bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurite outgrowth inhibitor Nogo‐A promotes denervation in an amyotrophic lateral sclerosis model
Authors: Jokic Natasa , Gonzalez de Aguilar Jose‐Luis , Dimou Leda , Lin Shuo , Fergani Anissa , Ruegg Markus A , Schwab Martin E , Dupuis Luc , Loeffler Jean‐Philippe
Published: October 2006

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss and muscle wasting. In muscles of ALS patients, Nogo‐A—a protein known to inhibit axon regeneration—is ectopically expressed at levels that correlate with the severity of the clinical symptoms. We now show that the genetic ablation of Nogo‐A extends survival and reduces muscle denervation in a mouse model of ALS. In turn, overexpression of Nogo‐A in wild‐type muscle fibres leads to shrinkage of the postsynapse and retraction of the presynaptic motor ending. This suggests that the expression of Nogo‐A occurring early in ALS skeletal muscle could cause repulsion and destabilization of the motor nerve terminals, and subsequent dying back of the axons and motor neurons.
Chinese-scorpion (Buthus martensi Karsch) toxin BmK αIV, a novel modulator of sodium channels: from genomic organization to functional analysis
Authors: Chai Zhi-Fang , Zhu Mang-Mang , Bai Zhan-Tao , Liu Tong , Tan Miao , Pang Xue-Yan , Ji Yong-Hua
Published: October 2006

In the present study, BmK αIV, a novel modulator of sodium channels, was cloned from venomous glands of the Chinese scorpion (Buthus martensi Karsch) and expressed successfully in Escherichia coli. The BmK αIV gene is composed of two exons separated by a 503 bp intron. The mature polypeptide contains 66 amino acids. BmK αIV has potent toxicity in mice and cockroaches. Surface-plasmon-resonance analysis found that BmK αIV could bind to both rat cerebrocortical synaptosomes and cockroach neuronal membranes, and shared similar binding sites on sodium channels with classical AaH II (α-mammal neurotoxin from the scorpion Androctonus australis Hector), BmK AS (β-like neurotoxin), BmK IT2 (the depressant insect-selective neurotoxin) and BmK abT (transitional neurotoxin), but not with BmK I (α-like neurotoxin). Two-electrode voltage clamp recordings on rNav1.2 channels expressed in Xenopus laevis oocytes revealed that BmK αIV increased the peak amplitude and prolonged the inactivation phase of Na+ currents. The structural and pharmacological properties compared with those of other scorpion α-toxins suggests that BmK αIV represents a novel subgroup or functional hybrid of α-toxins and might be an evolutionary intermediate neurotoxin for α-toxins.
Tankyrase recruitment to the lateral membrane in polarized epithelial cells: regulation by cell–cell contact and protein poly(ADP-ribosyl)ation
Authors: Yeh Tsung-Yin J. , Meyer Tobias N. , Schwesinger Catherine , Tsun Zhi-Yang , Lee Ray M. , Chi Nai-Wen
Published: October 2006

PARsylation [poly(ADP-ribosyl)ation] of proteins is implicated in the regulation of diverse physiological processes. Tankyrase is a molecular scaffold with this catalytic activity and has been proposed as a regulator of vesicular trafficking on the basis, in part, of its Golgi localization in non-polarized cells. Little is known about tankyrase localization in polarized epithelial cells. Using MDCK (Madin–Darby canine kidney) cells as a model, we found that E-cadherin-mediated intercellular adhesion recruits tankyrase from the cytoplasm to the lateral membrane (including the tight junction), where it stably associates with detergent-insoluble structures. This recruitment is mostly completed within 8 h of calcium-induced formation of cell–cell contact. Conversely, when intercellular adhesion is disrupted by calcium deprivation, tankyrase returns from the lateral membrane to the cytoplasm and becomes more soluble in detergents. The PARsylating activity of tankyrase promotes its dissociation from the lateral membrane as well as its ubiquitination and proteasome-mediated degradation, resulting in an apparent protein half-life of ∼2 h. Inhibition of tankyrase autoPARsylation using H2O2-induced NAD+ depletion or PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride] treatment results in tankyrase stabilization and accumulation at the lateral membrane. By contrast, stabilization through proteasome inhibition results in tankyrase accumulation in the cytoplasm. These data suggest that cell–cell contact promotes tankyrase association with the lateral membrane, whereas PARsylating activity promotes translocation to the cytosol, which is followed by ubiquitination and proteasome-mediated degradation. Since the lateral membrane is a sorting station that ensures domain-specific delivery of basolateral membrane proteins, the regulated tankyrase recruitment to this site is consistent with a role in polarized protein targeting in epithelial cells.
Mice deficient in Cu,Zn-superoxide dismutase are resistant to acetaminophen toxicity
Authors: Lei Xin Gen , Zhu Jian-Hong , McClung James P. , Aregullin Manuel , Roneker Carol A.
Published: October 2006

