Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China

Asthma,rhinitis and eczema(allergic or non-allergic)have increased throughout the world during the last decades,especially among children.Changes in the indoor environment are suspected to be important causes.China has experienced a dramatic change in indoor environmental exposures during the past two decades.However,such changes and their associations with children’s asthma and other health aspects have not been thoroughly studied.China,Children,Homes,Health(CCHH),Phase I,was a cross-sectional questionnaire survey of 48219 children 1–8 years old in 10 Chinese cities during 2010–2012.The questionnaire includes the International Study of Asthma and Allergies in Childhood(ISAAC)core health questions and additional questions regarding housing,life habits and outdoor environment.In health analyses,children aged 3–6 years old were included.The prevalences of doctor diagnosed asthma varied from 1.7%to 9.8%(mean 6.8%),a large increase from 0.91%in 1999 and 1.50%in2000.The prevalence of wheeze,rhinitis and atopic eczema(last 12 months)varied from 13.9%to 23.7%,24.0%to 50.8%and4.8%to 15.8%,respectively.Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest,except for wheezewhere the highest value was for Urumqi.We found(1)no obvious association between disease prevalences and ambient PM10concentrations and(2)higher prevalences of disease in humid climates with hot summers and cold winters,but with no centrally heated buildings.Associations between the diseases and economic status as indexed by Gross Domestic Product(GDP)requires further study.     

Structure prediction for the down state of a potassium channel voltage sensor

Voltage-gated potassium (Kv) channels, essential for regulating potassium uptake and cell volume in plants and electrical excitability in animals, switch between conducting and non-conducting states as a result of conformational changes in the four voltage-sensing domains (VSDs) that surround the channel pore. This process, known as gating, is initiated by a cluster of positively charged residues on the fourth transmembrane segment (S4) of each VSD, which drives the VSD into a 'down state' at negative voltages and an 'up state' at more positive voltages. The crystal structure of Kv1.2 probably corresponds to the up state, but the local environment of S4 in the down state and its motion in voltage gating remains unresolved. Here we employed several conditional lethal/second-site suppressor yeast screens to determine the transmembrane packing of the VSD in the down state. This screen relies on the ability of KAT1, a eukaryotic Kv channel, to conduct potassium when its VSDs are in the down state, thereby rescuing potassium-transport-deficient yeast. Starting with KAT1 channels bearing conditional lethal mutations, we identified second-site suppressor mutations throughout the VSD that recover yeast growth. We then constructed a down state model of the channel using six pairs of interacting residues as structural constraints and verified this model by engineering suppressor mutations on the basis of spatial considerations. A comparison of this down state model with the up state Kv1.2 structure suggests that the VSDs undergo large rearrangements during gating, whereas the S4 segment remains positioned between the central pore and the remainder of the VSD in both states.     

Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia

Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.     

Orthorhombic crystal structure of an insulin mutant B9Asp at 0.20 nm resolution

Human B9(Ser~i'Asp) insulin, a fast-absorption insulin analogue, was obtained by site-directed mutagenesis at B9 position. The orthorhombic crystal structure of B9Asp insulin was analyzed by crystallography at 0.20 nm resolution. Although no significant change of its overall conformation was observed, the local conformation flanking B9 site differed greatly from native T6 human insulin. The substitution of serine at B9 position by aspartic acid resulted in obvious alteration of local hydrophobic and hydrophilic interactions. As a result, the insulin dimer became unstable and the capability of the hexamer formation was diminished extensively. All these properties contribute to the fast-absorption of B9Asp, In addition, the open state of N-terminus of B-chain, which differs from T- or R- state, might suggest a new conformational state in the monomer or dimer insulin.     

The Generalised Liar Paradox: A Quantum Model and Interpretation

The formalism of abstracted quantum mechanics is applied in a model of the generalized Liar Paradox. Here, the Liar Paradox, a consistently testable configuration of logical truth properties, is considered a dynamic conceptual entity in the cognitive sphere (Aerts, Broekaert, &; Smets, [Foundations of Science 1999, 4, 115–132; International Journal of Theoretical Physics, 2000, 38, 3231–3239]; Aerts and colleagues[Dialogue in Psychology, 1999, 10; Proceedings of Fundamental Approachs to Consciousness, Tokyo ’99; Mind in Interaction]. Basically, the intrinsic contextuality of the truth-value of the Liar Paradox is appropriately covered by the abstracted quantum mechanical approach. The formal details of the model are explicited here for the generalized case. We prove the possibility of constructing a quantum model of the m-sentence generalizations of the Liar Paradox. This includes (i) the truth–falsehood state of the m-Liar Paradox can be represented by an embedded 2m-dimensional quantum vector in a (2m) ^m -dimensional complex Hilbert space, with cognitive interactions corresponding to projections, (ii) the construction of a continuous ‘time’ dynamics is possible: typical truth and falsehood value oscillations are described by Schrödinger evolution, (iii) Kirchoff and von Neumann axioms are satisfied by introduction of ‘truth-value by inference’ projectors, (iv) time invariance of unmeasured state.     

