A preliminary reconstruction of the paleoecological and paleoclimatic history of the Chinese Loess Plateau from the application of biomarkers

This study provides a preliminary reconstruction of paleoecological and paleoclimatic history over the central Chinese Loess Plateau (CLP) during the last 8.1 Ma based on biomarker records from the earliest of the Chaona stratigraphic section. Throughout the section, we found variations in n-alkane and n-alkan-2-one distributions and dramatic changes in six other biomarker proxies: 1) n-alkanes (C₂₇ + C₂₉)/(C₃₁ + C₃₃) ratios, 2) n-alkanes C₂₇/C₃₁ ratios, 3) CPI (carbon preference index) values for CPI_(H)ALK, 4) values for CPI_(H)KET, 5) n-alkane mean chain lengths ACL-ALK, and 6) n-alkan-2-ones C₂₉/C₃₁ ratios. The C₂₉ n-alkanes dominate the red clay sediments with little variability, indicating that trees dominated the CLP and that the climate was relatively stable and less variable during the 8.1–2.6 Ma period. In contrast, the C₃₁ n-alkanes dominate the loess–paleosol sediments, and biomarkers vary with relatively greater amplitude and higher frequency, indicating that grasses dominated the CLP and the climate was more arid and variable. These biomarker records chronicle a drying and cooling trend on the CLP since 4 Ma. These records can be further divided into four stages with boundaries around 5.6, 3.8 and 2.6 Ma, indicating that the CLP vegetation and climate experienced four evolutionary phases, broadly consistent with those inferred from other available proxy data.     

cDNA cloning, characterization, and variation analysis of chicken adipose triglyceride lipase (ATGL) gene

Adipose triglyceride lipase (ATGL) is an important triglyceride-specific lipase that catalyzes the initial step in triglyceride hydrolysis. In this study, cloning, sequencing, and mRNA real-time analyses were employed to characterize the chicken ATGL gene. We obtained a total of 1,528-bp long chicken ATGL cDNA fragment including 51-bp 5'UTR, 1,452-bp open reading frame (ORF), and 25-bp 3'UTR. The predicted chicken ATGL had 483 amino acids and a molecular weight of 53.5 kDa, giving rise to identities of 66.5%, 67.3%, 68.2%, 64.8%, and 66.5% with that of human, mouse, rat, pig, and cattle, respectively. The chicken ATGL gene spanned over 30,197 bp and comprised of nine exons and eight introns, in which the intron 1 (21,146 bp) was far longer than others. It predominantly expressed in subcutaneous fat and abdominal fat and then in kidney and lung. Very low but detectable mRNA level was also observed in other 15 tissues. However, no mRNA was detected in spleen. A total of 15 single nucleotide polymorphisms (SNPs) were identified in its complete cDNA sequences with an average of one SNP in every 102 bp and a summarized nucleotide diversity of 3.02 x 10(-3). Seven of the 15 SNPs were non-synonymous. All SNPs had allelic frequencies over 5% and could be considered as candidate markers for future marker-trait association analysis.     

The dynamics of a Lotka–Volterra predator–prey model with state dependent impulsive harvest for predator

According to the economic and biological aspects of renewable resources management, we propose a Lotka–Volterra predator–prey model with state dependent impulsive harvest. By using the Poincaré map, some conditions for the existence and stability of positive periodic solution are obtained. Moreover, we show that there is no periodic solution with order larger than or equal to three under some conditions. Numerical results are carried out to illustrate the feasibility of our main results. The bifurcation diagrams of periodic solutions are obtained by using the numerical simulations, and it is shown that a chaotic solution is generated via a cascade of period-doubling bifurcations, which implies that the presence of pulses makes the dynamic behavior more complex.     

A mathematical model of blood,cerebrospinal fluid and brain dynamics

Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid–solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.