Although antioxidants are used to treat an overdose of the analgaesic/antipyretic drug APAP (acetaminophen), roles of antioxidant enzymes in APAP-induced hepatotoxicity remain controversial. Our objective was to determine impacts of knockout of SOD1 (superoxide dismutase; Cu,Zn-SOD) alone or in combination with selenium-dependent GPX1 (glutathione peroxidase-1) on APAP-induced hepatotoxicity. All SOD1-null (SOD1−/−) and SOD1- and GPX1-double-knockout mice survived an intraperitoneal injection of 600 mg of APAP per kg of body mass, whereas 75% of WT (wild-type) and GPX1-null mice died within 20 h. Survival time of SOD1−/− mice injected with 1200 mg of APAP per kg of body mass was longer than that of the WT mice (934 compared with 315 min, P<0.05). The APAP-treated SOD1−/− mice had less (P<0.05) plasma ALT (alanine aminotransferase) activity increase and attenuated (P<0.05) hepatic glutathione depletion than the WT mice. The protection conferred by SOD1 deletion was associated with a block of the APAP-mediated hepatic protein nitration and a 50% reduction (P<0.05) in activity of a key APAP metabolism enzyme CYP2E1 (cytochrome P450 2E1) in liver. The SOD1 deletion also caused moderate shifts in the APAP metabolism profiles. In conclusion, deletion of SOD1 alone or in combination with GPX1 greatly enhanced mouse resistance to APAP overdose. Our results suggest a possible pro-oxidant role for the physiological level of SOD1 activity in APAP-mediated hepatotoxicity.
TAK1-binding protein 1 is a pseudophosphatase
Authors: Conner Sarah H. , Kular Gursant , Peggie Mark , Shepherd Sharon , Schüttelkopf Alexander W. , Cohen Philip , Van Aalten Daan M. F.
Published: October 2006

TAB1 [TAK1 (transforming growth factor-β-activated kinase 1)-binding protein 1] is one of the regulatory subunits of TAK1, a protein kinase that lies at the head of three pro-inflammatory kinase cascades. In the current study we report the crystal structure of the N-terminal domain of TAB1. Surprisingly, TAB1 possesses a fold closely related to that of the PPM (Mg2+- or Mn2+-dependent protein phosphatase) family as demonstrated by the close structural similarity with protein phosphatase 2Cα. However, we were unable to detect any phosphatase activity for TAB1 using a phosphopeptide or p-nitrophenyl phosphate as substrate. Although the overall protein phosphatase 2Cα fold is conserved in TAB1, detailed structural analyses and mutagenesis studies show that several key residues required for dual metal-binding and catalysis are not present in TAB1, although binding of a single metal is supported by soaking experiments with manganese and isothermal titration calorimetry. Thus, it appears that TAB1 is a ‘pseudophosphatase’, possibly binding to and regulating accessibility of phosphorylated residues on substrates downstream of TAK1 or on the TAK1 complex itself.
‘A People with Our Own Identity’: Toward a Cultural Politics of Development in Ecuadorian Amazonia
Authors: Perreault Thomas
Published: October 2006

In this paper I examine the cultural politics of international development among Ecuadorian indigenous federations. Many critiques, focused on the national or international scale, have portrayed development as monolithic, homogenizing, and depoliticized. However, when specific practices and discourses of development are examined, particularly among locally based rural peoples' organizations, it becomes clear that development is a diverse process, and its meaning is highly contested. I argue that, for Ecuadorian indigenous organizations, international development provides an idiom for negotiating civil and resource rights. This process is demonstrated through an institutional ethnography of an indigenous federation in the Ecuadorian Amazon, which highlights the ways that the federation uses the discourses of nationalist development and environmentalism in order to contest official understandings of citizenship and the nation.
Decentering the Movement: Collective Action, Place, and the ‘Sedimentation’ of Radical Political Discourses
Authors: Nelson Lise
Published: October 2006

The alternative political discourses and identities associated with social movements in Latin America are frequently examined at the height of mobilization and visibility of these same movements. In response to growing concern about the limits of such analyses, I propose thinking about the ‘sedimentation’ of social-movement discourses in place. ‘Sedimentation’ refers to the complex processes through which discourses (including ‘identities’, political vocabularies, and practices) deployed in moments of collective organization and protest become translated and socially embedded by a variety of actors, not only over time but through disparate social and political arenas. Social-movement theorists in geography and other disciplines could more fully understand the longer term political and cultural impacts of social movements if they engaged theories of place—particularly in ways that decenter ‘the movement’ as the central category of analysis. An approach that centers on place and sedimentation processes, rather than on the fate of ‘the movement’, facilitates understanding the complex (and often contradictory) ripple effects of collective protest over time and through various social arenas—some seemingly far removed from ‘the movement’ itself. To illustrate my argument I draw on ethnographic research that explores, over a ten-year period (1988–98), collective mobilization and changing political discourses in a Purhépechan indigenous community of Mexico.
Outsiders in Rural Society? Constructions of Rurality and Nature—Society Relations in the Racialisation of English Gypsy-Travellers, 1869 – 1934
Authors: Holloway Sarah L
Published: October 2006

In this paper I explore what Little (1999 Progress in Human Geography23 page 438) terms “the complexity and fluidity of rural otherness” through an examination of the racialisation of Gypsy-Travellers in late-19th-century and early-20th century England. Drawing on social-constructionist and psychoanalytic accounts of difference, I explore both the specificity of racialisation in different places, and the ways in which processes of racialisation can produce highly spatialised understandings of difference. In so doing, I consider the importance of nature – society relations in the othering of this minority group, and the contested construction of their place in the rural idyll.
Weil-Petersson volumes and intersection theory on the moduli space of curves
Authors: Mirzakhani Maryam
Published: October 2006

