bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies
Authors: Weaver V.M. , Petersen O.W. , Wang F. , Larabell C.A. , Briand P. , Damsky C. , Bissell M.J.
Published: July 2002

In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory β1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory β1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin–catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21cip,waf-1, and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either α6 or β4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the α6/β4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.
An Endocytosed TGN38 Chimeric Protein Is Delivered to the TGN after Trafficking through the Endocytic Recycling Compartment in CHO Cells
Authors: Ghosh Richik N. , Mallet William G. , Soe Thwe T. , McGraw Timothy E. , Maxfield Frederick R.
Published: July 2002

To examine TGN38 trafficking from the cell surface to the TGN, CHO cells were stably transfected with a chimeric transmembrane protein, TacTGN38. We used fluorescent and 125I-labeled anti-Tac IgG and Fab fragments to follow TacTGN38's postendocytic trafficking. At steady-state, anti-Tac was mainly in the TGN, but shortly after endocytosis it was predominantly in early endosomes. 11% of cellular TacTGN38 is on the plasma membrane. Kinetic analysis of trafficking of antibodies bound to TacTGN38 showed that after short endocytic pulses, 80% of internalized anti-Tac returned to the cell surface (t1/2 = 9 min), and the remainder trafficked to the TGN. When longer filling pulses and chases were used to load anti-Tac into the TGN, it returned to the cell surface with a t1/2 of 46 min. Quantitative confocal microscopy analysis also showed that fluorescent anti-Tac fills the TGN with a 46-min t1/2. Using the measured rate constants in a simple kinetic model, we predict that 82% of TacTGN38 is in the TGN, and 7% is in endosomes. TacTGN38 leaves the TGN slowly, which accounts for its steady-state distribution despite the inefficient targeting from the cell surface to the TGN.
Multiple Forces Contribute to Cell Sheet Morphogenesis for Dorsal Closure in Drosophila
Authors: Kiehart Daniel P. , Galbraith Catherine G. , Edwards Kevin A. , Rickoll Wayne L. , Montague Ruth A.
Published: July 2002

The molecular and cellular bases of cell shape change and movement during morphogenesis and wound healing are of intense interest and are only beginning to be understood. Here, we investigate the forces responsible for morphogenesis during dorsal closure with three approaches. First, we use real-time and time-lapsed laser confocal microscopy to follow actin dynamics and document cell shape changes and tissue movements in living, unperturbed embryos. We label cells with a ubiquitously expressed transgene that encodes GFP fused to an autonomously folding actin binding fragment from fly moesin. Second, we use a biomechanical approach to examine the distribution of stiffness/tension during dorsal closure by following the response of the various tissues to cutting by an ultraviolet laser. We tested our previous model (Young, P.E., A.M. Richman, A.S. Ketchum, and D.P. Kiehart. 1993. Genes Dev. 7:29–41) that the leading edge of the lateral epidermis is a contractile purse-string that provides force for dorsal closure. We show that this structure is under tension and behaves as a supracellular purse-string, however, we provide evidence that it alone cannot account for the forces responsible for dorsal closure. In addition, we show that there is isotropic stiffness/tension in the amnioserosa and anisotropic stiffness/tension in the lateral epidermis. Tension in the amnioserosa may contribute force for dorsal closure, but tension in the lateral epidermis opposes it. Third, we examine the role of various tissues in dorsal closure by repeated ablation of cells in the amnioserosa and the leading edge of the lateral epidermis. Our data provide strong evidence that both tissues appear to contribute to normal dorsal closure in living embryos, but surprisingly, neither is absolutely required for dorsal closure. Finally, we establish that the Drosophila epidermis rapidly and reproducibly heals from both mechanical and ultraviolet laser wounds, even those delivered repeatedly. During healing, actin is rapidly recruited to the margins of the wound and a newly formed, supracellular purse-string contracts during wound healing. This result establishes the Drosophila embryo as an excellent system for the investigation of wound healing. Moreover, our observations demonstrate that wound healing in this insect epidermal system parallel wound healing in vertebrate tissues in situ and vertebrate cells in culture (for review see Kiehart, D.P. 1999. Curr. Biol. 9:R602–R605).
Focal Exocytosis of Vamp3-Containing Vesicles at Sites of Phagosome Formation
Authors: Bajno Lydia , Peng Xiao-Rong , Schreiber Alan D. , Moore Hsiao-Ping , Trimble William S. , Grinstein Sergio
Published: July 2002

Phagocytosis involves the receptor-mediated extension of plasmalemmal protrusions, called pseudopods, which fuse at their tip to engulf a particle. Actin polymerizes under the nascent phagosome and may propel the protrusion of pseudopods. Alternatively, membrane extension could result from the localized insertion of intracellular membranes into the plasmalemma next to the particle. Here we show focal accumulation of VAMP3-containing vesicles, likely derived from recycling endosomes, in the vicinity of the nascent phagosome. Using green fluorescent protein (GFP) as both a fluorescent indicator and an exofacial epitope tag, we show that polarized fusion of VAMP3 vesicles precedes phagosome sealing. It is therefore likely that targeted delivery of endomembranes contributes to the elongation of pseudopods. In addition to mediating pseudopod formation, receptor-triggered focal secretion of endosomes may contribute to polarized membrane extension in processes such as lamellipodial elongation or chemotaxis.
Evidence That β3 Integrin-Induced Rac Activation Involves the Calpain-Dependent Formation of Integrin Clusters That Are Distinct from the Focal Complexes and Focal Adhesions That Form as Rac and Rhoa Become Active
Authors: Bialkowska Katarzyna , Kulkarni Sucheta , Du Xiaoping , Goll Darrel E. , Saido Takaomi C. , Fox Joan E.B.
Published: July 2002

