Regulation of nuclear lamin polymerization by importin alpha.

Nuclear lamins are integral components of the nuclear envelope and are important for the regulation of many aspects of nuclear function, including gene transcription and DNA replication. During interphase, the lamins form an intranuclear intermediate filament network that must be disassembled and reassembled when cells divide. Little is known about factors regulating this assembly/disassembly cycle.

Fibroblast adaptation and stiffness matching to soft elastic substrates.

Many cell types alter their morphology and gene expression profile when grown on chemically equivalent surfaces with different rigidities. One expectation of this change in morphology and composition is that the cell's internal stiffness, governed by cytoskeletal assembly and production of internal stresses, will change as a function of substrate stiffness. Atomic force microscopy was used to measure the stiffness of fibroblasts grown on fibronectin-coated polyacrylamide gels of shear moduli varying between 500 and 40,000 Pa.

Modulation of vesicle adhesion and spreading kinetics by hyaluronan cushions.

The adhesion of giant unilamellar phospholipid vesicles to planar substrates coated with extracellular matrix mimetic cushions of hyaluronan is studied using quantitative reflection interference contrast microscopy. The absolute height of the vesicle membrane at the vicinity of the substrate is measured by considering, for the first time, the refractive indices of the reflecting media. The thickness of the cushion is varied in the range of approximately 50-100 nm, by designing various coupling strategies.

Positional stability of single double-strand breaks in mammalian cells.

Formation of cancerous translocations requires the illegitimate joining of chromosomes containing double-strand breaks (DSBs). It is unknown how broken chromosome ends find their translocation partners within the cell nucleus. Here, we have visualized and quantitatively analysed the dynamics of single DSBs in living mammalian cells.

Artificially introduced aneuploid chromosomes assume a conserved position in colon cancer cells.

Background: Chromosomal aneuploidy is a defining feature of carcinomas. For instance, in colon cancer, an additional copy of Chromosome 7 is not only observed in early pre-malignant polyps, but is faithfully maintained throughout progression to metastasis. These copy number changes show a positive correlation with average transcript levels of resident genes.

Insulin-like growth factor-1 (IGF-1) induces WISP-2/CCN5 via multiple molecular cross-talks and is essential for mitogenic switch by IGF-1 axis in estrogen receptor-positive breast tumor cells.

Previously, we have shown that the expression of Wnt-1-induced signaling protein-2 (WISP-2), also known as CCN5, can be regulated by multiple stimulants in estrogen receptor (ER)-positive breast tumor cells to exert their mitogenic action in these cells. Here, we show that insulin-like growth factor-1 (IGF-1), a strong mitogen, enhanced the expression of the WISP-2/CCN5 gene parallel with the induction of proliferation of ER-positive breast tumor cells. An additive effect was also seen in combination with estrogen.

Expression pattern of Drosophila translin and behavioral analyses of the mutant.

Translin is an evolutionarily conserved approximately 27-kDa protein that binds to specific DNA and RNA sequences and has diverse cellular functions. Here, we report the cloning and characterization of the translin orthologue from the fruit fly Drosophila melanogaster. Under protein-denaturing conditions, purified Drosophila translin exists as a mixture of dimers and monomers just like human translin.

Tunneling conductance of graphene NIS junctions.

We show that, in contrast with conventional normal metal-insulator-superconductor (NIS) junctions, the tunneling conductance of a NIS junction in graphene is an oscillatory function of the effective barrier strength of the insulating region, in the limit of a thin barrier. The amplitude of these oscillations is maximum for aligned Fermi surfaces of the normal and superconducting regions and vanishes for a large Fermi surface mismatch. The zero-bias tunneling conductance, in sharp contrast to its counterpart in conventional NIS junctions, becomes maximum for a finite barrier strength.

Hard-core bosons on the kagome lattice: valence-bond solids and their quantum melting.

Using large scale quantum Monte Carlo simulations and dual vortex theory, we analyze the ground state phase diagram of hard-core bosons on the kagome lattice with nearest-neighbor repulsion. In contrast with the case of a triangular lattice, no supersolid emerges for strong interactions. While a uniform superfluid prevails at half filling, two novel solid phases emerge at densities rho=1/3 and rho=2/3.

Spreading of neutrophils: from activation to migration.

