bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling ATP utilization to protein remodeling by ClpB, a hexameric AAA+ protein
Authors: Hoskins Joel R. , Doyle Shannon M. , Wickner Sue
Published: November 2009

ClpB and Hsp104 are members of the AAA+ (ATPases associated with various cellular activities) family of proteins and are molecular machines involved in thermotolerance. They are hexameric proteins containing 12 ATP binding sites with two sites per protomer. ClpB and Hsp104 possess some innate protein remodeling activities; however, they require the collaboration of the DnaK/Hsp70 chaperone system to disaggregate and reactivate insoluble aggregated proteins. We investigated the mechanism by which ClpB couples ATP utilization to protein remodeling with and without the DnaK system. When wild-type ClpB, which is unable to remodel proteins alone in the presence of ATP, was mixed with a ClpB mutant that is unable to hydrolyze ATP, the heterohexamers surprisingly gained protein remodeling activity. Optimal protein remodeling by the heterohexamers in the absence of the DnaK system required approximately three active and three inactive protomers. In addition, the location of the active and inactive ATP binding sites in the hexamer was not important. The results suggest that in the absence of the DnaK system, ClpB acts by a probabilistic mechanism. However, when we measured protein disaggregation by ClpB heterohexamers in conjunction with the DnaK system, incorporation of a single inactive ClpB subunit blocked activity, supporting a sequential mechanism of ATP utilization. Taken together, the results suggest that the mechanism of ATP utilization by ClpB is adaptable and can vary depending on the specific substrate and the presence of the DnaK system.
Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells
Authors: Ezratty Ellen J. , Bertaux Claire , Marcantonio Eugene E. , Gundersen Gregg G.
Published: November 2009

Focal adhesion disassembly is regulated by microtubules (MTs) through an unknown mechanism that involves dynamin. To test whether endocytosis may be involved, we interfered with the function of clathrin or its adaptors autosomal recessive hypercholesteremia (ARH) and Dab2 (Disabled-2) and found that both treatments prevented MT-induced focal adhesion disassembly. Surface labeling experiments showed that integrin was endocytosed in an extracellular matrix–, clathrin-, and ARH- and Dab2-dependent manner before entering Rab5 endosomes. Clathrin colocalized with a subset of focal adhesions in an ARH- and Dab2-dependent fashion. Direct imaging showed that clathrin rapidly accumulated on focal adhesions during MT-stimulated disassembly and departed from focal adhesions with integrin upon their disassembly. In migrating cells, depletion of clathrin or Dab2 and ARH inhibited focal adhesion disassembly and decreased the rate of migration. These results show that focal adhesion disassembly occurs through a targeted mechanism involving MTs, clathrin, and specific clathrin adaptors and that direct endocytosis of integrins from focal adhesions mediates their disassembly in migrating cells.
GABA transporter function, oligomerization state, and anchoring: correlates with subcellularly resolved FRET
Authors: Moss Fraser J. , Imoukhuede P.I. , Scott Kimberly , Hu Jia , Jankowsky Joanna L. , Quick Michael W. , Lester Henry A.
Published: November 2009

The mouse γ-aminobutyric acid (GABA) transporter mGAT1 was expressed in neuroblastoma 2a cells. 19 mGAT1 designs incorporating fluorescent proteins were functionally characterized by [3H]GABA uptake in assays that responded to several experimental variables, including the mutations and pharmacological manipulation of the cytoskeleton. Oligomerization and subsequent trafficking of mGAT1 were studied in several subcellular regions of live cells using localized fluorescence, acceptor photobleach Förster resonance energy transfer (FRET), and pixel-by-pixel analysis of normalized FRET (NFRET) images. Nine constructs were functionally indistinguishable from wild-type mGAT1 and provided information about normal mGAT1 assembly and trafficking. The remainder had compromised [3H]GABA uptake due to observable oligomerization and/or trafficking deficits; the data help to determine regions of mGAT1 sequence involved in these processes. Acceptor photobleach FRET detected mGAT1 oligomerization, but richer information was obtained from analyzing the distribution of all-pixel NFRET amplitudes. We also analyzed such distributions restricted to cellular subregions. Distributions were fit to either two or three Gaussian components. Two of the components, present for all mGAT1 constructs that oligomerized, may represent dimers and high-order oligomers (probably tetramers), respectively. Only wild-type functioning constructs displayed three components; the additional component apparently had the highest mean NFRET amplitude. Near the cell periphery, wild-type functioning constructs displayed the highest NFRET. In this subregion, the highest NFRET component represented ∼30% of all pixels, similar to the percentage of mGAT1 from the acutely recycling pool resident in the plasma membrane in the basal state. Blocking the mGAT1 C terminus postsynaptic density 95/discs large/zona occludens 1 (PDZ)-interacting domain abolished the highest amplitude component from the NFRET distributions. Disrupting the actin cytoskeleton in cells expressing wild-type functioning transporters moved the highest amplitude component from the cell periphery to perinuclear regions. Thus, pixel-by-pixel NFRET analysis resolved three distinct forms of GAT1: dimers, high-order oligomers, and transporters associated via PDZ-mediated interactions with the actin cytoskeleton and/or with the exocyst.
Caveolin-3 Promotes Nicotinic Acetylcholine Receptor Clustering and Regulates Neuromuscular Junction Activity
Authors: Hezel Michael , de Groat William C. , Galbiati Ferruccio
Published: November 2009