Interaction of integrins with the extracellular matrix leads to transmission of signals, cytoskeletal reorganizations, and changes in cell behavior. While many signaling molecules are known to be activated within Rac-induced focal complexes or Rho-induced focal adhesions, the way in which integrin-mediated adhesion leads to activation of Rac and Rho is not known. In the present study, we identified clusters of integrin that formed upstream of Rac activation. These clusters contained a Rac-binding protein(s) and appeared to be involved in Rac activation. The integrin clusters contained calpain and calpain-cleaved β3 integrin, while the focal complexes and focal adhesions that formed once Rac and Rho were activated did not. Moreover, the integrin clusters were dependent on calpain for their formation. In contrast, while Rac- and Rho-GTPases were dependent on calpain for their activation, formation of focal complexes and focal adhesions by constitutively active Rac or Rho, respectively, occurred even when calpain inhibitors were present. Taken together, these data are consistent with a model in which integrin-induced Rac activation requires the formation of integrin clusters. The clusters form in a calpain-dependent manner, contain calpain, calpain-cleaved integrin, and a Rac binding protein(s). Once Rac is activated, other integrin signaling complexes are formed by a calpain-independent mechanism(s).
Matrix Metalloproteinase 9 and Vascular Endothelial Growth Factor Are Essential for Osteoclast Recruitment into Developing Long Bones
Authors: Engsig Michael T. , Chen Qing-Jun , Vu Thiennu H. , Pedersen Anne-Cecilie , Therkidsen Bente , Lund Leif R. , Henriksen Kim , Lenhard Thomas , Foged Niels T. , Werb Zena , Delaissé Jean-Marie
Published: July 2002

Bone development requires the recruitment of osteoclast precursors from surrounding mesenchyme, thereby allowing the key events of bone growth such as marrow cavity formation, capillary invasion, and matrix remodeling. We demonstrate that mice deficient in gelatinase B/matrix metalloproteinase (MMP)-9 exhibit a delay in osteoclast recruitment. Histological analysis and specialized invasion and bone resorption models show that MMP-9 is specifically required for the invasion of osteoclasts and endothelial cells into the discontinuously mineralized hypertrophic cartilage that fills the core of the diaphysis. However, MMPs other than MMP-9 are required for the passage of the cells through unmineralized type I collagen of the nascent bone collar, and play a role in resorption of mineralized matrix. MMP-9 stimulates the solubilization of unmineralized cartilage by MMP-13, a collagenase highly expressed in hypertrophic cartilage before osteoclast invasion. Hypertrophic cartilage also expresses vascular endothelial growth factor (VEGF), which binds to extracellular matrix and is made bioavailable by MMP-9 (Bergers, G., R. Brekken, G. McMahon, T.H. Vu, T. Itoh, K. Tamaki, K. Tanzawa, P. Thorpe, S. Itohara, Z. Werb, and D. Hanahan. 2000. Nat. Cell Biol. 2:737–744). We show that VEGF is a chemoattractant for osteoclasts. Moreover, invasion of osteoclasts into the hypertrophic cartilage requires VEGF because it is inhibited by blocking VEGF function. These observations identify specific actions of MMP-9 and VEGF that are critical for early bone development.
VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release
Authors: Madesh Muniswamy , Hajnóczky György
Published: July 2002

Enhanced formation of reactive oxygen species (ROS), superoxide (O2·−), and hydrogen peroxide (H2O2) may result in either apoptosis or other forms of cell death. Here, we studied the mechanisms underlying activation of the apoptotic machinery by ROS. Exposure of permeabilized HepG2 cells to O2·− elicited rapid and massive cytochrome c release (CCR), whereas H2O2 failed to induce any release. Both O2·− and H2O2 promoted activation of the mitochondrial permeability transition pore by Ca2+, but Ca2+-dependent pore opening was not required for O2·−-induced CCR. Furthermore, O2·− alone evoked CCR without damage of the inner mitochondrial membrane barrier, as mitochondrial membrane potential was sustained in the presence of extramitochondrial ATP. Strikingly, pretreatment of the cells with drugs or an antibody, which block the voltage-dependent anion channel (VDAC), prevented O2·−-induced CCR. Furthermore, VDAC-reconstituted liposomes permeated cytochrome c after O2·− exposure, and this release was prevented by VDAC blocker. The proapoptotic protein, Bak, was not detected in HepG2 cells and O2·−-induced CCR did not depend on Bax translocation to mitochondria. O2·−-induced CCR was followed by caspase activation and execution of apoptosis. Thus, O2·− triggers apoptosis via VDAC-dependent permeabilization of the mitochondrial outer membrane without apparent contribution of proapoptotic Bcl-2 family proteins.
Sla1p serves as the targeting signal recognition factor for NPFX(1,2)D-mediated endocytosis
Authors: Howard James P. , Hutton Jenna L. , Olson John M. , Payne Gregory S.
Published: July 2002

