bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐horizon seasoned equity offerings performance in Pacific Rim markets
Authors: Mathew Prem G
Published: November 2002

Previous studies of firms that issue seasoned equity in the US and Japan have found that these firms significantly underperform over the long‐run subsequent to the issue. I offer further evidence of this by examining Japanese seasoned offerings (SEOs) from 1975 to 1992. I find similar results for firms issuing seasoned equity in Hong Kong. However, I also find that Korean SEOs generate insignificant abnormal returns over a 36‐month period following the issue. These results suggest that the asymmetric information argument offered for the US and Japanese markets do not always hold, especially in markets where the regulatory and market structures vary greatly. Cross‐sectional results suggest that younger firms tend to perform worse than older firms.
Long‐term trends and cycles in ASEAN stock markets
Authors: Sharma Subhash C. , Wongbangpo Praphan
Published: November 2002

The objective of this study is to analyze the degree of long‐term and short‐term co‐movements in the stock markets of five ASEAN countries and to shed some light on the long‐term and short‐term market efficiency/inefficiency in the region. We observe a long‐run relationship among the stock markets of Indonesia, Malaysia, Singapore, and Thailand, but the Philippine market does not share this relationship. Thus, four cointegrated markets reveal long‐term market inefficiency in the region but the Philippine market can be considered efficient. Next, given that the four indices are cointegrated, the number of common cycles are investigated in these markets and each stock index series is decomposed into its trend and cyclical components. The trend–cycle decomposition reveals that in the short‐run four ASEAN markets can be categorized into two efficient groups, i.e., Malaysian and Singaporean markets in one group and Indonesian and Thai markets in the other. However, the markets within each group are inefficient.
Wind forcing in the equilibrium range of
wind-wave spectra
Authors: HARA TETSU , BELCHER STEPHEN E.
Published: November 2002

A new analytical model is developed for the equilibrium range of the spectrum of
wind-forced ocean surface gravity waves. We first show that the existing model of
Phillips (1985) does not satisfy overall momentum conservation at high winds. This
constraint is satisfied by applying recent understanding of the wind forcing of waves.
Waves exert a drag on the air flow so that they support a fraction of the applied wind
stress, which thus leaves a smaller turbulent stress near the surface to force growth
of shorter wavelength waves. Formulation of the momentum budget accounting for
this sheltering constrains the overall conservation of momentum and leads to a local
turbulent stress that reduces as the wavenumber increases. This local turbulent stress
then forces wind-induced wave growth. Following Phillips (1985), the wind sea is
taken to be a superposition of linear waves, and equilibrium is maintained by a
balance between the three sources and sinks of wave action.

These assumptions lead to analytical formulae for the local turbulent stress and the
degree of saturation, B(k), of waves in the equilibrium range. We identify a sheltering
wavenumber, ks, over which the local turbulent stress is significantly reduced by longer
waves. At low wavenumbers or at low winds, when k [Lt ] ks, the sheltering is weak
and B(k) has a similar form to the model of Phillips (1985). At higher wavenumbers
or at higher winds, ks, B(k) makes a transition to being proportional to k0. The
additional constraint of conservation of momentum also yields a formula for the
coefficient that appears in the solution for B(k). The spectra for mature seas are calculated from the model and are shown to agree with field observations. In particular,
our model predicts more realistic spectral levels toward the high wavenumber limit
compared to the previous model of Phillips (1985).

We suggest that the model may explain the overshoot phenomena observed in the
spectral energy levels as the fetch increases.
Erotic Literature in Nineteenth-Century Bali
Authors: Creese Helen , Bellows Laura
Published: November 2002

Two nineteenth-century Balinese genres in which the erotic predominates are epic kakawin poetry and tutur (religious manuals) on sexual yoga. The article points to the strong intertextual links between these diverse genres. Through their focus on practical sexual matters and on the pursuit of sexual pleasure as integral to spiritual growth, tutur and kakawin also offer insight into notions of gender and sexuality in nineteenth-century Bali.
Use design as a research yardstick!
Authors: Muirhead Thomas
Published: November 2002

Christine Hawley writes (arq 6/1, p5)
that true architectural research,
particularly that of a highly
theoretical kind, is not
acknowledged by the government
bodies responsible for evaluating
an architecture school's research
output – and thereby, its funding.
The colon‐selective spasmolytic otilonium bromide inhibits muscarinic M3 receptor‐coupled calcium signals in isolated human colonic crypts
Authors: Lindqvist Susanne , Hernon James , Sharp Paul , Johns Neil , Addison Sarah , Watson Mark , Tighe Richard , Greer Shaun , Mackay Jean , Rhodes Michael , Lewis Michael , Stebbings William , Speakman Chris , Evangelista Stefano , Johnson Ian , Williams Mark
Published: November 2002

Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB.

Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M3 receptor subtype (CHO‐M3). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques.

