bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
Authors: Lewkowich Ian P. , Herman Nancy S. , Schleifer Kathleen W. , Dance Matthew P. , Chen Brian L. , Dienger Krista M. , Sproles Alyssa A. , Shah Jaimin S. , Köhl Jörg , Belkaid Yasmine , Wills-Karp Marsha
Published: November 2005

The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.
Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow
Authors: Shapiro-Shelef Miriam , Lin Kuo-I , Savitsky David , Liao Jerry , Calame Kathryn
Published: November 2005

Long-lived plasma cells, residing primarily in the bone marrow, continuously secrete antibody and provide an important component of humoral memory. However, when such cells secrete autoantibodies or become transformed, they can be pathogenic. We have shown recently that the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp-1) is required for the formation of plasma cells. To determine what role Blimp-1 might play in maintenance of plasma cells, we generated mice in which the gene encoding Blimp-1 could be deleted in an inducible manner. Deletion of Blimp-1 either in vitro or in vivo leads to loss of previously formed B220LOCD138HI plasma cells. Using BrdU incorporation, we confirmed that Blimp-1 is required for the maintenance of nondividing, long-lived plasma cells in the bone marrow. Blimp-1 is also required for long-term maintenance of antigen-specific immunoglobulin in serum. Thus Blimp-1 is required not only for the formation but also for the maintenance of long-lived plasma cells. This finding provides the possibility of new drug design strategies for autoimmunity and multiple myeloma focused on blocking Blimp-1 expression or activity.
The Glutamate Transporter Subtypes EAAT4 and EAATs 1-3 Transport Glutamate with Dramatically Different Kinetics and Voltage Dependence but Share a Common Uptake Mechanism
Authors: Mim Carsten , Balani Poonam , Rauen Thomas , Grewer Christof
Published: November 2005

Here, we report the application of glutamate concentration jumps and voltage jumps to determine the kinetics of rapid reaction steps of excitatory amino acid transporter subtype 4 (EAAT4) with a 100-μs time resolution. EAAT4 was expressed in HEK293 cells, and the electrogenic transport and anion currents were measured using the patch-clamp method. At steady state, EAAT4 was activated by glutamate and Na+ with high affinities of 0.6 μM and 8.4 mM, respectively, and showed kinetics consistent with sequential binding of Na+-glutamate-Na+. The steady-state cycle time of EAAT4 was estimated to be >300 ms (at −90 mV). Applying step changes to the transmembrane potential, Vm, of EAAT4-expressing cells resulted in the generation of transient anion currents (decaying with a τ of ∼15 ms), indicating inhibition of steady-state EAAT4 activity at negative voltages (<−40 mV) and activation at positive Vm (>0 mV). A similar inhibitory effect at Vm < 0 mV was seen when the electrogenic glutamate transport current was monitored, resulting in a bell-shaped I-Vm curve. Jumping the glutamate concentration to 100 μM generated biphasic, saturable transient transport and anion currents (Km ∼ 5 μM) that decayed within 100 ms, indicating the existence of two separate electrogenic reaction steps. The fast electrogenic reaction was assigned to Na+ binding to EAAT4, whereas the second reaction is most likely associated with glutamate translocation. Together, these results suggest that glutamate uptake of EAAT4 is based on the same molecular mechanism as transport by the subtypes EAATs 1–3, but that its kinetics and voltage dependence are dramatically different from the other subtypes. EAAT4 kinetics appear to be optimized for high affinity binding of glutamate, but not rapid turnover. Therefore, we propose that EAAT4 is a high-affinity/low-capacity transport system, supplementing low-affinity/high-capacity synaptic glutamate uptake by the other subtypes.
Electrostatics in the Cytoplasmic Pore Produce Intrinsic Inward Rectification in Kir2.1 Channels
Authors: Yeh Shih-Hao , Chang Hsueh-Kai , Shieh Ru-Chi
Published: November 2005

Inward rectifier K+ channels are important in regulating membrane excitability in many cell types. The physiological functions of these channels are related to their unique inward rectification, which has been attributed to voltage-dependent block. Here, we show that inward rectification can also be induced by neutral and positively charged residues at site 224 in the internal vestibule of tetrameric Kir2.1 channels. The order of extent of inward rectification is E224K mutant > E224G mutant > wild type in the absence of internal blockers. Mutating the glycines at the equivalent sites to lysines also rendered weak inward rectifier Kir1.1 channels more inwardly rectifying. Also, conjugating positively charged methanethiosulfonate to the cysteines at site 224 induced strong inward rectification, whereas negatively charged methanethiosulfonate alleviated inward rectification in the E224C mutant. These results suggest that charges at site 224 may control inward rectification in the Kir2.1 channel. In a D172N mutant, spermine interacting with E224 and E299 induced channel inhibition during depolarization but did not occlude the pore, further suggesting that a mechanism other than channel block is involved in the inward rectification of the Kir2.1 channel. In this and our previous studies we showed that the M2 bundle crossing and selectivity filter were not involved in the inward rectification induced by spermine interacting with E224 and E299. We propose that neutral and positively charged residues at site 224 increase a local energy barrier, which reduces K+ efflux more than K+ influx, thereby producing inward rectification.
Separate Ion Pathways in a Cl−/H+ Exchanger
Authors: Accardi Alessio , Walden Michael , Nguitragool Wang , Jayaram Hariharan , Williams Carole , Miller Christopher
Published: November 2005