Efficient endocytosis requires cytoplasmic domain targeting signals that specify incorporation of cargo into endocytic vesicles. Adaptor proteins play a central role in cargo collection by linking targeting signals to the endocytic machinery. We have characterized NPFX(1,2) (NPFX[1,2]D) targeting signals and identified the actin-associated protein Sla1p as the adaptor for NPFX(1,2)D-mediated endocytosis in Saccharomyces cerevisiae. 11 amino acids encompassing an NPFX(1,2)D sequence were sufficient to direct uptake of a truncated form of the pheromone receptor Ste2p. In this context, endocytic targeting activity was not sustained by conservative substitutions of the phenylalanine or aspartate. An NPFX1,2D-related sequence was identified in native Ste2p that functions redundantly with ubiquitin-based endocytic signals. A two-hybrid interaction screen for NPFX(1,2)D-interacting proteins yielded SLA1, but no genes encoding Eps15 homology (EH) domains, protein modules known to recognize NPF peptides. Furthermore, EH domains did not recognize an NPFX(1,2)D signal when directly tested by two-hybrid analysis. SLA1 disruption severely inhibited NPFX(1,2)D-mediated endocytosis, but only marginally affected ubiquitin-directed uptake. NPFX(1,2)D-dependent internalization required a conserved domain of Sla1p, SLA1 homology domain, which selectively bound an NPFX(1,2)D-containing fusion protein in vitro. Thus, through a novel NPF-binding domain, Sla1p serves as an endocytic targeting signal adaptor, providing a means to couple cargo with clathrin- and actin-based endocytic machineries.
Bone abnormalities in latent TGF-β binding protein (Ltbp)-3–null mice indicate a role for Ltbp-3 in modulating TGF-β bioavailability
Authors: Dabovic Branka , Chen Yan , Colarossi Cristina , Obata Hiroto , Zambuto Laura , Perle Mary Ann , Rifkin Daniel B.
Published: July 2002

The TGF-βs are multifunctional proteins whose activities are believed to be controlled by interaction with the latent TGF-β binding proteins (LTBPs). In spite of substantial effort, the precise in vivo significance of this interaction remains unknown. To examine the role of the Ltbp-3, we made an Ltbp-3–null mutation in the mouse by gene targeting. Homozygous mutant animals develop cranio-facial malformations by day 10. At 2 mo, there is a pronounced rounding of the cranial vault, extension of the mandible beyond the maxilla, and kyphosis. Histological examination of the skulls from null animals revealed ossification of the synchondroses within 2 wk of birth, in contrast to the wild-type synchondroses, which never ossify. Between 6 and 9 mo of age, mutant animals also develop osteosclerosis and osteoarthritis. The pathological changes of the Ltbp-3–null mice are consistent with perturbed TGF-β signaling in the skull and long bones. These observations give support to the notion that LTBP-3 is important for the control of TGF-β action. Moreover, the results provide the first in vivo indication for a role of LTBP in modulating TGF-β bioavailability.
Identification of Podocalyxin-like Protein as a High Endothelial Venule Ligand for L-selectin: Parallels to CD34
Authors: Sassetti Christopher , Tangemann Kirsten , Singer Mark S. , Kershaw David B. , Rosen Steven D.
Published: July 2002

The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV). Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function.
A Kinetic Threshold between Negative and Positive Selection Based on the Longevity of the T Cell Receptor–Ligand Complex
Authors: Williams Calvin B. , Engle Deborah L. , Kersh Gilbert J. , Michael White J. , Allen Paul M.
Published: July 2002

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II– restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64–76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR–ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR–ligand complexes.
Differentiating between Memory and Effector Cd8 T Cells by Altered Expression of Cell Surface O-Glycans
Authors: Harrington Laurie E. , Galvan Marisa , Baum Linda G. , Altman John D. , Ahmed Rafi
Published: July 2002

Currently there are few reliable cell surface markers that can clearly discriminate effector from memory T cells. To determine if there are changes in O-glycosylation between these two cell types, we analyzed virus-specific CD8 T cells at various time points after lymphocytic choriomeningitis virus infection of mice. Antigen-specific CD8 T cells were identified using major histocompatibility complex class I tetramers, and glycosylation changes were monitored with a monoclonal antibody (1B11) that recognizes O-glycans on mucin-type glycoproteins. We observed a striking upregulation of a specific cell surface O-glycan epitope on virus-specific CD8 T cells during the effector phase of the primary cytotoxic T lymphocyte (CTL) response. This upregulation showed a strong correlation with the acquisition of effector function and was downregulated on memory CD8 T cells. Upon reinfection, there was again increased expression of this specific O-glycan epitope on secondary CTL effectors, followed once more by decreased expression on memory cells. Thus, this study identifies a new cell surface marker to distinguish between effector and memory CD8 T cells. This marker can be used to isolate pure populations of effector CTLs and also to determine the proportion of memory CD8 T cells that are recruited into the secondary response upon reencounter with antigen. This latter information will be of value in optimizing immunization strategies for boosting CD8 T cell responses.
Adjuvant Immunotherapy Is Dependent on Inducible Nitric Oxide Synthase
Authors: Kahn Daniel A. , Archer D. Clay , Gold Daniel P. , Kelly Carolyn J.
Published: July 2002

