bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocyte Chemoattractant Protein 1–Dependent Leukocytic Infiltrates Are Responsible for Autoimmune Disease in Mrl-Faslpr Mice
Authors: Tesch Gregory H. , Maifert Stefanie , Schwarting Andreas , Rollins Barrett J. , Kelley Vicki Rubin
Published: July 2002

Infiltrating leukocytes may be responsible for autoimmune disease. We hypothesized that the chemokine monocyte chemoattractant protein (MCP)-1 recruits macrophages and T cells into tissues that, in turn, are required for autoimmune disease. Using the MRL-Faslpr strain with spontaneous, fatal autoimmune disease, we constructed MCP-1–deficient MRL-Faslpr mice. In MCP-1–intact MRL-Faslprmice, macrophages and T cells accumulate at sites (kidney tubules, glomeruli, pulmonary bronchioli, lymph nodes) in proportion to MCP-1 expression. Deleting MCP-1 dramatically reduces macrophage and T cell recruitment but not proliferation, protects from kidney, lung, skin, and lymph node pathology, reduces proteinuria, and prolongs survival. Notably, serum immunoglobulin (Ig) isotypes and kidney Ig/C3 deposits are not diminished in MCP-1–deficient MRL-Faslpr mice, highlighting the requirement for MCP-1–dependent leukocyte recruitment to initiate autoimmune disease. However, MCP-1–deficient mice are not completely protected from leukocytic invasion. T cells surrounding vessels with meager MCP-1 expression remain. In addition, downstream effector cytokines/chemokines are decreased in MCP-1–deficient mice, perhaps reflecting a reduction of cytokine-expressing leukocytes. Thus, MCP-1 promotes MRL-Faslpr autoimmune disease through macrophage and T cell recruitment, amplified by increasing local cytokines/chemokines. We suggest that MCP-1 is a principal therapeutic target with which to combat autoimmune diseases.
Immunization and Infection Change the Number of Recombination Activating Gene (Rag)-Expressing B Cells in the Periphery by Altering Immature Lymphocyte Production
Authors: Nagaoka Hitoshi , Gonzalez-Aseguinolaza Gloria , Tsuji Moriya , Nussenzweig Michel C.
Published: July 2002

Recombination activating gene (RAG) expression in peripheral B cells increases after immunization with (4-hydroxy-3-nitrophenyl) acetyl coupled to chicken gamma globulin (NP-CGG) in alum. This increase could result from reinduction of RAG expression or, alternatively, from accumulation of RAG-expressing immature B cells in the periphery. We have used mice that carry a green fluorescent protein (GFP) RAG indicator transgene (RAG2-GFP) to characterize the RAG-expressing B cells in immunized spleens. Most of the RAG2-GFP–expressing B cells in unimmunized spleen are immature B cells. Injection with NP-CGG in alum initially suppresses lymphopoiesis in the bone marrow and decreases the number of immature RAG2-GFP–expressing B cells in the spleen. Recovery of lymphopoiesis in the bone marrow coincides with accumulation of RAG-expressing immature B cells in the spleen. Most of the RAG-expressing cells that accumulate in the spleen after immunization do not proliferate and they are not germinal center cells. Neither the initial suppression of lymphopoiesis nor the subsequent accumulation of RAG-expressing cells in the spleen is antigen dependent, since similar changes are seen with alum alone. Furthermore, such changes in the numbers of developing and circulating immature lymphoid cells are seen after injection with complete Freund's adjuvant or malaria infection. Our experiments suggest that adjuvants and infectious agents cause previously unappreciated alterations in lymphopoiesis resulting in the accumulation of RAG-expressing immature B cells in the spleen.
Downmodulation of the Inflammatory Response to Bacterial Infection by γδ T Cells Cytotoxic for Activated Macrophages
Authors: Egan Paul J. , Carding Simon R.
Published: July 2002

Although γδ T cells are involved in the regulation of inflammation after infection, their precise function is not known. Intraperitoneal infection of T cell receptor (TCR)-δ−/− mice with the intracellular bacterium Listeria monocytogenes resulted in the development of necrotic foci in the livers. In contrast, the peritoneal cavities of infected TCR-δ−/− mice contained an accumulation of low density activated macrophages and a reduced percentage of macrophages undergoing apoptosis. γδ T cell hybridomas derived from mice infected with Listeria were preferentially stimulated by low density macrophages from peritoneal exudates of infected mice. Furthermore, primary splenic γδ T cells isolated from Listeria-infected mice were cytotoxic for low density macrophages in vitro, and cytotoxicity was inhibited in the presence of antibodies to the γδ TCR. These results demonstrate a novel interaction between γδ T cells and activated macrophages in which γδ T cells are stimulated by terminally differentiated macrophages to acquire cytotoxic activity and which, in turn, induce macrophage cell death. This interaction suggests that γδ T cells regulate the inflammatory response to infection with intracellular pathogens by eliminating activated macrophages at the termination of the response.
B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1
Authors: Tsuji Sachiyo , Okamoto Mariko , Yamada Koichi , Okamoto Noriaki , Goitsuka Ryo , Arnold Rudiger , Kiefer Friedemann , Kitamura Daisuke
Published: July 2002