The molecular mechanisms that regulate the organization and activity of the neuromuscular junction remain to be fully identified. Caveolae are invaginations of the plasma membrane. Caveolin-3 is the structural protein component of caveolae in muscle cells. We show that caveolin-3 is expressed at the neuromuscular junction, that it associates with the nicotinic acetylcholine receptor (nAChR), and that a lack of caveolin-3 inhibits clustering of the nAChR in myotubes. At the molecular level, we demonstrate that caveolin-3 is a novel muscle-specific kinase (MuSK) binding protein and that altered nAChR clustering in caveolin-3–lacking myotubes results from inhibition of agrin-induced phosphorylation/activation of MuSK and activation of Rac-1. Functional studies in caveolin-3 null mice show abnormal neuromuscular junction activity that is consistent with altered nAChR localization at the sarcolemma. Together, these data identify caveolin-3 as a critical component of the signaling machinery that drives nicotinic acetylcholine receptor clustering and controls neuromuscular junction function.
Dissection of Combinatorial Control by the Met4 Transcriptional Complex
Authors: Lee Traci A. , Jorgensen Paul , Bognar Andrew L. , Peyraud Caroline , Thomas Dominique , Tyers Mike
Published: November 2009

Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.
Nuclear-Cytoplasmic Shuttling of Chibby Controls β-Catenin Signaling
Authors: Li Feng-Qian , Mofunanya Adaobi , Fischer Victoria , Hall Jason , Takemaru Ken-Ichi
Published: November 2009

In the canonical Wnt pathway, β-catenin acts as a key coactivator that stimulates target gene expression through interaction with Tcf/Lef transcription factors. Its nuclear accumulation is the hallmark of active Wnt signaling and is frequently associated with cancers. Chibby (Cby) is an evolutionarily conserved molecule that represses β-catenin–dependent gene activation. Although Cby, in conjunction with 14-3-3 chaperones, controls β-catenin distribution, its molecular nature remains largely unclear. Here, we provide compelling evidence that Cby harbors bona fide nuclear localization signal (NLS) and nuclear export signal (NES) motifs, and constitutively shuttles between the nucleus and cytoplasm. Efficient nuclear export of Cby requires a cooperative action of the intrinsic NES, 14-3-3, and the CRM1 nuclear export receptor. Notably, 14-3-3 docking provokes Cby binding to CRM1 while inhibiting its interaction with the nuclear import receptor importin-α, thereby promoting cytoplasmic compartmentalization of Cby at steady state. Importantly, the NLS- and NES-dependent shuttling of Cby modulates the dynamic intracellular localization of β-catenin. In support of our model, short hairpin RNA–mediated knockdown of endogenous Cby results in nuclear accumulation of β-catenin. Taken together, these findings unravel the molecular basis through which a combinatorial action of Cby and 14-3-3 proteins controls the dynamic nuclear-cytoplasmic trafficking of β-catenin.
Induction of a Massive Endoplasmic Reticulum and Perinuclear Space Expansion by Expression of Lamin B Receptor Mutants and the Related Sterol Reductases TM7SF2 and DHCR7
Authors: Zwerger Monika , Kolb Thorsten , Richter Karsten , Karakesisoglou Iakowos , Herrmann Harald
Published: November 2009

Lamin B receptor (LBR) is an inner nuclear membrane protein involved in tethering the nuclear lamina and the underlying chromatin to the nuclear envelope. In addition, LBR exhibits sterol reductase activity. Mutations in the LBR gene cause two different human diseases: Pelger-Huët anomaly and Greenberg skeletal dysplasia, a severe chrondrodystrophy causing embryonic death. Our study aimed at investigating the effect of five LBR disease mutants on human cultured cells. Three of the tested LBR mutants caused a massive compaction of chromatin coincidental with the formation of a large nucleus-associated vacuole (NAV) in several human cultured cell lines. Live cell imaging and electron microscopy revealed that this structure was generated by the separation of the inner and outer nuclear membrane. During NAV formation, nuclear pore complexes and components of the linker of nucleoskeleton and cytoskeleton complex were lost in areas of membrane separation. Concomitantly, a large number of smaller vacuoles formed throughout the cytoplasm. Notably, forced expression of the two structurally related sterol reductases transmembrane 7 superfamily member 2 and 7-dehydrocholesterol reductase caused, even in their wild-type form, a comparable phenotype in susceptible cell lines. Hence, LBR mutant variants and sterol reductases can severely interfere with the regular organization of the nuclear envelope and the endoplasmic reticulum.
A Novel Motif in Fungal Class 1 Histone Deacetylases Is Essential for Growth and Development ofAspergillus
Authors: Tribus Martin , Bauer Ingo , Galehr Johannes , Rieser Gudrun , Trojer Patrick , Brosch Gerald , Loidl Peter , Haas Hubertus , Graessle Stefan
Published: November 2009