Rodents immunized with complete Freund's adjuvant (CFA) are resistant to subsequent attempts to induce autoimmune disease, while animals immunized with incomplete Freund's adjuvant (IFA) remain susceptible. Mycobacterial extracts can stimulate inducible nitric oxide synthase (NOS2) gene transcription. Robust expression of NOS2 has been linked to suppression of T cell proliferation and alterations in immune responses. Our studies investigated the hypothesis that the immunoprotective effect of CFA before immunization requires functional NOS2. NOS2 gene expression is chronically elevated in lymph nodes and spleens of CFA-immunized mice. Maximal expression of NOS2 after CFA immunization requires the presence of functional type I tumor necrosis factor α receptor (TNFR1) and interferon γ. Groups of nontreated and CFA-preimmunized male C57BL/6J or C57BL/6NOS2−/− mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35–55 in CFA to induce experimental allergic encephalomyelitis (EAE). Wild-type C57BL/6J mice were protected from the development of symptoms of EAE, while the NOS2−/− mice failed to be protected. NOS2-dependent effects of CFA included an augmentation of the MOG-specific IgG1 response, a decrease in interleukin 6 production by MOG-reactive lymphocytes, and a marked decrease in mononuclear cell infiltrates in the central nervous system. These studies support the hypothesis that CFA immunization modulates immune responses through a nitric oxide–dependent mechanism.
Temperature Dependence of Fast and Slow Gating Relaxations of ClC-0 Chloride Channels
Authors: Pusch Michael , Ludewig Uwe , Jentsch Thomas J.
Published: July 2002

The chloride channel from the Torpedo electric organ, ClC-0, is the best studied member of a large gene-family (Jentsch, T.J. 1996. Curr. Opin. Neurobiol. 6:303–310.). We investigate the temperature dependence of both the voltage- and chloride-dependent fast gate and of the slow gate of the “double-barreled” ClC-0 expressed in Xenopus oocytes. Kinetics of the fast gate exhibit only a moderate temperature dependence with a Q10 of 2.2. Steady-state popen of the fast gate is relatively independent of temperature. The slow gate, in contrast, is highly temperature sensitive. Deactivation kinetics at positive voltages are associated with a Q10 of ∼40. Steady-state open probability of the slow gate (popenslow(V)) can be described by a Boltzmann distribution with an apparent gating valence of ≈2 and a variable “offset” at positive voltages. We note a positive correlation of this offset (i.e., the fraction of channels that are not closed by the slow gate) with the amount of expression. This offset is also highly temperature sensitive, being drastically decreased at high temperatures. Paradoxically, the maximum degree of activation of the slow gate also decreases at higher temperatures. The strong temperature dependence of the slow gate was also observed at the single channel level in inside-out patches. The results imply that within a Markovian-type description at least two open and two closed states are needed to describe slow gating. The strong temperature dependence of the slow gate explains the phenotype of several ClC-0 point-mutants described recently by Ludewig et al. (Ludewig, U., T.J. Jentsch, and M. Pusch. 1996. J. Physiol. (Lond.). In press). The large Q10 of slow gating kinetics points to a complex rearrangement. This, together with the correlation of the fraction of noninactivating channels with the amount of expression and the fact that the slow gate closes both protochannels simultaneously suggests that the slow gate is coupled to subunit interaction of the multimeric ClC-0 channel.
Site-Directed Spin-Labeling Analysis of Reconstituted Mscl in the Closed State
Authors: Perozo Eduardo , Kloda Anna , Cortes D. Marien , Martinac Boris
Published: July 2002

The mechanosensitive channel from Escherichia coli (Eco-MscL) responds to membrane lateral tension by opening a large, water-filled pore that serves as an osmotic safety valve. In an attempt to understand the structural dynamics of MscL in the closed state and under physiological conditions, we have performed a systematic site-directed spin labeling study of this channel reconstituted in a membrane bilayer. Structural information was derived from an analysis of probe mobility, residue accessibility to O2 or NiEdda and overall intersubunit proximity. For the majority of the residues studied, mobility and accessibility data showed a remarkable agreement with the Mycobacterium tuberculosis crystal structure, clearly identifying residues facing the large water-filled vestibule at the extracellular face of the molecule, the narrowest point along the permeation pathway (residues 21–26 of Eco-MscL), and the lipid-exposed residues in the peripheral transmembrane segments (TM2). Overall, the present dataset demonstrates that the transmembrane regions of the MscL crystal structure (obtained in detergent and at low pH) are, in general, an accurate representation of its structure in a membrane bilayer under physiological conditions. However, significant differences between the EPR data and the crystal structure were found toward the COOH-terminal end of TM2.
Marketing institutional journal subscriptions to academic libraries
Authors: Kidd Tony
Published: July 2002