The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as phospholipase Cγ (PLCγ)2 and Vav, while the function of its COOH-terminal src homology 2 domain is unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant inhibited IκB kinase β (IKKβ) activation by BCR engagement. These results reveal a novel BCR signaling pathway leading to the activation of HPK1 and subsequently IKKβ, in which BASH recruits tyrosine-phosphorylated HPK1 into the BCR signaling complex.
Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II–positive Dendritic Cells Derived from MHC Class II–negative Grafts
Authors: Liu Ying , Hamrah Pedram , Zhang Qiang , Taylor Andrew W. , Dana M. Reza
Published: July 2002

To examine the widely accepted dogmas that corneal grafts lack passenger leukocytes or cells capable of migrating directly to lymph nodes (LNs), we tracked the migration of corneal graft-derived transgenic green fluorescent protein (GFP; Iab) cells into the draining LNs of allogeneic (Iad) recipients. GFP+ cells were identified in cervical LNs several hours after transplantation, and this traffic was significantly enhanced when grafts were placed in inflamed recipient beds. Draining cells were Iab+, CD45+, and CD11c+, and examination of ungrafted corneas revealed numerous similarly CD45+CD11c+CD3−CD8α− cells that uniformly lacked major histocompatibility complex (MHC) class II expression; transmission electron microscopy confirmed the presence of morphologically similar cells. After transplantation, or placement in culture, these CD11c+ cells became class II+ in a time-dependent manner and were capable of allostimulatory function. However, the stimulatory capacity of these cornea-derived dendritic cells (DCs) was suppressed compared with splenic controls. These results demonstrate for the first time that the cornea is endowed with resident DCs that are universally MHC class II− but that are capable of expressing class II antigen after surgery and migrating to draining LNs of allografted hosts. These data refute the tenet that the cornea is immune privileged due to lack of resident lymphoreticular cells or due to antigenic sequestration from systemic immunity.
Dihydropyridine Action on Voltage-dependent Potassium Channels Expressed in Xenopus Oocytes
Authors: Avdonin Vladimir , Shibata Erwin F. , Hoshi Toshinori
Published: July 2002

Dihydropyridines (DHPs) are well known for their effects on L-type voltage-dependent Ca2+ channels. However, these drugs also affect other voltage-dependent ion channels, including Shaker K+ channels. We examined the effects of DHPs on the Shaker K+ channels expressed in Xenopus oocytes. Intracellular applications of DHPs quickly and reversibly induced apparent inactivation in the Shaker K+ mutant channels with disrupted N- and C-type inactivation. We found that DHPs interact with the open state of the channel as evidenced by the decreased mean open time. The DHPs effects are voltage-dependent, becoming more effective with hyperpolarization. A model which involves binding of two DHP molecules to the channel is consistent with the results obtained in our experiments.
Halide Permeation in Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels
Authors: Tabcharani Joseph A. , Linsdell Paul , Hanrahan John W.
Published: July 2002

Permeation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels by halide ions was studied in stably transfected Chinese hamster ovary cells by using the patch clamp technique. In cell-attached patches with a high Cl− pipette solution, the CFTR channel displayed outwardly rectifying currents and had a conductance near the membrane potential of 6.0 pS at 22°C or 8.7 pS at 37°C. The current–voltage relationship became linear when patches were excised into symmetrical, N-tris(hydroxymethyl)methyl-2-aminomethane sulfonate (TES)-buffered solutions. Under these conditions, conductance increased from 7.0 pS at 22°C to 10.9 pS at 37°C. The conductance at 22°C was ∼1.0 pS higher when TES and HEPES were omitted from the solution, suggesting weak, voltage-independent block by pH buffers. The relationship between conductance and Cl− activity was hyperbolic and well fitted by a Michaelis-Menten–type function having a Km of ∼38 mM and maximum conductance of 10 pS at 22°C. Dilution potentials measured with NaCl gradients indicated high anion selectivity (PNa/PCl = 0.003–0.028). Biionic reversal potentials measured immediately after exposure of the cytoplasmic side to various test anions indicated PI (1.8) > PBr (1.3) > PCl (1.0) > PF (0.17), consistent with a “weak field strength” selectivity site. The same sequence was obtained for external halides, although inward F− flow was not observed. Iodide currents were protocol dependent and became blocked after 1–2 min. This coincided with a large shift in the (extrapolated) reversal potential to values indicating a greatly reduced I−/Cl− permeability ratio (PI/PCl < 0.4). The switch to low I− permeability was enhanced at potentials that favored Cl− entry into the pore and was not observed in the R347D mutant, which is thought to lack an anion binding site involved in multi-ion pore behavior. Interactions between Cl− and I− ions may influence I− permeation and be responsible for the wide range of PI/PCl ratios that have been reported for the CFTR channel. The low PI/PCl ratio usually reported for CFTR only occurred after entry into an altered permeability state and thus may not be comparable with permeability ratios for other anions, which are obtained in the absence of iodide. We propose that CFTR displays a “weak field strength” anion selectivity sequence.
Caffeine-induced Release of Intracellular Ca2+ from Chinese Hamster Ovary Cells Expressing Skeletal Muscle Ryanodine Receptor
Authors: Bhat Manjunatha B. , Zhao Jiying , Zang Weijin , Balke C. William , Takeshima Hiroshi , Wier W. Gil , Ma Jianjie
Published: July 2002

