Case-control study of birth characteristics and the risk of hepatoblastoma

Background: Hepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology. Methods: We matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n = 218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates. Results: We observed increased risks for hepatoblastoma among children with low [1500–2499 g, Odds Ratio (OR) = 2.02, 95% confidence interval (CI) 1.29–3.15] and very low birthweight (<1500 g, OR = 15.4, 95% CI 10.7–22.3), preterm birth <33 weeks (OR = 7.27, 95% CI 5.00, 10.6), small size for gestational age (OR = 1.75, 95% CI 1.25–2.45), and with multiple birth pregnancies (OR = 2.52, 95% CI 1.54–4.14). We observed a number of pregnancy and labor complications to be related to hepatoblastoma, including preeclampsia, premature labor, fetal distress, and congenital anomalies. Conclusion: These findings confirm previously reported associations with low birthweight and preeclampsia. The relation with multiple birth pregnancies has been previously reported and may indicate a relation to infertility treatments.     

Response of Acala cotton to nitrogen rates in the San Joaquin Valley of California

The responses of Acala cotton (Gossypium hirsutum L.) in California to a range of applied nitrogen (N) treatments were investigated in a 5-year, multisite experiment. The experiment's goals were to identify crop growth and yield responses to applied N and provide information to better assess the utility of soil residual N estimates in improving fertilizer management. Baseline fertilizer application rates for the lowest applied N treatments were based on residual soil nitrate-N (NO3-N) levels determined on soil samples from the upper 0.6 m of the soil collected prior to spring N fertilization and within 1 week postplanting each year. Results have shown positive cotton lint yield responses to increases in applied N across the 56 to 224 kg N/ha range in only 41% (16 out of 39) of test sites. Soil NO3-N monitoring to a depth of 2.4 m in the spring (after planting) and fall (postharvest) indicate most changes in soil NO3- occur within the upper 1.2 m of soil. However, some sites (those most prone to leaching losses of soluble nutrients) also exhibited net increases in soil NO3-N in the 1.2- to 2.4-m depth zone when comparing planting time vs. postharvest data. The lack of yield responses and soil NO3-N accumulations at some sites indicate that more efforts should be put into identifying the amount of plant N requirements that can be met from residual soil N, rather than solely from fertilizer N applications.     

CHOBIMALT: a cholesterol-based detergent

Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems, a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3?4 μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210±30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1.     

SH2B1beta (SH2-Bbeta) enhances expression of a subset of nerve growth factor-regulated genes important for neuronal differentiation including genes encoding urokinase plasminogen activator receptor and matrix metalloproteinase 3/10

Previous work showed that the adapter protein SH2B adapter protein 1beta (SH2B1) (SH2-B) binds to the activated form of the nerve growth factor (NGF) receptor TrkA and is critical for both NGF-dependent neurite outgrowth and maintenance. To identify SH2B1beta-regulated genes critical for neurite outgrowth, we performed microarray analysis of control PC12 cells and PC12 cells stably overexpressing SH2B1beta (PC12-SH2B1beta) or the dominant-negative SH2B1beta(R555E) [PC12-SH2B1beta(R555E)]. NGF-induced microarray expression of Plaur and Mmp10 genes was greatly enhanced in PC12-SH2B1beta cells, whereas NGF-induced Plaur and Mmp3 expression was substantially depressed in PC12-SH2B1beta(R555E) cells. Plaur, Mmp3, and Mmp10 are among the 12 genes most highly up-regulated after 6 h of NGF. Their protein products [urokinase plasminogen activator receptor (uPAR), matrix metalloproteinase 3 (MMP3), and MMP10] lie in the same pathway of extracellular matrix degradation; uPAR has been shown previously to be critical for NGF-induced neurite outgrowth. Quantitative real-time PCR analysis revealed SH2B1beta enhancement of NGF induction of all three genes and the suppression of NGF induction of all three when endogenous SH2B1 was reduced using short hairpin RNA against SH2B1 and in PC12-SH2B1beta(R555E) cells. NGF-induced levels of uPAR and MMP3/10 and neurite outgrowth through Matrigel (MMP3-dependent) were also increased in PC12-SH2B1beta cells. These results suggest that SH2B1beta stimulates NGF-induced neuronal differentiation at least in part by enhancing expression of a specific subset of NGF-sensitive genes, including Plaur, Mmp3, and/or Mmp10, required for neurite outgrowth.     

Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis

Neisseria meningitidis encodes three DsbA oxidoreductases (NmDsbA1-NmDsbA3) that are vital for the oxidative folding of many membrane and secreted proteins, and these three enzymes are considered to exhibit different substrate specificities. This has led to the suggestion that each N. meningitidis DsbA (NmDsbA) may play a specialized role in different stages of pathogenesis; however, the molecular and structural bases of the different roles of NmDsbAs are unclear. With the aim of determining the molecular basis for substrate specificity and how this correlates to pathogenesis, we undertook a biochemical and structural characterization of the three NmDsbAs. We report the 2.0-Å-resolution crystal structure of the oxidized form of NmDsbA1, which adopted a canonical DsbA fold similar to that observed in the structures of NmDsbA3 and Escherichia coli DsbA (EcDsbA). Structural comparisons revealed variations around the active site and candidate peptide-binding region. Additionally, we demonstrate that all three NmDsbAs are strong oxidases with similar redox potentials; however, they differ from EcDsbA in their ability to be reoxidized by E. coli DsbB. Collectively, our studies suggest that the small structural differences between the NmDsbA enzymes and EcDsbA are functionally significant and are the likely determinants of substrate specificity.     

Tempo and mode of performance evolution across multiple independent origins of adhesive toe pads in lizards

Understanding macroevolutionary dynamics of trait evolution is an important endeavor in evolutionary biology. Ecological opportunity can liberate a trait as it diversifies through trait space, while genetic and selective constraints can limit diversification. While many studies have examined the dynamics of morphological traits, diverse morphological traits may yield the same or similar performance and as performance is often more proximately the target of selection, examining only morphology may give an incomplete understanding of evolutionary dynamics. Here, we ask whether convergent evolution of pad‐bearing lizards has followed similar evolutionary dynamics, or whether independent origins are accompanied by unique constraints and selective pressures over macroevolutionary time. We hypothesized that geckos and anoles each have unique evolutionary tempos and modes. Using performance data from 59 species, we modified Brownian motion (BM) and Ornstein–Uhlenbeck (OU) models to account for repeated origins estimated using Bayesian ancestral state reconstructions. We discovered that adhesive performance in geckos evolved in a fashion consistent with Brownian motion with a trend, whereas anoles evolved in bounded performance space consistent with more constrained evolution (an Ornstein–Uhlenbeck model). Our results suggest that convergent phenotypes can have quite distinctive evolutionary patterns, likely as a result of idiosyncratic constraints or ecological opportunities.     

Effect of pH and calcium on short-term NO3- fluxes in roots of barley seedlings

The effect of pH and Ca2+ on net NO3- uptake, influx, and efflux by intact roots of barley (Hordeum vulgare L.) seedlings was studied. Seedlings were induced with NO3- or NO2-. Net NO3- uptake and efflux, respectively, were determined by following its depletion from, and accumulation in, the external solution. Since roots of both uninduced and NO2(-)-induced seedlings contain little internal NO3- initial net uptake rates are equivalent to influx (M. Aslam, R.L. Travis, R.C. Huffaker [1994] Plant Physiol 106: 1293-1301). NO3-, uptake (influx) by these roots was little affected at acidic pH. In contrast, in NO3(-)-induced roots, which accumulate NO3-, net uptake rates decreased in response to acidic pH. Under these conditions, NO3- efflux was stimulated and was a function of root NO3- concentration. Conversely, at basic pH, NO3- uptake by NO3- and NO2(-)-induced and uninduced roots decreased, apparently because of the inhibition of influx. Calcium had little effect on NO3- uptake (influx) by NO2(-)-induced roots at either pH 3 or 6. However, in NO3(-)-induced roots, lack of Ca2+ at pH 3 significantly decreased net NO3- uptake and stimulated efflux. The results indicate that at acidic pH the decrease in net NO3- uptake is due to the stimulation of efflux, whereas at basic pH, it is due to the inhibition of influx.