Acetylation of the N-terminal tails of core histones is an important regulatory mechanism in eukaryotic organisms. In filamentous fungi, little is known about the enzymes that modify histone tails. However, it is increasingly evident that histone deacetylases and histone acetyltransferases are critical factors for the regulation of genes involved in fungal pathogenicity, stress response, and production of secondary metabolites such as antibiotics or fungal toxins. Here, we show that depletion of RpdA, an RPD3-type histone deacetylase of Aspergillus nidulans, leads to a pronounced reduction of growth and sporulation of the fungus. We demonstrate that a so far unnoticed motif in the C terminus of fungal RpdA histone deacetylases is required for the catalytic activity of the enzyme and consequently is essential for the viability of A. nidulans. Moreover, we provide evidence that this motif is also crucial for the survival of other, if not all, filamentous fungi, including pathogens such as Aspergillus fumigatus or Cochliobolus carbonum. Thus, the extended C terminus of RpdA-type enzymes represents a promising target for fungal-specific histone deacetylase-inhibitors that may have potential as novel antifungal compounds with medical and agricultural applications.
Fast Microtubule Dynamics in Meiotic Spindles Measured by Single Molecule Imaging: Evidence That the Spindle Environment Does Not Stabilize Microtubules
Authors: Needleman Daniel J. , Groen Aaron , Ohi Ryoma , Maresca Tom , Mirny Leonid , Mitchison Tim
Published: November 2009

Metaphase spindles are steady-state ensembles of microtubules that turn over rapidly and slide poleward in some systems. Since the discovery of dynamic instability in the mid-1980s, models for spindle morphogenesis have proposed that microtubules are stabilized by the spindle environment. We used single molecule imaging to measure tubulin turnover in spindles, and nonspindle assemblies, in Xenopus laevis egg extracts. We observed many events where tubulin molecules spend only a few seconds in polymer and thus are difficult to reconcile with standard models of polymerization dynamics. Our data can be quantitatively explained by a simple, phenomenological model—with only one adjustable parameter—in which the growing and shrinking of microtubule ends is approximated as a biased random walk. Microtubule turnover kinetics did not vary with position in the spindle and were the same in spindles and nonspindle ensembles nucleated by Tetrahymena pellicles. These results argue that the high density of microtubules in spindles compared with bulk cytoplasm is caused by local enhancement of nucleation and not by local stabilization. It follows that the key to understanding spindle morphogenesis will be to elucidate how nucleation is spatially controlled.
Basic Fibroblast Growth Factor Elicits Formation of Interstitial Axonal Branches via Enhanced Severing of Microtubules
Authors: Qiang Liang , Yu Wenqian , Liu Mei , Solowska Joanna M. , Baas Peter W.
Published: November 2009

The formation of interstitial axonal branches involves the severing of microtubules at sites where new branches form. Here we wished to ascertain whether basic fibroblast growth factor (bFGF) enhances axonal branching through alterations in proteins involved in the severing of microtubules. We found that treatment of cultured hippocampal neurons with bFGF heightens expression of both katanin and spastin, which are proteins that sever microtubules in the axon. In addition, treatment with bFGF enhances phosphorylation of tau at sites expected to cause it to dissociate from microtubules. This is important because tau regulates the access of katanin to the microtubule. In live-cell imaging experiments, axons of neurons treated with bFGF displayed greater numbers of dynamic free ends of microtubules, as well as greater numbers of short mobile microtubules. Entirely similar enhancement of axonal branching, short microtubule transport, and frequency of microtubule ends was observed when spastin was overexpressed in the neurons. Depletion of either katanin or spastin with siRNA diminished but did not eliminate the enhancement in branching elicited by bFGF. Collectively, these results indicate that bFGF enhances axonal branch formation by augmenting the severing of microtubules through both a spastin-based mode and a katanin-based mode.
Expertomica Cells: analysis of cell monolayer development
Authors: Levitner Tomáš , Timr Štepán , Štys Dalibor
Published: November 2009

Summary: Expertomica Cells is a program for the creation and analysis of pedigree plots from time-lapse micrographs of cell monolayers. It enables recording the basic events in a cell cycle, cell neighbourhoods and spatial migration. The output is both numeric and graphical. The software helps to lower main hurdles in the manual analysis of cell monolayer development to practical limits; it reduces the operator processing time of typical experiment containing 5000 consecutive images from the usual 3 months to 3–10 h.

Availability and Implementation: Freely available on the web at http://www.expertomicacells.tk or http://www.expertomicacells.wu.cz. The source code is implemented in JAVA 6 and supported by Linux, Mac and MS Windows.