In this paper, we establish a relationship between the Weil- Petersson volume

V

g
,
n

(
b
)

V_{g,n}(b)

of the moduli space

M

g
,
n

(
b
)

\mathcal {M}_{g,n}(b)

of hyperbolic Riemann surfaces with geodesic boundary components of lengths

b

1

b_{1}

, …,

b

n

b_{n}

, and the intersection numbers of tautological classes on the moduli space

M

¯

g
,
n

\overline {\mathcal {M}}_{g,n}

of stable curves. As a result, by using the recursive formula for

V

g
,
n

(
b
)

V_{g,n}(b)

obtained in the author’s Simple geodesics and Weil-Petersson volumes of moduli spaces of bordered Riemann surfaces, preprint, 2003, we derive a new proof of the Virasoro constraints for a point. This result is equivalent to the Witten-Kontsevich formula.
A formula of two-partition Hodge integrals
Authors: Liu Chiu-Chu Melissa , Liu Kefeng , Zhou Jian
Published: October 2006

Motivated by the Mariño-Vafa formula of Hodge integrals and physicists’ predictions on local Gromov-Witten invariants of toric Fano surfaces in a Calabi-Yau threefold, the third author conjectured a formula of certain Hodge integrals in terms of certain Chern-Simons invariants of the Hopf link. We prove this formula by virtual localization on moduli spaces of relative stable morphisms.
Universally optimal distribution of points on spheres
Authors: Cohn Henry , Kumar Abhinav
Published: October 2006

We study configurations of points on the unit sphere that minimize potential energy for a broad class of potential functions (viewed as functions of the squared Euclidean distance between points). Call a configuration sharp if there are

m
m

distances between distinct points in it and it is a spherical

(
2
m
−
1
)

(2m-1)

-design. We prove that every sharp configuration minimizes potential energy for all completely monotonic potential functions. Examples include the minimal vectors of the

E
8

E_8

and Leech lattices. We also prove the same result for the vertices of the

600
600

-cell, which do not form a sharp configuration. For most known cases, we prove that they are the unique global minima for energy, as long as the potential function is strictly completely monotonic. For certain potential functions, some of these configurations were previously analyzed by Yudin, Kolushov, and Andreev; we build on their techniques. We also generalize our results to other compact two-point homogeneous spaces, and we conclude with an extension to Euclidean space.
Boundary behavior of SLE
Authors: Kang Nam-Gyu
Published: October 2006

We show that the normalized (pre-)Schwarzian derivative of SLE, after we subtract a negligible term, is a complex BMO martingale. Its BMO norm gives strong evidence for Duplantier’s duality conjecture. We also show that it has correlations that decay exponentially in the hyperbolic distance. We reexamine S. Rohde and O. Schramm’s derivative expectation to derive the conjectured sharp estimate for the Hölder exponent unless the parameter of SLE is 4.
Atorvastatin interferes with activation of human CD4+ T cells via inhibition of small guanosine triphosphatase (GTPase) activity and caspase-independent apoptosis
Authors: Brinkkoetter P-T , Gottmann U , Schulte J , Van Der Woude F J , Braun C , Yard B A
Published: October 2006

Although a beneficial effect of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e. statins, on cell-mediated immunity has been suggested in vivo and in vitro, little is known about the molecular and biochemical events by which statins inhibit T cell proliferation. To address this question, we investigated the effects of atorvastatin (AT) on intracellular cytokine production, T cell activation markers, cell cycle progression and apoptosis in human CD4+ T cells. AT did not influence intracellular cytokine production after short-term stimulation of whole blood with phorbol myristate acetate (PMA)/ionomycin or superantigen (SEB). In contrast, AT influenced CD45RA to RO switching dose-dependently, as well as CD25 expression, and caused cell cycle arrest in the G1 phase after long-term T cell stimulation. This occurred in conjunction with a reduced expression of cyclin-dependent kinases 2 and 4 and p21wav1/cip1 and was paralleled by an increased protein expression of p27kip1. In addition to G1 arrest, increased apoptosis was observed in AT-treated cells. In line with this, the expression of Bcl-xl and pBad were decreased by AT. Apoptosis was independent of caspases 3 and 9 activation. The inhibitory effect of AT on T cell proliferation could be overcome by addition of mevalonic acid or geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate or squalen, suggesting reduced protein prenylation. Activation of Rho, Rac and Ras were strongly reduced in AT-treated T cells, suggesting that impaired geranylation of these molecules might underlie the inhibitory effect of AT on T cell proliferation.
The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to bacille Calmette–Guérin vaccination in southern England and northern Malawi
Authors: Weir R E , Black G F , Nazareth B , Floyd S , Stenson S , Stanley C , Branson K , Sichali L , Chaguluka S D , Donovan L , Crampin A C , Fine P E M , Dockrell H M
Published: October 2006