The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC50 of 14 μM. The muscarinic receptor antagonists 4‐DAMP, AF‐DX 384, pirenzepine and methroctamine inhibited the ACh‐induced calcium signal with the following respective IC50 (pKb) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8).

Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M3 receptor subtype expression at the crypt‐base.

Otilonium bromide inhibited the generation of ACh‐induced calcium signals in a dose dependent manner (IC50=880 nM).

In CHO‐M3 cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine‐induced colonic crypt calcium signals.

The present studies have demonstrated that OB inhibited M3 receptor‐coupled calcium signals in human colonic crypts and CHO‐M3 cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M3 receptor‐coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti‐secretory action in IBS patients suffering with diarrhoea.

British Journal of Pharmacology (2002) 137, 1134–1142. doi:10.1038/sj.bjp.0704942
The role of mitochondrial KATP channels in antiarrhythmic effects of ischaemic preconditioning in dogs
Authors: Vegh Ágnes , Parratt James R
Published: November 2002

In the canine a single brief (5 min) coronary artery occlusion protects the myocardium against the severe ventricular arrhythmias and reduces the ischaemic changes that result from a subsequent, more prolonged (25 min) occlusion. The main purpose of the present study was to examine whether mitochondrial KATP channels are involved in this protection.

In chloralose‐urethane anaesthetized dogs, preconditioning (PC) was induced by a single 5 min period occlusion of the left anterior descending (LAD) coronary artery, 20 min prior to a 25 min occlusion of the same artery. In some of these PC dogs 5‐hydroxydecanoate (5‐HD; 150 μg kg−1 min−1 by intracoronary infusion) was given over a period of 30 min either before, or after PC. In other dogs the mitochondrial KATP channel opener diazoxide (1 mg kg−1; i.c.) was given, either alone or in the presence of 5‐HD. Control dogs (infused with saline) were simply subjected to a 25 min occlusion and reperfusion.

Compared to controls, both PC and diazoxide significantly reduced the number of ventricular premature beats (VPBs; 295±67 to 89±28 and 19±11, respectively; P<0.05), the number of episodes of ventricular tachycardia (VT; 8.3±4.2 to 1.6±0.9 and 0.2±0.1; P<0.05) and the incidences of VT (100 to 43 and 33%; P<0.05) and ventricular fibrilation (VF; 60 to 0 and 17%; P<0.05) during the 25 min occlusion of the LAD. Further, 43% of the PC dogs and 58% of the diazoxide treated dogs survived the combined ischaemia‐reperfusion insult (cp. 0% in the controls; P<0.05). The protection afforded by PC and diazoxide was abolished by 5‐HD, especially when it was given prior to the PC occlusion. In the presence of 5‐HD, three out of 10 dogs fibrillated during the PC occlusion and another three dogs died following reperfusion. Furthermore, there were no survivors in this group from the prolonged ischaemia/reperfusion insult. 5‐HD given after PC only attenuated the antiarrhythmic protection.

Opening of mitoKATP channels prior to ischaemia by preconditioning and diazoxide protects the myocardium against ischaemia and reperfusion‐induced arrhythmias. This protection is abolished if the opening of these channels is prevented by the prior administration of 5‐HD but only attenuated if 5‐HD is given after preconditioning. The results indicate that opening of mitoKATP channels prior to ischaemia is mandatory for protection against ischaemia and reperfusion‐induced arrhythmias.

British Journal of Pharmacology (2002) 137, 1107–1115. doi:10.1038/sj.bjp.0704966
Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate
Authors: Homer Kerry L , Wanstall Janet C
Published: November 2002

Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z‐1‐{N‐methyl‐N‐[6‐(N‐methylammoniohexyl)amino]}diazen‐1‐ium‐1,2‐diolate) was investigated. The aims were to compare its anti‐aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor, ODQ (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one), and to investigate the possible role of activation of sarco‐endoplasmic reticulum calcium‐ATPase (SERCA), independent of soluble guanylate cyclase, using thapsigargin.

MAHMA NONOate concentration‐dependently inhibited sub‐maximal aggregation responses to collagen (2–10 μg ml−1) and adenosine diphosphate (ADP; 2 μM) in platelet rich plasma. It was (i) more effective at inhibiting aggregation induced by collagen than by ADP, and (ii) less potent at inhibiting platelet aggregation than relaxing rat pulmonary artery.

ODQ (10 μM) caused only a small shift (approximately half a log unit) in the concentration‐response curve to MAHMA NONOate irrespective of the aggregating agent.

The NO‐independent activator of soluble guanylate cyclase, YC‐1 (3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzyl indazole; 1–100 μM), did not inhibit aggregation. The cGMP analogue, 8‐pCPT‐cGMP (8‐(4‐chlorophenylthio)guanosine 3′5′ cyclic monophosphate; 0.1–1 mM), caused minimal inhibition.

On collagen‐aggregated platelets responses to MAHMA NONOate (ODQ 10 μM present) were abolished by thapsigargin (200 nM). On ADP‐aggregated platelets thapsigargin caused partial inhibition.