Contact:  levitner@ufb.jcu.cz

Supplementary information:  Supplementary data available at Bioinformatics online.
Attenuated Cardiac Mitochondrial‐Dependent Apoptotic Effects by Li‐Fu Formula in Hamsters Fed with a Hypercholesterol Diet
Authors: Kuo Wei-Wen , Hsu Tsai-Ching , Chain Mei-Haung , Lai Chao-Hung , Wang Wen-Hong , Tsai Fuu-Jen , Tsai Chang-Hai , Wu Chieh-His , Huang Chih-Yang , Tzang Bor-Show
Published: November 2009

Apoptosis involves in the pathogenesis of various cardiac abnormalities. This study intends to evaluate the effects of Li‐Fu formula on cardiac apoptosis induced by hyper‐cholesterol diet. Twenty‐four male Golden Syrian hamsters were randomly divided into Control, Cholesterol and Li‐Fu formula groups. Histopathological analysis, western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure the effects of Li‐Fu formula on left ventricle. Significantly reduced TUNEL‐positive cells and mitochondria‐ dependent apoptosis were observed in the left ventricle of hamsters from Li‐Fu formula group compared to the Cholesterol group. Additionally, induced cardiac insulin like growth factor I receptor (IGFIR)‐dependent survival pathway was detected in the Li‐Fu formula group compared to the Cholesterol group. Besides, minor fibrosis, increased collagen deposition, and myofibril disarray was detected in the Cholesterol group, whereas the reductions of collagen deposition and myofibril disarray were observed in the Li‐Fu formula group. This study demonstrated that Li‐Fu formula not only reduced the mitochondria‐dependent apoptosis and fibrosis, but also enhanced the IGF‐I survival pathway in the left ventricle from high cholesterol‐fed hamsters. We suggest the protective effects of Li‐Fu formula on cardiac apoptosis and therapeutic potentials against cardiovascular disease.
Difficulties and Perspectives of Immunomodulatory Therapy with Mistletoe Lectins and Standardized Mistletoe Extracts in Evidence‐Based Medicine
Authors: Hajtó Tibor , Fodor Krisztina , Perjési Pál , Németh Pèter
Published: November 2009

Viscum album preparations are aqueous mistletoe plant extracts used in complementary and alternative medicine as immunomodulators in cancer therapy. However, evidence of immunological efficacy of mistletoe extracts (MEs) used in clinical trials is often lacking. Mechanisms involved in anti‐tumor properties of ME and mistletoe lectins (MLs) modify both innate and adaptive immune systems, according to animal model experiments. In the background of these effects, a selective binding of ML on CD75 ganglioside receptors of interleukin 12 (IL‐12)‐producing macrophages or dendritic cells can play an important role. Immunological effects of ME correlate with their lectin activity, showing a bell‐shaped dose‐response curve of efficacy. Therefore, a correct determination of MLs for the standardization of commercial ME is essential. However, plant MLs exhibit heterogeneity, which most likely results from post‐translational processing. In addition, amino acid analysis of ML has revealed numerous conservative substitutions along their amino acid sequence. Consequently, ML research needs new perspectives, and the advantages and disadvantages of purified and biologically better defined ML preparations are also discussed in this article.
Strategic Approach to the Globalization of Sasang Constitutional Medicine
Authors: Lee Myeong Soo
Published: November 2009

The workshop on “Strategic Approach to the Globalization of Sasang Constitutional Medicine (SCM)” was held in the Korea Institute of Oriental Medicine (KIOM) on September 18, 2009. This workshop was designed to discuss and brainstorm the strategic approach to the globalization of SCM, one of the unique systems in Korean Traditional Medicine, with three topics and an extensive panel discussion. Professor Edwin Cooper, Editor‐in‐Chief of eCAM, gave a commemorative lecture for publication of the second supplement of eCAM entitled “Sasang Constitutional Medicine as a Holistic Tailored Medicine”. The other two presenters suggested some practical methods for globalization of SCM on the basis of their experiences. After the three main presentations, there was a panel discussion session for further development of workshop topics, extended by five other external experts. They discussed the benefits, limitations and essentials for globalization of Korean Traditional Medicine, specifically SCM, from bench to bedside.
Spatial patterns of infauna, epifauna, and demersal fish communities in the North Sea
Authors: Reiss Henning , Degraer Steven , Duineveld Gerard C. A. , Kröncke Ingrid , Aldridge John , Craeymeersch Johan A. , Eggleton Jacqueline D. , Hillewaert Hans , Lavaleye Marc S. S. , Moll Andreas , Pohlmann Thomas , Rachor Eike , Robertson Mike , Vanden Berghe Edward , van Hoey Gert , Rees Hubert L.
Published: November 2009