We report a large study of the effect of BCG vaccination on the in vitro 6-day whole blood interferon-gamma (IFN-γ) response to antigens from eight species of mycobacteria among schoolchildren in south-eastern England, where bacille Calmette–Guérin (BCG) vaccination is highly protective against pulmonary tuberculosis, and among young adults in northern Malawi, where BCG vaccination is not protective. In the UK children, BCG induced an appreciable increase in IFN-γ response to antigens from most species of mycobacteria. The degree of change was linked to the relatedness of the species to Mycobacterium bovis BCG, and provides further evidence of the cross-reactivity of mycobacterial species in priming of the immune system. IFN-γ responses to purified protein derivatives (PPDs) from M. tuberculosis and environmental mycobacteria were more prevalent in the Malawian than the UK group prior to vaccination; BCG vaccination increased the prevalence of responses to these PPDs in the UK group to a level similar to that in Malawi. There was no evidence that the vaccine-induced change in IFN-γ response was dependent upon the magnitude of the initial response of the individual to environmental mycobacteria in the United Kingdom or in Malawi. These observations should assist the development and interpretation of human clinical trials of new vaccines against M. tuberculosis in areas of both low and high exposure to environmental mycobacteria.
C-reactive protein is expressed and secreted by peripheral blood mononuclear cells
Authors: Haider D G , Leuchten N , Schaller G , Gouya G , Kolodjaschna J , Schmetterer L , Kapiotis S , Wolzt M
Published: October 2006

C-reactive protein (CRP) protects against bacterial pathogens and is a predictor of cardiovascular events. CRP is produced by vascular and organ-specific cells but the generation of CRP from peripheral blood mononuclear cells (PBMC) is poorly established. In a randomized, double-blind, placebo-controlled, two-way cross-over trial six healthy volunteers received a bolus infusion of 20 IU/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo. Intracellular CRP protein and CRP secretion of peripheral blood mononuclear cells (PBMC) was measured at baseline and 6 h after LPS by flow cytometry and enzyme-linked immubosorbent assay (ELISA), respectively. CRP mRNA expression was determined by real-time polymerase chain reaction (PCR). Regulation of the expression pathway was assessed using specific inhibitors in vitro. Small amounts of CRP protein and mRNA were detectable in PBMC, which were up-regulated between two- and eightfold by endotoxaemia in vivo. Augmented expression and release of CRP by LPS was consistent in PBMC cell culture experiments. LPS, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-α increased and IL-10 reduced CRP expression in PBMC. Toll-like receptor (TLR)-4, nuclear factor (NF)-κB and protein kinase C (PKC) activation were identified as intracellular signal transduction pathways of LPS-induced CRP expression. Constitutive CRP expression and release in PBMC is enhanced by inflammatory stimuli in vivo and in vitro. LPS might induce CRP generation via activation of TLR-4, NF-κB and PKC.
Inter‐sexual combat and resource allocation into body parts in the spider, Stegodyphus lineatus
Authors: MAKLAKOV ALEXEI A. , BILDE TRINE , LUBIN YAEL
Published: October 2006

Abstract 1. Sexual conflict, which results from the divergence of genetic interests between males and females, is predicted to affect multiple behavioural, physiological, and morphological traits.

2. Sexual conflict over mating may interact with population density to produce predictable changes in resource allocation into inter‐sexual armament.

3. In the spider Stegodyphus lineatus, males fight with females over re‐mating. The outcome of the fight is influenced by the cephalothorax size of the contestants. The investment in armament – the cephalothorax, may be traded‐off against investment in abdomen, which is a trait that affects survival and fecundity. Pay‐offs may depend on population density. Both sexes are expected to adjust resource allocation into different body parts accordingly.

4. Males had increased cephalothorax/body size ratio in low densities where probability of finding another receptive female is low and females had increased cephalothorax/body size ratio in high densities where cumulative costs of multiple mating are high.

5. The results support the theoretical conjecture that population density affects resource allocation into inter‐sexual armament and call for further research on the interaction between sexual selection and population density.
Ecological distribution and niche segregation of sibling species: the case of bean beetles, Acanthoscelides obtectus Say and A. obvelatus Bridwell
Authors: ALVAREZ NADIR , MERCIER LÉNY , HOSSAERT‐MCKEY MARTINE , CONTRERAS‐GARDUÑO JORGE , KUNSTLER GEORGES , AEBI ALEXANDRE , BENREY BETTY
Published: October 2006

Abstract 1. Molecular techniques have greatly added to the number of known sympatric cryptic species in insects. Ecological differences between these newly distinguished species are little explored, but niches often appear to overlap strongly. These cases are good models for exploring new ideas about species coexistence and community structure.

2. Acanthoscelides obtectus and A. obvelatus are two sister species of bean bruchids, which have been confused until the last decade. One important ecological difference between them has emerged, however: A. obtectus is multivoltine and now distributed worldwide, whereas A. obvelatus is univoltine and restricted to Mesoamerica. Where their ranges overlap, the two species share the same host plants and larvae can sometimes complete development in the same seed.

3. The analysis of 27 622 Mexican individuals of the two species in 2001‐2002 and 2002‐2003 indicates that their niches overlap, but are differentiated with respect to altitude and the kind of beans (wild vs. domesticated). The principal patterns in their relative abundance in different habitats, and at different seasons, were constant from one year to the next.