The ryanodine receptor (RyR)/Ca2+ release channel is an essential component of excitation–contraction coupling in striated muscle cells. To study the function and regulation of the Ca2+ release channel, we tested the effect of caffeine on the full-length and carboxyl-terminal portion of skeletal muscle RyR expressed in a Chinese hamster ovary (CHO) cell line. Caffeine induced openings of the full length RyR channels in a concentration-dependent manner, but it had no effect on the carboxyl-terminal RyR channels. CHO cells expressing the carboxyl-terminal RyR proteins displayed spontaneous changes of intracellular [Ca2+]. Unlike the native RyR channels in muscle cells, which display localized Ca2+ release events (i.e., “Ca2+ sparks” in cardiac muscle and “local release events” in skeletal muscle), CHO cells expressing the full length RyR proteins did not exhibit detectable spontaneous or caffeine-induced local Ca2+ release events. Our data suggest that the binding site for caffeine is likely to reside within the amino-terminal portion of RyR, and the localized Ca2+ release events observed in muscle cells may involve gating of a group of Ca2+ release channels and/or interaction of RyR with muscle-specific proteins.
The Interaction of Na+ and K+ in Voltage-gated Potassium Channels
Authors: Kiss Laszlo , Immke David , LoTurco Joseph , Korn Stephen J.
Published: July 2002

Voltage-gated potassium (K+) channels are multi-ion pores. Recent studies suggest that, similar to calcium channels, competition between ionic species for intrapore binding sites may contribute to ionic selectivity in at least some K+ channels. Molecular studies suggest that a putative constricted region of the pore, which is presumably the site of selectivity, may be as short as one ionic diameter in length. Taken together, these results suggest that selectivity may occur at just a single binding site in the pore. We are studying a chimeric K+ channel that is highly selective for K+ over Na+ in physiological solutions, but conducts Na+ in the absence of K+. Na+ and K+ currents both display slow (C-type) inactivation, but had markedly different inactivation and deactivation kinetics; Na+ currents inactivated more rapidly and deactivated more slowly than K+ currents. Currents carried by 160 mM Na+ were inhibited by external K+ with an apparent IC50 <30 μM. K+ also altered both inactivation and deactivation kinetics of Na+ currents at these low concentrations. In the complementary experiment, currents carried by 3 mM K+ were inhibited by external Na+, with an apparent IC50 of ∼100 mM. In contrast to the effects of low [K+] on Na+ current kinetics, Na+ did not affect K+ current kinetics, even at concentrations that inhibited K+ currents by 40–50%. These data suggest that Na+ block of K+ currents did not involve displacement of K+ from the high affinity site involved in gating kinetics. We present a model that describes the permeation pathway as a single high affinity, cation-selective binding site, flanked by low affinity, nonselective sites. This model quantitatively predicts the anomalous mole fraction behavior observed in two different K+ channels, differential K+ and Na+ conductance, and the concentration dependence of K+ block of Na+ currents and Na+ block of K+ currents. Based on our results, we hypothesize that the permeation pathway contains a single high affinity binding site, where selectivity and ionic modulation of gating occur.
Extracellular Mg2+ Modulates Slow Gating Transitions and the Opening of Drosophila Ether-à-Go-Go Potassium Channels
Authors: Tang Chih-Yung , Bezanilla Francisco , Papazian Diane M.
Published: July 2002

We have characterized the effects of prepulse hyperpolarization and extracellular Mg2+ on the ionic and gating currents of the Drosophila ether-à-go-go K+ channel (eag). Hyperpolarizing prepulses significantly slowed channel opening elicited by a subsequent depolarization, revealing rate-limiting transitions for activation of the ionic currents. Extracellular Mg2+ dramatically slowed activation of eag ionic currents evoked with or without prepulse hyperpolarization and regulated the kinetics of channel opening from a nearby closed state(s). These results suggest that Mg2+ modulates voltage-dependent gating and pore opening in eag channels. To investigate the mechanism of this modulation, eag gating currents were recorded using the cut-open oocyte voltage clamp. Prepulse hyperpolarization and extracellular Mg2+ slowed the time course of ON gating currents. These kinetic changes resembled the results at the ionic current level, but were much smaller in magnitude, suggesting that prepulse hyperpolarization and Mg2+ modulate gating transitions that occur slowly and/or move relatively little gating charge. To determine whether quantitatively different effects on ionic and gating currents could be obtained from a sequential activation pathway, computer simulations were performed. Simulations using a sequential model for activation reproduced the key features of eag ionic and gating currents and their modulation by prepulse hyperpolarization and extracellular Mg2+. We have also identified mutations in the S3–S4 loop that modify or eliminate the regulation of eag gating by prepulse hyperpolarization and Mg2+, indicating an important role for this region in the voltage-dependent activation of eag.
Asymmetric and Independent Contribution of the Second Transmembrane Segment 12′ Residues to Diliganded Gating of Acetylcholine Receptor Channels
Authors: Grosman Claudio , Auerbach Anthony
Published: July 2002