Results with S‐nitrosoglutathione (GSNO) resembled those with MAHMA NONOate. Glyceryl trinitrate and sodium nitroprusside were poor inhibitors of aggregation.

Thus inhibition of rat platelet aggregation by MAHMA NONOate (like GSNO) is largely ODQ‐resistant and, by implication, independent of soluble guanylate cyclase. A likely mechanism of inhibition is activation of SERCA.

British Journal of Pharmacology (2002) 137, 1071–1081. doi:10.1038/sj.bjp.0704971
Pacific ciguatoxin‐1b effect over Na+ and K+ currents, inositol 1,4,5‐triphosphate content and intracellular Ca2+ signals in cultured rat myotubes
Authors: Hidalgo Jorge , Liberona José Luis , Molgó Jordi , Jaimovich Enrique
Published: November 2002

The action of the main ciguatoxin involved in ciguatera fish poisoning in the Pacific region (P‐CTX‐1b) was studied in myotubes originated from rat skeletal muscle cells kept in primary culture.

The effect of P‐CTX‐1b on sodium currents at short times of exposure (up to 1 min) showed a moderate increase in peak Na+ current. During prolonged exposures, P‐CTX‐1b decreased the peak Na+ current. This action was always accompanied by an increase of leakage currents, tail currents and outward Na+ currents, resulting in an intracellular Na+ accumulation. This effect is blocked by prior exposure to tetrodotoxin (TTX) and becomes evident only after washout of TTX.

Low to moderate concentrations of P‐CTX‐1b (2–5 nM) partially blocked potassium currents in a manner that was dependent on the membrane potential.

P‐CTX‐1b (2–12 nM) caused a small membrane depolarization (3–5 mV) and an increase in the frequency of spontaneous action potential discharges that reached in general low frequencies (0.1–0.5 Hz).

P‐CTX‐1b (10 nM) caused a transient increase of intracellular inositol 1,4,5‐trisphosphate (IP3) mass levels, which was blocked by TTX.

In the presence of P‐CTX‐1b (10 nM) and in the absence of external Ca2+, the intracellular Ca2+ levels show a transient increase in the cytoplasm as well as in the nuclei. The time course of this effect may reflect the action of IP3 over internal stores activated by P‐CTX‐1b‐induced membrane depolarization.

British Journal of Pharmacology (2002) 137, 1055–1062. doi:10.1038/sj.bjp.0704980
Quantifying signaling-induced reorientation of T cell receptors during immunological synapse formation
Authors: Moss William C. , Irvine Darrell J. , Davis Mark M. , Krummel Matthew F.
Published: November 2002

Productive T cell recognition of antigen-presenting cells (APCs) is normally accompanied by the formation of a cell–cell contact called the “immunological synapse.” Our understanding of the steps leading up to this formation has been limited by the absence of tools for analyzing 3D surfaces and surface distributions as they change over time. Here we use a 3D fluorescence quantitation method to show that T cell receptors are recruited in bulk within the first minute after the onset of activation and with velocities ranging from 0.04 to 0.1 μm/s; a speed significantly greater than unrestricted diffusion. Our method reveals a second feature of this reorientation: a conformational change as the T cell pushes more total membrane into the interface creating a larger contact area for additional receptors. Analysis of individual T cell receptor velocities using a single-particle tracking method confirms our velocity measurement. This method should permit the quantitation of other dynamic membrane events and the associated movement of cell-surface molecules.
Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging
Authors: Atamna Hani , Killilea David W. , Killilea Alison Nisbet , Ames Bruce N.
Published: November 2002

Heme, a major functional form of iron in the cell, is synthesized in the mitochondria by ferrochelatase inserting ferrous iron into protoporphyrin IX. Heme deficiency was induced with
N
-methylprotoporphyrin IX, a selective inhibitor of ferrochelatase, in two human brain cell lines, SHSY5Y (neuroblastoma) and U373 (astrocytoma), as well as in rat primary hippocampal neurons. Heme deficiency in brain cells decreases mitochondrial complex IV, activates nitric oxide synthase, alters amyloid precursor protein, and corrupts iron and zinc homeostasis. The metabolic consequences resulting from heme deficiency seem similar to dysfunctional neurons in patients with Alzheimer's disease. Heme-deficient SHSY5Y or U373 cells die when induced to differentiate or to proliferate, respectively. The role of heme in these observations could result from its interaction with heme regulatory motifs in specific proteins or secondary to the compromised mitochondria. Common causes of heme deficiency include aging, deficiency of iron and vitamin B6, and exposure to toxic metals such as aluminum. Iron and B6 deficiencies are especially important because they are widespread, but they are also preventable with supplementation. Thus, heme deficiency or dysregulation may be an important and preventable component of the neurodegenerative process.
Production of transgenic rats by lentiviral transduction of male germ-line stem cells
Authors: Hamra F. Kent , Gatlin Joel , Chapman Karen M. , Grellhesl Dana M. , Garcia J. Victor , Hammer Robert E. , Garbers David L.
Published: November 2002