4. As sympatry of these species seems to be of recent origin, the observed niche differentiation may not have evolved in response to competition, but could instead be the consequence of physiological differences, evolved independently in each species in allopatry, that pre‐adapted them for different altitudes and kinds of resources.

5. The combination of biological and historical factors thus appears to allow these two sibling species to coexist in sympatry, despite their broadly overlapping ecological niches.
Effects of organic matter and calcium on soil structural stability
Authors: Wuddivira M. N. , Camps‐Roach G.
Published: October 2006

The cationic bridging effect of the calcium ion (Ca2+) and the flocculating ability of clay and organic matter are crucial in the formation and stability of soil aggregates. They are therefore likely to influence the soil’s saturated hydraulic conductivity (Ks). We tested the individual effects of these factors on aggregate stability and related hydraulic properties, and studied the influence of clay mineralogy also. Samples from the surface (0–10 cm) of three contrasting soils in Trinidad were used. The soils were treated with three levels of Ca2+ and three levels of organic matter in a 3 × 3 × 3 factorial design and incubated for 14 days. Both aggregate stability and saturated hydraulic conductivity were influenced by all factor combinations. Interactions between soil type and Ca2+ revealed the importance of polyvalent cations in aggregate stability of soils with low activity minerals. The influence of organic matter varied with quantity; the more there was, the more stable the soil became, particularly in the soil containing little clay. Clay dispersion and slaking of expanding minerals occurred even with large additions of Ca2+ and organic matter, emphasizing the overall influence of mineralogy in determining the response of soils to stability treatments.
Inference about soil variability from the structure of the best wavelet packet basis
Authors: Lark R. M.
Published: October 2006

The plausibility of the assumption that soil variation can be treated as a realization of a random spatial process that is stationary in the variance can break down in various ways. It is possible to test the assumption using methods based on the wavelet transform. To date these approaches have been applied using the discrete wavelet transform. A drawback of this approach is that it uses a partition of the spatial frequencies represented in the data into intervals (scales) that are arbitrarily defined in advance and are not necessarily suitable for the representation of the variation of the data in question. A solution to this problem is to identify the best basis for the data from a wavelet packet library. An interesting question is whether the structure of this best basis is in itself informative about the plausibility of the stationarity assumption. In this paper, I show that this is indeed the case. The best basis for a stationary random variable from some packet library is the basis on the maximum dilation of the mother wavelet, which gives the finest resolution in the frequency domain. I propose the ratio of the entropy cost functional for this basis to that of the empirical best basis as a measure of evidence against the null hypothesis of stationarity in the variance. Critical values of this statistic may be obtained by Monte Carlo methods. I demonstrate the method using data on the clay content of soil on a transect in central England. The null hypothesis of stationarity in the variance may be rejected. Tests for the uniformity of variance can then be applied to wavelet packets in the best basis. The dominant local feature that is reflected in this behaviour is the unique pattern of variation in alluvium around a drainage channel that crosses the transect. This variation contrasts with that seen at most positions on the transect, variation that arises from a more or less regular pattern of boundaries between contrasting Jurassic strata.
Comparison of methods for estimating the spread of a non‐indigenous species
Authors: Tobin Patrick C. , Liebhold Andrew M. , Anderson Roberts E.
Published: October 2006

Aim To compare different quantitative approaches for estimating rates of spread in the exotic species gypsy moth,Lymantria disparL., using county‐level presence/absence data and spatially extensive trapping grids.

Location USA

Methods We used county‐level presence/absence records of the gypsy moth's distribution in the USA, which are available beginning in 1900, and extensive grids of pheromone‐baited traps, which are available in selected areas beginning in 1981. We compared a regression approach and a boundary displacement approach for estimating gypsy moth spread based on these sources of data.

Results We observed relative congruence between methods and data sources in estimating overall rates of gypsy moth spread through time, and among regions.

Main conclusions The ability to estimate spread in exotic invasive species is a primary concern in management programmes and one for which there is a lack of information on the reliability of methods. Also, in most invading species, there is generally a lack of data to explore methods of estimating spread. Extensive data available on gypsy moth in the USA allowed for such a comparison. We show that, even with spatially crude records of presence/absence, overall rates of spread do not differ substantially from estimates obtained from the more costly deployment of extensive trapping grids. Moreover, these methods can also be applied to the general study of species distributional changes, such as range expansion or retraction, in response to climate change or other environmental effects.
Modern pollen–vegetation relationships in subarctic southern Greenland and the interpretation of fossil pollen data from the Norselandnám
Authors: Edward Schofield J. , Edwards Kevin J. , Andy McMullen J.
Published: October 2006

Aim The objective of this paper is to explore the relationships that exist between vegetation and modern pollen rain in the open, largely treeless landscape of subarctic Greenland. The implications of these results for the interpretation of fossil pollen assemblages from the time of the Norselandnámare then examined.

Location The study area is the sheep farming district of Qassiarsuk in the subarctic, subcontinental vegetational and climatic zone of southern Greenland (61° N, 45° W). Betweenc.ad1000–1500 this region was contained within the Norse Eastern Settlement.

Methods Detrended Correspondence Analysis (DCA) of harmonized plant–pollen data sets is used to compare plant cover in 64 vegetation quadrats with pollen assemblages obtained from moss polsters at matching locations. Presence/absence data are also used to calculate indices of association, over‐ and under‐representation for pollen types.

