Early growth and adult health: focus on blood pressure, glucose tolerance status and body composition

Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Thesis studies aimed to characterize associations between early growth and some components of the metabolic syndrome cluster. Participants belong to two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. In the 65-75 year old men and women, the well-known inverse relationship between birth weight and systolic blood pressure (SBP) was confined to people who had established hypertension. Among them a 1-kg increase in birth weight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in SBP. This relationship was further confined to people with the prevailing Pro12Pro polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene. People with low birth weight were more likely to receive angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03), and, again, this relationship was confined to the carriers of the Pro12Pro (p=0.01 for interaction). These results suggest that the inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the renin-angiotensin system leading to raised BP levels. Habitual physical activity protected men and women who were small at birth, and thus at increased risk for the development of type 2 diabetes, against glucose intolerance more strongly. Among subjects with birth weight ≤3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Rapid gain in body mass index (BMI), i.e. crossing from an original BMI percentile to a higher one, before the age of 2 years increased adult lean mass index (LMI, lean mass/height squared) without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in LMI, resulted in a relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.

Spotless decided per incuriam? - A contrary view

The article considers the implications of the decision of the High Court in Spotless Services Pty Ltd (1996) 141 ALR 92; 34 ATR 183. It argues in particular that the decision was made per incuriam.

FTIR-spektroskopia kasviuutteiden analysoinnissa

FTIR-spektroskopia (Fourier-muunnosinfrapunaspektroskopia) on nopea analyysimenetelmä. Fourier-laitteissa interferometrin käyttäminen mahdollistaa koko infrapunataajuusalueen mittaamisen muutamassa sekunnissa. ATR-liitännäisellä varustetun FTIR-spektrometrin käyttö ei edellytä juuri näytteen valmistusta ja siksi menetelmä on käytössä myös helppo. ATR-liitännäinen mahdollistaa myös monien erilaisten näytteiden analysoinnin. Infrapunaspektrin mittaaminen onnistuu myös sellaisista näytteistä, joille perinteisiä näytteenvalmistusmenetelmiä ei voida käyttää. FTIR-spektroskopian avulla saatu tieto yhdistetään usein tilastollisiin monimuuttuja-analyyseihin. Klusterianalyysin avulla voidaan spektreistä saatu tieto ryhmitellä samanlaisuuteen perustuen. Hierarkkisessa klusterianalyysissa objektien välinen samanlaisuus määritetään laskemalla niiden välinen etäisyys. Pääkomponenttianalyysin avulla vähennetään datan ulotteisuutta ja luodaan uusia korreloimattomia pääkomponentteja. Pääkomponenttien tulee säilyttää mahdollisimman suuri määrä alkuperäisen datan variaatiosta. FTIR-spektroskopian ja monimuuttujamenetelmien sovellusmahdollisuuksia on tutkittu paljon. Elintarviketeollisuudessa sen soveltuvuutta esimerkiksi laadun valvontaan on tutkittu. Menetelmää on käytetty myös haihtuvien öljyjen kemiallisten koostumusten tunnistukseen sekä öljykasvien kemotyyppien havaitsemiseen. Tässä tutkimuksessa arvioitiin menetelmän käyttöä suoputken uutenäytteiden luokittelussa. Tutkimuksessa suoputken eri kasvinosien uutenäytteiden FTIR-spektrejä vertailtiin valikoiduista puhdasaineista mitattuihin FTIR-spektreihin. Puhdasaineiden FTIR-spektreistä tunnistettiin niiden tyypilliset absorptiovyöhykkeet. Furanokumariinien spektrien intensiivisten vyöhykkeiden aaltolukualueet valittiin monimuuttuja-analyyseihin. Monimuuttuja-analyysit tehtiin myös IR-spektrin sormenjälkialueelta aaltolukualueelta 1785-725 cm-1. Uutenäytteitä pyrittiin luokittelemaan niiden keräyspaikan ja kumariinipitoisuuden mukaan. Keräyspaikan mukaan ryhmittymistä oli havaittavissa, mikä selittyi vyöhykkeiden aaltolukualueiden mukaan tehdyissä analyyseissa pääosin kumariinipitoisuuksilla. Näissä analyyseissa uutenäytteet pääosin ryhmittyivät ja erottuivat kokonaiskumariinipitoisuuksien mukaan. Myös aaltolukualueen 1785-725 cm-1 analyyseissa havaittiin keräyspaikan mukaan ryhmittymistä, mitä kumariinipitoisuudet eivät kuitenkaan selittäneet. Näihin ryhmittymisiin vaikuttivat mahdollisesti muiden yhdisteiden samanlaiset pitoisuudet näytteissä. Analyyseissa käytettiin myös muita aaltolukualueita, mutta tulokset eivät juuri poikenneet aiemmista. 2. kertaluvun derivaattaspektrien monimuuttuja-analyysit sormenjälkialueelta eivät myöskään muuttaneet tuloksia havaittavasti. Jatkotutkimuksissa nyt käytettyä menetelmää on mahdollista edelleen kehittää esimerkiksi tutkimalla monimuuttuja-analyyseissa 2. kertaluvun derivaattaspektreistä suppeampia, tarkkaan valittuja aaltolukualueita.