Mutagenesis studies have suggested that the second transmembrane segment (M2) plays a critical role during acetylcholine receptor liganded gating. An adequate description of the relationship between gating and structure of the M2 domain, however, has been hampered by the fact that many M2 mutations increase the opening rate constant to levels that, in the presence of acetylcholine, are unresolvably fast. Here, we show that the use of saturating concentrations of choline, a low-efficacy agonist, is a convenient tool to circumvent this problem. In the presence of 20 mM choline: (a) single-channel currents occur in clusters; (b) fast blockade by choline itself reduces the single-channel conductance by ∼50%, yet the excess open-channel noise is only moderate; (c) the kinetics of gating are fitted best by a single-step, C ↔ O model; and (d) opening and closing rate constants are within a well resolvable range. Application of this method to a series of recombinant adult mouse muscle M2 12′ mutants revealed that: (a) the five homologous M2 12′ positions make independent and asymmetric contributions to diliganded gating, the δ subunit being the most sensitive to mutation; (b) mutations at δ12′ increase the diliganded gating equilibrium constant in a manner that is consistent with the sensitivity of the transition state to mutation being ∼30% like that of the open state and ∼70% like that of the closed state; (c) the relationship between δ12′ amino acid residue volume, hydrophobicity or α-helical tendency, and the gating equilibrium constant of the corresponding mutants is not straightforward; however, (d) rate and equilibrium constants for the mutant series are linearly correlated (on log–log plots), which suggests that the conformational rearrangements upon mutation are mostly local and that the position of the transition state along the gating reaction coordinate is unaffected by these mutations.
Protein Translocation across Planar Bilayers by the Colicin Ia Channel-Forming Domain
Authors: Kienker Paul K. , Jakes Karen S. , Finkelstein Alan
Published: July 2002

Colicin Ia, a 626-residue bactericidal protein, consists of three domains, with the carboxy-terminal domain (C domain) responsible for channel formation. Whole colicin Ia or C domain added to a planar lipid bilayer membrane forms voltage-gated channels. We have shown previously that the channel formed by whole colicin Ia has four membrane-spanning segments and an ∼68-residue segment translocated across the membrane. Various experimental interventions could cause a longer or shorter segment within the C domain to be translocated, making us wonder why translocation normally stops where it does, near the amino-terminal end of the C domain (approximately residue 450). We hypothesized that regions upstream from the C domain prevent its amino-terminal end from moving into and across the membrane. To test this idea, we prepared C domain with a ligand attached near its amino terminus, added it to one side of a planar bilayer to form channels, and then probed from the opposite side with a water-soluble protein that can specifically bind the ligand. The binding of the probe had a dramatic effect on channel gating, demonstrating that the ligand (and hence the amino-terminal end of the C domain) had moved across the membrane. Experiments with larger colicin Ia fragments showed that a region of more than 165 residues, upstream from the C domain, can also move across the membrane. All of the colicin Ia carboxy-terminal fragments that we examined form channels that pass from a state of relatively normal conductance to a low-conductance state; we interpret this passage as a transition from a channel with four membrane-spanning segments to one with only three.
Mg2+ Modulates Voltage-Dependent Activation in Ether-à-Go-Go Potassium Channels by Binding between Transmembrane Segments S2 and S3
Authors: Silverman William R. , Tang Chih-Yung , Mock Allan F. , Huh Kyung-Bong , Papazian Diane M.
Published: July 2002

Extracellular Mg2+ directly modulates voltage-dependent activation in ether-à-go-go (eag) potassium channels, slowing the kinetics of ionic and gating currents (Tang, C.-Y., F. Bezanilla, and D.M. Papazian. 2000. J. Gen. Physiol. 115:319-337). To exert its effect, Mg2+ presumably binds to a site in or near the eag voltage sensor. We have tested the hypothesis that acidic residues unique to eag family members, located in transmembrane segments S2 and S3, contribute to the Mg2+-binding site. Two eag-specific acidic residues and three acidic residues found in the S2 and S3 segments of all voltage-dependent K+ channels were individually mutated in Drosophila eag, mutant channels were expressed in Xenopus oocytes, and the effect of Mg2+ on ionic current kinetics was measured using a two electrode voltage clamp. Neutralization of eag-specific residues D278 in S2 and D327 in S3 eliminated Mg2+-sensitivity and mimicked the slowing of activation kinetics caused by Mg2+ binding to the wild-type channel. These results suggest that Mg2+ modulates activation kinetics in wild-type eag by screening the negatively charged side chains of D278 and D327. Therefore, these residues are likely to coordinate the bound ion. In contrast, neutralization of the widely conserved residues D284 in S2 and D319 in S3 preserved the fast kinetics seen in wild-type eag in the absence of Mg2+, indicating that D284 and D319 do not mediate the slowing of activation caused by Mg2+ binding. Mutations at D284 affected the eag gating pathway, shifting the voltage dependence of Mg2+-sensitive, rate limiting transitions in the hyperpolarized direction. Another widely conserved residue, D274 in S2, is not required for Mg2+ sensitivity but is in the vicinity of the binding site. We conclude that Mg2+ binds in a water-filled pocket between S2 and S3 and thereby modulates voltage-dependent gating. The identification of this site constrains the packing of transmembrane segments in the voltage sensor of K+ channels, and suggests a molecular mechanism by which extracellular cations modulate eag activation kinetics.
Schur-convex functions and isoperimetric inequalities
Authors: Zhang Xin-Min
Published: July 2002

In this paper, we establish some analytic inequalities for Schur-convex functions that are made of solutions of a second order nonlinear differential equation. We apply these analytic inequalities to obtain some geometric inequalities.
On the center conditions of certain cubic systems
Authors: Alwash M.
Published: July 2002

This paper provides a new simple proof of a recent result by C. B. Collins (Differential and Integral Equations 10 (1997), 333–356) to derive the center conditions for a class of planar cubic systems. The idea is to consider periodic solutions of a related scalar non-autonomous equation.
Regularity and Algebras of Analytic Functions in Infinite Dimensions
Authors: Aron R. , Galindo P. , García D. , Maestre M.
Published: July 2002

A Banach space

E
E

is known to be Arens regular if every continuous linear mapping from

E
E

to

E
′

E’

is weakly compact. Let

U
U

be an open subset of

E
E

, and let

H
b

(
U
)

H_b(U)

denote the algebra of analytic functions on

U
U

which are bounded on bounded subsets of

U
U

lying at a positive distance from the boundary of

U
.