Results Good correspondence between paired vegetation–pollen samples occurs in many cases, particularly in locations whereSalix glauca–Betula glandulosadwarf shrub heath is dominant, and across herbaceous field boundaries and meadows. Pollen samples are found to be poor at reflecting actual ground cover where ericales orJuniperus communisare the locally dominant shrubs. Dominant or ubiquitous taxa within this landscape (Betula,Salixand Poaceae) are found to be over‐represented in pollen assemblages, as are several of the ‘weeds’ generally accepted as introduced by the Norse settlers.

Main conclusions Due to their over‐representation in the pollen rain, many of the Norse apophytes and introductions (e.g.Rumex acetosaandR. acetosella) traditionally used to infer human activity in Greenland should be particularly sensitive indicators forlandnám, allowing early detection of Norse activity in fossil assemblages. Pteridophyte spores are found to be disassociated with the ground cover of ferns and clubmosses, but are over‐represented in pollen assemblages, indicating extra‐local or regional sources and long residence times in soil/sediment profiles for these microfossils. A pollen record forHordeum‐type registered in close proximity to a field containing barley suggests that summer temperatures under the current climatic regime are, at least on occasion, sufficient to allow flowering.
Neisseria gonorrhoeae requires expression of TonB and the putative transporter TdfF to replicate within cervical epithelial cells
Authors: Hagen Tracey A. , Cornelissen Cynthia Nau
Published: October 2006

Neisseria gonorrhoeae has evolved a repertoire of iron acquisition systems that facilitate essential iron uptake in the human host. Acquisition of iron requires both the energy‐harnessing cytoplasmic membrane protein, TonB, as well as specific outer membrane TonB‐dependent transporters (TdTs.) Survival within host epithelial cells is important to the pathogenesis of gonococcal disease and may contribute to the persistence of infection. However, the mechanisms by which gonococci acquire iron within this intracellular niche are not currently understood. In this study, we investigated the survival of gonococcal strain FA1090 within ME180 human cervical epithelial cells with respect to high affinity iron acquisition. Intracellular survival was dependent upon iron supplied by the host cell. TonB was expressed in the host cell environment and this protein was critical to gonococcal intracellular survival. Furthermore, expression of the characterized outer membrane transporters TbpA, FetA and LbpA and putative transporters TdfG, TdfH and TdfJ were not necessary for intracellular survival. Conversely, intracellular survival was dependent on expression of the putative transporter, TdfF. Expression of TdfF was detected in the presence of epithelial cell culture media containing fetal bovine serum. Expression was further modulated by iron availability. To our knowledge, this study is the first to demonstrate the specific requirement for a single iron transporter in the survival of a bacterial pathogen within host epithelial cells.
Functional studies of the Ssk1p response regulator protein of Candida albicans as determined by phenotypic analysis of receiver domain point mutants
Authors: Menon Veena , Li Dongmei , Chauhan Neeraj , Rajnarayanan Rajendram , Dubrovska Alla , West Ann H. , Calderone Richard
Published: October 2006

The Candida albicans response regulator protein Ssk1p regulates oxidant adaptation through the MAPK HOG1 pathway. Deletion mutants lacking SSK1 are oxidant sensitive in vitro and are killed more than wild‐type (WT) cells by human neutrophils. Furthermore, the mutants are avirulent in an invasive murine model, and unable to adhere to human esophageal cells. Transcriptional profiling has indicated that approximately 25% of all changes occur in genes encoding cell wall and stress adaptation functions. In this study, we have investigated the role of amino acid residues in the Ssk1p receiver (or regulatory) domain by constructing point mutants at positions D556 (putative site of protein phosphorylation) and D513 (putative role in divalent metal binding, phosphorylation and conformational switching). For each point mutant, their sensitivity to a variety of oxidant stress conditions was assessed and correlated with in vitro phosphorylation of each Ssk1p receiver domain, phosphorylation of the Hog1p MAP kinase, and translocation to the nucleus. We show that a D556N mutant is sensitive to 5 mM H2O2 or t‐butyl hydroperoxide, similar to a gene knock‐out ssk1 mutant, even though Hog1p is phosphorylated in the D556N mutant. To resolve this apparent paradox, we also demonstrate that Hog1p translocation to the nucleus in the D556N mutant is significantly reduced compared with WT cells (CAF2‐1). In a second point mutant, D513 was changed to a lysine residue (D513K). This mutant had WT levels of resistance to peroxide, but in comparison to WT cells and the D556N mutant, morphogenesis (yeast to hyphae transition) was inhibited in 10% serum or in M‐199 medium at 37°C. In the D513K point mutant, constitutive phosphorylation of Hog1p was observed, suggesting that a non‐conservative change (D513K) traps Ssk1p in an active conformation and therefore constitutive Hog1p phosphorylation. The inhibition of morphogenesis in D513K is related to a downregulation of the transcription factors of morphogenesis, EFG1 and CPH1. Another non‐conserved point mutant (D556R) was also constructed and phenotypically was like the D513K mutant. The receiver domains of the D556N and the D513K mutants could not be appreciably phosphorylated in vitro indicating that constitutive activation of Hog1p occurs in vivo due to the inability of Ssk1p to be phosphorylated at least in the D513K mutant. We speculate that the non‐conservative changes described above in Ssk1p response regulator may cause conformational changes in the Ssk1p that account for phenotype differences compared with the D556N mutant that are also Hog‐independent.
Acyl carrier protein/SpoT interaction, the switch linking SpoT‐dependent stress response to fatty acid metabolism
Authors: Battesti Aurélia , Bouveret Emmanuelle
Published: October 2006