Crystal structures of Salmonella typhimurium propionate kinase and its complex with Ap4A: evidence for a novel Ap4A synthetic activity

Propionate kinase catalyses the last step in the anaerobic breakdown of L-threonine to propionate in which propionyl phosphate and ADP are converted to propionate and ATR Here we report the structures of propionate kinase (TdcD) in the native form as well as in complex with diadenosine 5 ',5 '''-P-1,P-4-tetraphosphate (AP(4)A) by X-ray crystallography. Structure of TdcD obtained after cocrystallization with ATP showed Ap(4)A bound to the active site pocket suggesting the presence of Ap(4)A synthetic activity in TdcD. Binding of Ap(4)A to the enzyme was confirmed by the structure determination of a TdcD-Ap(4)A complex obtained after cocrystallization of TdcD with commercially available Ap(4)A. Mass spectroscopic studies provided further evidence for the formation of Ap(4)A by propionate kinase in the presence of ATP. In the TdcD-Ap(4)A complex structure, Ap(4)A is present in an extended conformation with one adenosine moiety present in the nucleotide binding site and other in the proposed propionate binding site. These observations tend to support direct in-line transfer of phosphoryl group during the kinase reaction.

Effect of SDS on human hair: Study on the molecular structure and morphology

This paper presents a model study to understand the effect of surfactants on the physicochemical properties of human hair. FT-IR ATR spectroscopy has been employed to understand the chemical changes induced by sodium dodecyl sulfate (SDS) on human scalp hair. In particular, the SDS induced changes in the secondary structure of protein present in the outer protective layer of hair, i.e. cuticle, have been investigated. Conformational changes in the secondary structure of protein were studied by curve fitting of the amide I band after every phase of SDS treatment. It has been found that SDS brings rearrangements in the protein backbone conformations by transforming beta-sheet structure to random coil and beta-turn. Additionally, AFM and SEM studies were carried out to understand the morphological changes induced on the hair surface. SEM and AFM images demonstrated the rupture and partial erosion of cuticle sublayers.