This paper examines different influences on the journal cancellation and selection policies of university libraries in the UK. Changing funding arrangements are outlined, followed by a discussion of varied criteria that are used during journal cancellation exercises, and how publishers can influence this process. The paper then considers changes consequent upon the advent of the electronic journal, and suggests that this, together with budget devolution and greater library liaison with academic staff, is increasing the influence of library staff in journal selection. As a result of these various trends, direct contacts between publishers and library staff are increasing.
(In)Efficient market models: the reality behind economic models in the publishing industry
Authors: Arjoon Roger
Published: July 2002

The literature on evolving economic models in the electronic publishing industry of academic and scholarly communication has primarily been based on an ideology of economic efficiency. This ideology implies the role of print journals and publishers will become less dominant in the publishing industry since market forces predict a significant change in the flow of incentives and information between the various stakeholders. However, recent research suggests that this conclusion may be premature. Resisting forces, which manifest themselves via institutional, infrastructural and informational channels, seem strong enough to maintain the viability of print publishing in the medium term.
Degrees, kernels and quasikernels of monolithic characters
Authors: Berkovich Yakov
Published: July 2002

Theorem 5 yields the condition sufficient for a group to be a direct product of a

π
\pi

-group and an abelian

π
′

\pi ’

-group. We also obtain characterizations of nilpotent groups, prime power groups,

p
p

-nilpotent and

p
p

-closed groups in the language of characters. Proofs of some results depend on the classification of finite simple groups. Some problems are posed and discussed.
A criterion for correct solvability of the Sturm-Liouville equation in the space 𝐿_{𝑝}(𝑅)
Authors: Chernyavskaya N. , Shuster L.
Published: July 2002

We consider an equation
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout 1st Row with Label left-parenthesis 1 right-parenthesis EndLabel minus y left-parenthesis x right-parenthesis plus q left-parenthesis x right-parenthesis y left-parenthesis x right-parenthesis equals f left-parenthesis x right-parenthesis comma x element-of upper R comma EndLayout">

(1)

−
y
(
x
)
+
q
(
x
)
 
y
(
x
)
=
f
(
x
)
,

x
∈
R
,

\begin{equation}\tag {1} -y(x) + q(x)\ y(x) = f(x),\qquad x\in R, \end{equation}

where
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="f left-parenthesis x right-parenthesis element-of upper L Subscript p Baseline left-parenthesis upper R right-parenthesis comma p element-of left-bracket 1 comma normal infinity right-bracket left-parenthesis double-vertical-bar f double-vertical-bar Subscript normal infinity Baseline colon equals upper C left-parenthesis upper R right-parenthesis right-parenthesis">

f
(
x
)
∈

L

p

(
R
)
,
 
p
∈
[
1
,
∞
]
 

(
‖
f

‖

∞

:=
C
(
R
)
)

f(x) \in L_{p}(R),\ p\in [1,\infty ]\ \left (\| f \|_{\infty } := C (R) \right )

, and

0
≤
q
(
x
)
∈

L

1

loc

(
R
)
.

0 \le q(x)\in L_{1}^{\operatorname {loc}} (R).

By a solution of equation (1), we mean any function

y
(
x
)

y(x)

such that

y
(
x
)
,

y
′

(
x
)
∈
A

C

loc

(
R
)
,

y(x), y’(x) \in AC^{\operatorname {loc}} (R),

and equality (1) holds almost everywhere on

R
.

R.

In this paper, we obtain a criterion for the correct solvability of (1) in

L

p

(
R
)

L_{p} (R)

,

p
∈
[
1
,
∞
]
.

p \in [1,\infty ].
Package deal theorems and splitting orders in dimension 1
Authors: Levy Lawrence , Odenthal Charles
Published: July 2002

Let

Λ
\Lambda

be a module-finite algebra over a commutative noetherian ring

R
R

of Krull dimension 1. We determine when a collection of finitely generated modules over the localizations

Λ

m

\Lambda _{\mathbf {m}}

, at maximal ideals of

R
R

, is the family of all localizations

M

m

M_{\mathbf {m}}

of a finitely generated

Λ
\Lambda

-module

M
M

. When

R
R

is semilocal we also determine which finitely generated modules over the

J
(
R
)

J(R)

-adic completion of

Λ
\Lambda

are completions of finitely generated

Λ
\Lambda

-modules. If

Λ
\Lambda

is an

R
R

-order in a semisimple artinian ring, but not contained in a maximal such order, several of the basic tools of integral representation theory behave differently than in the classical situation. The theme of this paper is to develop ways of dealing with this, as in the case of localizations and completions mentioned above. In addition, we introduce a type of order called a “splitting order” of

Λ
\Lambda

that can replace maximal orders in many situations in which maximal orders do not exist.
Another note on Weyl’s theorem
Authors: Harte Robin , Lee Woo
Published: July 2002

“Weyl’s theorem holds" for an operator

T
T

on a Banach space

X
X

when the complement in the spectrum of the “Weyl spectrum" coincides with the isolated points of spectrum which are eigenvalues of finite multiplicity. This is close to, but not quite the same as, equality between the Weyl spectrum and the “Browder spectrum", which in turn ought to, but does not, guarantee the spectral mapping theorem for the Weyl spectrum of polynomials in