U.

We endow

H
b

(
U
)

H_b(U)

with the usual Fréchet topology.

M
b

(
U
)

M_b(U)

denotes the set of continuous homomorphisms

ϕ
:

H
b

(
U
)
→

C

\phi :H_b(U) \to \mathbb {C}

. We study the relation between the Arens regularity of the space

E
E

and the structure of

M
b

(
U
)

M_b(U)

.
Some uniqueness and exact multiplicity results for a predator-prey model
Authors: Du Yihong , Lou Yuan
Published: July 2002

In this paper, we consider positive solutions of a predator-prey model with diffusion and under homogeneous Dirichlet boundary conditions. It turns out that a certain parametermmin this model plays a very important role. A good understanding of the existence, stability and number of positive solutions is gained whenmmis large. In particular, we obtain various results on the exact number of positive solutions. Our results for largemmreveal interesting contrast with that for the well-studied casem=0m=0, i.e., the classical Lotka-Volterra predator-prey model.
Resolution of singularities and modular Galois theory
Authors: Abhyankar Shreeram
Published: July 2002

I shall sketch a brief history of the desingularization problem from Riemann thru Zariski to Hironaka, including the part I played in it and the work on Galois theory which this led me to, and how that caused me to search out many group theory gurus. I shall also formulate several conjectures and suggest numerous thesis problems.
Selected new aspects of the calculus of variations in the large
Authors: Ekeland Ivar , Ghoussoub Nassif
Published: July 2002

We discuss some of the recent developments in variational methods while emphasizing new applications to nonlinear problems. We touch on several issues: (i) the formulation of variational set-ups which provide more information on the location of critical points and therefore on the qualitative properties of the solutions of corresponding Euler-Lagrange equations; (ii) the relationships between the energy of variationally generated solutions, their Morse indices, and the Hausdorff measure of their nodal sets; (iii) the gluing of several topological obstructions; (iv) the preservation of critical levels after deformation of functionals; (v) and the various ways to recover compactness in certain borderline variational problems.
Pointwise theorems for amenable groups
Authors: Lindenstrauss Elon
Published: July 2002

In this paper we describe proofs of the pointwise ergodic theorem and Shannon-McMillan-Breiman theorem for discrete amenable groups, along Følner sequences that obey some restrictions. These restrictions are mild enough so that such sequences exist for all amenable groups.
Dynamics of the family 𝜆tan𝑧
Authors: Keen Linda , Kotus Janina
Published: July 2002

We study the the tangent family

F

=
{
λ
tan
⁡
z
,
λ
∈

C

−
{
0
}
}

{\mathcal F} = \{\lambda \tan z, \lambda \in {\mathbb C} - \{0\}\}

and give a complete classification of their stable behavior. We also characterize the the hyperbolic components and give a combinatorial description of their deployment in the parameter plane.
The class 2 selenophosphate synthetase gene of Drosophila contains a functional mammalian‐type SECIS
Authors: Hirosawa‐Takamori Mitsuko , Jäckle Herbert , Vorbrüggen Gerd
Published: July 2002

Synthesis of monoselenophosphate, the selenium donor required for the synthesis of selenocysteine (Sec) is catalyzed by the enzyme selenophosphate synthetase (SPS), first described in Escherichia coli. SPS homologs were identified in archaea, mammals and Drosophila. In the latter, however, an amino acid replacement is present within the catalytic domain and lacks selenide‐dependent SPS activity. We describe the identification of a novel Drosophila homolog, Dsps2. The open reading frame of Dsps2 mRNA is interrupted by an UGA stop codon. The 3′UTR contains a mammalian‐like Sec insertion sequence which causes translational readthrough in both transfected Drosophila cells and transgenic embryos. Thus, like vertebrates, Drosophila contains two SPS enzymes one with and one without Sec in its catalytic domain. Our data indicate further that the selenoprotein biosynthesis machinery is conserved between mammals and fly, promoting the use of Drosophila as a genetic tool to identify components and mechanistic features of the synthesis pathway.
Bacterial Na+‐ATP synthase has an undecameric rotor
Authors: Stahlberg Henning , Müller Daniel J , Suda Kitaru , Fotiadis Dimitrios , Engel Andreas , Meier Thomas , Matthey Ulrich , Dimroth Peter
Published: July 2002