Angelman Syndrome Protein UBE3A Interacts with Primary Microcephaly Protein ASPM, Localizes to Centrosomes and Regulates Chromosome Segregation

Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH) proteins localize at the centrosome. Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome (also characterized by severe microcephaly) protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. To gain insight into the function of the most commonly mutated MCPH gene ASPM, we used the yeast two-hybrid technique to screen a human fetal brain cDNA library with an ASPM bait. The analysis identified Angelman syndrome gene product UBE3A as an ASPM interactor. Like ASPM, UBE3A also localizes to the centrosome. The identification of UBE3A as an ASPM interactor is not surprising as more than 80% of Angelman syndrome patients have microcephaly. However, unlike in MCPH, microcephaly is postnatal in Angelman syndrome patients. Our results show that UBE3A is a cell cycle regulated protein and its level peaks in mitosis. The shRNA knockdown of UBE3A in HEK293 cells led to many mitotic abnormalities including chromosome missegregation, abnormal cytokinesis and apoptosis. Thus our study links Angelman syndrome protein UBE3A to ASPM, centrosome and mitosis for the first time. We suggest that a defective chromosome segregation mechanism is responsible for the development of microcephaly in Angelman syndrome.

Optimization of bus allocation to depots by minimizing dead kilometers

In metropolitan cities, public transportation service plays a vital role in mobility of people, and it has to introduce new routes more frequently due to the fast development of the city in terms of population growth and city size. Whenever there is introduction of new route or increase in frequency of buses, the nonrevenue kilometers covered by the buses increases as depot and route starting/ending points are at different places. This non-revenue kilometers or dead kilometers depends on the distance between depot and route starting point/ending point. The dead kilometers not only results in revenue loss but also results in an increase in the operating cost because of the extra kilometers covered by buses. Reduction of dead kilometers is necessary for the economic growth of the public transportation system. Therefore, in this study, the attention is focused on minimizing dead kilometers by optimizing allocation of buses to depots depending upon the shortest distance between depot and route starting/ending points. We consider also depot capacity and time period of operation during allocation of buses to ensure parking safety and proper maintenance of buses. Mathematical model is developed considering the aforementioned parameters, which is a mixed integer program, and applied to Bangalore Metropolitan Transport Corporation (BMTC) routes operating presently in order to obtain optimal bus allocation to depots. Database for dead kilometers of depots in BMTC for all the schedules are generated using the Form-4 (trip sheet) of each schedule to analyze depot-wise and division-wise dead kilometers. This study also suggests alternative locations where depots can be located to reduce dead kilometers. Copyright (C) 2015 John Wiley & Sons, Ltd.

The role of the term spread in an augmented Taylor rule: An empirical investigation

Using US data for the period 1967:5-2002:4, this paper empirically investigates the performance of an augmented version of the Taylor rule (ATR) that (i) allows for the presence of switching regimes, (ii) considers the long-short term spread in addition to the typical variables, (iii) uses an alternative monthly indicator of general economic activity suggested by Stock and Watson (1999), and (iv) considers interest rate smoothing. The estimation results show the existence of switching regimes, one characterized by low volatility and the other by high volatility. Moreover, the scale of the responses of the Federal funds rate to movements in the term spread, inflation and the economic activity index depend on the regime. The estimation results also show robust empirical evidence that the ATR has been more stable during the term of office of Chairman Greenspan than in the pre-Greenspan period. However, a closer look at the Greenspan period shows the existence of two alternative regimes and that the response of the Fed funds rate to inflation has not been significant during this period once the term spread is considered.