T
T

. In this note we try to explore these distinctions.
Hardy spaces, BMO, and boundary value problems for the Laplacian on a smooth domain in 𝐑^{𝐍}
Authors: Chang Der-Chen , Dafni Galia , Stein Elias
Published: July 2002

We study two different local

H
p

H^p

spaces,

0
>
p
≤
1

0 > p \leq 1

, on a smooth domain in

R

n

\mathbf {R}^n

, by means of maximal functions and atomic decomposition. We prove the regularity in these spaces, as well as in the corresponding dual BMO spaces, of the Dirichlet and Neumann problems for the Laplacian.
Representation Theory of Reductive Normal Algebraic Monoids
Authors: Doty Stephen
Published: July 2002

New results in the representation theory of “semisimple” algebraic monoids are obtained, based on Renner’s monoid version of Chevalley’s big cell. (The semisimple algebraic monoids have been classified by Renner.) The rational representations of such a monoid are the same thing as “polynomial” representations of the associated reductive group of units in the monoid, and this representation category splits into a direct sum of subcategories by “homogeneous” degree. We show that each of these homogeneous subcategories is a highest weight category, in the sense of Cline, Parshall, and Scott, and so equivalent with the module category of a certain finite-dimensional quasihereditary algebra, which we show is a generalized Schur algebra in S. Donkin’s sense.
Calculation of Gauss-Kronrod quadrature rules
Authors: Laurie Dirk
Published: July 2002

The Jacobi matrix of the

(
2
n
+
1
)

(2n+1)

-point Gauss-Kronrod quadrature rule for a given measure is calculated efficiently by a five-term recurrence relation. The algorithm uses only rational operations and is therefore also useful for obtaining the Jacobi-Kronrod matrix analytically. The nodes and weights can then be computed directly by standard software for Gaussian quadrature formulas.
A new class of asynchronous iterative algorithms with order intervals
Authors: Miellou J. , El Baz D. , Spiteri P.
Published: July 2002

This paper deals with a new class of parallel asynchronous iterative algorithms for the solution of nonlinear systems of equations. The main feature of the new class of methods presented here is the possibility of flexible communication between processors. In particular partial updates can be exchanged. Approximation of the associated fixed point mapping is also considered. A detailed convergence study is presented. A connection with the Schwarz alternating method is made for the solution of nonlinear boundary value problems. Computational results on a shared memory multiprocessor IBM 3090 are briefly presented.
Hecke algebra representations related to spherical varieties
Authors: Mars J. , Springer T.
Published: July 2002

Let

G
G

be a connected reductive group over the algebraic closure of a finite field and let

Y
Y

be a spherical variety for

G
G

. We consider perverse sheaves on

G
G

and on

Y
Y

which have a weight for the action of a Borel subgroup

B
B

and are endowed with an action of Frobenius. This leads to the definition of a “generalized Hecke algebra”, attached to

G
G

, and of a module over that algebra, attached to

Y
Y

. The same algebra and the same module can also be defined using constructible sheaves. Comparison of the two definitions gives, in the case of a symmetric variety

Y
Y

and

B
B

-equivariant sheaves, a geometric proof of results which Lusztig and Vogan obtained by representation theoretic means.
Schizosaccharomyces pombepfh1+Encodes an Essential 5′ to 3′ DNA Helicase That Is a Member of thePIF1Subfamily of DNA Helicases
Authors: Zhou Jin-Qiu , Qi Haiyan , Schulz Vincent P. , Mateyak Maria K. , Monson Ellen K. , Zakian Virginia A.
Published: July 2002

The Saccharomyces cerevisiae Pif1p DNA helicase is the prototype member of a helicase subfamily conserved from yeast to humans. S. cerevisiae has two PIF1-like genes, PIF1 itself and RRM3, that have roles in maintenance of telomeric, ribosomal, and mitochondrial DNA. Here we describe the isolation and characterization ofpfh1+, aSchizosaccharomyces pombe gene that encodes a Pif1-like protein. Pfh1p was the only S. pombe protein with high identity to Saccharomyces Pif1p. Unlike the twoS. cerevisiae Pif1 subfamily proteins, the S. pombe Pfh1p was essential. Like SaccharomycesPif1p, a truncated form of the S. pombe protein had 5′ to 3′ DNA helicase activity. Point mutations in an invariant lysine residue in the ATP binding pocket of Pfh1p had the same phenotype as deleting pfh1+, demonstrating that the ATPase/helicase activity of Pfh1p was essential. Although mutant spores depleted for Pfh1p proceeded through S phase, they arrested with a terminal cellular phenotype consistent with a postinitiation defect in DNA replication. Telomeric DNA was modestly shortened in the absence of Pfh1p. However, genetic analysis demonstrated that maintenance of telomeric DNA was not the sole essential function of S. pombe Pfh1p.
PhyloDraw: a phylogenetic tree drawing system
Authors: Choi Jeong-Hyeon , Jung Ho-Youl , Kim Hye-Sun , Cho Hwan-Gue
Published: July 2002

Summary: PhyloDraw is a unified viewing tool for phylogenetic trees. PhyloDraw supports various kinds of multi-alignment formats (Dialign2, Clustal-W, Phylip format, NEXUS, MEGA, and pairwise distance matrix) and visualizes various kinds of tree diagrams, e.g. rectangular cladogram, slanted cladogram, phylogram, unrooted tree, and radial tree. By using several control parameters, users can easily and interactively manipulate the shape of phylogenetic trees. This program can export the final tree layout to BMP (bitmap image format) and PostScript.

