Boron Phosphate and Aluminum Phosphate Aerogels

Anhydrous sol-gel condensation of triethyl phosphate [(CH3CH2O)3PO] with boron trichloride (BCL3 ) or triethyl aluminum [(CH3CH2 ) 3A1] in organic solvents, led to formation of metallophosphate gels. The pore fluid of the gels was removed under supercritical conditions in a pressurized vessel to form aerogels. The aerogels were then calcined at progressively higher temperatures to produce high surface area phosphates. Since the initial gel reagent mixtures contained several NMR active nuclei, the condensation chemistry prior to the gel point was monitored by solution nB NMR. The surface areas, distribution of pore sizes, and total pore volumes of the aerogel products were determined using nitrogen gas physisorption methods

Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants

RATIONALE: Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood. OBJECTIVES: To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g. METHODS: Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age. MEASUREMENTS AND MAIN RESULTS: After adjusting for covariates, we found that maternal smoking prior to preterm birth increased the odds of having an infant with BPD by twofold (P = 0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the neonatal intensive care unit admission. Preexisting hypertension was associated with a twofold (P = 0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. Twenty-two percent of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. CONCLUSIONS: We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking not only will lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants

Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH); however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signaling pathways with the risk for BPD or PH. We prospectively enrolled infants with gestational age <34 wk and collected blood samples during their first week of life. BPD and PH were assessed at 36 wk postmenstrual age. Samples were assayed for each of the 1,121 peptides included in the SOMAscan scan technology, with subsequent pathway analysis. Of 102 infants in the study, 82 had BPD, and 13 had PH. Multiple angiogenic proteins (PF-4, VEGF121, ANG-1, bone morphogenetic protein 10 [BMP10], hepatocyte growth factor (HGF), ANG-2) were associated with the subsequent diagnosis of BPD; and FGF-19, PF-4, connective tissue activating peptide (CTAP)-III, and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH. We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research

Early Pulmonary Vascular Disease in Preterm Infants Is Associated with Late Respiratory Outcomes in Childhood

Rationale: Early pulmonary vascular disease (PVD) after preterm birth is associated with a high risk for developing bronchopulmonary dysplasia (BPD), but its relationship with late respiratory outcomes during early childhood remains uncertain. Objectives: To determine whether PVD at 7 days after preterm birth is associated with late respiratory disease (LRD) during early childhood. Methods: This was a prospective study of preterm infants born before 34 weeks postmenstrual age (PMA). Echocardiograms were performed at 7 days and 36 weeks PMA. Prenatal and early postnatal factors and postdischarge follow-up survey data obtained at 6, 12, 18, and 24 months of age were analyzed in logistic regression models to identify early risk factors for LRD, defined as a physician diagnosis of asthma, reactive airways disease, BPD exacerbation, bronchiolitis, or pneumonia, or a respiratory-related hospitalization during follow-up. Measurements and Main Results: Of the 221 subjects (median, 27 wk PMA; interquartile range, 25-28 and 920 g; interquartile range, 770-1090 g) completing follow-up, 61% met LRD criteria. Gestational diabetes and both mechanical ventilator support and PVD at 7 days were associated with LRD. The combination of PVD and mechanical ventilator support at 7 days was among the strongest prognosticators of LRD (odds ratio, 8.1; confidence interval, 3.1-21.9; P <0.001). Modeled prenatal and early postnatal factors accurately informed LRD (area under the curve, 0.764). Adding BPD status at 36 weeks PMA to the model did not change the accuracy (area under the curve, 0.771). Conclusions: Early echocardiographic evidence of PVD after preterm birth in combination with other perinatal factors is a strong risk factor for LRD, suggesting that early PVD may contribute to the pathobiology of BPD

Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia

RATIONALE: Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown. OBJECTIVES: To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA). METHODS: Prospectively enrolled preterm infants with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH. MEASUREMENTS AND MAIN RESULTS: A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03-1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33). Infants with late PH had greater duration of oxygen therapy and increased mortality in the first year of life (P < 0.05). CONCLUSIONS: Early pulmonary vascular disease is associated with the development of BPD and with late PH in preterm infants. Echocardiograms at 7 days of age may be a useful tool to identify infants at high risk for BPD and PH