Synthesis of adenosine triphosphate (ATP) by the F1F0 ATP synthase involves a membrane‐embedded rotary engine, the F0 domain, which drives the extra‐membranous catalytic F1 domain. The F0 domain consists of subunits a1b2 and a cylindrical rotor assembled from 9–14 α‐helical hairpin‐shaped c‐subunits. According to structural analyses, rotors contain 10 c‐subunits in yeast and 14 in chloroplast ATP synthases. We determined the rotor stoichiometry of Ilyobacter tartaricus ATP synthase by atomic force microscopy and cryo‐electron microscopy, and show the cylindrical sodium‐driven rotor to comprise 11 c‐subunits.
Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation
Authors: Tutt Andrew N J , van Oostrom Conny Th M , Ross Gillian M , van Steeg Harry , Ashworth Alan
Published: July 2002

The breast cancer predisposition gene BRCA2 encodes a protein involved in the repair of DNA double‐strand breaks, which arise spontaneously and following exposure to ionizing radiation (IR). To develop a mouse model that examines the effect of BRCA2 mutation and IR exposure on in vivo somatic mutation acquisition, we crossed mice with targeted disruption of Brca2 with a LacZ transgenic mutation reporter strain. Loss of both wild‐type Brca2 alleles caused a 2.3‐fold increase, equivalent to an extra 100 mutations per cell, in the in vivo acquisition of spontaneous somatic mutation by 2 weeks gestation. IR (4 Gy) had a disproportionate effect on animals homozygous for Brca2 disruption, inducing 3.4‐fold more mutations compared with wild‐type animals. These data provide the first evidence that loss of Brca2 increases in vivo somatic mutation acquisition and synergizes with IR exposure, with potential attendant implications for mammographic screening and therapeutic IR in mutation carriers.
Distinct but overlapping domains of AKAP95 are implicated in chromosome condensation and condensin targeting
Authors: Eide Turid , Carlson Cathrine , Taskén Kristin A , Hirano Tatsuya , Taskén Kjetil , Collas Philippe
Published: July 2002

A‐kinase (or PKA)‐anchoring protein AKAP95 is a zinc‐finger protein implicated in mitotic chromosome condensation by acting as a targeting molecule for the condensin complex. We have identified determinants of chromatin‐binding, condensin‐targeting and chromosome‐condensation activities of AKAP95. Binding of AKAP95 to chromatin is conferred by residues 387–450 and requires zinc finger ZF1. Residues 525–569 are essential for condensation of AKAP95‐free chromatin and condensin recruitment to chromosomes. Mutation of either zinc finger of AKAP95 abolishes condensation. However, ZF1 is dispensable for condensin targeting, whereas the C‐terminal ZF2 is required. AKAP95 interacts with Xenopus XCAP‐H condensin subunit in vitro and in vivo but not with the human hCAP‐D2 subunit. The data illustrate the involvement of overlapping, but distinct, domains of AKAP95 for condensin recruitment and chromosome condensation and argue for a key role of ZF1 in chromosome condensation and ZF2 in condensin targeting. Moreover, condensin recruitment to chromatin is not sufficient to promote condensation.
Reading the copepod personal ads: increasing encounter probability with hydromechanical signals
Authors: Duren Luca A. van , Stamhuis Eize J. , Videler John J.
Published: July 2002

Females of the calanoid copepodTemora longicornisreact to chemical exudates of male conspecifics with little hops, quite distinct from their normal smooth uniform swimming motion. These hops possibly serve to create a hydrodynamical signal in the surrounding water, to increase encounter probability with potential mates. Laser sheet particle image velocimetry was used to investigate the flow fields associated with these hops and to compare them to the flow of the feeding current of an adult female. During, and immediately after a hop, the flow field around the copepod showed a marked difference from that of a foraging animal. During foraging, the highest velocity gradients were located around the feeding appendages of the copepod. During a hop, high velocity gradients are located behind the animal. About 0.5 seconds after the start of swimming leg movement, effects of the hop had virtually dissipated and the flow field resembled that around a foraging animal. The estimated volume of influence (i.e. the volume around the copepod where the animal has a significant influence on the water) increased about 12–fold during the hop compared with the situation around a foraging animal. Furthermore, the rate of viscous energy dissipation within the copepods' volume of influence increased nearly 80–fold. Hops may serve to increase encounter probability, but due to the short duration of the effect and the high energetic costs they would only be adaptive when other cues have indicated that suitable sexual partners are in the vicinity.
From neuronal inclusions to neurodegeneration: neuropathological investigation of a transgenic mouse model of Huntington'sdisease
Authors: Davies Stephen W. , Mark Turmaine , Cozens Barbara A. , Raza Aysha S. , Mahal Amarbirpal , Mangiarini Laura , Bates Gillian P.
Published: July 2002

Huntington'sdisease (HD) is an inherited progressive neurodegenerative disease caused by the expansion of a polyglutamine repeat sequence within a novel protein. Recent work has shown that abnormal intranuclear inclusions of aggregated mutant protein within neurons is a characteristic feature shared by HD and several other diseases involving glutamine repeat expansion. This suggests that in each of the these disorders the affected nerve cells degenerate as a result of these abnormal inclusions. A transgenic mouse model of HD has been generated by introducing exon 1 of the HD gene containing a highly expanded CAG sequence into the mouse germline. These mice develop widespread neuronal intranuclear inclusions and neurodegeneration specifically within those areas of the brain known to degenerate in HD. We have investigated the sequence of pathological changes that occur after the formation of nuclear inclusions and that precede neuronal cell death in these cells. Although the relation between inclusion formation and neurodegeneration has recently been questioned, a full characterization of the pathways linking protein aggregation and cell death will resolve some of these controversies and will additionally provide new targets for potential therapies.
Mining thePlasmodiumgenome database to define organellar function: what does the apicoplast do?
Authors: Roos David S. , Crawford Michael J. , Donald Robert G. K. , Fraunholz Martin , Harb Omar S. , He Cynthia Y. , Kissinger Jessica C. , Shaw Michael K. , Striepen Boris
Published: July 2002