Reiss, H., Degraer, S., Duineveld, G. C. A., Kröncke, I., Aldridge, J., Craeymeersch, J., Eggleton, J. D., Hillewaert, H., Lavaleye, M. S. S., Moll, A., Pohlmann, T., Rachor, E., Robertson, M., vanden Berghe, E., van Hoey, G., and Rees, H. L. 2010. Spatial patterns of infauna, epifauna, and demersal fish communities in the North Sea. – ICES Journal of Marine Science, 67: 278–293. Understanding the structure and interrelationships of North Sea benthic invertebrate and fish communities and their underlying environmental drivers is an important prerequisite for conservation and spatial ecosystem management on scales relevant to ecological processes. Datasets of North Sea infauna, epifauna, and demersal fish (1999–2002) were compiled and analysed to (i) identify and compare spatial patterns in community structure, and (ii) relate these to environmental variables. The multivariate analyses revealed significantly similar large-scale patterns in all three components with major distinctions between a southern community (Oyster Ground and German Bight), an eastern Channel and southern coastal community, and at least one northern community (>50 m deep). In contrast, species diversity patterns differed between the components with a diversity gradient for infauna and epifauna decreasing from north to south, and diversity hotspots of demersal fish, e.g. near the major inflows of Atlantic water. The large-scale hydrodynamic variables were the main drivers for the structuring of communities, whereas sediment characteristics appeared to be less influential, even for the infauna communities. The delineation of ecologically meaningful ecosystem management units in the North Sea might be based on the structure of the main faunal ecosystem components.
Frequency matching of vocalizations to inner-ear sensitivity along an altitudinal gradient in the coqui frog
Authors: Meenderink Sebastiaan W. F. , Kits Mirja , Narins Peter M.
Published: November 2009

Acoustic communication involves both the generation and the detection of a signal. In the coqui frog (Eleutherodactylus coqui), it is known that the spectral contents of its calls systematically change with altitude above sea level. Here, distortion product otoacoustic emissions are used to assess the frequency range over which the inner ear is sensitive. It is found that both the spectral contents of the calls and the inner-ear sensitivity change in a similar fashion along an altitudinal gradient. As a result, the call frequencies and the auditory tuning are closely matched at all altitudes. We suggest that the animal's body size determines the frequency particulars of the call apparatus and the inner ear.
Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammatory diseases
Authors: Ulbrich Wiebke , Lamprecht Alf
Published: November 2009

Limitations in therapy induced by adverse effects due to unselective drug availability and therefore the use of potentially too high doses are a common problem. One prominent example for this dilemma are inflammatory diseases. Colloidal carriers allow one to improve delivery of drugs to the site of action and appear promising to overcome this general therapeutic drawback. Specific uptake of nanoparticles by immune-related cells in inflamed barriers offers selective drug targeting to the inflamed tissue. Here we focus on nanocarrier-based drug delivery strategies for the treatment of common inflammatory disorders like rheumatoid arthritis, multiple sclerosis, uveitis or inflammatory bowel disease.
What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of
Streptococcus pneumoniae
?
Authors: Colijn Caroline , Cohen Ted , Fraser Christophe , Hanage William , Goldstein Edward , Givon-Lavi Noga , Dagan Ron , Lipsitch Marc
Published: November 2009

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of
Streptococcus pneumoniae
there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.
Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes
Authors: Lundbæk Jens A. , Collingwood Shemille A. , Ingólfsson Helgi I. , Kapoor Ruchi , Andersen Olaf S.
Published: November 2009

Membrane protein function is regulated by the host lipid bilayer composition. This regulation may depend on specific chemical interactions between proteins and individual molecules in the bilayer, as well as on non-specific interactions between proteins and the bilayer behaving as a physical entity with collective physical properties (e.g. thickness, intrinsic monolayer curvature or elastic moduli). Studies in physico-chemical model systems have demonstrated that changes in bilayer physical properties can regulate membrane protein function by altering the energetic cost of the bilayer deformation associated with a protein conformational change. This type of regulation is well characterized, and its mechanistic elucidation is an interdisciplinary field bordering on physics, chemistry and biology. Changes in lipid composition that alter bilayer physical properties (including cholesterol, polyunsaturated fatty acids, other lipid metabolites and amphiphiles) regulate a wide range of membrane proteins in a seemingly non-specific manner. The commonality of the changes in protein function suggests an underlying physical mechanism, and recent studies show that at least some of the changes are caused by altered bilayer physical properties. This advance is because of the introduction of new tools for studying lipid bilayer regulation of protein function. The present review provides an introduction to the regulation of membrane protein function by the bilayer physical properties. We further describe the use of gramicidin channels as molecular force probes for studying this mechanism, with a unique ability to discriminate between consequences of changes in monolayer curvature and bilayer elastic moduli.
Fast-forward of adiabatic dynamics in quantum mechanics
Authors: Masuda Shumpei , Nakamura Katsuhiro
Published: November 2009