Neutrophils rely on rapid changes in morphology to ward off invaders. Time-resolved dynamics of spreading human neutrophils after activation by the chemoattractant fMLF (formyl methionyl leucyl phenylalanine) was observed by RICM (reflection interference contrast microscopy). An image-processing algorithm was developed to identify the changes in the overall cell shape and the zones of close contact with the substrate.

WISP-2/CCN5 is involved as a novel signaling intermediate in phorbol ester-protein kinase Calpha-mediated breast tumor cell proliferation.

PMA and active phorbol esters stimulate the proliferation of various tumor cells, including ER-positive human breast tumor cell lines. However, the specific signaling pathways involved in the PMA-induced mitogenic effect on breast tumor cells have not been fully elucidated. In the present study, we explored the mechanisms associated with the mitogenic influence of PMA on breast tumor cells.

Tumor formation via loss of a molecular motor protein.

Aneuploidy has long been suggested to be causal in tumor formation. Direct testing of this hypothesis has been difficult because of the absence of methods to specifically induce aneuploidy. The chromosome-associated kinesin motor KIF4 plays multiple roles in mitosis, and its loss leads to multiple mitotic defects including aneuploidy.

Breast cancer cells secreted platelet-derived growth factor-induced motility of vascular smooth muscle cells is mediated through neuropilin-1.

Motility of vascular smooth muscle cells (SMCs) is an essential step for both normal and pathologic angiogenesis. We report here that breast tumor cells, such as MCF-7 and MDA-MB-231, can modulate this SMC migration. We present evidence that the tumor cell-derived platelet-derived growth factor (PDGF) is the key regulator of vascular SMCs motility induced by breast cancer cells.

Coupling artificial actin cortices to biofunctionalized lipid monolayers.

We report the assembly of protein supramolecular structures at an air-water interface and coupling of artificial actin cortices to such structures. The coupling strategies adopted include electrostatic binding of actin to monolayers doped with lipids, exposing positively charged poly(ethylene glycol) headgroups; binding of biotinylated actin to lipids carrying biotin headgroups through avidin; binding of actin to membranes through biotinylated hisactophilin (a cellular actin-membrane coupler) using an avidin-biotin linkage; and coupling of actin to membranes carrying chelating lipids through a 15-nm-diameter protein capsid (bacterial lumazine synthase or LuSy) exhibiting histidine tags (which bind both to actin and to the chelating lipid). The distribution of the proteins in a direction normal to the interface was measured by neutron reflectivity under different conditions of pH and ionic strength.

Modulation of cell-cycle regulatory signaling network by 2-methoxyestradiol in prostate cancer cells is mediated through multiple signal transduction pathways.

2-Methoxyestradiol (2-ME(2)), a promising anticancer drug, induces growth arrest and apoptosis in various androgen-dependent (LNCaP) and -independent (DU145 and PC-3) prostate cancer cell lines. Moreover, flow cytometric analysis indicated a novel dual impact of 2-ME(2) on the cell division cycle of prostate cancer cells. Chronic exposure of high doses of 2-ME(2) enhance the accumulation of cells in S and G2/M phases, while cell numbers in the G1 phase were reduced significantly by this treatment.

GTP-induced conformational changes in translin: a comparison between human and Drosophila proteins.

Human translin is a conserved protein, unique in its ability to bind both RNA and DNA. Interestingly, GTP binding has been implicated as a regulator of RNA/DNA binding function of mouse translin (TB-RBP). We cloned and overexpressed the translin orthologue from Drosophila melanogaster and compared its DNA/RNA binding properties in relation to GTP effects with that of human protein.

Safety and Toxicological Evaluation of a Novel, Standardized 3-O-Acetyl-11-keto-beta-Boswellic Acid (AKBA)-Enriched Boswellia serrata Extract (5-Loxin(R)).

The novel anti-inflammatory properties of the gum resin derived from Boswellia serrata, also known as Salai guggal in Ayurvedic medicine, are well recognized and highly recommended for human consumption. The active constituents of the gum resin are boswellic acids (BAs). Among the BAs, AKBA potently inhibits 5-lipoxygenase product formation with an IC(50) of 1.

Frequency-dependent shape changes of colloidal clusters under transverse electric field.