CLC-ec1 is a prokaryotic CLC-type Cl−/H+ exchange transporter. Little is known about the mechanism of H+ coupling to Cl−. A critical glutamate residue, E148, was previously shown to be required for Cl−/H+ exchange by mediating proton transfer between the protein and the extracellular solution. To test whether an analogous H+ acceptor exists near the intracellular side of the protein, we performed a mutagenesis scan of inward-facing carboxyl-bearing residues and identified E203 as the unique residue whose neutralization abolishes H+ coupling to Cl− transport. Glutamate at this position is strictly conserved in all known CLCs of the transporter subclass, while valine is always found here in CLC channels. The x-ray crystal structure of the E203Q mutant is similar to that of the wild-type protein. Cl− transport rate in E203Q is inhibited at neutral pH, and the double mutant, E148A/E203Q, shows maximal Cl− transport, independent of pH, as does the single mutant E148A. The results argue that substrate exchange by CLC-ec1 involves two separate but partially overlapping permeation pathways, one for Cl− and one for H+. These pathways are congruent from the protein's extracellular surface to E148, and they diverge beyond this point toward the intracellular side. This picture demands a transport mechanism fundamentally different from familiar alternating-access schemes.
Sphericalization and flattening
Authors: Balogh Zoltán , Buckley Stephen
Published: November 2005

The conformal deformations of flattening and sphericalization of length metric spaces are considered. These deformations are dual to each other if the space satisfies a simple quantitative connectivity property. Moreover, the quasihyperbolic metrics corresponding to the flat and the spherical metrics are bilipschitz equivalent if a weaker connectivity condition is satisfied.
Mutations in Tap Uncouple RNA Export Activity from Translocation through the Nuclear Pore Complex
Authors: Lévesque Lyne , Bor Yeou-Cherng , Matzat Leah H. , Jin Li , Berberoglu Stephen , Rekosh David , Hammarskjöld Marie-Louise , Paschal Bryce M.
Published: November 2005

Interactions between transport receptors and phenylalanine-glycine (FG) repeats on nucleoporins drive the translocation of receptor-cargo complexes through nuclear pores. Tap, a transport receptor that mediates nuclear export of cellular mRNAs, contains a UBA-like and NTF2-like folds that can associate directly with FG repeats. In addition, two nuclear export sequences (NESs) within the NTF2-like region can also interact with nucleoporins. The Tap-RNA complex was shown to bind to three nucleoporins, Nup98, p62, and RanBP2, and these interactions were enhanced by Nxt1. Mutations in the Tap-UBA region abolished interactions with all three nucleoporins, whereas the effect of point mutations within the NTF2-like domain of Tap known to disrupt Nxt1 binding or nucleoporin binding were nucleoporin dependent. A mutation in any of these Tap domains was sufficient to reduce RNA export but was not sufficient to disrupt Tap interaction with the NPC in vivo or its nucleocytoplasmic shuttling. However, shuttling activity was reduced or abolished by combined mutations within the UBA and either the Nxt1-binding domain or NESs. These data suggest that Tap requires both the UBA- and NTF2-like domains to mediate the export of RNA cargo, but can move through the pores independently of these domains when free of RNA cargo.
Golgi Inheritance in Mammalian Cells Is Mediated through Endoplasmic Reticulum Export Activities
Authors: Altan-Bonnet Nihal , Sougrat Rachid , Liu Wei , Snapp Erik L. , Ward Theresa , Lippincott-Schwartz Jennifer
Published: November 2005

Golgi inheritance during mammalian cell division occurs through the disassembly, partitioning, and reassembly of Golgi membranes. The mechanisms responsible for these processes are poorly understood. To address these mechanisms, we have examined the identity and dynamics of Golgi proteins within mitotic membranes using live cell imaging and electron microscopy techniques. Mitotic Golgi fragments, seen in prometaphase and telophase, were found to localize adjacent to endoplasmic reticulum (ER) export domains, and resident Golgi transmembrane proteins cycled rapidly into and out of these fragments. Golgi proteins within mitotic Golgi haze—seen during metaphase—were found to redistribute with ER markers into fragments when the ER was fragmented by ionomycin treatment. The temperature-sensitive misfolding mutant ts045VSVG protein, when localized to the Golgi at the start of mitosis, became trapped in the ER at the end of mitosis in cells shifted to 40°C. Finally, reporters for Arf1 and Sar1 activity revealed that Arf1 and Sar1 undergo sequential inactivation during mitotic Golgi breakdown and sequential reactivation upon Golgi reassembly at the end of mitosis. Together, these findings support a model of mitotic Golgi inheritance that involves inhibition and subsequent reactivation of cellular activities controlling the cycling of Golgi components into and out of the ER.
SNAP25, but Not Syntaxin 1A, Recycles via an ARF6-regulated Pathway in Neuroendocrine Cells
Authors: Aikawa Yoshikatsu , Xia Xiaofeng , Martin Thomas F.J.
Published: November 2005

Soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) proteins mediate cellular membrane fusion events and provide a level of specificity to donor–acceptor membrane interactions. However, the trafficking pathways by which individual SNARE proteins are targeted to specific membrane compartments are not well understood. In neuroendocrine cells, synaptosome-associated protein of 25 kDa (SNAP25) is localized to the plasma membrane where it functions in regulated secretory vesicle exocytosis, but it is also found on intracellular membranes. We identified a dynamic recycling pathway for SNAP25 in PC12 cells through which plasma membrane SNAP25 recycles in ∼3 h. Approximately 20% of the SNAP25 resides in a perinuclear recycling endosome–trans-Golgi network (TGN) compartment from which it recycles back to the plasma membrane. SNAP25 internalization occurs by constitutive, dynamin-independent endocytosis that is distinct from the dynamin-dependent endocytosis that retrieves secretory vesicle constituents after exocytosis. Endocytosis of SNAP25 is regulated by ADP-ribosylation factor (ARF)6 (through phosphatidylinositol bisphosphate synthesis) and is dependent upon F-actin. SNAP25 endosomes, which exclude the plasma membrane SNARE syntaxin 1A, merge with those derived from clathrin-dependent endocytosis containing endosomal syntaxin 13. Our results characterize a robust ARF6-dependent internalization mechanism that maintains an intracellular pool of SNAP25, which is compatible with possible intracellular roles for SNAP25 in neuroendocrine cells.
Nuclear Envelope Breakdown Is Coordinated by Both Nup358/RanBP2 and Nup153, Two Nucleoporins with Zinc Finger Modules
Authors: Prunuske Amy J. , Liu Jin , Elgort Suzanne , Joseph Jomon , Dasso Mary , Ullman Katharine S.
Published: November 2005

When higher eukaryotic cells transition into mitosis, the nuclear envelope, nuclear pore complexes, and nuclear lamina are coordinately disassembled. The COPI coatomer complex, which plays a major role in membrane remodeling at the Golgi, has been implicated in the process of nuclear envelope breakdown and requires interactions at the nuclear pore complex for recruitment to this new site of action at mitosis. Nup153, a resident of the nuclear pore basket, was found to be involved in COPI recruitment, but the molecular nature of the interface between COPI and the nuclear pore has not been fully elucidated. To better understand what occurs at the nuclear pore at this juncture, we have probed the role of the nucleoporin Nup358/RanBP2. Nup358 contains a repetitive zinc finger domain with overall organization similar to a region within Nup153 that is critical to COPI association, yet inspection of these two zinc finger domains reveals features that also clearly distinguish them. Here, we found that the Nup358 zinc finger domain, but not a zinc finger domain from an unrelated protein, binds to COPI and dominantly inhibits progression of nuclear envelope breakdown in an assay that robustly recapitulates this process in vitro. Moreover, the Nup358 zinc finger domain interferes with COPI recruitment to the nuclear rim. Consistent with a role for this pore protein in coordinating nuclear envelope breakdown, Nup358-specific antibodies impair nuclear disassembly. Significantly, targeting either Nup153 or Nup358 for inhibition perturbs nuclear envelope breakdown, supporting a model in which these nucleoporins play nonredundant roles, perhaps contributing to COPI recruitment platforms on both the nuclear and cytoplasmic faces of the pore. We found that an individual zinc finger is the minimal interface for COPI association, although tandem zinc fingers are optimal. These results provide new information about the critical components of nuclear membrane remodeling and lay the foundation for a better understanding of how this process is regulated.
Seventeen a-Subunit Isoforms ofParameciumV-ATPase Provide High Specialization in Localization and Function
Authors: Wassmer Thomas , Kissmehl Roland , Cohen Jean , Plattner Helmut
Published: November 2005

In the Paramecium tetraurelia genome, 17 genes encoding the 100-kDa-subunit (a-subunit) of the vacuolar-proton-ATPase were identified, representing by far the largest number of a-subunit genes encountered in any organism investigated so far. They group into nine clusters, eight pairs with >82% amino acid identity and one single gene. Green fluorescent protein-tagging of representatives of the nine clusters revealed highly specific targeting to at least seven different compartments, among them dense core secretory vesicles (trichocysts), the contractile vacuole complex, and phagosomes. RNA interference for two pairs confirmed their functional specialization in their target compartments: silencing of the trichocyst-specific form affected this secretory pathway, whereas silencing of the contractile vacuole complex-specific form altered organelle structure and functioning. The construction of chimeras between selected a-subunits surprisingly revealed the targeting signal to be located in the C terminus of the protein, in contrast with the N-terminal targeting signal of the a-subunit in yeast. Interestingly, some chimeras provoked deleterious effects, locally in their target compartment, or remotely, in the compartment whose specific a-subunit N terminus was used in the chimera.
Biogenesis of Tubular ER-to-Golgi Transport Intermediates
Authors: Simpson Jeremy C. , Nilsson Tommy , Pepperkok Rainer
Published: November 2005