Bacteria respond to nutritional stresses by producing an intracellular alarmone, guanosine 5′‐(tri)diphosphate, 3′‐diphosphate [(p)ppGpp], which triggers the stringent response resulting in growth arrest and expression of resistance genes. In Escherichia coli, upon fatty acid or carbon starvation, SpoT enzyme activity switches from (p)ppGpp degradation to (p)ppGpp synthesis, but the signal and mechanism for this response remain totally unknown. Here, we characterize for the first time a physical interaction between SpoT and acyl carrier protein (ACP) using affinity co‐purifications and two‐hybrid in E. coli. ACP, as a central cofactor in fatty acid synthesis, may be an ideal candidate as a mediator signalling starvation to SpoT. Accordingly, we show that the ACP/SpoT interaction is specific of SpoT and ACP functions because ACP does not interact with the homologous RelA protein and because SpoT does not interact with a non‐functional ACP. Using truncated SpoT fusion proteins, we demonstrate further that ACP binds the central TGS domain of SpoT, consistent with a role in regulation. The behaviours of SpoT point mutants that do not interact with ACP reveal modifications of the balance between the two opposite SpoT catalytic activities thereby changing (p)ppGpp levels. More importantly, these mutants fail to trigger (p)ppGpp accumulation in response to fatty acid synthesis inhibition, supporting the hypothesis that the ACP/SpoT interaction may be involved in SpoT‐dependent stress response. This leads us to propose a model in which ACP carries information describing the status of cellular fatty acid metabolism, which in turn can trigger the conformational switch in SpoT leading to (p)ppGpp accumulation.
The causes and consequences of variation in offspring size: a case study usingDaphnia
Authors: GUINNEE M. A. , GARDNER A. , HOWARD A. E. , WEST S. A. , LITTLE T. J.
Published: October 2006

Offspring size can have large and direct fitness implications, but we still do not have a complete understanding of what causes offspring size to vary.Daphnia(water fleas) generally produce fewer and larger offspring when food is limited. Here, we use a mathematical model to show that this could be explained by either: (1) an advantage of producing larger eggs when food is limited; or (2) a lower boundary on egg volume (below which eggs do not have sufficient resources to be viable), that is similar in volume to the evolutionarily stable egg volume predicted by standard clutch size models. We tested the first possibilities experimentally by placing offspring from mothers kept at two food treatments (high and low – leading to relatively small and large eggs respectively) into two food treatments (same as maternal treatments, in a fully factorial design) and measuring their fitness (reproduction, age at maturity, and size at maturity). We also tested survival under starvation conditions of offspring produced from mothers at low and high food treatments. We found that (larger) offspring produced by low‐food mothers actually had lower fitness as they took longer to reproduce, regardless of their current food treatment. Additionally, we found no survival advantage to being born of a food‐stressed mother. Consequently, our results do not support the hypothesis that there is an advantage to producing larger eggs when food is limited. In contrast, data from the literature support the importance of a lower boundary on egg size.
Brain‐derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment
Authors: Rossi Chiara , Angelucci Andrea , Costantin Laura , Braschi Chiara , Mazzantini Mario , Babbini Francesco , Fabbri Maria Elena , Tessarollo Lino , Maffei Lamberto , Berardi Nicoletta , Caleo Matteo
Published: October 2006

Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain‐derived neurotrophic factor (BDNF+/–) and mice lacking neurotrophin‐4 (NT‐4–/–) together with their wild‐type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild‐type and enriched NT‐4–/– mice showed a two‐fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU‐positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/– mice. Failure to up‐regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT‐4 is required for the environmental induction of neurogenesis.
Mechanisms involved in modulation of trigeminal primary afferent activity in rats with peripheral mononeuropathy
Authors: Kitagawa Junichi , Takeda Mamoru , Suzuki Ikuko , Kadoi Jun , Tsuboi Yoshiyuki , Honda Kuniya , Matsumoto Shigeji , Nakagawa Hiroshi , Tanabe Aya , Iwata Koichi
Published: October 2006