Primary cultures of rat spermatogenic cells that did not bind to collagen matrices were able to colonize and form mature spermatozoa when transferred to testes of recipient males. Up to 73% of the progeny from matings with recipient males were derived from the transferred spermatogenic cells. Subsequently, two populations of germ cells were obtained by selection on laminin matrices. Both populations expressed the spermatogenic cell marker, DAZL, but not the somatic cell marker, vimentin. The cells that bound to laminin represented ≈5% of the total population and were greatly enriched in ability to colonize a recipient testis, suggesting an enrichment in germ-line stem cells. The colonization potential was maintained for at least 7 days in culture. These cells were subsequently transduced with a lentiviral enhanced GFP reporter vector and then transferred to WT recipient males. After mating, 26 of 44 pups were derived from the cultured donor germ cells, and 13 pups carried the lentiviral transgene. Based on Southern analysis, the transgene was integrated at a different genetic locus in each animal and was transmitted to ≈50% of pups in the F
2
generation. Thus, by using these procedures, ≈30% of pups in the F
1
generation inherited and stably transmitted a lentiviral transgene that integrated at various genomic sites.
DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the
Drosophila
ovary
Authors: Song Xiaoqing , Xie Ting
Published: November 2002

Evidence from many systems has shown that stem cells are maintained in “niches” or specific regulatory microenvironments formed by stromal cells. The question of how stem cells are maintained in their niches is important, and further studies will lead to a better understanding of stem cell regulation and enhance the future use of stem cells in regenerative medicine. Here we show that cadherin-mediated cell adhesion is required for anchoring somatic stem cells (SSCs) to their niches in the
Drosophila
ovary. DE-cadherin and Armadillo/β-catenin accumulate in the junctions between SSCs and their neighboring cells, inner germarial sheath cells. Removal of DE-cadherin from SSCs results in stem cell loss in the adult ovary. Furthermore, the cadherin-mediated adhesion is also important for maintaining SSCs in their niches before adulthood. This study provides further support that SSCs are located in a niche formed by their neighboring cells. We have previously shown that DE-cadherin-mediated cell adhesion is essential for anchoring germ-line stem cells to their niches in the
Drosophila
ovary. This study further implicates cadherin-mediated cell adhesion as a general mechanism for anchoring stem cells to their niches in a variety of systems.
Pre-steady-state DNA unwinding by bacteriophage T4 Dda helicase reveals a monomeric molecular motor
Authors: Nanduri Bindu , Byrd Alicia K. , Eoff Robert L. , Tackett Alan J. , Raney Kevin D.
Published: November 2002

Helicases are molecular motor enzymes that unwind and translocate nucleic acids. One of the central questions regarding helicase activity is whether the process of coupling ATP hydrolysis to DNA unwinding requires an oligomeric form of the enzyme. We have applied a pre-steady-state kinetics approach to address this question with the bacteriophage T4 Dda helicase. If a helicase can function as a monomer, then the burst amplitude in the pre-steady state might be similar to the concentration of enzyme, whereas if the helicase required oligomerization, then the amplitude would be significantly less than the enzyme concentration. DNA unwinding of an oligonucleotide substrate was conducted by using a Kintek rapid quench-flow instrument. The substrate consisted of 12 bp adjacent to 12 nucleotides of single-stranded DNA. Dda (4 nM) was incubated with substrate (16 nM) in buffer, and the unwinding reaction was initiated by the addition of ATP (5 mM) and Mg
2+
(10 mM). The reaction was stopped by the addition of 400 mM EDTA. Product formation exhibited biphasic kinetics, and the data were fit to the equation for a single exponential followed by a steady state. The amplitude of the first phase was 3.5 ± 0.2 nM, consistent with a monomeric helicase. The burst amplitude of product formation was measured over a range of enzyme and substrate concentrations and remained consistent with a functional monomer. Thus, Dda can rapidly unwind oligonucleotide substrates as a monomer, indicating that the functional molecular motor component of a helicase can reside within a single polypeptide.
Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders
Authors: Frungieri Mónica B. , Weidinger Stephan , Meineke Viktor , Köhn Frank M. , Mayerhofer Artur
Published: November 2002