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Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PBand PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5´-deiodinase I (5´-DI) activity to &lt; 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein-coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress-related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression. could be obtained that correlate with clinical and pathological end points in rats, and determine whether profiles are predictive of the carcinogenic potential of each chemical in rats. Materials and Methods In Vivo Studies Adult male Crl:CD (SD)IGS BR rats, approximately 8 weeks of age, were treated with NaI, PB, and PTU for 14 consecutive days. NaI, PB, and PTU were purchased from Sigma Chemical Company (St. Louis, MO). Rats (n = 20/group) were dosed by oral gavage with vehicle (water or 0.25% methylcellulose), NaI (0.1, 1, 10, or 100 mg/kg/day), PB (100 mg/kg/day), or PTU (10 mg/kg/day) at a dose volume of 5 mL/kg. NaI was dissolved in water, whereas PB and PTU were dissolved in methylcellulose. On day 15, all rats were euthanized by carbon dioxide anesthesia and exsanguination. Blood samples were collected from the inferior vena cava of each animal at necropsy to measure serum levels of TSH, T 4 , T 3 , and reverse T 3 (rT 3 ). Terminal body, thyroid gland, and liver weights were recorded for the first 10 animals of each dose group. The thyroid gland and surrounding tissue from the first 10 animals of each dose group were processed for histopathological evaluation. A liver sample from the first five animals of each dose group was processed to measure 5´-deiodinase I (5´-DI) and uridine diphosphateglucuronyltransferase (UDPGT) activity. Thyroid glands from the last 10 animals (five from methylcellulose group) from each dose group were removed and placed in RNALater (Ambion, Austin, TX) overnight at 4°C. The next day, thyroids were removed from the RNALater and stored at -80°C until processed for total RNA. The research described in this publication was conducted in a laboratory accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International, and the investigators complied with the regulations and standards of the Animal Welfare Act and adhered to the principles of the Guide for the Care and Use of Laboratory Animals (National Research Council 1996). Pathological Evaluations After euthanization the thyroid glands and surrounding tissue from the first 10 animals from each group were removed and placed into formalin fixative for at least 48 hr before trimming and weighing. After fixation, one individual performed a final dissection under a dissecting microscope. This was done in order to reduce the variability of the dissection procedure, thereby reducing the variability of the thyroid gland weights. Organ weights were calculated relative to body weight. The formalin-fixed thyroid glands were examined microscopically. Hormonal Measurements Blood was collected at the time of euthanization from all animals. Serum was prepared and stored between -65°C and -85°C until analyzed for serum hormone concentrations. Serum TSH (Amersham Biosciences Corp., Piscataway, NJ), T 3 and T 4 (Diagnostic Products Corp., Los Angeles, CA), and rT 3 (Polymedco Corp., Cortlandt Manor, NY) concentrations were measured using commercially available RIA kits. Microsomal Preparations At necropsy, a section of the liver from the first five animals from each group was removed, and hepatic microsomes were prepared for biochemical evaluation. A portion of the liver was homogenized (1 g tissue/8 mL buffer) in buffer containing 50 mM Tris-HCl, 0.25 M sucrose, and 5.4 mM EDTA, pH 7.4. The homogenates were centrifuged at 15,000 × g for 15 min at 4°C. The resulting supernatants were removed and centrifuged at 100,000 × g for 70 min at 4°C; these pellets contained the microsomal fractions. The microsomal pellets were resuspended in the homogenization buffer at a protein concentration of 10-20 mg/mL, aliquoted, and stored between -65°C and -85°C until analyzed for UDPGT and 5´-DI. The protein content of the microsomes was measured before and after analyses by the BioRad method 5´-Deiodenase I Measurements Microsomal 5´-DI activity was determined using modifications of the methods of PazosMoura et al. (1991) and UDPGT Measurements Microsomal UDPGT activity was determined spectrophotometrically using a modification of the method of Microarray Analysis RNA preparation and analysis was done according to the Affymetrix-recommended protocol (Affymetrix 2002). Briefly, total RNA from four animals from each dose group was prepared individually using the TRIzol procedure (Invitrogen, Carlsbad, CA) and cleaned using the Qiagen RNeasy mini RNA cleanup protocol (Qiagen, Valencia, CA). The integrity of each RNA sample was determined using an Agilent 2100 Bioanalyzer (Agilent, Foster City, CA). After this, double-stranded cDNA from three of the four samples was prepared from 16 µg of total RNA using Superscript II reverse transcriptase (Invitrogen) and a T7 primer (Genset, Boulder, CO) for first-strand synthesis, and DNA polymerase and ligase (Invitrogen) for second-strand synthesis. Subsequently, labeled cRNA was synthesized from the cDNA using the Enzo RNA transcript labeling kit (Affymetrix, Santa Clara, CA) according to the manufacturer&apos;s instructions. Approximately 20 µg of biotin-labeled cRNA was then fragmented in a solution of 40 mM Tris-acetate, pH 8.1, 100 mM KOAc, and 30 mM MgOAc at 94°C for 35 min. Labeled cRNA was hybridized to the Affymetrix GeneChip Test2 Array (Affymetrix) to verify the quality of labeled cRNA. After this, cRNA was hybridized to the Affymetrix Rat Genome U34A GeneChip Probe Array (RG-U34A; Affymetrix). The cRNA in hybridization Gene expression profiles of rat thyroid toxicity Environmental Health Perspectives • VOLUME 113 | NUMBER 10 | October 2005 1355 cocktail was incubated overnight at 45°C while rotating in a hybridization oven. After approximately 16 hr of hybridization, the cocktail was removed and the arrays were washed