We propose a method to accelerate adiabatic dynamics of wave functions (WFs) in quantum mechanics to obtain a final adiabatic state except for the spatially uniform phase in any desired short time. In our previous work, acceleration of the dynamics of WFs was shown to obtain the final state in any short time by applying driving potential. We develop the previous theory of fast-forward to derive a driving potential for the fast-forward of adiabatic dynamics. A typical example is the fast-forward of adiabatic transport of a WF, which is the ideal transport in the sense that a stationary WF is transported to an aimed position in any desired short time without leaving any disturbance at the final time of the fast-forward. As other important examples, we show accelerated manipulations of WFs, such as their splitting and squeezing. The theory is also applicable to macroscopic quantum mechanics described by the nonlinear Schrödinger equation.
Freezing of a supercooled spherical droplet with mixed boundary conditions
Authors: Tabakova Sonia , Feuillebois François , Radev Stefan
Published: November 2009

The freezing of a supercooled droplet occurs in two steps: recalescence, that is, a rapid return to thermodynamic equilibrium at the freezing temperature leading to a liquid–solid mixture and a longer stage of complete freezing. The second freezing step can be modelled by the one-phase Stefan problem for an inward solidification of a sphere, assuming the droplet to be spherical. A convective heat transfer with the ambient immiscible fluid is modelled by a mixed boundary condition on the outer surface of the droplet. This condition depends on the Biot number (ratio of the heat transfer resistances inside the droplet and at its surface). A novel asymptotic solution is developed for a small Stefan number and an arbitrary Biot number. Applying the method of matched asymptotic expansions, uniformly valid solutions are obtained for the temperature profile and freezing front evolution in the whole stage of complete freezing. For an infinite Biot number, that is, for a fixed temperature at the droplet outer boundary, known solutions are recovered. In parallel, numerical results are obtained for an arbitrary Stefan number using a finite-difference scheme based on the enthalpy method. The asymptotic and numerical solutions are in good agreement.
Skull and buccal cavity allometry increase mass-specific engulfment capacity in fin whales
Authors: Goldbogen Jeremy A. , Potvin Jean , Shadwick Robert E.
Published: November 2009

Rorqual whales (Balaenopteridae) represent not only some of the largest animals of all time, but also exhibit a wide range in intraspecific and interspecific body size. Balaenopterids are characterized by their extreme lunge-feeding behaviour, a dynamic process that involves the engulfment of a large volume of prey-laden water at a high energetic cost. To investigate the consequences of scale and morphology on lunge-feeding performance, we determined allometric equations for fin whale body dimensions and engulfment capacity. Our analysis demonstrates that larger fin whales have larger skulls and larger buccal cavities relative to body size. Together, these data suggest that engulfment volume is also allometric, increasing with body length as. The positive allometry of the skull is accompanied by negative allometry in the tail region. The relative shortening of the tail may represent a trade-off for investing all growth-related resources in the anterior region of the body. Although enhanced engulfment volume will increase foraging efficiency, the work (energy) required to accelerate the engulfed water mass during engulfment will be relatively higher in larger rorquals. If the mass-specific energetic cost of a lunge increases with body size, it will have major consequences for rorqual foraging ecology and evolution.
Temperature-dependent transmission of rotavirus in Great Britain and The Netherlands
Authors: Atchison C. J. , Tam C. C. , Hajat S. , van Pelt W. , Cowden J. M. , Lopman B. A.
Published: November 2009

In Europe, rotavirus gastroenteritis peaks in late winter or early spring suggesting a role for weather factors in transmission of the virus. In this study, multivariate regression models adapted for time-series data were used to investigate effects of temperature, humidity and rainfall on reported rotavirus infections and the infection-rate parameter, a derived measure of infection transmission that takes into account population immunity, in England, Wales, Scotland and The Netherlands. Delayed effects of weather were investigated by introducing lagged weather terms into the model. Meta-regression was used to pool together country-specific estimates. There was a 13 per cent (95% confidence interval (CI), 11–15%) decrease in reported infections per 1°C increase in temperature above a threshold of 5°C and a 4 per cent (95% CI, 3–5%) decrease in the infection-rate parameter per 1°C increase in temperature across the whole temperature range. The effect of temperature was immediate for the infection-rate parameter but delayed by up to four weeks for reported infections. There was no overall effect of humidity or rainfall. There is a direct and simple relationship between cold weather and rotavirus transmission in Great Britain and The Netherlands. The more complex and delayed temperature effect on disease incidence is likely to be mediated through the effects of weather on transmission.
Brooding fathers, not siblings, take up nutrients from embryos
Authors: Sagebakken Gry , Ahnesjö Ingrid , Mobley Kenyon B. , Gonçalves Inês Braga , Kvarnemo Charlotta
Published: November 2009

