Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987–2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD

Distinct Septin Heteropolymers Co-Exist during Multicellular Development in the Filamentous Fungus <i>Aspergillus nidulans</i>

<div><p>Septins are important components of the cytoskeleton that are highly conserved in eukaryotes and play major roles in cytokinesis, patterning, and many developmental processes. Septins form heteropolymers which assemble into higher-order structures including rings, filaments, and gauzes. In contrast to actin filaments and microtubules, the molecular mechanism by which septins assemble is not well-understood. Here, we report that in the filamentous fungus <i>Aspergillus nidulans</i>, four core septins form heteropolymeric complexes. AspE, a fifth septin lacking in unicellular yeasts, interacts with only one of the core septins, and only during multicellular growth. AspE is required for proper localization of three of the core septins, and requires this same subset of core septins for its own unique cortical localization. The Δ<i>aspE</i> mutant lacks developmentally-specific septin higher-order structures and shows reduced spore production and slow growth with low temperatures and osmotic stress. Our results show that at least two distinct septin heteropolymer populations co-exist in <i>A. nidulans</i>, and that while AspE is not a subunit of either heteropolymer, it is required for assembly of septin higher-order structures found in multicellular development.</p></div

AspE localization is highly cortical and requires AspB^Cdc3, AspA^Cdc11 and AspC^Cdc12, but not AspD^Cdc10.

<p>AspE-GFP is highly cortical throughout early development. Images are arranged chronologically and represent dormant conidia, unicellular polar and multicellular stages of growth. Note <i>aspE-gfp</i> Δ<i>aspA</i>, <i>aspE-gfp</i> Δ<i>aspC, and aspE-gfp</i> Δ<i>aspA</i>Δ<i>aspC</i> strains all showed identical cytoplasmic localization. Scale bar, 5 μm.</p

Interactions among <i>A. nidulans</i> septins in early development.

<p>A) Heterooctamer formation in <i>S. cerevisiae</i> vegetative growth (based on Bertin et al, 2008). The wide end of septin subunit (dark blue) represents the NC interface and the narrow end (gold) represents the G interface. B) Clustal W tree of representative fungal septins. Sc_<i>S. cerevisiae</i>, Ag_<i>A. gossypii,</i> An_<i>A. nidulans</i> and Mo_<i>M. oryzae</i>. C) <i>A. nidulans</i> early developmental stages. I_Isotropic, U_Unicellular polar, and M_Multicellular. Scale bar 5 μm.</p

<i>ΔaspE</i> shows reduced conidial production and slow growth at low temperatures with increased osmoticum.

<p>Wild type and Δ<i>aspE</i> strains were inoculated at the same spore concentration to minimal medium (MM) with or without 1.2 M sorbitol and incubated for 7 or 14 days as indicated. A) Plates were incubated for 7 days at 18°C, 26°C, 30°C, 37°C or 42°C, and colony diameter (mm) was measured. Averages were taken from 3 biological replicates. Error bars show standard deviation. B) Plates were incubated for 7 or 14 days. Colony diameter was measured and conidia were harvested in water and counted. Averages were taken from 3 biological replicates. C) Plates were incubated at 26°C for 7 or 14 days as indicated. Representative colony growth is shown. Note irregular colony periphery and shiny appearance typical of colony autolysis seen in Δ<i>aspE</i> colonies at 14 days.</p

Core septins interact in immunoprecipitation.