Tubular transport intermediates (TTIs) have been described as one class of transport carriers in endoplasmic reticulum (ER)-to-Golgi transport. In contrast to vesicle budding and fusion, little is known about the molecular regulation of TTI synthesis, transport and fusion with target membranes. Here we have used in vivo imaging of various kinds of GFP-tagged proteins to start to address these questions. We demonstrate that under steady-state conditions TTIs represent ∼20% of all moving transport carriers. They increase in number and length when more transport cargo becomes available at the donor membrane, which we induced by either temperature-related transport blocks or increased expression of the respective GFP-tagged transport markers. The formation and motility of TTIs is strongly dependent on the presence of intact microtubules. Microinjection of GTPγS increases the frequency of TTI synthesis and the length of these carriers. When Rab proteins are removed from membranes by microinjection of recombinant Rab-GDI, the synthesis of TTIs is completely blocked. Microinjection of the cytoplasmic tails of the p23 and p24 membrane proteins also abolishes formation of p24-containing TTIs. Our data suggest that TTIs are ER-to-Golgi transport intermediates that form preferentially when transport-competent cargo exists in excess at the donor membrane. We propose a model where the interaction of the cytoplasmic tails of membrane proteins with microtubules are key determinants for TTI synthesis and may also serve as a so far unappreciated model for aspects of transport carrier formation.
A Complex of Two Centrosomal Proteins, CAP350 and FOP, Cooperates with EB1 in Microtubule Anchoring
Authors: Yan Xiumin , Habedanck Robert , Nigg Erich A.
Published: November 2005

The anchoring of microtubules (MTs) to subcellular structures is critical for cell shape, polarity, and motility. In mammalian cells, the centrosome is a prominent MT anchoring structure. A number of proteins, including ninein, p150Glued, and EB1, have been implicated in centrosomal MT anchoring, but the process is far from understood. Here we show that CAP350 and FOP (FGFR1 oncogene partner) form a centrosomal complex required for MT anchoring. We show that the C-terminal domain of CAP350 interacts directly with FOP and that both proteins localize to the centrosome throughout the cell cycle. FOP also binds to EB1 and is required for localizing EB1 to the centrosome. Depletion of either CAP350, FOP, or EB1 by siRNA causes loss of MT anchoring and profound disorganization of the MT network. These results have implications for the mechanisms underlying MT anchoring at the centrosome and they attribute a key MT anchoring function to two novel centrosomal proteins, CAP350 and FOP.
Faecal glucocorticoid metabolites and alarm calling in free-living yellow-bellied marmots
Authors: Blumstein Daniel T , Patton Marilyn L , Saltzman Wendy
Published: November 2005

When individuals of a variety of species encounter a potential predator, some, but not all, emit alarm calls. To explain the proximate basis of this variation, we compared faecal glucocorticoid metabolite concentrations in live-trapped yellow-bellied marmots (
Marmota flaviventris
) between occasions when they did and did not emit alarm calls. We found that marmots had significantly higher glucocorticoid levels when they called than when they did not call, suggesting that stress or arousal may play an important role in potentiating alarm calls. Marmots are sensitive to variation in the reliability of callers. The present finding provides one possible mechanism underlying caller variation: physiological arousal influences the propensity to emit alarm calls.
Sex and the single (-eared) female: leg function, limb autotomy and mating history trade-offs in field crickets (
Gryllus bimaculatus
)
Authors: Bateman Philip W , Fleming Patricia A
Published: November 2005

Both male and female field crickets (
Gryllus bimaculatus
) autotomize front (tympanal) limbs more slowly than hind limbs. Arguably, this pattern could reflect possible differences in the mechanism of limb autotomy. However, we demonstrate that, for females, limb autotomy is also dependent on their mating status: virgin females autotomize front legs significantly more slowly than mated females. This response suggests a central control for leg autotomy in these animals, and less readiness to autotomize a front leg, possibly because the tympanum is crucial for mate location.
An unusual choanoflagellate protein released by Hedgehog autocatalytic processing
Authors: Snell Elizabeth A , Brooke Nina M , Taylor William R , Casane Didier , Philippe Hervé , Holland Peter W.H
Published: November 2005

Hedgehog proteins are important cell–cell signalling proteins utilized during the development of multicellular animals. Members of the
hedgehog
gene family have not been detected outside the Metazoa, raising unanswered questions about their evolutionary origin. Here we report a highly unusual
hedgehog
-related gene from a choanoflagellate, a close unicellular relative of the animals. The deduced C-terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog proteins and is predicted to function in autocatalytic cleavage of the precursor peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a secreted protein with an enormous threonine-rich domain of unprecedented size and purity (over 200 threonine residues) and two polysaccharide-binding domains. Structural modelling reveals that these domains have a novel combination of features found in cellulose-binding domains (CBD) of types IIa and IIb, and are expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are homologous, but Hh-N and Hoglet-N are not, we argue that metazoan
hedgehog
genes evolved by fusion of two distinct genes.
Costs of breeding and their effects on the direction of sexual selection
Authors: Simmons Leigh W , Kvarnemo Charlotta
Published: November 2005