Investigations of Pyrrole-Imidazole Polyamide Effects on DNA Replication

Pyrrole–Imidazole polyamides are programmable, cell-permeable small molecules that bind in the minor groove of double-stranded DNA sequence-specifically. Polyamide binding has been shown to alter the local helical structure of DNA, disrupt protein-DNA interactions, and modulate endogenous gene expression. Py–Im polyamides targeted to the androgen receptor-DNA interface have been observed to decrease expression of androgen-regulated genes, upregulate p53, and induce apoptosis in a hormone-sensitive prostate cancer cell line. Here we report that androgen response element (ARE)-targeted polyamides induced DNA replication stress in a hormone-insensitive prostate cancer cell line. The ATR checkpoint kinase was activated in response to this stress, causing phosphorylation of MCM2, and FANCD2 was monoubiquitinated. Surprisingly, little single-stranded DNA was exhibited, and the ATR targets RPA2 and Chk1 were not phosphorylated. We conclude that polyamide induces relatively low level replication stress, and suggest inhibition of the replicative helicase as a putative mechanism based on in vitro assays. We also demonstrate polyamide-induced inhibition of DNA replication in cell free extracts from X. laevis oocytes. In this system, inhibition of chromatin decondensation is observed, preventing DNA replication initiation. Finally, we show that Py-Im polyamides targeted to the ARE and ETS binding sequence downregulate AR- and ERG-driven signaling in a prostate cancer cell line harboring the TMPRSS2-ERG fusion. In a mouse xenograft model, ARE-targeted polyamide treatment reduced growth of the tumor.

Fixação de complexo de ferro II em matriz de poli(acrilato de sódio)

Neste trabalho estudou-se a complexação do poli(acrilato de sódio), PAS, com aminpentacianoferrato de sódio,APCF. As reações de complexação ocorreram imediatamente com a formação de uma coloração amarela com total solubilização do polímero na solução 0,032 M molar do complexo. As soluções mostraram-se estáveis por 48 h e após esse período observou-se alterações na natureza do complexo polimérico com a formação de precipitado. O UV foi usado como ferramenta de caracterização do complexo. O máximo de absorção obtido após dissolução imediata foi de 405 nm com desvio para o azul (398 nm) e um pequeno efeito hipercrômico. As amostras mantidas à temperatura ambiente por mais de 48 h deram origem a precipitados, que como a solução, absorveram com máximo de 364, 389 e 398 nm. O Complexo PAS-APCF foi também caracterizado através de FTIR por ATR e apresentou pequenas variações no espectro do material de partida (PAS). Um incremento na intensidade da deformação axial assimétrica do grupo carboxilato (1651 cm-1) e a presença do estiramento em 2055 cm-1 do grupo cianeto, diferentemente do APCF (2048 cm-1), confirmaram a formação do complexo PAS-APCF. As freqüências de absorção observadas para o complexo foram compatíveis com a presença de estruturas mono e bidentadas de complexação. As análises de TGA e DSC também foram utilizadas para a caracterização das estruturas. O estudo modelo envolvendo a complexação de sais sódicos de diácidos orgânicos de diferentes tamanhos de cadeia (oxalato, malonato, succinato, glutarato e adipato), diferentemente do PAS, promoveu um desvio para o vermelho na frequência máxima de absorção junto de um pequeno efeito hipercrômico (421 nm). Esta variação pode também ser observada quando do emprego de acetato de sódio, indicando, provavelmente, apenas a formação de estruturas monodentadas

Educação infantil e direito: práticas de controle como campo de análise

O presente estudo objetiva colocar em análise a Edu cação Infantil como um direito incorporado às políticas públicas para a infância, a partir de 1988, no contexto da nova Constituição Federal. A universalização do acesso à escola desde o nascimento é celebrada como uma conquista, em nome do direito, mas, como isto se dá na prática, para além da legislação? A partir de análises de implicação, conforme propõe René Lourau, colocamos em questão o que nos une ao campo da Educação Infantil enquanto direito da primeira infâ ncia, problematizando a própria condição dos especialismos que atravessam e são atr avessados no cotidiano dos estabelecimentos de atendimento. A construção da Educação Infantil como direito, no contexto da sociedade de controle, obriga pensar em relações de direito, responsabilidade, acesso e coerção, apontadas como fundamentais à boa formação. Tendo como norte o caminho genealógico proposto por Foucault, interessa pensar os sentidos que produzem este ou aquele caminho. Por certo, não é a formulação de um instrumento, de um dispositivo, uma lei, por si só, que nos leva a algo, mas as suas formas de aplicação. Trazemos para a discussão , então, as produções de verdades, as relações de saber-poder e, consequentemente, as subjetividades que vão se constituindo em nome da garantia do direito. Nesta perspectiva, o uso de alguns conceitos como cidadania e direitos, como paradigmas, pode acabar nos engessando em conceitos modelares e no enquadramento como discurso de oportunidades iguais para todos. Consideramos, assim, a possibilidade de se estabelecer na Educação Infantil um espaço redimensionado enquanto fluxo de resistências na sociedade de controle (PASSETTI), n ão no sentido de institucionalizar as crianças, para enquadrá-las em comportamentos idealizados, mas para trabalhar firmando constantemente a importância de um olhar sensível para o entorno, os devires na perspectiva de Deleuze os sorrisos, os gestos, as diferenças