Apicomplexan species constitute a diverse group of parasitic protozoa, which are responsible for a wide range of diseases in many organisms. Despite differences in the diseases they cause, these parasites share an underlying biology, from the genetic controls used to differentiate through the complex parasite life cycle, to the basic biochemical pathways employed for intracellular survival, to the distinctive cell biology necessary for host cell attachment and invasion. Different parasites lend themselves to the study of different aspects of parasite biology:Eimeriafor biochemical studies,Toxoplasmafor molecular genetic and cell biological investigation, etc. ThePlasmodium falciparumGenome Project contributes the first large–scale genomic sequence for an apicomplexan parasite. ThePlasmodiumGenome Database (http://PlasmoDB.org) has been designed to permit individual investigators to ask their own questions, even prior to formal release of the referenceP. falciparumgenome sequence. As a case in point, PlasmoDB has been exploited to identify metabolic pathways associated with the apicomplexan plastid, or ‘apicoplast’ – an essential organelle derived by secondary endosymbiosis of an alga, and retention of the algal plastid.
Comparing function and structure between entire proteomes
Authors: Liu Jinfeng , Rost Burkhard
Published: July 2002

More than 30 organisms have been sequenced entirely. Here, we applied a variety of simple bioinformatics tools to analyze 29 proteomes for representatives from all three kingdoms: eukaryotes, prokaryotes, and archaebacteria. We confirmed that eukaryotes have relatively more long proteins than prokaryotes and archaes, and that the overall amino acid composition is similar among the three. We predicted that ∼15%–30% of all proteins contained transmembrane helices. We could not find a correlation between the content of membrane proteins and the complexity of the organism. In particular, we did not find significantly higher percentages of helical membrane proteins in eukaryotes than in prokaryotes or archae. However, we found more proteins with seven transmembrane helices in eukaryotes and more with six and 12 transmembrane helices in prokaryotes. We found twice as many coiled‐coil proteins in eukaryotes (10%) as in prokaryotes and archaes (4%–5%), and we predicted ∼15%–25% of all proteins to be secreted by most eukaryotes and prokaryotes. Every tenth protein had no known homolog in current databases, and 30%–40% of the proteins fell into structural families with >100 members. A classification by cellular function verified that eukaryotes have a higher proportion of proteins for communication with the environment. Finally, we found at least one homolog of experimentally known structure for ∼20%–45% of all proteins; the regions with structural homology covered 20%–30% of all residues. These numbers may or may not suggest that there are 1200–2600 folds in the universe of protein structures. All predictions are available at http://cubic.bioc.columbia.edu/genomes.
Evaluating innovation in studio physics
Authors: Cummings Karen , Marx Jeffrey , Thornton Ronald , Kuhl Dennis
Published: July 2002

In 1993, Rensselaer introduced the first Studio Physics course. Two years later, the Force Concept Inventory (FCI) was used to measure the conceptual learning gain 〈g〉 in the course. This was found to be a disappointing 0.22, indicating that Studio Physics was no more effective at teaching basic Newtonian concepts than a traditional course. Our study verified that result, 〈gFCI,98〉=0.18±0.12 (s.d.), and thereby provides a baseline measurement of conceptual learning gains in Studio Physics I for engineers. These low gains are especially disturbing because the studio classroom appears to be interactive and instructors strive to incorporate modern pedagogies. The goal of our investigation was to determine if incorporation of research-based activities into Studio Physics would have a significant effect on conceptual learning gains. To measure gains, we utilized the Force Concept Inventory and the Force and Motion Conceptual Evaluation (FMCE). In the process of pursuing this goal, we verified the effectiveness of Interactive Lecture Demonstrations [〈gFCI〉=0.35±0.06 (s.d.) and 〈gFMCE〉=0.45±0.03 (s.d.)] and Cooperative Group Problem Solving (〈gFCI〉=0.36 and 〈gFMCE〉=0.36), and examined the feasibility of using these techniques in the studio classroom. Further, we have assessed conceptual learning in the standard Studio Physics course [〈gFCI,98〉=0.18±0.12 (s.d.) and 〈gFMCE,98〉=0.21±0.05 (s.d.)]. In this paper, we will clarify the issues noted above. We will also discuss difficulties in implementing these techniques for first time users and implications for the future directions of the Studio Physics courses at Rensselaer.
Another reason that physics students learn by rote
Authors: Elby Andrew
Published: July 2002

Using written questionnaires, I surveyed introductory physics students about how they study and about how they would advise a hypothetical student to study if she were trying to learn physics deeply with no grade pressure. The survey teases apart students’ “epistemological” beliefs about learning and understanding physics from their more course-specific beliefs about how to earn high grades. The results indicate that students perceive “trying to understand physics well” to be a significantly different activity from “trying to do well in the course.”
Two-dimensional noise source imaging with a T-shaped microphone cross array
Authors: Boone Marinus M. , Kinneging Niels , van den Dool Teun
Published: July 2002