<p>Protein was isolated from multicellular stage wildtype and strains carrying a single S-tagged septin. Protein was immunoprecipitated by anti-Stag antibodies, separated by SDS PAGE and either stained with Coomassie Brilliant Blue (left panel) or probed with anti S-tag antibodies (right panel). S-tagged septin used as bait in immunoprecipitation is indicated below lane. Asterisk indicates S-tagged septin. Positions of core septins are indicated on the left. Note AspA^Cdc11 and AspC^Cdc12 are very close in mass and appear to run as a single protein band. Molecular mass markers are indicated on the right. Lane 1)wildtype; 2) AspA^Cdc11-Stag strain; 3) AspB^Cdc3-Stag strain; 4) AspC^Cdc12-Stag strain; 5) AspD^Cdc10-Stag strain; 6) AspE^-Stag strain; 7) Over-exposure of lane 6 to better show immunoprecipitation result. Proteins and predicted mass: AspA^Cdc11 (43 kDa), AspA^Cdc11-Stag (AS, 45 kDa), AspB^Cdc3 (52 kDa), AspB^Cdc3-Stag (BS, 55 kDa), AspC^Cdc12 (44 kDa), AspC^Cdc12-Stag (CS, 46 kDa), AspD^Cdc10 (39 kDa), AspD^Cdc10-Stag (DS, 41 kDa), AspE (65 kDa), AspE-Stag (ES, 67 kDa), AspE-Stag smaller band (Es2, ∼55 kDa).</p

LC-MS/MS Analysis of affinity purified septins.

<p><i>A. nidulans</i> wildtype (WT_No Tag) and septin S-tag strains were grown for 4–5 h (isotropic), 8–9 h (unicellular) and 16 h (multicellular) at 30°C in liquid media with shaking. Developmental stages were monitored by microscopy. Proteins were isolated, immunoprecipitated and analyzed by LC-MS/MS. The average of two biological replicates is shown.</p

Core septins interact in the absence of AspE. AspE does not substitute for a core septin.

<p>Protein was isolated from multicellular stage wildtype and strains carrying a single GFP-tagged septin in combination with a single septin deletion. Protein was immunoprecipitated by anti-GFP antibodies, separated by SDS PAGE and stained with Coomassie Brilliant Blue. GFP-tagged septin used as bait in immunoprecipitation and septin deletion background are indicated below lane. Asterisk indicates GFP-tagged septin. Positions of core septins are indicated on the left and of molecular mass markers on the right. Note, for AspE-GFP immunoprecipitates lanes 5–10, approximately twice the amount of protein was loaded in each lane to improve visualization. Arrowheads indicate nonspecific bands faintly visible in wildtype. Lane 1) <i>aspA^CDC11-gfp ΔaspE</i> strain; 2) <i>aspB^CDC3-gfp ΔaspE</i> strain; 3) <i>aspC^CDC12-gfp ΔaspE</i> strain; 5) <i>aspD^CDC10-gfp ΔaspE</i> strain; 5) wildtype strain; 6) <i>aspE^-gfp</i> strain; 7) <i>aspE^-gfp ΔaspA^cdc11</i> strain; 8) <i>aspE^-gfp ΔaspB^cdc3</i> strain; 9) <i>aspE^-gfp Δ aspC^cdc12</i>strain; 10) <i>aspE^-gfp Δ aspD^cdc10</i>strain.</p

Aplicación de las Tecnologías para la enseñanza de la matemática, física, química y biología: implicaciones didácticas. Experiencias en América Latina

Por fortuna una buena parte de los profesores en Colombia y en América Latina han mantenido su incertidumbre viva y su capacidad crítica como parte de la esencia que orienta su ejercicio profesional en la enseñanza de las ciencias, es así como esta obra presenta una compilación de experiencias que articulan la investigación, la tecnología y la sociedad como una triada sinérgica en el desarrollo de competencias básicas y científicas en los procesos educativos en diferentes niveles de formación, estas experiencias sin duda alguna enriquecen el discurso que alimenta la reflexión crítica y permanente sobre la didáctica de las Ciencias y que en el marco del Simposio Internacional De La Aplicación De La Tecnología Para La Enseñanza De La Matemática, La Física, La Química Y La Biología. El problema es tan complejo como compleja es la humanidad misma, pero definitivamente la creación e implementación de políticas educativas debe estar iluminada por la investigación, por la inversión efectiva de recursos que garanticen la equidad, su implementación, reconocimiento y resignificación del papel del maestro desde su formación inicial