and stained in a Fluidics Station 400 (Affymetrix) according to the Affymetrixrecommended protocol (Affymetrix 2002). Briefly, several cycles of washes were done initially with a nonstringent buffer (1 M NaCl, 67 mM NaH 2 PO 4 , 6.7 mM EDTA, 0.01% Tween 20) at 25°C and then with stringent buffer [100 mM MES, 0.1 M Na + , 0.01% Tween 20] at 50°C. The arrays were then stained in streptavidin phycoerythrin (SAPE) solution (10 µg/mL SAPE, 2 mg/mL acetylated BSA, 100 mM MES, 1 M Na + , 0.05% Tween 20) at 25°C, washed in nonstringent buffer, stained in antibody solution (2 mg/mL acetylated BSA, 100 mM MES, 1 M [Na + ], 0.05% Tween 20, 0.1 mg/mL normal goat IgG, 3 µg/mL anti-streptavidin biotinylated antibody) at 25°C, stained again in SAPE solution at 25°C, and then washed again in nonstringent buffer at 30°C. Arrays were then scanned on a GeneArray scanner (Agilent). Image analysis, quantification of raw gene expression values, mismatched probe background subtraction, and present/absent calls were performed using the Microarray Suite software (version 5.0; Affymetrix). Data Analysis Differential gene expression was determined by the regularized t-test, which uses a Bayesian procedure (Baldi and Long 2001). Briefly, the expression level of each gene is assumed to be from a normal distribution with µ and σ 2 . Using a conjugate prior, the mean of the posterior (MP) estimate of µ is the sample mean. The MP estimate of σ 2 is where n is the sample size, s 2 is the sample variance, v 0 is the degrees of freedom of the prior (a value of 10 is used in the analysis), and σ 0 2 is the mean of sample variances of genes in the neighborhood of the gene under consideration. The neighborhood is the 50 genes with sample means immediately above and below the sample mean of the gene under consideration; that is, the neighborhood consists of the 101 genes centered on the gene. After the MP estimates of µ and σ 2 are obtained, the t-test of unequal variances is used to calculate a p-value of differential expression. Multiple linear regressions are used to determine dose-dependent expression after NaI treatments of 0.1, 1, 10, or 100 mg/kg/day. Some genes respond to NaI linearly, but for other genes, the induction or repression of expression may become saturated after some dose levels. Therefore, two types of multiple linear regressions were performed. The first type was the linear regression of the gene expression levels and the dose levels, and the other type was the linear regression of the gene expression levels and the logarithms of the dose levels. A principal component analysis was also performed on the data. Three animals were measured within each treatment for each gene. The treatment means were then subjected to principal component analysis. The components were thus determined on a per-treatment basis rather than a per-gene basis, as in Results Liver Weights and Hormone Metabolism After the 2-week exposure period, liver weights were increased in a dose-dependent manner and were significantly higher in rats administered 10 and 100 mg/kg/day NaI (8-13% increase) and 100 mg/kg/day PB (44% increase) compared with control rats that received water alone UDPGT activity was significantly higher (99% increase) in rats administered 100 mg/ kg/day PB compared with controls ( Thyroid Hormone Levels and Histopathology Treatment-related effects on thyroid hormone levels were observed in the 100 mg/kg/day PB and 10 mg/kg/day PTU groups. Compared with controls, T 3 , T 4 , and rT 3 levels were reduced 23, 40, and 28%, respectively, in PBtreated rats and 80, 99, and 56%, respectively, in PTU-treated rats Treatment-related changes in thyroid gland histopathology were observed in the PB and PTU treatment groups gland weights (percent of body weight) were also significantly increased (~3-fold) in the PTU treatment group compared with controls Thyroid Gland Gene Expression Principal component analysis. Thyroid gene expression data were analyzed using principal component analysis, a regularized t-test and multiple linear regressions. Principal component analysis of gene expression data from all 24 samples demonstrated grouping according to treatment. Six principal components were identified To understand these principal components, it is helpful to express each as a linear combination of the means of the six treatments Large negative values (i.e., negative numbers large in absolute value) of this component tend to be associated with down-regulation in one of more NaI treatments. The second component is an indicator for an effect due to PB and PTU. A large value of Pcomp2 (principal component 2) indicates an up-regulation, whereas a large negative value indicates a downregulation. Component 3 is primarily a contrast between the PB and PTU treatments. The fourth principal component is primarily an indicator of effect at low doses of NaI. Based on these principal component analysis findings, further gene ontology work was directed to the first two principal components, namely, genomic profiles associated with NaI exposure or PB and PTU exposure. Multiple linear regressions. Dose-dependent expression, as determined by multiple linear regressions, was observed after NaI treatment. Transcript levels most influenced by dose (p ≤ 0.001), included the NIS [Slc5a5; GenBank accession no. U60282; (http:// www.ncbi.nlm.gov)] and antioxidant enzymes such as glutathione peroxidase 2 (Gpx2), thioredoxin reductase (Txnrd1), and glutathione S-transferase pi (GST-pi; Gstp2) ( Regularized t-test (Bayesian procedure). In a separate analysis using the regularized t-test, 872, 948, and 1552 gene transcripts (of 8,740 transcripts present in all samples) were significantly (p &lt; 0.01) changed by 100 mg/kg/day NaI, 100 mg/kg/day PB, and 10 mg/kg/day PTU administration compared with controls, respectively. To further characterize these genomic changes according to biological function and identify molecular pathways involved in the mode of action of each chemical, these gene lists were uploaded into GenMAPP (Gene Map Annotator and Pathway Profiler, version 1.0