Vähähiilisen puurakentamisen aluetaloudelliset vaikutukset Kymenlaaksossa ja Kouvolassa

Tutkimuksessa vertailtiin kolmea päiväkodin rakentamistapaa. Ensimmäisessä materiaalina käytetään mahdollisimman paljon puuta. Toisessa käytetään puun lisäksi soveltuvin osin myös betonia. Kolmas vaihtoehto on moduuleina toteutettava päiväkoti, joka vietäisiin Uudellemaalle ja rakennettaisiin sinne Kouvolan seutukunnan työvoimaa käyttäen. Tulosten mukaan kaikki tutkitut päiväkodin rakennustavat tukevat Kymenlaakson maakunnan ja Kouvolan seutukunnan elintason, työllisyyden, palkkojen ja työtulojen kasvua. Rakentamisen aikana syntyy uusia työpaikkoja useille rakentamisen alihankintaketjun toimialoille. Uusien työpaikkojen määrä on korkein moduulivaihtoehdossa (8,0). Seuraavana on puusta rakentaminen, joka tuo 6,8 uutta työpaikkaa. Betonivaihtoehto tuo vähiten 5,8, uutta työpaikkaa. Tutkimuksen johtopäätös on, että päiväkodin rakentaminen on aluetalouden kannalta myönteinen asia elintasolla ja työllisyydellä mitattuna. Päiväkodin rakentaminen käyttäen mahdollisimman paljon paikallisia puumateriaaleja toisi yhden työpaikan enemmän kuin jos käytettäisiin puun lisäksi soveltuvin osin betonia

Messenger RNA targeting to endoplasmic reticulum stress signalling sites.

Deficiencies in the protein-folding capacity of the endoplasmic reticulum (ER) in all eukaryotic cells lead to ER stress and trigger the unfolded protein response (UPR). ER stress is sensed by Ire1, a transmembrane kinase/endoribonuclease, which initiates the non-conventional splicing of the messenger RNA encoding a key transcription activator, Hac1 in yeast or XBP1 in metazoans. In the absence of ER stress, ribosomes are stalled on unspliced HAC1 mRNA. The translational control is imposed by a base-pairing interaction between the HAC1 intron and the HAC1 5' untranslated region. After excision of the intron, transfer RNA ligase joins the severed exons, lifting the translational block and allowing synthesis of Hac1 from the spliced HAC1 mRNA to ensue. Hac1 in turn drives the UPR gene expression program comprising 7-8% of the yeast genome to counteract ER stress. Here we show that, on activation, Ire1 molecules cluster in the ER membrane into discrete foci of higher-order oligomers, to which unspliced HAC1 mRNA is recruited by means of a conserved bipartite targeting element contained in the 3' untranslated region. Disruption of either Ire1 clustering or HAC1 mRNA recruitment impairs UPR signalling. The HAC1 3' untranslated region element is sufficient to target other mRNAs to Ire1 foci, as long as their translation is repressed. Translational repression afforded by the intron fulfils this requirement for HAC1 mRNA. Recruitment of mRNA to signalling centres provides a new paradigm for the control of eukaryotic gene expression

Overexpression of neutrophil neuronal nitric oxide synthase in Parkinson's disease

Much evidence supports a role of nitric oxide (·NO) and peroxynitrite (ONOO-) in experimental and idiopathic Parkinson's disease (PD); moreover, an overexpression of neuronal nitric oxide synthase (nNOS) was recently reported in the basal ganglia of PD patients. In accord, we previously found a 50% increased ·NO production rate during the respiratory burst of circulating neutrophils (PMN) from PD patients. As PMN express the nNOS isoform, the objective of the present study was to ascertain whether this increased ·NO production is representative of nNOS gene upregulation. PMN were isolated from blood samples obtained from seven PD patients and seven age- and sex-matched healthy donors; nNOS mRNA was amplified by reverse transcriptase-polymerase chain reaction and the products were hybridized with a probe for nNOS. Nitrotyrosine-containing proteins and nNOS were detected by Western blot and NO production rate was measured spectrophotometrically by the conversion of oxymyoglobin to metmyoglobin. The results showed that both ·NO production and protein tyrosine nitration were significantly increased in PMN isolated from PD patients (PD 0.09 ± 0.01 vs 0.06 ± 0.008 nmol min-1 106 cells-1; P < 0.05). In addition, five of the seven PD patients showed about 10-fold nNOS mRNA overexpression; while two of the seven PD patients showed an expression level similar to that of the controls; detection of nNOS protein was more evident in the former group. In summary, it is likely that overexpression of nNOS and formation of ONOO- in PMN cells from PD patients emphasizes a potential causal role of ·NO in the physiopathology of the illness. (C) 2000 Academic Press.Fil: Gatto, Emilia Mabel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Riobó, Natalia A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cherñavsky, Alejandra Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rubio, Andrea. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; ArgentinaFil: Satz, M. Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; ArgentinaFil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentin

Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment.