Mast-cell products can stimulate fibroblast proliferation, implying that these cells are key players in fibrosis. One mast-cell product, the serine protease tryptase, is known to activate protease-activated receptor 2 (PAR2) and cause proliferation of fibroblasts. We found that recombinant tryptase, human mast-cell (HMC-1) supernatant, which contains tryptase, and the PAR2-activating peptide SLIGKV exert fibroproliferative actions in human fibroblasts. Here we report insights into this action, which after activation of PAR2 leads to increased expression of cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins, and consequently to enhanced prostaglandin synthesis. Subsequent cell proliferation is mediated by the prostaglandin 15-deoxy-Δ12,14-prostaglandin J2, which acts via the nuclear peroxisome proliferator-activated receptor γ (PPARγ). Fibroblast proliferation induced by tryptase and PAR2 agonist peptide can be blocked by antagonists of COX2 and PPARγ, implying that the proliferative effect of tryptase is PAR2-initiated but depends on COX2, 15-deoxy-Δ12,14-prostaglandin J2, and PPARγ. This previously uncharacterized pathway could be of relevance for human fibrotic diseases. For instance, increased numbers of activated mast cells are correlated with fibrosis in testes of infertile men. In these cases all components of the signaling pathway of tryptase were detected as well as expression of COX2. Therefore, our study describes as-yet-unknown interactions between mast cells and fibroblasts, which could be relevant for human fibrotic diseases.
Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy
Authors: Liu Mingfu , Douthwaite Stephen
Published: November 2002

The macrolide antibiotic tylosin has been used extensively in veterinary medicine and exerts potent antimicrobial activity against Gram-positive bacteria. Tylosin-synthesizing strains of the Gram-positive bacterium
Streptomyces fradiae
protect themselves from their own product by differential expression of four resistance determinants,
tlrA
,
tlrB
,
tlrC
, and
tlrD
. The
tlrB
and
tlrD
genes encode methyltransferases that add single methyl groups at 23S rRNA nucleotides G748 and A2058, respectively. Here we show that methylation by neither TlrB nor TlrD is sufficient on its own to give tylosin resistance, and resistance is conferred by the G748 and A2058 methylations acting together in synergy. This synergistic mechanism of resistance is specific for the macrolides tylosin and mycinamycin that possess sugars extending from the 5- and 14-positions of the macrolactone ring and is not observed for macrolides, such as carbomycin, spiramycin, and erythromycin, that have different constellations of sugars. The manner in which the G748 and A2058 methylations coincide with the glycosylation patterns of tylosin and mycinamycin reflects unambiguously how these macrolides fit into their binding site within the bacterial 50S ribosomal subunit.
Increased mitochondrial mass in mitochondrial myopathy mice
Authors: Wredenberg Anna , Wibom Rolf , Wilhelmsson Hans , Graff Caroline , Wiener Heidi H. , Burden Steven J. , Oldfors Anders , Westerblad Håkan , Larsson Nils-Göran
Published: November 2002

We have generated an animal model for mitochondrial myopathy by disrupting the gene for mitochondrial transcription factor A (
Tfam
) in skeletal muscle of the mouse. The knockout animals developed a myopathy with ragged-red muscle fibers, accumulation of abnormally appearing mitochondria, and progressively deteriorating respiratory chain function in skeletal muscle. Enzyme histochemistry, electron micrographs, and citrate synthase activity revealed a substantial increase in mitochondrial mass in skeletal muscle of the myopathy mice. Biochemical assays demonstrated that the increased mitochondrial mass partly compensated for the reduced function of the respiratory chain by maintaining overall ATP production in skeletal muscle. The increased mitochondrial mass thus was induced by the respiratory chain deficiency and may be beneficial by improving the energy homeostasis in the affected tissue. Surprisingly,
in vitro
experiments to assess muscle function demonstrated that fatigue development did not occur more rapidly in myopathy mice, suggesting that overall ATP production is sufficient. However, there were lower absolute muscle forces in the myopathy mice, especially at low stimulation frequencies. This reduction in muscle force is likely caused by deficient formation of force-generating actin–myosin cross bridges and/or disregulation of Ca
2+
homeostasis. Thus, both biochemical measurements of ATP-production rate and
in vitro
physiological studies suggest that reduced mitochondrial ATP production might not be as critical for the pathophysiology of mitochondrial myopathy as thought previously.
Uncoupling direct and indirect components of female choice in the wild
Authors: Calsbeek Ryan , Sinervo Barry
Published: November 2002

One of the most controversial debates in evolutionary biology concerns the fitness consequences of female choice in nature. Discriminating females may benefit from high-quality territories and/or sires with high-quality genes. Here we experimentally dissociate female preferences for high-quality territories and male body size in a wild population of side-blotched lizards,
Uta stansburiana
. Females preferred experimentally improved territories but still chose high-quality sires for their progeny. High-quality territories were associated with earlier egg-laying dates and larger eggs. These maternal effects, evidently stimulated by high-quality territories, have been shown to enhance competitive ability and therefore the likelihood that philopatric offspring will capitalize on the direct benefits of superior territories, previously shown to promote progeny growth rate and survival (most offspring do not disperse from their natal area). Paternity analysis within clutches co-sired by two males revealed that female preferences for large males were also adaptive in terms of indirect benefits. Females used sperm from large sires to produce sons and sperm from small sires to produce daughters. Differential allocation of resources and progeny sex was adaptive and demonstrates a high degree of female control in the mating system.
Two Distinctly Localized P-Type ATPases Collaborate to Maintain Organelle Homeostasis Required for Glycoprotein Processing and Quality Control
Authors: Vashist Shilpa , Frank Christian G. , Jakob Claude A. , Ng Davis T.W.
Published: November 2002