Availability: http://pearl.cs.pusan.ac.kr/phylodraw/

Contact: jhchoi@pearl.cs.pusan.ac.kr
Dotlet: diagonal plots in a Web browser
Authors: Junier Thomas , Pagni Marco
Published: July 2002

Summary: Dotlet is a program for comparing sequences by the diagonal plot method. It is designed to be platform-independent and to run in a Web browser, thus enabling the majority of researchers to use it.

Availability: The applet can be tested at http://www.isrec.isb-sib.ch/java/dotlet/Dotlet.html, and the source code is available upon request.

Contact: (Thomas.Junier—Marco.Pagni)@isrec.unil.ch

Supplementary information: The full documentation about dotlet is available from the above URL.
Prediction of quaternary structure from primary structure
Authors: Garian Robert
Published: July 2002

Motivation: The ‘sequence implies conformation’ principle has been the motivation for the construction of numerous systems of secondary and tertiary structure prediction. Computational experiments have shown that this principle can now be extended to quaternary structure prediction. This work appears to be the first effort to predict quaternary structure properties from sequence.

Results: The software developed to conduct these experiments was the Quaternary Structure Explorer (QSE). Successful rule-based classifiers have been found that can discriminate between the primary sequences of homodimers and non-homodimers.

Availability: The homodimer classifier can be accessed at http://www.mericity.com

Contact: rgar@science.gmu.edu
Characteristics of post‐transcriptional gene silencing
Authors: Chicas Agustin , Macino Giuseppe
Published: July 2002

A number of gene silencing phenomena that inactivate genes at the post‐transcriptional level have been identified. Due to its potential for studying gene function, post‐transcriptional gene silencing (PTGS) has become an intense area of research. In this review we describe the different means of inducing PTGS and discuss the possible biological roles of these artificially induced phenomena. We also discuss other features of PTGS such as the mechanism of mRNA degradation, the nature of the silencing signal and the mechanism of PTGS inhibition by viral proteins.
Functional reconstitution of purified metabotropic glutamate receptor expressed in the fly eye
Authors: Eroglu Çagla , Cronet Philippe , Panneels Valérie , Beaufils Philippe , Sinning Irmgard
Published: July 2002

G‐protein‐coupled receptors (GPCRs) form one of the largest superfamilies of membrane proteins. Obtaining high yields of GPCRs remains one of the major factors limiting a detailed understanding of their structure and function. Photoreceptor cells (PRCs) contain extensive stacks of specialized membranes where high levels of rhodopsins are naturally present, which makes them ideal for the overexpression of GPCRs. We have generated transgenic flies expressing a number of GPCRs in the PRCs. Drosophila melanogaster metabotropic glutamate receptor (DmGluRA) expressed by this novel strategy was purified to homogeneity, giving at least 3‐fold higher yields than conventional baculovirus expression systems due to the higher membrane content of the PRCs. Pure DmGluRA was then reconstituted into liposomes of varying composition. Interestingly, glutamate binding was strictly dependent on the presence of ergosterol.
STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis
Authors: Prieto Ignacio , Pezzi Nieves , Buesa José M , Kremer Leonor , Barthelemy Isabel , Carreiro Candelas , Roncal Fernando , Martínez Alicia , Gómez Lucio , Fernández Raúl , Martínez‐A Carlos , Barbero José L
Published: July 2002

STAG/SA proteins are specific cohesin complex subunits that maintain sister chromatid cohesion in mitosis and meiosis. Two members of this family, STAG1/SA1 and STAG2/SA2, ‡are classified as mitotic cohesins, as they are found in human somatic cells and in Xenopus laevis as components of the cohesinSA1 and cohesinSA2 complexes, in which the shared subunits are Rad21/SCC1, SMC1 and SMC3 proteins. A recently reported third family member, STAG3, is germinal cell‐specific and is a subunit of the meiotic cohesin complex. To date, the meiosis‐specific cohesin complex has been considered to be responsible for sister chromatid cohesion during meiosis. We studied replacement of the mitotic by the meiotic cohesin complex during mouse germinal cell maturation, and we show that mammalian STAG2 and Rad21 are also involved in several meiosis stages. Immunofluorescence results suggest that a cohesin complex containing Rad21 and STAG2 cooperates with a STAG3‐specific complex to maintain sister chromatid cohesion during the diplotene stage of meiosis.
Epidemiology and pathogenesis of influenza
Authors: Zambon Maria C.
Published: July 2002