Spatial cross-correlation beamsteering with a T-shaped sparse array can provide an efficient procedure to identify the directions and to obtain the emission levels of multiple uncorrelated noise sources. The procedure can be applied to stationary or moving sources. It provides two-dimensional image resolution equivalent to that of a full array, but requires significantly fewer microphones. This results in substantially reduced requirements for data acquisition and signal processing, with a material cost reduction. Simulation, laboratory measurement, and field measurement of a train moving at high speed illustrate application of the procedure.
Modeling, vibration, and stability of elastically tailored composite thin-walled beams carrying a spinning tip rotor
Authors: Song Ohseop , Kwon Hyuck-Dong , Librescu Liviu
Published: July 2002

The problems of the mathematical modeling, eigenvibration, and stability of cantilevered thin-walled beams carrying a spinning rotor at its tip are investigated. The structure modeled as a thin-walled beam encompasses nonclassical features such as anisotropy, transverse shear, and secondary warping, and in this context, a special ply-angle configuration inducing a structural coupling between flapping-lagging-transverse shear is implemented. The implications of combined gyroscopic effects and conservative force upon the free vibration and stability of this structural system are revealed and a number of pertinent conclusions are outlined. Among others, it is shown that the judicious implementation of the tailoring technique can yield dramatic enhancements of both the vibrational and stability behavior of the system.
Target spectral, dynamic spectral, and duration cues in infant perception of German vowels
Authors: Bohn Ocke-Schwen , Polka Linda
Published: July 2002

Previous studies of vowel perception have shown that adult speakers of American English and of North German identify native vowels by exploiting at least three types of acoustic information contained in consonant–vowel–consonant (CVC) syllables: target spectral information reflecting the articulatory target of the vowel, dynamic spectral information reflecting CV- and -VC coarticulation, and duration information. The present study examined the contribution of each of these three types of information to vowel perception in prelingual infants and adults using a discrimination task. Experiment 1 examined German adults’ discrimination of four German vowel contrasts (/i/–/e/, /e/–/ɪ/, /ɪ/–/ɛ/, /o/–/ʊ/), originally produced in /dVt/ syllables, in eight experimental conditions in which the type of vowel information was manipulated. Experiment 2 examined German-learning infants’ discrimination of the same vowel contrasts using a comparable procedure. The results show that German adults and German-learning infants appear able to use either dynamic spectral information or target spectral information to discriminate contrasting vowels. With respect to duration information, the removal of this cue selectively affected the discriminability of two of the vowel contrasts for adults. However, for infants, removal of contrastive duration information had a larger effect on the discrimination of all contrasts tested.
A method of applying Fourier analysis to high-speed laryngoscopy
Authors: Granqvist Svante , Lindestad Per-Åke
Published: July 2002

A new method for analysis of digital high-speed recordings of vocal-fold vibrations is presented. The method is based on the extraction of light-intensity time sequences from consecutive images, which in turn are Fourier transformed. The spectra thus acquired can be displayed in four different modes, each having its own benefits. When applied to the larynx, the method visualizes oscillations in the entire laryngeal area, not merely the glottal region. The method was applied to two laryngoscopic high-speed image sequences. Among these examples, covibrations in the ventricular folds and in the mucosa covering the arytenoid cartilages were found. In some cases the covibrations occurred at other frequencies than those of the glottis.
Acoustic radiation of cylindrical elastic shells subjected to a point source: Investigation in terms of helical acoustic rays
Authors: Lecable Christophe , Conoir Jean-Marc , Lenoir Olivier
Published: July 2002

The paper deals with the acoustic radiation of a cylindrical elastic shell with no internal loading surrounded by a fluid medium when its external surface is subjected to a point source. The problem is addressed via the use of the spatial Fourier transform. An expression is obtained for the radiated pressure that is evaluated for the far field using both the stationary phase method and the fast Fourier transform (FFT). The acoustic field calculated from the FFT is much more complicated than that obtained by using only the stationary phase method. In agreement with the geometrical theory of diffraction (GTD), alternative interpretations of the radiated field in terms of helical acoustic rays allows one to understand the reason for this result. The outstanding phenomenon underlined by the use of the FFT is the emergence of an infinite number of spatial dispersion curves associated with each leaky wave propagating in shells when excited by a point source.
Regulating glottal airflow in phonation: Application of the maximum power transfer theorem to a low dimensional phonation model
Authors: Titze Ingo R.
Published: July 2002

Two competing views of regulating glottal airflow for maximum vocal output are investigated theoretically. The maximum power transfer theorem is used as a guide. A wide epilarynx tube (laryngeal vestibule) matches well with low glottal resistance (believed to correspond to the “yawn-sigh” approach in voice therapy), whereas a narrow epilarynx tube matches well with a higher glottal resistance (believed to correspond to the “twang-belt” approach). A simulation model is used to calculate mean flows, peak flows, and oral radiated pressure for an impedance ratio between the vocal tract (the load) and the glottis (the source). Results show that when the impedance ratio approaches 1.0, maximum power is transferred and radiated from the mouth. A full update of the equations used for simulating driving pressures, glottal flow, and vocal tract input pressures is provided as a programming guide for those interested in model development.