Biology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. We show that the corona can be selectively displaced with a molecular cue, exposing the 'sticky' core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria

Tos Ferina en una lactante no inmunizada: a propósito de un caso

ResumenIntroducciónLas afecciones respiratorias son un problema de salud común entre los lactantes.Reporte de casoUna lactante de 75 días de edad fue llevada a urgencias por disnea y tos paroxística espasmódica, emetizante y cianosante. No estaba inmunizada contra tos ferina y tuvo contacto con su gemela, que tenía una infección por probable Bordetella pertussis. El diagnóstico de egreso fue bronquiolitis. Días después, reingresó por disnea.DiscusiónEn los lactantes, la tos ferina, el síndrome coqueluchoide y la bronquiolitis tienen manifestaciones clínicas comunes. Este caso resalta la importancia de seguir las guías de práctica clínica y los procedimientos de diagnóstico de B. pertussis, así como el análisis epidemiológico de los casos probables, debido a que de ello depende el tratamiento etiológico y, por lo tanto, el pronóstico de los pacientes.AbstractIntroductionRespiratory tract infections are a common cause of infant morbidity, and even mortality.Case reportA two-month old female was taken to the Emergency Department after she suddenly developed dyspnoea and a paroxysmal, spasmodic, cyanosing cough. Her vaccination scheme was incomplete and she had contact with her twin sister, who had an infection probably caused by Bordetella pertussis. The discharge diagnosis was bronchiolitis. She was re-admitted to hospital a few days later with an exacerbation of her dyspnoea.DiscussionThis case highlights the importance of following the clinical practice guidelines and the standard procedures for the diagnosis of B. pertussis, while the epidemiological context of patients should always be considered. It is important to correctly identify the aetiological agent, as the specific treatment is based on the aetiology, and both of them determine the prognosis of the patients

Genomic epidemiology of the primary methicillin-resistant Staphylococcus aureus clones causing invasive infections in Paraguayan children

Address correspondence to Fátima Rodríguez, [email protected] Staphylococcus aureus (MRSA) is one of the major human pathogens. It could carry numerous resistance genes and virulence factors in its genome, some of which are related to the severity of the infection. An observational, descriptive, cross-sectional study was designed to molecularly analyze MRSA isolates that cause invasive infections in Paraguayan children from 2009 to 2013. Ten representative MRSA isolates of the main clonal complex identified were analyzed with short-read paired-end sequencing and assessed for the virulome, resistome, and phylogenetic relationships. All the genetically linked MRSA isolates were recovered from diverse clinical sources, patients, and hospitals at broad gap periods. The pan-genomic analysis of these clones revealed three major and different clonal complexes (CC30, CC5, and CC8), each composed of clones closely related to each other. The CC30 genomes prove to be a successful clone, strongly installed and disseminated throughout our country, and closely related to other CC30 public genomes from the region and the world. The CC5 shows the highest genetic variability, and the CC8 carried the complete arginine catabolic mobile element (ACME), closely related to the USA300-NAE-ACME+, identified as the major cause of CA-MRSA infections in North America. Multiple virulence and resistance genes were identified for the first time in this study, highlighting the complex virulence profiles of MRSA circulating in the country. This study opens a wide range of new possibilities for future projects and trials to improve the existing knowledge on the epidemiology of MRSA circulating in Paraguay.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Financiamiento para la vinculación de científicos y tecnólogo

Evaluación y rehabilitación neuropsicológica en oncología pediátrica.

Objetivo. El presente trabajo tiene como objetivo el estudio de los efectos neuropsicológicos a largo plazo del cáncer infantil y sus tratamientos así como plantear propuestas para la rehabilitación cognitiva. Método. El método ha consistido en una revisión sistemática de los resultados en la literatura científica acerca de los efectos de la quimioterapia y la radioterapia sobre el SNC y en las funciones cognitivas y conductuales detectados a través de estudios de neuroimagen como calcificaciones y cambios en la sustancia blanca. Presentamos, además, el protocolo de evaluación neuropsicológica ejemplificado con un diagnóstico frecuente que presenta deterioro generalizado. Proponemos un programa de rehabilitación neuropsicológica basado en el Attention Process Training (APT) de Mateer y Sohlberg. Resultado. La radioterapia craneal y el metotrexato producen alteraciones generalizadas que se reflejan en déficit neuropsicológicos: CI, atención, memoria, habilidades académicas y motoras. Conclusiones. El avance en los tratamientos ha supuesto la disminución del número e intensidad de las secuelas. No obstante, sigue siendo frecuente que en los tumores del SNC y en las leucemias aparezcan alteraciones cognitivas y conductuales. La evaluación neuropsicológica continua y los modelos de sustancia blanca nos ayudan a entender estos efectos a largo plazo. Asimismo, esta evaluación es fundamental para diagnosticar los déficit evitando falsas atribuciones y expectativas inadecuadas. Destacamos la necesidad de una unidad de seguimiento y del trabajo interdisciplinario para promover la calidad de vida de los niños con cáncer