Influenza A, B and C all have a segmented genome, although only certain influenza A subtypes and influenza B cause severe disease in humans. The two major proteins of influenza are the surface glycoproteins—haemagglutinin (HA) and neuraminidase (NA). HA is the major antigen for neutralizing antibodies and is involved in the binding of virus particles to receptors on host cells. Pandemics are a result of novel virus subtypes of influenza A, created by reassortment of the segmented genome (antigenic shift), whereas annual epidemics are a result of evolution of the surface antigens of influenza A and B virus (antigenic drift). The rapid evolution of influenza viruses highlights the importance of surveillance in identifying novel circulating strains. Infectivity of influenza depends on the cleavage of HA by specific host proteases, whereas NA is involved in the release of progeny virions from the cell surface and prevents clumping of newly formed virus. In birds, the natural hosts of influenza, the virus causes gastrointestinal infection and is transmitted via the faeco-oral route. Virulent avian influenza strains, which cause systemic disease, have an HA that is cleaved by proteases present in all cells of the body, rather than by proteases restricted to the intestinal tract. In mammals, replication of influenza subtypes appears restricted to respiratory epithelial cells. Most symptoms and complications, therefore, involve the respiratory tract. However, systemic complications are sometimes observed and other viral genes besides the HA, including the NA, may be involved in determination of virulence of influenza strains in mammals.
Evolutionary patterns from mass originations and mass extinctions
Authors: Hewzulla D. , Boulter M. C. , Benton M. J. , Halley J. M.
Published: July 2002

The Fossil Record 2 database gives a stratigraphic range of most known animal and plant families. We have used it to plot the number of families extant through time and argue for an exponential fit, rather than a logistic one, on the basis of power spectra of the residuals from the exponential. The times of origins and extinctions, when plotted for all families of marine and terrestrial organisms over the last 600 Myr, reveal different origination and extinction peaks. This suggests that patterns of biological evolution are driven by its own internal dynamics as well as responding to upsets from external causes. Spectral analysis shows that the residuals from the exponential model of the marine system are more consistent with 1/fnoise suggesting that self–organized criticality phenomena may be involved.
Evolution of microbial pathogens
Authors: Morschhäuser Joachim , Köhler Gerwald , Ziebuhr Wilma , Blum–Oehler Gabriele , Dobrindt Ulrich , Hacker Jörg
Published: July 2002

Various genetic mechanisms including point mutations, genetic rearrangements and lateral gene transfer processes contribute to the evolution of microbes. Long-term processes leading to the development of new species or subspecies are termed macroevolution, and short–term developments, which occur during days or weeks, are considered as microevolution. Both processes, macro– and microevolution need horizontal gene transfer, which is particularly important for the development of pathogenic microorganisms. Plasmids, bacteriophages and so–called pathogenicity islands (PAIs) play a crucial role in the evolution of pathogens. During microevolution, genome variability of pathogenic microbes leads to new phenotypes, which play an important role in the acute development of an infectious disease. Infections due to
Staphylococcus epidermidis
,
Candida albicans
and
Escherichia coli
will be described with special emphasis on processes of microevolution. In contrast, the development of PAIs is a process involved in macroevolution. PAIs are especially important in processes leading to new pathotypes or even species. In this review, particular attention will be given to the fact that the evolution of pathogenic microbes can be considered as a specific example for microbial evolution in general.
Roles for inositol-phosphoryl ceramide synthase 1 (IPC1) in pathogenesis ofC. neoformans
Authors: Luberto Chiara , Toffaletti Dena L. , Wills Elizabeth A. , Tucker Stephanie C. , Casadevall Arturo , Perfect John R. , Hannun Yusuf A. , Del Poeta Maurizio
Published: July 2002

Cryptococcus neoformansis a leading cause of life-threatening fungal infection in immunocompromised patients. Inositol-phosphoryl ceramide synthase 1 (Ipc1) is a fungus-specific enzyme, encoded by the essentialIPC1gene, that catalyzes the formation of complex sphingolipids and may also regulate the levels of phytoceramide and diacylglycerol. Here, we investigated the functions of this essential gene by modulating its expression inC. neoformansusing a galactose-inducible promoter. Down-regulation ofIPC1significantly lowers the expression of certain virulence traits such as melanin pigmentation and, remarkably, impairs pathogenicity ofC. neoformansin an established rabbit model. Interestingly, we found thatIPC1down-regulation significantly decreases the intracellular growth ofC. neoformansin the J774.16 murine macrophage-like cells. Finally, we studied the effect ofIPC1expression under different stress conditions and found that down-regulation ofIPC1confers a defect on in vitro growth at low pH. Because this environment is similar to that in the phagolysosome of J774.16 macrophage-like cells, our findings indicate that down-regulation ofIPC1confers a growth defect in vivo through a pH-dependent mechanism. In conclusion, our study is the first to define a novel and crucial function of Ipc1 in fungal pathogenesis.
Harmonographs. I. Pendulum design
Authors: Whitaker Robert J.
Published: July 2002

Mechanical devices that undergo various kinds of repetitive motion and which draw the curves produced from this motion are known as “harmonographs.” One such class of these devices are those that operate by means of pendulum action. These devices range from modifications of a simple pendulum to various physical and compound pendulums. This paper traces the history of the development of this class of apparatus.
A quantum bouncing ball
Authors: Gea-Banacloche Julio
Published: July 2002

The dynamics of a quantum wave packet bouncing on a hard surface under the influence of gravity are studied. This is a system that might be realized experimentally with cold atoms dropped onto an “atomic mirror.” The classical limit is discussed and interesting departures from classical behavior are pointed out and explained.