A recent life-history model has challenged the importance of the operational sex ratio and the potential reproductive rates of males and females as the factors most important for the control of sexual selection, arguing that the cost of breeding, interpreted as the probability of dying as a consequence of the current breeding attempt, is the single most important factor that best predicts a mating system. In one species of bushcricket, the mating system can be reversed by resource manipulation. Here, we examine the costs of breeding in this system. Consistent with the model, increased costs of breeding can explain female competition and increased male choosiness under resource limitation. However, this is due to differences in the time required for a breeding attempt, rather than differences in breeding mortality which did not differ between the sexes. In general, males lived longer than females and we discuss the possible reasons behind this pattern of sex-biased non-breeding mortality.
How effective are maternal effects at having effects?
Authors: Beckerman Andrew P , Benton Tim G , Lapsley Craig T , Koesters Nils
Published: November 2005

The well studied trade-off between offspring size and offspring number assumes that offspring fitness increases with increasing per-offspring investment. Where mothers differ genetically or exhibit plastic variation in reproductive effort, there can be variation in per capita investment in offspring, and via this trade-off, variation in fecundity. Variation in per capita investment will affect juvenile performance directly—a classical maternal effect—while variation in fecundity will also affect offspring performance by altering the offsprings' competitive environment. The importance of this trade-off, while a focus of evolutionary research, is not often considered in discussions about population dynamics. Here, we use a factorial experiment to determine what proportion of variation in offspring performance can be ascribed to maternal effects and what proportion to the competitive environment linked to the size–number trade-off. Our results suggest that classical maternal effects are significant, but that in our system, the competitive environment, which is linked to maternal environments by fecundity, can be a far more substantial influence.
Adaptive adjustment of offspring sex ratio and maternal reproductive effort in an iteroparous mammal
Authors: Holand Øystein , Mysterud Atle , Røed Knut H , Coulson Tim , Gjøstein Hallvard , Weladji Robert B , Nieminen Mauri
Published: November 2005

Large mammals in seasonal environments have a pattern of high-reproductive synchrony in spring, but how the timing of reproduction affects resource allocation decisions at different stages of the reproductive cycle remains largely unexplored. By manipulating the timing of conception in reindeer (
Rangifer tarandus
), we tested how the timing of conception affected sex ratio, gestation length and weight development of mother and offspring. Females that conceived at their first ovulation within the rut had a 60.5% probability of producing a male; in contrast, females that conceived a cycle later had a 31.3% probability of producing a male. Late conceiving females had gestation times that were 10 days shorter and the calves were 0.6 kg (9.2%) lighter at birth and 7.4 kg (14.7%) lighter in autumn. Over the year, female weight changes was similar between the groups suggesting reindeer follow a bet-hedging strategy; reducing the quality of this year's offspring to ensure their own future reproduction and survival. Harvesting is often selective leading to skewed sex ratios and age structure, which may influence the timing of reproduction due to females hesitation to mate with young males. Whenever this hesitation is strong enough to increase the frequency of recycling, harvesting is likely to have profound life history consequences.
ADrosophilamale pheromone affects female sexual receptivity
Authors: Grillet Micheline , Dartevelle Laurence , Ferveur Jean-François
Published: November 2005

Sex pheromones are chemical signals frequently required for mate choice, but their reciprocal role on mate preference has rarely been shown in both sexes. InDrosophila melanogasterflies, the predominant cuticular hydrocarbons (CHs) are sexually dimorphic: only females produce 7,11-dienes, whereas 7-tricosene (7-T) is the principal male CH. Males generally prefer females with 7,11-dienes, but the role of 7-T on female behaviour remains unclear. With perfumed males, control females mated faster and more often with males carrying increased levels of 7-T showing that this CH acts as a chemical stimulant forD. melanogasterfemales. Control females—but not antenna-less females—could detect small variation of 7-T. Finally, our finding thatdesat1mutant female showed altered response towards 7-T provides an additional role for this gene which affects the production and the perception of pheromones involved in mate choice, in both sexes.
Hypervariable prophage WO sequences describe an unexpected high number of
Wolbachia
variants in the mosquito
Culex pipiens
Authors: Duron Olivier , Fort Philippe , Weill Mylène
Published: November 2005

