase (methanotrophs). Subsequent oxidation of HA is catalyzed by heme proteins, including cytochromes P460 and multiheme hydroxylamine oxidoreductases, the former contributing to emissions of NO, an ozone-depleting greenhouse gas.

Complicated pneumonia in children.

Complicated community-acquired pneumonia in a previously well child is a severe illness characterised by combinations of local complications (eg, parapneumonic effusion, empyema, necrotising pneumonia, and lung abscess) and systemic complications (eg, bacteraemia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and, rarely, death). Complicated community-acquired pneumonia should be suspected in any child with pneumonia not responding to appropriate antibiotic treatment within 48-72 h. Common causative organisms are Streptococcus pneumoniae and Staphylococcus aureus.

Viral infections and wheezing-asthma inception in childhood: is there a role for immunomodulation by oral bacterial lysates?

Severe and recurrent infections of the respiratory tract in early childhood constitute major risk factors for the development of bronchial hyper-responsiveness and obstructive respiratory diseases in later life. In the first years of life, the vast majority of respiratory tract infections (RTI) leading to wheezing and asthma are of a viral origin and severity and recurrence are the consequence of a greater exposure to infectious agents in a period when the immune system is still relatively immature. Therefore, boosting the efficiency of the host immune response against viral infections seems to be a rational preventative approach.

Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS.

Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV.

Aneurysmal Dilatation of Ductus Arteriosus and Pulmonary Artery in Association With ACTA2 Mutation.

Actin α2 (ACTA2) is a protein crucial for proper functioning of contractile apparatus in smooth muscles. A specific mutation resulting in substitution of arginine at position 179 by histidine (p.R179 H) in has been shown to be associated with multisystemic smooth muscle dysfunction syndrome.

Viral strategies predisposing to respiratory bacterial superinfections.

Acute respiratory infections are amongst the leading causes of childhood morbidity and mortality globally. Viruses are the predominant cause of such infections, but mixed etiologies with bacteria has for decades raised the question of the interplay between them in causality and determination of the outcome of such infections. In this review, we examine recent microbiological, biochemical, and immunological advances that contribute to elucidating the mechanisms by which infections by specific viruses enable bacterial infections in the airway, and exacerbate them.

Correction: One fold, two functions: cytochrome P460 and cytochrome c'-β from the methanotroph (Bath).

[This corrects the article DOI: 10.1039/C8SC05210G.].

Immune imbalance and activation are associated with lower lung function in youth with perinatally acquired HIV.

High CD8 T-cells and low CD4/CD8 are associated with lower lung function among youth living with perinatally-acquired HIV, despite antiretroviral therapy and CD4 preservation/reconstitution. Understanding these underlying mechanisms is critical to mitigate lung function impairment.

European Respiratory Society guideline on long-term management of children with bronchopulmonary dysplasia.

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and who have been discharged from the hospital, or who were >36 weeks of postmenstrual age. The guideline was based on predefined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the task force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence.

A unique case of vision loss in a patient with hypotrichosis and juvenile macular dystrophy and primary ciliary dyskinesia.

Purpose: We describe a unique case of CDH3-related hypotrichosis with juvenile macular dystrophy (HJMD) and DNAH5-related primary ciliary dyskinesia (PCD) with progressive vision loss in a young Indian female without positive family history. Both mutations in this patient have not been previously described in the literature.

Observations: An 11-year-old girl of Indian descent from a consanguineous family presented to our clinic with poor central visual acuity, recurrent sinopulmonary infections, hypotrichosis, and gradual hearing loss.

One fold, two functions: cytochrome P460 and cytochrome '-β from the methanotroph (Bath).

Nature is adept at utilising highly similar protein folds to carry out very different functions, yet the mechanisms by which this functional divergence occurs remain poorly characterised. In certain methanotrophic bacteria, two homologous pentacoordinate c-type heme proteins have been identified: a cytochrome P460 (cyt P460) and a cytochrome '-β (cyt cp-β). Cytochromes P460 are able to convert hydroxylamine to nitrous oxide (NO), a potent greenhouse gas.