Omics as Environmental Health study tools

Deaths caused by environmental pollution are agrowing public health issue. Most of the premature deaths related to pollution are caused by non communicable diseases such as chronic obstructive pulmonary disease, type-2 diabetes, cardiovascular disease and cancer. They are considered complex diseases because of their multicausality and the various mechanisms involved in their emergence and evolution.Knowledge of disease-causing mechanismsis increasing and the identification of disease-associated biomarkers improving thanks to technological progress, in particular that of the technologiesthat are applied to the measurement and interpretation of molecular components—the so-called “Omics” technologies. These technologies have allowed the cellular causes of some complex diseases to be identified: genetic variants of susceptibility or protection to pollutants (Genomics), as well as changes in the DNA (Epigenomics) and their effects on the process of transcription of specific genes for repair, on metabolism or on the non-coding RNA associated with diseases (Transcriptomics). In addition, Proteomics and Metabolomics do not cease to provide information on proteins and metabolites involved in disease processes. Bioinformatics has evolved parallel to the development of omics, which has allowed the results of the measurements of hundreds of molecules to be interpreted and organized into networks that show the relationships among them.Omics are mainly used to develop disease risk models based on population studies, but information on genomes, transcriptomes, epigenomes, microbiomes, proteomes and metabolomesis also used to decipher diseases in order to facilitate prognosis and guide patient treatment, thus contributing to personalized, precision medicine. However, their clinical application is still limited by their cost and their technical, regulatory and ethical implications.</p