Wolbachia
are maternally inherited endosymbiotic bacteria that infect many arthropod species and may induce cytoplasmic incompatibility (CI) resulting in abortive embryonic development. Among all the described host species, mosquitoes of the
Culex pipiens
complex display the highest variability of CI crossing types. Paradoxically, searches for polymorphism in
Wolbachia
infecting strains and field populations hitherto failed or produced very few markers. Here, we show that an abundant source of the long-sought polymorphism lies in WO prophage sequences present in multiple copies dispersed in the genome of
Wolbachia
infecting
C. pipiens
(
w
Pip). We identified up to 66 different
Wolbachia
variants in
C. pipiens
strains and field populations and no occurrence of superinfection was observed. At least 49 different
Wolbachia
occurred in Southern Europe
C. pipiens
populations, and up to 10 different
Wolbachia
were even detected in a single population. This is in sharp contrast with North African and Cretan samples, which exhibited only six variants. The WO polymorphism appeared stable over time, and was exclusively transferred maternally. Interestingly, we found that the CI pattern previously described correlates with the variability of Gp15, a prophage protein similar to a bacterial virulence protein. WO prophage sequences thus represent variable markers that now open routes for approaching the molecular basis of CI, the host effects, the structure and dynamics of
Wolbachia
populations.
An evolutionary perspective on caching by corvids
Authors: de Kort Selvino R , Clayton Nicola S
Published: November 2005

A principal finding in the food-caching literature is that species differences in hoarding propensity are positively correlated with species differences in degree of adaptations to caching behaviour, such as performance on spatial memory tasks and hippocampal volume. However, there are examples that do not fit this pattern. We argue that these examples can be better understood by considering the phylogenetic relatedness between species. We reconstruct the ancestral state for caching behaviour in corvids and assess when transitions in caching behaviour occurred within the corvid phylogeny. Our analysis shows that the common ancestor of all corvids was a moderate cacher. This result suggests that corvids followed a bi-directional evolutionary trajectory in which caching was secondarily lost twice and there were at least two independent transitions from moderate to specialized caching. The independent evolution of specialized cachers in the two groups must, therefore, be a case of convergent evolution. This is exemplified by the fact that specialized cachers show structurally different adaptations serving the same function to intense caching, such as different pouches to transport food. Finally, we argue that convergent evolution may have led to adaptations in memory and hippocampus that serve the same function but differ in design, and that these different adaptations may explain the examples that do not fit the pattern predicted by the adaptive specialization hypothesis.
Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges?
Authors: Smith R.J
Published: November 2005

The question of determining how many doses may be skipped before HIV treatment response is adversely affected by the emergence of drug-resistance is addressed. Impulsive differential equations are used to develop a prescription to minimize the emergence of drug-resistance for protease-sparing regimens. A threshold for the maximal number of missable doses is determined. If the number of missed doses is below this threshold, then resistance levels are negligible and dissipate quickly, assuming perfect adherence subsequently. If the number of missed doses exceeds this threshold, even for 24 h, resistance levels are extremely high and will not dissipate for weeks, even assuming perfect adherence subsequently. After this interruption, the minimum number of successive doses that should be taken is determined. Estimates are provided for all protease-sparing drugs approved by the US Food and Drug Administration. Estimates for the basic reproductive ratios for the wild-type and mutant strains of the virus are also calculated, for a long-term average fractional degree of adherence. There are regions within this fraction of adherence where the outcome is not predictable and may depend on a patient's entire history of drug-taking.
The brainstem reticular formation is a small-world, not scale-free, network
Authors: Humphries M.D , Gurney K , Prescott T.J
Published: November 2005

Recently, it has been demonstrated that several complex systems may have simple graph-theoretic characterizations as so-called ‘small-world’ and ‘scale-free’ networks. These networks have also been applied to the gross neural connectivity between primate cortical areas and the nervous system ofCaenorhabditis elegans. Here, we extend this work to a specific neural circuit of the vertebrate brain—the medial reticular formation (RF) of the brainstem—and, in doing so, we have made three key contributions. First, this work constitutes the first model (and quantitative review) of this important brain structure for over three decades. Second, we have developed the first graph-theoretic analysis of vertebrate brain connectivity at the neural network level. Third, we propose simple metrics to quantitatively assess the extent to which the networks studied are small-world or scale-free. We conclude that the medial RF is configured to create small-world (implying coherent rapid-processing capabilities), but not scale-free, type networks under assumptions which are amenable to quantitative measurement.
Tropical forests and the changing earth system
Authors: Lewis Simon L
Published: November 2005

Tropical forests are global epicentres of biodiversity and important modulators of the rate of climate change. Recent research on deforestation rates and ecological changes within intact forests, both areas of recent research and debate, are reviewed, and the implications for biodiversity (species loss) and climate change (via the global carbon cycle) addressed. Recent impacts have most likely been: (i) a large source of carbon to the atmosphere, and major loss of species, from deforestation and (ii) a large carbon sink within remaining intact forest, accompanied by accelerating forest dynamism and widespread biodiversity changes. Finally, I look to the future, suggesting that the current carbon sink in intact forests is unlikely to continue, and that the tropical forest biome may even become a large net source of carbon, via one or more of four plausible routes: changing photosynthesis and respiration rates, biodiversity changes in intact forest, widespread forest collapse via drought, and widespread forest collapse via fire. Each of these scenarios risks potentially dangerous positive feedbacks with the climate system that could dramatically accelerate and intensify climate change. Given that continued land-use change alone is already thought to be causing the sixth mass extinction event in Earth's history, should such feedbacks occur, the resulting biodiversity and societal consequences would be even more severe.
Climate change, species–area curves and the extinction crisis
Authors: Lewis Owen T
Published: November 2005