We have studied clustering of colloidal particles under the influence of an ac electric field as a function of frequency. The field was applied in a direction perpendicular to the confining walls. Two regimes are observed, a low frequency regime where the clusters are isotropic with a local triangular order, as reported earlier in the literature, and a new high-frequency regime where the clusters are highly elongated (anisotropic) with no local order.

Epidermal growth factor induces WISP-2/CCN5 expression in estrogen receptor-alpha-positive breast tumor cells through multiple molecular cross-talks.

Epidermal growth factor (EGF) is a mitogen for estrogen receptor (ER)-positive breast tumor cells, and it has been proven that EGF occasionally mimicked estrogen action and cross-talks with ER-alpha to exert its activity. Therefore, the present study was undertaken to explore whether EGF is able to modulate the expression of Wnt-1-induced signaling protein-2/connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 5 (WISP-2/CCN5), an estrogen-responsive gene, in normal and transformed cell lines of the human breast and, if so, whether this induction is critical for EGF mitogenesis and what downstream signaling pathways are associated with this event. Here, we show that EGF-induced WISP-2 expression in ER- and EGF receptor-positive noninvasive MCF-7 breast tumor cells was dose and time dependent and that expression was modulated at transcription level.

Motion compensated lossy-to-lossless compression of 4-D medical images using integer wavelet transforms.

This paper proposes a method for progressive lossy-to-lossless compression of four-dimensional (4-D) medical images (sequences of volumetric images over time) by using a combination of three-dimensional (3-D) integer wavelet transform (IWT) and 3-D motion compensation. A 3-D extension of the set-partitioning in hierarchical trees (SPIHT) algorithm is employed for coding the wavelet coefficients. To effectively exploit the redundancy between consecutive 3-D images, the concepts of key and residual frames from video coding is used.

Epidermal growth factor receptor: is a novel therapeutic target for pancreatic cancer?

Expression of epidermal growth factor receptors (EGFR) is exaggerated in pancreatic adenocarcinoma and activation of EGFR appears to have an important role in the growth and differentiation of this and in other tumors. Therefore, blockade or inactivation of EGFR by monoclonal antibodies or by tyrosine kinase inhibitors has significant potential as an effective anti-cancer therapy. One of the very recent significant developments in the field of molecular biology involves the use of antisense of EGFR or EGFR gene silencing in pancreatic cancer cells as a potential targeted therapy for patients with pancreatic adenocarcinoma.

Growth factors involved in prostate carcinogenesis.

Prostate cancer is the most common non-skin cancer affecting men in United States and the second leading cause of death after lung cancer. The clinical course of patients after given diagnosis of prostate cancer is highly variable and the underlying reasons for such variability remain elusive. To better understand the pathophysiology of prostate cancer, there has been a push to elucidate the molecular mechanisms that mediate the development and progression of prostate cancer.

Differential expression of VEGF-A mRNA by 17beta-estradiol in breast tumor cells lacking classical ER-alpha may be mediated through a variant form of ER-alpha.

Beta-estradiol (17beta-E2) augments VEGF-A expression in various estrogen targeted organs and cells including breast tumor derived cell lines, via an ER-alpha mediated pathway. Ironically, 17beta-E2 is able to regulate some genes via ER-alpha independent pathways. In the present study, we sought to determine whether 17beta-E2 can modulate VEGF-A expression in absence of ER-alpha, and therefore, three different cell lines including ER-alpha+ MCF-7, and ER-alpha SKBR-3 and HMEC were used for this study.

Topographical pattern dynamics in passive adhesion of cell membranes.

Strong adhesion of highly active cells often nucleates focal adhesions, synapses, and related structures. Red cells lack such complex adhesion systems and are also nonmotile, but they are shown here to dynamically evolve complex spatial patterns beyond an electrostatic threshold for strong adhesion. Spreading of the cell onto a dense, homogeneous poly-L-lysine surface appears complete in <1 s with occasional blisters that form and dissipate on a similar timescale; distinct rippled or stippled patterns in fluorescently labeled membrane components emerge later, however, on timescales more typical of long-range lipid diffusion (approximately minutes).

Reversible renal medullary hyperechogenicity in neonatal hypernatremic dehydration.

Three exclusively breastfed term neonates were admitted with lethargy, poor feeding, and oligoanuria. All three babies were severely dehydrated and had a weight loss ranging from 18% to 40%. Serum sodium of more than 180 mEq/l and renal failure were observed in all three.