In order to clarify the mechanisms underlying the changes in primary afferent neurons in trigeminal neuropathic pain, a chronic constriction nerve injury model of the infraorbital nerve (ION‐CCI) was developed in rats. Mechanical allodynia was observed at 3 days after ION‐CCI and lasted more than 14 days. Single‐unit activities were recorded from the ION of anesthetized rats. C‐, Aβ‐ and Aδ‐units were identified on the basis of their conduction velocity. Aδ‐units were frequently encountered at a later period after ION‐CCI. The highest Aδ‐spontaneous activity was recorded at 3 days after ION‐CCI and progressively decreased after that, but spontaneous activity was still higher at 14 days after ION‐CCI than that of naïve rats. Mechanical‐evoked responses of Aδ‐units were also highest at 3 days after ION‐CCI and then gradually decreased. In consideration of these data, patch‐clamp recordings were performed on medium to large size neurons of the dissociated trigeminal ganglion (TRG). Patch‐clamp recordings revealed that the IK (sustained) and IA (transient) in rats with ION‐CCI were significantly smaller than those of naïve rats, and correlated with an increase in duration of repolarization phase and a decrease in duration of depolarization phase, respectively. The hyperpolarization‐activated current (Ih) was significantly larger in TRG neurons of rats with ION‐CCI as compared with those of naïve rats. The present results suggest that Ih, IK and IA in Aδ‐afferent neurons in TRG are significantly involved in the changes in afferent spontaneous activity and mechanically evoked activity that accompany mechanical allodynia produced by trigeminal nerve injury.
Activation of muscarinic cholinergic receptors inhibits giant neurones in the caudal pontine reticular nucleus
Authors: Bosch Daniel , Schmid Susanne
Published: October 2006

Giant neurones in the caudal pontine reticular nucleus (PnC) play a crucial role in mediating the mammalian startle response. They receive input from cochlear, trigeminal and vestibular nuclei and project directly to motoneurones. Furthermore, they integrate modulatory input from different brain regions either enhancing or inhibiting startle responses. One prominent startle modulation is prepulse inhibition where a non‐startling stimulus presented prior to the startle stimulus inhibits a subsequent startle response. Several behavioural studies have indicated that this inhibition is mediated by muscarinic receptors at the level of the PnC. Here, we performed whole‐cell patch‐clamp recordings from PnC giant neurones in acute rat brain slices in order to examine muscarinic inhibition. We stimulated afferent trigeminal and auditory fibres and applied muscarinic agonists and antagonists in order to investigate their effect on excitatory postsynaptic current amplitudes, paired‐pulse ratio and passive membrane properties of PnC giant neurones. The cholinergic agonist carbachol and the muscarinic agonist oxotremorine significantly reduced excitatory postsynaptic current amplitudes and increased the paired‐pulse ratio. Carbachol additionally reduced the membrane resistance of postsynaptic PnC giant neurones. The subtype‐specific antagonists AF‐DX116 (M2 preferring) and tropicamide (M4 preferring) antagonized the oxotremorine effect indicating that M4 and possibly M2 receptor subtypes are involved in this inhibition. The G‐protein‐activated inward rectifying potassium channel blocker tertiapin‐Q had no effect on oxotremorine‐induced inhibition of giant neurones. Our results show a mainly presynaptically mediated strong inhibition of PnC giant neurones by activation of M4 and possibly M2 receptors that presumably contribute to prepulse inhibition.
Neuropathic pain and the endocannabinoid system in the dorsal raphe: pharmacological treatment and interactions with the serotonergic system
Authors: Palazzo Enza , De Novellis Vito , Petrosino Stefania , Marabese Ida , Vita Daniela , Giordano Catia , Di Marzo Vincenzo , Mangoni Giuseppe Salvatore , Rossi Francesco , Maione Sabatino
Published: October 2006

We used a model of neuropathic pain consisting of rats with chronic constriction injury (CCI) of the sciatic nerve, in order to investigate whether endocannabinoid levels are altered in the dorsal raphe (DR) and to assess the effect of repeated treatment with (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl)pyrrolo[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐naphthalenylmethanone mesylate, a synthetic cannabinoid agonist, or N‐(4‐hydroxyphenyl)‐5Z,8Z,11Z,14Z‐eicosatetraenamide (AM404), an inhibitor of endocannabinoid reuptake, on DR serotonergic neuronal activity and on behavioural hyperalgesia. CCI resulted in significantly elevated anandamide but not 2‐arachidonoylglycerol levels in the DR. Furthermore, as well as thermal and mechanical hyperalgesia, CCI caused serotonergic hyperactivity (as shown by the increase of basal activity of serotonergic neurones, extracellular serotonin levels and expression of 5‐HT1Areceptor gene). Repeated treatment with either (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl)pyrrolo[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐naphthalenylmethanone mesylate or AM404 reverted the hyperalgesia and enhanced serotonergic activity induced by CCI in a way attenuated by N‐piperidino‐5‐(4‐chlorophenyl)‐1‐(2,4dichlorophenyl)‐4‐methyl‐3‐pyrazolecarboxamide, a selective cannabinoid subtype 1 (CB1) receptor antagonist. Despite the elevated levels of anandamide following CCI, N‐piperidino‐5‐(4‐chlorophenyl)‐1‐(2,4dichlorophenyl)‐4‐methyl‐3‐pyrazolecarboxamide did not produce hyperalgesia or any other effect on serotonergic neuronal activity when administered alone. Furthermore, the effects of AM404 were not accompanied by an increase in endocannabinoid levels in the DR. In conclusion, following CCI of the sciatic nerve, the endocannabinoid and serotonergic systems are activated in the DR, where repeated stimulation of CB1receptors with exogenous compounds restores DR serotonergic activity, as well as thermal and mechanical nociceptive thresholds, to pre‐surgery levels. However, an elevated level of endogenous anandamide in the DR does not necessarily contribute to the CB1‐mediated tonic control of analgesia and serotonergic neuronal activity.