Spider silk proteins: recent advances in recombinant production,structure–function relationships and biomedical applications

Spider dragline silk is an outstanding material made up of unique proteins—spidroins. Analysis of the amino acid sequences of full-length spidroins reveals a tripartite composition: an N-terminal non-repetitive domain, a highly repetitive central part composed of approximately 100 polyalanine/glycine rich co-segments and a C-terminal non-repetitive domain. Recent molecular data on the terminal domains suggest that these have different functions. The composite nature of spidroins allows for recombinant production of individual and combined regions. Miniaturized spidroins designed by linking the terminal domains with a limited number of repetitive segments recapitulate the properties of native spidroins to a surprisingly large extent, provided that they are produced and isolated in a manner that retains water solubility until fibre formation is triggered. Biocompatibility studies in cell culture or in vivo of native and recombinant spider silk indicate that they are surprisingly well tolerated, suggesting that recombinant spider silk has potential for biomedical applications.     

Pet-keeping and its impact on asthma and allergies among preschool children in Shanghai, China

Whether early pet-keeping is a risk factor for children’s asthma and allergies remains controversial. To investigate associations between asthma, allergies and airway symptoms among children and the indoor environment, a cross-sectional study was conducted in 5 districts of Shanghai. A number of 13335 questionnaires (response rate: 85.3%) of 4-6 year old children were analyzed. Families in urban areas have more pets except for dogs than families in suburbs. Fish are the most common pets in urban districts. The prevalence of doctor-diagnosed asthma was 10.3%, wheeze (ever) 28.3%, rhinitis (ever) 54.1%, doctor-diagnosed hay fever 12.6% and eczema (ever) 22.9%. In logistic regression analyses, early furred pet-keeping was positively associated with most of the symptoms and significantly with rhinitis (ever, adjusted OR=1.41, 95% CI=1.14–1.76) and doctor-diagnosed hay fever (1.38, 1.02–1.88). Current furred pet-keeping was significantly negatively associated with doctor-diagnosed asthma (0.57, 0.39–0.83). Persistent furred pet-keeping was significantly positively associated with rhinitis on pet or pollen exposure. However, current pet-keeping is not randomly distributed in the population. Children in families with “allergy” or with “pet avoidance behavior” (due to allergies in the family) have more symptoms, but have avoided cats and dogs, leading to the conclusion that such animals are “protective”, namely the “Healthy Pet-Keeping” effect. Moreover, rodents and birds are risks for children’s health. Fish-keeping is also seemingly a risk. This study indicates that early pet-keeping is a risk factor for asthma and allergies in families with a history of allergies, and part of residents in Shanghai have pet-avoidance behavior.     

An unpublished autograph by Christiaan Huygens: His letter to David Gregory of 19 January 1694

A letter written by Christiaan Huygens to David Gregory (19 January 1694) is published here for the first time. After an introduction about the contacts between the two correspondents, an annotated English translation of the letter is given. The letter forms part of the wider correspondence about the ‘new calculus’, in which L'Hospital and Leibniz also participated, and gives some new evidence about Huygens's ambivalent attitude towards the new developments. Therefore, two mathematical passages in the letter are discussed separately. An appendix contains the original Latin text.     

Lucifensin, the long-sought antimicrobial factor of medicinal maggots of the blowfly Lucilia sericata

A novel homologue of insect defensin designated lucifensin (Lucilia defensin) was purified from the extracts of various tissues (gut, salivary glands, fat body, haemolymph) of green bottle fly (Lucilia sericata) larvae and from their excretions/secretions. The primary sequence of this peptide of 40 residues and three intramolecular disulfide bridges was determined by ESI-QTOF mass spectrometry and Edman degradation and is very similar to that of sapecin and other dipteran defensins. We assume that lucifensin is the key antimicrobial component that protects the maggots when they are exposed to the highly infectious environment of a wound during the medicinal process known as maggot therapy. We also believe that lucifensin is that long-sought larger molecular weight antimicrobial factor of the Lucilia sericata excretions/secretions believed to be effective against pathogenic elements of the wound microbial flora.