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Association of three-gene interaction among MTHFR, ALOX5AP and NOTCH3 with thrombotic stroke: a multicenter case–control study

Stroke is a common complex trait and does not follow Mendelian pattern of inheritance. Gene–gene or gene–environment interactions may be responsible for the complex trait. How the interactions contribute to stroke is still under research. This study aimed to explore the association between gene–gene interactions and stroke in Chinese in a large case–control study. Nearly 4,000 participants were recruited from seven clinical centers. Eight variants in five candidate genes were examined for stroke risk. Gene–gene interactions were explored by using Generalized Multifactor Dimensionality Reduction (GMDR). A significant gene–gene interaction was found by GMDR. The best model including MTHFR C677T, ALOX5AP T2354A and NOTCH3 C381T scored 10 for Cross-Validation Consistency and 9 for Sign Test (P = 0.0107). The individuals with combination of MTHFR 677TT, ALOX5AP 2354AA and NOTCH3 381TT/TC had a significantly higher risk of thrombotic stroke (OR 3.165, 95% CI 1.461–6.858, P = 0.003). Our results show that combination of these alleles conferred higher risk for stroke than single risk allele. The gene–gene interaction may serve as a novel area for stroke research. The three-locus combination may change the susceptibility of particular subjects to the disease.     

Co‐activator activator (CoAA) prevents the transcriptional activity of Runt domain transcription factors

Runx proteins are essential for a number of developmental processes and are aberrantly expressed in many human cancers. Runx factors bind DNA and co‐factors to activate or repress genes crucial for bone formation, hematopoiesis, and neuronal development. Co‐activator activator (CoAA) is a nuclear protein that regulates gene expression, RNA splicing and is overexpressed in many human tumors. In this study, we identified CoAA as a Runx2 binding protein. CoAA repressed Runx factor‐dependent activation of reporter genes in a histone deacetylase‐independent manner. CoAA also blocked Runx2‐mediated repression of the Axin2 promoter, a novel Runx target gene. The carboxy‐terminus of CoAA is essential for binding the Runt domains of Runx1 and Runx2. In electophoretic mobility shift assays, CoAA inhibited Runx2 interactions with DNA. These data indicate that CoAA is an inhibitor of Runx factors and can negate Runx factor regulation of gene expression. CoAA is expressed at high levels in human fetal osteoblasts and osteosarcoma cell lines. Suppression of CoAA expression by RNA interference reduced osteosarcoma cell viability in vitro, suggesting that it contributes to the proliferation and/or survival of osteoblast lineage cells. J. Cell. Biochem. 108: 378–387, 2009. © 2009 Wiley‐Liss, Inc.     

Ectopic expression of Ligand-of-Numb protein X promoted TGF-β induced epithelial to mesenchymal transition of proximal tubular epithelial cells

Ligand-of-Numb protein X (LNX) was initially characterized as a RING finger type E3 ubiquitin ligase that targeted the intrinsic cell fate determinant Numb for ubiquitination dependent degradation. However, the physiological function of LNX remains largely unknown. In the present study, we demonstrate that ectopic expression of LNX in human proximal tubular epithelial cells (HK-2 cells) significantly enhanced TGF-β1 induced epithelial to mesenchymal transition (EMT). The EMT-promoting effect of LNX manifested as strong inhibition of E-cadherin expression, enhanced expression of vimentin, fibronectin or PAI-1, and increased cell migration. This function of LNX was shown to be independent of its ligase activity because ectopic expression of a mutant form of LNX (C48ALNX) that lacks E3 ligase activity had the similar effect as the wild-type LNX. Overexpression of E-cadherin could inhibit LNX augmented EMT. This study suggests a potential role for LNX in promoting EMT in human proximal tubular epithelial cells.     

Application of alkaline treatment for sludge decrement and humic acid recovery

A new method was introduced to reduce waste activated sludge and extract humic acid for liquid fertilizer. Sludge was disintegrated with NaOH (0.4 g/g dry solid, 8 h) and then centrifuged to obtain the supernatant. The residual sludge was then dewatered, while the supernatant was used to extract humic acid with an ultrafiltration membrane. The results showed that the alkaline treatment dissolved more than half of the sludge organic matter, which was composed of 24% humic acid by mass. After the supernatant was concentrated 20 times using a membrane with a molecular weight cutoff of 1000, the retentate contained 94.5% of the dissolved organics and could be used to produce humic acid fertilizer. Additionally, only 26% of the NaOH was consumed and the residual NaOH in the permeate flux could be reused. Due to the removal of water and organics, the dewatered sludge could be reduced by 60% when compared to samples that did not receive the alkaline treatment.     

Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: Tuning of receptor selectivity and in vivo efficacy

In the previous article we demonstrated how certain CCK2R-selective anthranilic amides could be structurally modified to afford high-affinity, selective CCK1R activity. We now describe our efforts at modulating and optimizing the CCK1R and CCK2R affinities aimed at producing compounds with good pharmacokinetics properties and in vivo efficacy in rat models of gastric acid and pancreatic amylase secretion.