An article published in the journalNaturein January 2004—in which an international team of biologists predicted that climate change would, by 2050, doom 15–37% of the earth's species to extinction—attracted unprecedented, worldwide media attention. The predictions conflict with the conventional wisdom that habitat change and modification are the most important causes of current and future extinctions. The new extinction projections come from applying a well-known ecological pattern, the species–area relationship (SAR), to data on the current distributions and climatic requirements of 1103 species. Here, I examine the scientific basis to the claims made in theNaturearticle. I first highlight the potential and pitfalls of using the SAR to predict extinctions in general. I then consider the additional complications that arise when applying SAR methods specifically to climate change. I assess the extent to which these issues call into question predictions of extinctions from climate change relative to other human impacts, and highlight a danger that conservation resources will be directed away from attempts to slow and mitigate the continuing effects of habitat destruction and degradation, particularly in the tropics. I suggest that the most useful contributions of ecologists over the coming decades will be in partitioning likely extinctions among interacting causes and identifying the practical means to slow the rate of species loss.
The silence RNA keeps:
cis
mechanisms of RNA mediated epigenetic silencing in mammals
Authors: Tufarelli Cristina
Published: November 2005

One of the fundamental questions of modern biology is to unravel how genes are switched on and off at the right time and in the correct tissues. It is well recognized that gene regulation depends on a dynamic balance between activating and repressing forces, and multiple mechanisms are involved in both gene silencing and activation. Work over the last decade has revealed that in some cases transcriptional silencing of specific genes is mediated by RNAs that specifically recruit repressing complexes to homologous DNA sequences. Examples of both
cis
and
trans
RNA driven transcriptional silencing have been reported. This review focuses on those examples of transcriptional gene silencing in which the RNA component seems to act uniquely in
cis
. Speculative models of how such
cis
acting transcripts may trigger transcriptional silencing are proposed. Future experimental testing of these and other mechanisms is important to gain a fuller understanding of how genes are regulated and to identify instances in which such mechanisms are defective, leading to disease. Understanding the basic molecular basis of these phenomena will provide us with invaluable tools for the future development of targeted therapies and drugs for those diseases in which they are faulty.
The Cinderella story of metabolic profiling: does metabolomics get to go to the functional genomics ball?
Authors: Griffin Julian L
Published: November 2005

To date most global approaches to functional genomics have centred on genomics, transcriptomics and proteomics. However, since a number of high-profile publications, interest in metabolomics, the global profiling of metabolites in a cell, tissue or organism, has been rapidly increasing. A range of analytical techniques, including
1
H NMR spectroscopy, gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS), Fourier Transform mass spectrometry (FT–MS), high performance liquid chromatography (HPLC) and electrochemical array (EC-array), are required in order to maximize the number of metabolites that can be identified in a matrix. Applications have included phenotyping of yeast, mice and plants, understanding drug toxicity in pharmaceutical drug safety assessment, monitoring tumour treatment regimes and disease diagnosis in human populations. These successes are likely to be built on as other analytical and bioinformatic approaches are developed to fully exploit the information obtained in metabolic profiles. To assist in this process, databases of metabolomic data will be necessary to allow the passage of information between laboratories. In this prospective review, the capabilities of metabolomics in the field of medicine will be assessed in an attempt to predict the impact this ‘Cinderella approach’ will have at the ‘functional genomic ball’.
From famine to feast? Selecting nuclear DNA sequence loci for plant species-level phylogeny reconstruction
Authors: Hughes Colin E , Eastwood Ruth J , Donovan Bailey C
Published: November 2005

Phylogenetic analyses of DNA sequences have prompted spectacular progress in assembling the Tree of Life. However, progress in constructing phylogenies among closely related species, at least for plants, has been less encouraging. We show that for plants, the rapid accumulation of DNA characters at higher taxonomic levels has not been matched by conventional sequence loci at the species level, leaving a lack of well-resolved gene trees that is hindering investigations of many fundamental questions in plant evolutionary biology. The most popular approach to address this problem has been to use low-copy nuclear genes as a source of DNA sequence data. However, this has had limited success because levels of variation among nuclear intron sequences across groups of closely related species are extremely variable and generally lower than conventionally used loci, and because no universally useful low-copy nuclear DNA sequence loci have been developed. This suggests that solutions will, for the most part, be lineage-specific, prompting a move away from ‘universal’ gene thinking for species-level phylogenetics. The benefits and limitations of alternative approaches to locate more variable nuclear loci are discussed and the potential of anonymous non-genic nuclear loci is highlighted. Given the virtually unlimited number of loci that can be generated using these new approaches, it is clear that effective screening will be critical for efficient selection of the most informative loci. Strategies for screening are outlined.
Niche metabolism in parasitic protozoa
Authors: Ginger Michael L
Published: November 2005