Avaliação de microplásticos em praias da Baía de Guanabara, Rio de Janeiro, RJ, Brasil

Neste trabalho foram analisados sedimentos marinhos de três praias da Baía de Guanabara (praia de São Bento e praia da Bica, na Ilha do Governador, e praia de São Francisco, em Niterói), Rio de Janeiro, para avaliar a presença de microplásticos (fragmentos plásticos com tamanho ≤ 5 mm) nestes ambientes. Os detritos plásticos visíveis (macroplástico) foram separados dos sedimentos manualmente e pesados. Os detritos plásticos não visíveis foram separados por densidade com solução saturada de cloreto de sódio. Os fragmentos plásticos obtidos com a separação por densidade foram caracterizados por microscopia óptica para avaliar forma e superfície, e foram classificados e quantificados em função de seu tamanho. Os fragmentos microplásticos foram separados e caracterizados por espectrometria de absorção na região do infravermelho por reflexão atenuada (ATR FT IR). Os espectros obtidos foram comparados com espectros padrão de polímeros. As três praias se apresentam contaminadas com lixo macroplástico e com lixo microplástico. Na praia da Bica, foram coletados 173 fragmentos, dos quais 73% são microplásticos. Na praia de São Bento foram 81 fragmentos e na praia de São Francisco foram 73 fragmentos, dos quais 70% e 86%, respectivamente, são microplásticos. Nas três praias foram encontrados fragmentos microplásticos de poliestireno expandido. Nas praias da Bica e de São Bento foram encontrados fragmentos de polietileno; nas praias de São Bento e São Francisco foram encontrados fragmentos microplásticos de polipropileno. O descarte irregular de lixo e atividades industriais e comerciais no entorno da baía podem ser apontados como possíveis fontes contaminantes

Preparação e Avaliação da Atividade Catalítica de Polímeros de Condensação de Metilpiridinas e Tereftalaldeído em Reações de Nitroaldol e Cicloadição Heterodipolar [3+2]

Nesse estudo, foram preparadas bases poliméricas derivadas de 2,6-dimetilpiridinas e tereftaladeído utilizando a 2,4,6-trimetilpiridina como agente de reticulação. As resinas foram sintetizadas sob aquecimento convencional e purificadas por precipitação em metanol, apresentando rendimentos variando de 59 a 95%. Os copolímeros produzidos foram caracterizados por análise termogravimétrica (TGA), ressonância nuclear magnética de núcleo de hidrogênio (RMN-1H) e espectroscopia na região do infravermelho com técnica de ATR (FTIR - ATR), além de sua atividade básica. A capacidade catalítica do material produzido foi avaliada em reações nitroaldólicas, do tipo Henry, tanto em aquecimento convencional quanto com o uso de reator de micro-ondas. Não sendo observada atividade catalítica significativa para as resinas testadas, nestas reações. O material polimérico produzido também foi testado como suporte para cobre na catálise de reações de cicloadição heterodipolar do tipo [3+2] com benzilazida e propiolato de etila, para a formação de triazóis, processadas em reator de micro-ondas e sob aquecimento convencional. A reação mostrou-se regiosseletiva e processos de reciclo do catalisador se mostrou eficiente em reações consecutivas