Membrane transporter proteins are essential for the maintenance of cellular ion homeostasis. In the secretory pathway, the P-type ATPase family of transporters is found in every compartment and the plasma membrane. Here, we report the identification of COD1/SPF1(control of HMG-CoA reductase degradation/SPF1) through genetic strategies intended to uncover genes involved in protein maturation and endoplasmic reticulum (ER)-associated degradation (ERAD), a quality control pathway that rids misfolded proteins. Cod1p is a putative ER P-type ATPase whose expression is regulated by the unfolded protein response, a stress-inducible pathway used to monitor and maintain ER homeostasis. COD1 mutants activate the unfolded protein response and are defective in a variety of functions apart from ERAD, which further support a homeostatic role.COD1 mutants display phenotypes similar to strains lacking Pmr1p, a Ca2+/Mn2+pump that resides in the medial-Golgi. Because of its localization, the previously reported role of PMR1 in ERAD was somewhat enigmatic. A clue to their respective roles came from observations that the two genes are not generally required for ERAD. We show that the specificity is rooted in a requirement for both genes in protein-linked oligosaccharide trimming, a requisite ER modification in the degradation of some misfolded glycoproteins. Furthermore, Cod1p, like Pmr1p, is also needed for the outer chain modification of carbohydrates in the Golgi apparatus despite its ER localization. In strains deleted of both genes, these activities are nearly abolished. The presence of either protein alone, however, can support partial function for both compartments. Taken together, our results reveal an interdependent relationship between two P-type ATPases to maintain homeostasis of the organelles where they reside.
The Diaphanous-related Formin mDia1 Controls Serum Response Factor Activity through its Effects on Actin Polymerization
Authors: Copeland John W. , Treisman Richard
Published: November 2002

SRF-dependent transcription is regulated by the small GTPase RhoA via its effects on actin dynamics. The diaphanous-related formin (DRF) proteins have been identified as candidate RhoA effectors mediating signaling to SRF. Here we investigate the relationship between SRF activation and actin polymerization by the DRF mDia1. We show that the ability of mDia1 to potentiate SRF activity is strictly correlated with its ability to promote F-actin assembly. Both processes can occur independently of the mDia1 FH1 domain but require sequences in an extended C-terminal region encompassing the conserved FH2 domain. mDia-mediated SRF activation, but not F-actin assembly, can be blocked by a nonpolymerizable actin mutant, placing actin downstream of mDia in the signal pathway. The SRF activation assay was used to identify inactive mDia1 derivatives that inhibit serum- and LPA-induced signaling to SRF. We show that these interfering mutants also block F-actin assembly, whether induced by mDia proteins or extracellular signals. These results identify novel functional elements of mDia1 and show that it regulates SRF activity by inducing depletion of the cellular pool of G-actin.
ε-Tubulin Is an Essential Component of the Centriole
Authors: Dutcher Susan K. , Morrissette Naomi S. , Preble Andrea M. , Rackley Craig , Stanga John
Published: November 2002

Centrioles and basal bodies are cylinders composed of nine triplet microtubule blades that play essential roles in the centrosome and in flagellar assembly. Chlamydomonas cells with thebld2-1 mutation fail to assemble doublet and triplet microtubules and have defects in cleavage furrow placement and meiosis. Using positional cloning, we have walked 720 kb and identified a 13.2-kb fragment that contains ε-tubulin and rescues the Bld2 defects. The bld2-1 allele has a premature stop codon and intragenic revertants replace the stop codon with glutamine, glutamate, or lysine. Polyclonal antibodies to ε-tubulin show peripheral labeling of full-length basal bodies and centrioles. Thus, ε-tubulin is encoded by the BLD2 allele and ε-tubulin plays a role in basal body/centriole morphogenesis.
An Algal Nucleus-encoded Subunit of Mitochondrial ATP Synthase Rescues a Defect in the Analogous Human Mitochondrial-encoded Subunit
Authors: Ojaimi Joseline , Pan Junmin , Santra Sumana , Snell William J. , Schon Eric A.
Published: November 2002

