Anticoagulant potential and total phenolic content of six species of the genus Ficus from Azad Kashmir, Pakistan

Purpose: To investigate the total phenolic and flavonoid contents of Ficus benghalensis, Ficus elasticaa, Ficus palmata, Ficus religiosa, Ficus semicordata and Ficus auriculata, and to determine their anticoagulant potential. Methods: Crude methanol extracts were prepared from the plant leaves, and fractionated using liquidliquid partition with n-hexane, chloroform and ethyl acetate. The total flavonoid and total phenolic contents of the extracts and their fractions were determined. The anticoagulant potential of the six Ficus species were evaluated in healthy human plasma, using activated partial thromboplastin time (APTT) and prothrombin time (PT) methods. Results: Phytochemical analysis showed the presence of considerable amounts of flavonoids ranging from 5.3 ± 0.7 to 11.8 ± 0.3 mg rutin equivalents (RE)/g, and phenolic compounds ranging from 8.0 ± 0.7 to 86.5 ± 1.5 mg gallic acid equivalents (GAE)/g in each fraction of the six species. Results from in vitro anticoagulant potential assays showed significant anticoagulant properties, with prothrombin time (PT) ranging from 17.7 ± 0.7 to 26.7 ± 2.2 s, and activated partial thromboplastin time (APTT) varying from 47.7 ± 3.3 to 72.3 ± 5.4 s. Conclusion: The results indicate that F. semicordata and F. Religiosa have higher anticoagulant potential than the other Ficus species studied

The Determination of Titan Gravity Field from Doppler Tracking of the Cassini Spacecraft

In its tour of the Saturnian system, the spacecraft Cassini is carrying out measurements of the gravity field of Titan, whose knowledge is crucial for constraining the internal structure of the satellite. In the five flybys devoted to gravity science, the spacecraft is tracked in X (8.4 GHz) and Ka band (32.5 GHz) from the antennas of NASA's Deep Space Network. The use of a dual frequency downlink is used to mitigate the effects of interplanetary plasma, the largest noise source affecting Doppler measurements. Variations in the wet path delay are effectively compensated by means of advanced water vapor radiometers placed close to the ground antennas. The first three flybys occurred on February 27, 2006, December 28, 2006, and June 29, 2007. Two additional flybys are planned in July 2008 and May 2010. This paper presents the estimation of the mass and quadrupole field of Titan from the first two flybys, carried out by the Cassini Radio Science Team using a short arc orbit determination. The data from the two flybys are first independently fit using a dynamical model of the spacecraft and the bodies of the Saturnian system, and then combined in a multi-arc solution. Under the assumption that the higher degree harmonics are negligible, the estimated values of the gravity parameters from the combined, multi-arc solution are GM = 8978.1337 +/- 0.0025 km(exp 3) / s(exp 2), J (sub 2) = (2.7221 +/- 0.0185) 10 (exp -5) and C (sub 22) = (1.1159 +/- 0.0040) 10 (exp -5) The excellent agreement (within 1.7 sigma) of the results from the two flybys further increases the confidence in the solution and provides an a posteriori validation of the dynamical model

Protocadherin-18 Is a Novel Differentiation Marker and an Inhibitory Signaling Receptor for CD8+ Effector Memory T Cells

CD8+ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling previously shown to result from inactivation of p56lck kinase. We identify a novel interacting partner for p56lck in nonlytic TIL, Protocadherin-18 (‘pcdh18’), and show that pcdh18 is transcribed upon in vitro or in vivo activation of all CD8+ central memory T cells (CD44+CD62LhiCD127+) coincident with conversion into effector memory cells (CD44+CD62LloCD127+). Expression of pcdh18 in primary CD8+ effector cells induces the phenotype of nonlytic TIL: defective proximal TCR signaling, cytokine secretion, and cytolysis, and enhanced AICD. pcdh18 contains a motif (centered at Y842) shared with src kinases (QGQYQP) that is required for the inhibitory phenotype. Thus, pcdh18 is a novel activation marker of CD8+ memory T cells that can function as an inhibitory signaling receptor and restrict the effector phase

Wdr18 Is Required for Kupffer's Vesicle Formation and Regulation of Body Asymmetry in Zebrafish

Correct specification of the left-right (L-R) axis is important for organ morphogenesis. Conserved mechanisms involving cilia rotation inside node-like structures and asymmetric Nodal signaling in the lateral plate mesoderm (LPM), which are important symmetry-breaking events, have been intensively studied. In zebrafish, the clustering and migration of dorsal forerunner cells (DFCs) is critical for the formation of the Kuppfer's vesicle (KV). However, molecular events underlying DFC clustering and migration are less understood. The WD-repeat proteins function in a variety of biological processes, including cytoskeleton assembly, intracellular trafficking, mRNA splicing, transcriptional regulation and cell migration. However, little is known about the function of WD-repeat proteins in L-R asymmetry determination. Here, we report the identification and functional analyses of zebrafish wdr18, a novel gene that encodes a WD-repeat protein that is highly conserved among vertebrate species. wdr18 was identified from a Tol2 transposon-mediated enhancer trap screen. Follow-up analysis of wdr18 mRNA expression showed that it was detected in DFCs or the KV progenitor cells and later in the KV at early somitogenesis stages. Morpholino knockdown of wdr18 resulted in laterality defects in the visceral organs, which were preceded by the mis-expression of Nodal-related genes, including spaw and pitx2. Examination of morphants at earlier stages revealed that the KV had fewer and shorter cilia which are immotile and a smaller cavity. We further investigated the organization of DFCs in wdr18 morphant embryos using ntl and sox17 as specific markers and found that the clustering and migration of DFC was altered, leading to a disorganized KV. Finally, through a combination of wdr18 and itgb1b morpholino injections, we provided evidence that wdr18 and itgb1b genetically interact in the laterality determination process. Thus, we reveal a new and essential role for WD-repeat proteins in the determination and regulation of L-R asymmetry and propose a potential mechanism for wdr18 in the regulation of DFC clustering and migration and KV formation

Novel roles of the chemorepellent axon guidance molecule RGMa in cell migration and adhesion

The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease

B1 SOX Coordinate Cell Specification with Patterning and Morphogenesis in the Early Zebrafish Embryo

The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT–PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1) early dorsoventral patterning by controlling bmp2b/7; (2) gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3) neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively) and ascl1a (negatively), and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4) neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo

Determinants of Minority-White Differentials in Child Poverty

This paper uses data from the 1993-2001 March Current Population Survey to estimate the extent to which child living arrangements, parental work patterns, and immigration attributes shape racial and ethnic variation in child poverty. Results from multivariate analyses and a standardization technique reveal that parental work patterns as well as child living arrangements are especially consequential for black and Puerto-Rican economic circumstances. Child immigration generation and parental length of residence seem to play a detrimental role in shaping poverty among Asian, Mexican, and Central/South American children. We also found that the extent to which differences in the composition of and returns to parental resources determine white-minority economic gaps varies substantially across racial and ethnic lines. The social and economic implications of the findings for understanding racial and ethnic inequality are discussed in the final section of the article