Complete or partial genome sequences have recently become available for several medically and evolutionarily important parasitic protozoa. Through the application of bioinformatics complete metabolic repertoires for these parasites can be predicted. For experimentally intractable parasites insight provided by metabolic maps generatedin silicohas been startling. At its more extreme end, such bioinformatics reckoning facilitated the discovery in some parasites of mitochondria remodelled beyond previous recognition, and the identification of a non-photosynthetic chloroplast relic in malarial parasites. However, for experimentally tractable parasites, mapping of the general metabolic terrain is only a first step in understanding how the parasite modulates its streamlined, yet still often puzzlingly complex, metabolism in order to complete life cycles within host, vector, or environment. This review provides a comparative overview and discussion of metabolic strategies used by several different parasitic protozoa in order to subvert and survive host defences, and illustrates how genomic data contribute to the elucidation of parasite metabolism.
High-resolution MRI:
in vivo
histology?
Authors: Bridge Holly , Clare Stuart
Published: November 2005

For centuries scientists have been fascinated with the question of how the brain works. Investigators have looked at both where different functions are localized and how the anatomical microstructure varies across the brain surface. Here we discuss how advances in magnetic resonance imaging (MRI) have allowed
in vivo
visualization of the fine structure of the brain that was previously only visible in post-mortem brains. We present data showing the correspondence between definitions of the primary visual cortex defined anatomically using very high-resolution MRI and functionally using functional MRI. We consider how this technology can be applied to allow the investigation of brains that differ from normal, and what this ever-evolving technology may be able to reveal about
in vivo
brain structure in the next few years.
Polar Localizing Class V Myosin Chitin Synthases Are Essential during Early Plant Infection in the Plant Pathogenic FungusUstilago maydis
Authors: Weber Isabella , Aßmann Daniela , Thines Eckhard , Steinberg Gero
Published: November 2005

Fungal chitin synthases (CHSs) form fibers of the cell wall and are crucial for substrate invasion and pathogenicity. Filamentous fungi contain up to 10 CHSs, which might reflect redundant functions or the complex biology of these fungi. Here, we investigate the complete repertoire of eight CHSs in the dimorphic plant pathogen Ustilago maydis. We demonstrate that all CHSs are expressed in yeast cells and hyphae. Green fluorescent protein (GFP) fusions to all CHSs localize to septa, whereas Chs5-GFP, Chs6-GFP, Chs7-yellow fluorescent protein (YFP), and Myosin chitin synthase1 (Mcs1)-YFP were found at growth regions of yeast-like cells and hyphae, indicating that they participate in tip growth. However, only the class IV CHS genes chs7 and chs5 are crucial for shaping yeast cells and hyphae ex planta. Although most CHS mutants were attenuated in plant pathogenicity, Δchs6, Δchs7, and Δmcs1 mutants were drastically reduced in virulence. Δmcs1 showed no morphological defects in hyphae, but Mcs1 became essential during invasion of the plant epidermis. Δmcs1 hyphae entered the plant but immediately lost growth polarity and formed large aggregates of spherical cells. Our data show that the polar class IV CHSs are essential for morphogenesis ex planta, whereas the class V myosin-CHS is essential during plant infection.
Relay ramp evolution and mass flow deposition (Upper Kimmeridgian–Lower Volgian) in the Tail End Graben, Danish North Sea
Authors: Bruhn Rikke , Vagle Kåre
Published: November 2005

The Central Graben in the Danish North Sea sector consists of a series of N–S to NW–SE trending, eastward‐tilted half‐grabens, bound to the east by the Coffee Soil Fault zone. This fault zone has a complex Jurassic history that encompasses at least two fault populations; N–S to NNW–SSE striking faults active in the Late Aalenian–Early Oxfordian, and NNW–SSE to WNW–ESE striking faults forming in Late Kimmeridgian time (sensu gallico), following a short period of tectonic quiescence. Sediment transport across the Coffee Soil Fault zone was controlled by fault array evolution, and in particular the development of relay ramps that formed potential entry points for antecedent drainage systems from the Ringkøbing–Fyn High east of the rift. Fault and isochore trends of the Upper Kimmeridgian–Lower Volgian succession in the northeast Danish Central Graben show that accommodation space was initially generated close to several minor, isolated or overlapping faults. Subsidence became focused along a few master faults in the Early Volgian through progressive linkage of selected faults. Seismic time isochore geometries, seismic facies, amplitude trends and well ties indicate the presence of coarse clastic lithologies locally along the fault zone. The deposits probably represent submarine mass flow deposits supplied from footwall degradation and possibly also from the graben hinterland via a relay ramp. The latter source appears to have been cut off as the relay ramp was breached and the footwall block are uplifted. Fault growth and linkage processes thus controlled the spatial and temporal trends of accommodation space generation and sediment supply to the rift basin.