It is well known that many animals with placenta-like structures provide their embryos with nutrients and oxygen. However, we demonstrate here that nutrients can pass the other way, from embryos to the parent. The study was done on a pipefish,Syngnathus typhle, in which males brood fertilized eggs in a brood pouch for several weeks. Earlier research has found a reduction of embryo numbers during the brooding period, but the fate of the nutrients from these ‘reduced’ embryos has been unknown. In this study, we considered whether (i) the brooding male absorbs the nutrients, (ii) siblings absorb them, or (iii) a combination of both. Males were mated to two sets of females, one of which had radioactively labelled eggs (using14C-labelled amino acids), such that approximately half the eggs in the brood pouch were labelled. This allowed us to trace nutrient uptake from these embryos. We detected that14C-labelled amino acids were transferred to the male brood pouch, liver and muscle tissue. However, we did not detect any significant14C-labelled amino-acid absorption by the non-labelled half-siblings in the brood pouch. Thus, we show, to our knowledge, for the first time, that males absorb nutrients derived from embryos through their paternal brood pouch.
Ecologically relevant spatial memory use modulates hippocampal neurogenesis
Authors: LaDage Lara D. , Roth Timothy C. , Fox Rebecca A. , Pravosudov Vladimir V.
Published: November 2009

The adult hippocampus in birds and mammals undergoes neurogenesis and the resulting new neurons appear to integrate structurally and functionally into the existing neural architecture. However, the factors underlying the regulation of new neuron production is still under scrutiny. In recent years, the concept that spatial memory affects adult hippocampal neurogenesis has gained acceptance, although results attempting to causally link memory use to neurogenesis remain inconclusive, possibly owing to confounds of motor activity, task difficulty or training for the task. Here, we show that ecologically relevant, spatial memory-based experiences of food caching and retrieving directly affect hippocampal neurogenesis in mountain chickadees (Poecile gambeli). We found that restricting memory experiences in captivity caused significantly lower rates of neurogenesis, as determined by doublecortin expression, compared with captive individuals provided with such experiences. However, neurogenesis rates in both groups of captive birds were still greatly lower than those in free-ranging conspecifics. These findings show that ecologically relevant spatial memory experiences can directly modulate neurogenesis, separate from other confounds that may also independently affect neurogenesis.
Extreme contagion in global habitat clearance
Authors: Boakes Elizabeth H. , Mace Georgina M. , McGowan Philip J. K. , Fuller Richard A.
Published: November 2009

Habitat clearance remains the major cause of biodiversity loss, with consequences for ecosystem services and for people. In response to this, many global conservation schemes direct funds to regions with high rates of recent habitat destruction, though some also emphasize the conservation of remaining large tracts of intact habitat. If the pattern of habitat clearance is highly contagious, the latter approach will help prevent destructive processes gaining a foothold in areas of contiguous intact habitat. Here, we test the strength of spatial contagion in the pattern of habitat clearance. Using a global dataset of land-cover change at 50 × 50 km resolution, we discover that intact habitat areas in grid cells are refractory to clearance only when all neighbouring cells are also intact. The likelihood of loss increases dramatically as soon as habitat is cleared in just one neighbouring cell, and remains high thereafter. This effect is consistent for forests and grassland, across biogeographic realms and over centuries, constituting a coherent global pattern. Our results show that landscapes become vulnerable to wholesale clearance as soon as threatening processes begin to penetrate, so actions to prevent any incursions into large, intact blocks of natural habitat are key to their long-term persistence.
Multiple markers and multiple individuals refine true seal phylogeny and bring molecules and morphology back in line
Authors: Fulton Tara Lynn , Strobeck Curtis
Published: November 2009

Despite decades of study, some aspects of Phocidae (Pinnipedia, Carnivora) phylogeny still remain unresolved. Using the largest novel dataset to date, including all extant phocids and comprising 15 nuclear and 13 mitochondrial genes, we illustrate the utility of including multiple individuals per species in resolving rapid radiations, and provide new insight into phocid phylogeny. In line with longstanding morphological views,Pusais recovered as monophyletic for the first time with genetic data. The data are also used to explore the relationship between genetic distance and taxonomic rank. Intraspecific sampling also highlights the discrepancy between molecular and morphological rates of evolution within Phocidae.
Avian retinal oil droplets: dietary manipulation of colour vision?
Authors: Knott Ben , Berg Mathew L. , Morgan Eric R. , Buchanan Katherine L. , Bowmaker James K. , Bennett Andrew T. D.
Published: November 2009

Avian vision is highly developed, with bird retinas containing rod and double-cone photoreceptors, plus four classes of single cones subserving tetrachromatic colour vision. Cones contain an oil droplet, rich in carotenoid pigments (except VS/ultraviolet-sensitive cones), that acts as a filter, substantially modifying light detected by the photoreceptor. Using dietary manipulations, we tested the effects of carotenoid availability on oil droplet absorbance properties in two species:Platycercus elegansandTaeniopygia guttata. Using microspectrophotometry, we determined whether manipulations affected oil droplet carotenoid concentration and whether changes would alter colour discrimination ability. In both species, increases in carotenoid concentration were found in carotenoid-supplemented birds, but only in the double cones. Magnitudes of effects of manipulations were often dependent on retinal location. The study provides, to our knowledge, the first experimental evidence of dietary intake over a short time period affecting carotenoid concentration of retinal oil droplets. Moreover, the allocation of carotenoids to the retina by both species is such that the change potentially preserves the spectral tuning of colour vision. Our study generates new insights into retinal regulation of carotenoid concentration of oil droplets, an area about which very little is known, with implications for our understanding of trade-offs in carotenoid allocation in birds.
Repeated stress exposure results in a survival–reproduction trade-off inDrosophila melanogaster
Authors: Marshall Katie E. , Sinclair Brent J.
Published: November 2009