Unlike most organisms, the mitochondrial DNA (mtDNA) ofChlamydomonas reinhardtii, a green alga, does not encode subunit 6 of F0F1-ATP synthase. We hypothesized that C. reinhardtii ATPase 6 is nucleus encoded and identified cDNAs and a single-copy nuclear gene specifying this subunit (CrATP6, with eight exons, four of which encode a mitochondrial targeting signal). Although the algal and humanATP6 genes are in different subcellular compartments and the encoded polypeptides are highly diverged, their secondary structures are remarkably similar. When CrATP6 was expressed in human cells, a significant amount of the precursor polypeptide was targeted to mitochondria, the mitochondrial targeting signal was cleaved within the organelle, and the mature polypeptide was assembled into human ATP synthase. In spite of the evolutionary distance between algae and mammals, C. reinhardtii ATPase 6 functioned in human cells, because deficiencies in both cell viability and ATP synthesis in transmitochondrial cell lines harboring a pathogenic mutation in the human mtDNA-encoded ATP6 gene were overcome by expression of CrATP6. The ability to express a nucleus-encoded version of a mammalian mtDNA-encoded protein may provide a way to import other highly hydrophobic proteins into mitochondria and could serve as the basis for a gene therapy approach to treat human mitochondrial diseases.
Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?
Authors: Vogel Thorsten U. , Friedrich Thomas C. , O'Connor David H. , Rehrauer William , Dodds Elizabeth J. , Hickman Heather , Hildebrand William , Sidney John , Sette Alessandro , Hughes Austin , Horton Helen , Vielhuber Kathy , Rudersdorf Richard , de Souza Ivna P. , Reynolds Matthew R. , Allen Todd M. , Wilson Nancy , Watkins David I.
Published: October 2002

It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79GY9), and one from the Nef protein (Nef159-167YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35SL8, which reproducibly selects for escape variants during acute infection, and Gag181-189CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.
Characterization of a Putative α-Helix across the Capsid-SP1 Boundary That Is Critical for the Multimerization of Human Immunodeficiency Virus Type 1 Gag
Authors: Liang Chen , Hu Jing , Russell Rodney S. , Roldan Ariel , Kleiman Lawrence , Wainberg Mark A.
Published: October 2002

A 14-amino-acid spacer peptide termed SP1 that separates the capsid (CA) and nucleocapsid (NC) sequences plays an active role in the assembly of human immunodeficiency virus type 1. This activity of SP1 involves its amino-terminal residues that, together with adjacent CA residues, constitute a putative α-helical structure spanning Gag residues from positions 359 to 371. In this study, we have determined that the virus assembly determinants within this putative α-helix were residues H359, K360, A361, L364, A367, and M368, of which K360 and A367 contribute to virus production to lesser extents. Notably, changes of the two basic amino acids H359 and K360 to arginine (R) impaired virus production, whereas mutations L364I and M368I, in contrast to L364A and M368A, generated near-wild-type levels of virus particles. This suggests that within Gag complexes, amino acids H359 and K360 are involved in stricter steric interactions than L364 and M368. Since L364 and M368 are separated by four residues and thus presumably located on the same side of the helical surface, they may initiate synergistic hydrophobic interactions to stabilize Gag association. Further analysis in the context of the protease-negative mutation D185H confirmed the key roles of amino acids H359, A361, L364, and M368 in virus assembly. Importantly, when transfected cells were subjected to Dounce homogenization and the cell lysates were treated by ultracentrifugation at 100,000 ×
g
, Gag molecules containing each of the H359A, A361V, L364A, and M368A mutations were found mainly in the supernatant fraction (S100), whereas approximately 80% of wild-type Gag proteins were found in the pellet. Therefore, these four mutations must have prevented Gag from generating large complexes.
Characterization of Porcine Endogenous Retrovirus γ
pro-pol
Nucleotide Sequences
Authors: Klymiuk Nikolai , Müller Mathias , Brem Gottfried , Aigner Bernhard
Published: October 2002

Endogenous retroviral sequences in the pig genome (PERV) represent a potential infectious risk in xenotransplantation. All known infectious PERV have been asssigned to the PERV γ1 family, consisting of the subfamilies A, B, and C. The aim of the study was the concise examination of PERV γ by the analysis of the retroviral
pro
-
pol
sequences. The analysis of 52
pro
-
pol
clones amplified in this study revealed eight PERV γ families. In addition to four already-described families (γ1, γ4, γ5, γ6), four novel families (γ7, γ8, γ9, γ10) were identified. Quantitative analysis of the novel PERV γ sequences in selected breeds revealed variations in the endogenous retroviral load. Open reading frames (ORF) in the amplified proviral fragment were only found for PERV γ1. In addition, novel ORF-containing PERV γ1 clones consisting of hybrid sequences were revealed. Sequence comparison from published full-length PERV γ1 clones of the PERV subfamilies A, B, and C resulted in a lack of strict correlation of the classification of
pro
-
pol
and
env
. The results indicated the occurrence of causative recombination events between retroviral genomes. Thus, our study on PERV γ provides new data for the evaluation and selection of pigs intended to be used in xenotransplantation.
CONSTRAINTS ON YUKAWA-TYPE HYPOTHETICAL INTERACTIONS FROM RECENT CASIMIR FORCE MEASUREMENTS
Authors: KLIMCHITSKAYA G. L. , MOHIDEEN U.
Published: November 2002