As "Ómicas" como ferramenta no estudo da Saúde Ambiental

Deaths caused by environmental pollution are agrowing public health issue. Most of the premature deaths related to pollution are caused by non communicable diseases such as chronic obstructive pulmonary disease, type-2 diabetes, cardiovascular disease and cancer. They are considered complex diseases because of their multicausality and the various mechanisms involved in their emergence and evolution.Knowledge of disease-causing mechanismsis increasing and the identification of disease-associated biomarkers improving thanks to technological progress, in particular that of the technologiesthat are applied to the measurement and interpretation of molecular components—the so-called “Omics” technologies. These technologies have allowed the cellular causes of some complex diseases to be identified: genetic variants of susceptibility or protection to pollutants (Genomics), as well as changes in the DNA (Epigenomics) and their effects on the process of transcription of specific genes for repair, on metabolism or on the non-coding RNA associated with diseases (Transcriptomics). In addition, Proteomics and Metabolomics do not cease to provide information on proteins and metabolites involved in disease processes. Bioinformatics has evolved parallel to the development of omics, which has allowed the results of the measurements of hundreds of molecules to be interpreted and organized into networks that show the relationships among them.Omics are mainly used to develop disease risk models based on population studies, but information on genomes, transcriptomes, epigenomes, microbiomes, proteomes and metabolomesis also used to decipher diseases in order to facilitate prognosis and guide patient treatment, thus contributing to personalized, precision medicine. However, their clinical application is still limited by their cost and their technical, regulatory and ethical implications.Las muertes provocadas por la contaminación ambiental son un problema de salud pública en incremento. La mayoría de las muertes prematuras provocadas por la contaminación son enfermedades no transmisibles, como enfermedad pulmonar obstructiva crónica, diabetes tipo 2, enfermedades cardiovasculares y cáncer. Estas son consideradas enfermedades complejas por su multicausalidad y los diversos mecanismos involucrados en su aparición y evolución. El conocimiento del mecanismo de producción de la enfermedad, y la identificación de biomarcadores asociados a enfermedad está avanzando gracias al avance de la tecnología, y específicamente de la tecnología aplicada a medición e interpretación de componentes moleculares: las tecnologías “ÓMICAS”. Estas han permitido identificar causas celulares de algunas enfermedades complejas: variantes genéticas de susceptibilidad o protección a agentes contaminantes (Genómica), así como cambios sobre el ADN (Epigenómica) y sus efectos en el proceso de transcripción de genes específicos de reparación, metabolismo o bien RNA no codificante asociado a enfermedades (Transcriptómica); además la Proteómica y la Metabolómica aportan constante información sobre las proteínas y metabolitos involucrados en los procesos de enfermedad. Paralelo al desarrollo de las tecnologías ómicas ha evolucionado la bioinformática, que ha permitido la interpretación de los resultados de mediciones de cientos de moléculas para organizarlos en redes que traducen las relaciones entre ellas. Las tecnologías ómicas se aplican principalmente para determinar modelos de riesgo de enfermedad en base a estudios poblacionales, pero también la información del genoma, transcriptoma, el epigenoma, el microbioma, el proteoma y el metaboloma se utilizarán para ayudar a descifrar la enfermedad a fin de facilitar el pronóstico y guiar el tratamiento de pacientes, ayudando a la medicina individualizada y medicina de precisión. Sin embargo, su aplicación clínica está aún limitada por el costo y las implicaciones técnicas, regulatorias y éticas.As mortes causadas pela poluição ambiental sãoum problema de saúde pública crescente. A maioria das mortes prematuras causadas por contaminação sãodoençasnãotransmissíveis, como doença pulmonar obstrutiva crónica, diabetes tipo 2, doenças cardiovasculares e cancro. Estas são consideradas doenças complexas pela sua multicausalidade e pelos vários mecanismos envolvidos no seu aparecimento e evolução. O conhecimento do mecanismo de produção da doença e a identificação de biomarcadores associados à doençaestá a avançar graçasao desenvolvimento da tecnologia e, especificamente, à tecnologia aplicada à medição e interpretação de componentes moleculares: as tecnologias “ÓMICAS”. Estas permitiram identificar as causas celulares de algumasdoenças complexas: variantes genéticas de suscetibilidade ouproteção a agentes contaminantes (Genómica), bem como alterações no DNA (Epigenética) e os seusefeitos no processo de transcrição de genes específicos de reparação, metabolismo ou RNAnão-codificanteassociado a doenças (Transcriptómica);acresce a Proteómica e a Metabolómica que fornecem informação sobre as proteínas e metabólitosenvolvidos nos processos de doença. Paralelamente ao desenvolvimento das novas técnicas biotecnológicas, geralmente denominadas por “Ómicas”, evoluiu a bioinformática, o que permitiu a interpretação dos resultados das análises de centenas de moléculas para organizá-las em redes que traduzem as relações entre elas. As tecnologias “Ómicas” aplicam-se principalmente para determinar modelos de risco de doença com base em estudos populacionais, mas igualmente a informação do genoma, do transcriptoma, do epigenoma, do microbioma, do proteoma e do metaboloma será usada para ajudar a decifrar a doença, a fim de facilitar o prognóstico e orientar o tratamento dos pacientes, auxiliado a medicina individualizada e a medicina de precisão. No entanto, a sua aplicação clínica ainda é limitada pelo custo e implicações técnicas, regulamentares e éticas

Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney

Glutamine, the most abundant amino acid in mammals, is critical for cell and organ functions. Its metabolism depends on the ability of cells to take up or release glutamine by transporters located in the plasma membrane. Several solute carrier (SLC) families transport glutamine, but the SLC38 family has been thought to be mostly responsible for glutamine transport. We demonstrate that despite the large number of glutamine transporters, the loss of Snat3/Slc38a3 glutamine transporter has a major impact on the function of organs expressing it. Snat3 mutant mice were generated by N-ethyl-N-nitrosurea (ENU) mutagenesis and showed stunted growth, altered amino acid levels, hypoglycemia, and died around 20 days after birth. Hepatic concentrations of glutamine, glutamate, leucine, phenylalanine, and tryptophan were highly reduced paralleled by downregulation of the mTOR pathway possibly linking reduced amino acid availability to impaired growth and glucose homeostasis. Snat3-deficient mice had altered urea levels paralleled by dysregulation of the urea cycle, gluconeogenesis, and glutamine synthesis. Mice were ataxic with higher glutamine but reduced glutamate and gamma-aminobutyric acid (GABA) levels in brain consistent with a major role of Snat3 in the glutamine-glutamate cycle. Renal ammonium excretion was lower, and the expression of enzymes and amino acid transporters involved in ammoniagenesis were altered. Thus, SNAT3 is a glutamine transporter required for amino acid homeostasis and determines critical functions in various organs. Despite the large number of glutamine transporters, loss of Snat3 cannot be compensated, suggesting that this transporter is a major route of glutamine transport in the liver, brain, and kidney