T he hormone leptin is the product of the obese (ob) gene, primarily produced by white adipose tissue (1) and typically circulates in proportion to body fat mass (2). Leptin acts on specific regions in the hypothalamus to inhibit food intake and raise energy expenditure. Elevated leptin levels in obese subjects are believed to be indicative of resistance to leptin. Leptin has also been shown to inhibit insulin secretion and preproinsulin gene expression in pancreatic ␤-cells (3-6), thereby establishing an adipoinsular feedback loop in concert with stimulatory action of insulin on leptin secretion from the adipose tissue (7,8). Dysregulation of this adipoinsular axis with the establishment of leptin resistance in pancreatic ␤-cells may lead to hyperinsulinemia, which could contribute to obesity and insulin resistance.Leptin signal transduction occurs through a distinct receptor of the class 1 cytokine superfamily of receptors (9), which is intracellularly coupled to the janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway (10). Several leptin receptor (ObR) isoforms are known, but the majority of physiological effects appear to be mediated via the longest form (ObRb) (11,12). In previous experiments, we and others have demonstrated that ObR isoforms, including ObRb, are expressed and functional in pancreatic ␤-cell lines and primary pancreatic islets (3,13). Binding of leptin to ObRb activates the receptor-associated kinase JAK2 via transphosphorylation and phosphorylates tyrosine residues on ObRb. Subsequently, transcription factors of the STAT family are recruited to the receptor and also phosphorylated. Phosphorylated STATs dimerize and translocate to the nucleus to regulate gene transcription (14). STATs have mainly been shown to transcriptionally enhance gene expression. However, we previously determined that leptin increases binding of STAT5b to the upstream sequences of the rat preproinsulin 1 promoter (6) and inhibits insulin biosynthesis via transcriptional repression (5). In this study, we sought to characterize this apparent contradiction at the molecular level.Suppressors of cytokine signaling (SOCS) belong to a family of molecules that inhibit cytokine signaling by inhibiting JAK-STAT signal transduction. These molecules contain a central Src-homology 2 domain and a conserved COOH-terminal SOCS box. Through the Src-homology 2 domain, they bind directly to tyrosine-phosphorylated residues on the cytokine receptor-associated kinase JAK2, which blocks the access of STATs to receptor binding sites and leads to inactivation of the JAKs (15). Expression of SOCS proteins is induced by various cytokines and hormones, including interleukin-6, leukemia inhibitory factor, erythropoietin, growth hormone, and leptin (16 -18). Accumulating evidence suggests that SOCS3 is a leptininduced negative feedback regulator of leptin receptor GFP, green fluorescent protein; JAK, janus kinase; ␣PY, anti-phosphotyrosine; SOCS, suppressor of cytokine signaling; STAT, signal transducer an...

Mercury intrusion capillary pressure (MICP), nuclear magnetic resonance (NMR), routine core analysis, thin sections, and scanning electron microscope (SEM) analysis were used to gain insight into the pore structure of the Eocene Sha-3 (the third member of the Shahejie formation) low-permeability sandstones in the Raoyang sag, including pore type, pore geometry, and pore size. Quantitative NMR parameters and petrophysical properties were integrated to build up the relationship between microscopic pore structure and macroscopic performance. The pore systems of Sha-3 sandstones are dominantly of residual intergranular pores, intragranular dissolution pores, and intercrystallite micropores associated with authigenic clay minerals. The high threshold pressure and low mercury withdrawal efficiencies from MICP analysis indicate the poor pore connectivity and strong heterogeneous. Both uni-and bimodal transverse relaxation time (T 2 ) spectrum can be found because of the coexistence of small and large pores, and the T 2 of major pore size occurring at about 1.0 to 100 ms. The Sha-3 sandstones have a relatively high irreducible water content and short T 2 components in the T 2 range. Long T 2 components can only be observed in samples rich in large pores or microfractures. T 2gm (the geometric mean of the T 2 distribution) correlates well with irreducible water saturation and permeability. A methodology for pore structure classification is presented integrating NMR parameters of T 2gm , bulk volume of immovable fluid (BVI), and petrophysical parameters such as reservoir quality index (RQI) and permeability. Consequently, four types of pore structures (types A, B, C, and D) are identified, and characteristics of individual pore structure are summarized. The comprehensive analysis of NMR measurements combined with thin sections, SEM and MICP analysis is useful for describing microscopic pore structure, which is important to maintaining and enhancing petroleum recovery in low-permeability sandstone reservoirs.

Angiogenesis of PGBC is significantly related to the biological behaviors of PGBC. The expression of iNOS is related to the biological behaviors of PGBC. The detection of MVD and the expression of iNOS in PGBC can be used as parameters to determine the degree of malignancy and prognosis.

The last paragraph of the Abstract should have read:Conclusions/interpretation In rodent beta cell lines, we demonstrate hKLF11 overexpression-mediated inhibition of human proinsulin gene expression and characterise a prominent role for the CACCC box in maintaining basal proinsulin promoter activity.