Constraints on the Yukawa-type long-range interactions following from the Casimir effect are considered. The constraints obtained from the recent Casimir force measurements by means of a torsion pendulum and an atomic force microscope are collected and compared. New constraints are obtained from the measurement of the lateral Casimir force. The conclusion is made that the Casimir effect has an advantage over the conventional methods in obtaining stronger constraints on hypothetical interactions.
TIME VARIATIONS OF G IN DIFFERENT MODELS
Authors: MELNIKOV VITALY N.
Published: November 2002

The problem of time-varying gravitational constant is discussed in frames of different theories of gravitation. Predictions for Ġ from multidimensional models and from generalized scalar-tensor theories are considered.
INFLATION IN EXTRA DIMENSIONS
Authors: PIRES C. A. DE S.
Published: November 2002

We discuss inflation in the Arkani-Hamed, Dimopoulos and Dvali scenario for extra dimensions. Basically we compare brane and bulk inflation. We restrict our discussion to chaotic and hybrid inflation models.
ON THE COSMOLOGICAL CONSTANT AND THE COSMIC COINCIDENCE PROBLEM
Authors: SCHÜTZHOLD RALF
Published: November 2002

According to a recently proposed idea the indirectly observed negative pressure of our present universe might be explained by the trace anomaly of quantum chromo-dynamics (QCD) as a non-perturbative effect of quantum fields in curved space-times. Examining some of the consequences of the proposed mechanism for the cosmic evolution yields no apparent contradiction with our present picture of the universe. In conjunction with the weak anthropic principle a natural explanation of the cosmic coincidence can be provided. Further aspects such as the late-time behavior are also addressed.
CASIMIR ENERGY DENSITY IN CLOSED HYPERBOLIC UNIVERSES
Authors: MÜLLER DANIEL , FAGUNDES HELIO V.
Published: November 2002

The original Casimir effect results from the difference in the vacuum energies of the electromagnetic field, between that in a region of space with boundary conditions and that in the same region without boundary conditions. In this paper we develop the theory of a similar situation, involving a scalar field in spacetimes with closed spatial sections of negative curvature.
What Can History Teach Us? A Retrospective Examination of Long-Term Energy Forecasts for the United States
Authors: Craig Paul P. , Gadgil Ashok , Koomey Jonathan G.
Published: October 2002

▪ Abstract  This paper explores how long-term energy forecasts are created and why they are useful. It focuses on forecasts of energy use in the United States for the year 2000 but considers only long-term predictions, i.e., those covering two or more decades. The motivation is current interest in global warming forecasts, some of which run beyond a century. The basic observation is that forecasters in the 1950–1980 period underestimated the importance of unmodeled surprises. A key example is the failure to foresee the ability of the United States economy to respond to the oil embargos of the 1970s by increasing efficiency. Not only were most forecasts of that period systematically high, but forecasters systematically underestimated uncertainties. Long-term energy forecasts must make assumptions about both technologies and social systems. At their most successful, they influence how people act by showing the consequences of not acting. They are useful when they provide insights to energy planners, influence the perceptions of the public and the energy policy community, capture current understanding of underlying physical and economic principles, or highlight key emerging social or economic trends.

It is true that at best we see dimly into the future, but those who acknowledge their duty to posterity will feel impelled to use their foresight upon what facts and guiding principles we do possess. Though many data are at present wanting or doubtful, our conclusions may be rendered so far probable as to lead to further inquiries… ( 1 ), p. 4.
Development and Function of the Angiosperm Female Gametophyte
Authors: Drews Gary N. , Yadegari Ramin
Published: November 2002

▪ Abstract  The plant life cycle alternates between a diploid sporophyte generation and a haploid gametophyte generation. The angiosperm female gametophyte is critical to the reproductive process. It is the structure within which egg cell production and fertilization take place. In addition, the female gametophyte plays a role in pollen tube guidance, the induction of seed development, and the maternal control of seed development. Genetic analysis in Arabidopsis has uncovered mutations that affect female gametophyte development and function. Mutants defective in almost all stages of development have been identified, and analysis of these mutants is beginning to reveal features of the female gametophyte developmental program. Other mutations that affect female gametophyte function have uncovered regulatory genes required for the induction of endosperm development. From these studies, we are beginning to understand the regulatory networks involved in female gametophyte development and function. Further investigation of the female gametophyte will require complementary approaches including expression-based approaches to obtain a complete profile of the genes functioning within this critical structure.
Transvection Effects in Drosophila
Authors: Duncan Ian W.
Published: November 2002

▪ Abstract  An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals.
Toward Maintaining the Genome: DNA Damage and Replication Checkpoints
Authors: Nyberg Kara A. , Michelson Rhett J. , Putnam Charles W. , Weinert Ted A.
Published: November 2002

▪ Abstract  DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase. Also discussed are the molecular signals that activate checkpoint responses, including single-strand DNA, double-strand breaks, and aberrant replication forks. We address the connection between checkpoint proteins and damage repair mechanisms, how cells recover from an arrest response, and additional roles that checkpoint proteins play in DNA metabolism. Finally, the connection between checkpoint gene mutation and genomic instability is considered.