While insect cold tolerance has been well studied, the vast majority of work has focused on the effects of a single cold exposure. However, many abiotic environmental stresses, including temperature, fluctuate within an organism's lifespan. Given that organisms may trade-off survival at the cost of future reproduction, we investigated the effects of multiple cold exposures on survival and fertility in the model organismDrosophila melanogaster. We found that multiple cold exposures significantly decreased mortality compared with the same length of exposure in a single sustained bout, but significantly decreased fecundity (as measured byr, the intrinsic rate of increase) as well, owing to a shift in sex ratio. This change was reflected in a long-term decrease in glycogen stores in multiply exposed flies, while a brief effect on triglyceride stores was observed, suggesting flies are reallocating energy stores. Given that many environments are not static, this trade-off indicates that investigating the effects of repeated stress exposure is important for understanding and predicting physiological responses in the wild.
Mixed genotype transmission bodies and virions contribute to the maintenance of diversity in an insect virus
Authors: Clavijo Gabriel , Williams Trevor , Muñoz Delia , Caballero Primitivo , López-Ferber Miguel
Published: November 2009

An insect nucleopolyhedrovirus naturally survives as a mixture of at least nine genotypes. Infection by multiple genotypes results in the production of virus occlusion bodies (OBs) with greater pathogenicity than those of any genotype alone. We tested the hypothesis that each OB contains a genotypically diverse population of virions. Few insects died following inoculation with an experimental two-genotype mixture at a dose of one OB per insect, but a high proportion of multiple infections were observed (50%), which differed significantly from the frequencies predicted by a non-associated transmission model in which genotypes are segregated into distinct OBs. By contrast, insects that consumed multiple OBs experienced higher mortality and infection frequencies did not differ significantly from those of the non-associated model. Inoculation with genotypically complex wild-type OBs indicated that genotypes tend to be transmitted in association, rather than as independent entities, irrespective of dose. To examine the hypothesis that virions may themselves be genotypically heterogeneous, cell culture plaques derived from individual virions were analysed to reveal that one-third of virions was of mixed genotype, irrespective of the genotypic composition of the OBs. We conclude that co-occlusion of genotypically distinct virions in each OB is an adaptive mechanism that favours the maintenance of virus diversity during insect-to-insect transmission.
Beyond cuticular hydrocarbons: evidence of proteinaceous secretion specific to termite kings and queens
Authors: Hanus Robert , Vrkoslav Vladimír , Hrdý Ivan , Cvačka Josef , Šobotník Jan
Published: November 2009

In 1959, P. Karlson and M. Lüscher introduced the term ‘pheromone’, broadly used nowadays for various chemicals involved in intraspecific communication. To demonstrate the term, they depicted the situation in termite societies, where king and queen inhibit the reproduction of nest-mates by an unknown chemical substance. Paradoxically, half a century later, neither the source nor the chemical identity of this ‘royal’ pheromone is known. In this study, we report for the first time the secretion of polar compounds of proteinaceous origin by functional reproductives in three termite species,Prorhinotermes simplex,Reticulitermes santonensisandKalotermes flavicollis. Aqueous washes of functional reproductives contained sex-specific proteinaceous compounds, virtually absent in non-reproducing stages. Moreover, the presence of these compounds was clearly correlated with the age of reproductives and their reproductive status. We discuss the putative function of these substances in termite caste recognition and regulation.
Kin selection in Columbian ground squirrels (
Urocitellus columbianus
): littermate kin provide individual fitness benefits
Authors: Viblanc Vincent A. , Arnaud Coline M. , Dobson F. Stephen , Murie Jan O.
Published: November 2009

Since W. D. Hamilton's seminal work on the evolution of sociality, a large body of research has accumulated on how kin selection might explain the evolution of cooperation in many group-living species. Our study examined the evolutionary basis of philopatry and cooperation; specifically, whether individuals benefit from the presence of close kin. We applied an individual fitness approach to a 16-year study of Columbian ground squirrels (
Urocitellus columbianus
) to investigate potential causal paths by which the presence of kin might act on individual fitness. Our results indicate that individual fitness benefits resulted from associations of philopatric female kin, and support the hypothesis that increased tolerance of proximity of kin is a proximate mechanism for these benefits. The major life-history influence of kin on individual fitness was through improved reproductive success, and this benefit may have been owing to philopatric settlement of kin that were recognized through familiarization in the natal burrow. Thus, we demonstrated an evolutionary basis necessary for ongoing kin-selected cooperation in Columbian ground squirrels, though the mechanism of familiarity may determine which kin individuals benefit from cooperative behaviours.