bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic network for the clock of
Neurospora crassa
Authors: Yu Yihai , Dong Wubei , Altimus Cara , Tang Xiaojia , Griffith James , Morello Melissa , Dudek Lisa , Arnold Jonathan , Schüttler Heinz-Bernd
Published: February 2007

A diverse array of organisms from bacteria to humans may have evolved the ability to tell time in the presence or absence of external environmental cues. In the lowly bread mould,
Neurospora crassa
, biomolecular reactions involving the
white-collar-1
(
wc-1
),
white-collar-2
(
wc-2
), and
frequency
(
frq
) genes and their products constitute building blocks of a biological clock. Here we use genetic network models to explain quantitatively, from a systems perspective, how these building blocks interact, and how a complex trait like clock oscillation emerges from these interactions. We use a recently developed method of genetic network identification to find an ensemble of oscillating network models quantitatively consistent with available RNA and protein profiling data on the
N. crassa
clock. Predicted key features of the
N. crassa
clock system are a dynamically frustrated closed feedback loop, cooperativity in
frq
gene activation, and/or WC-1/WC-2 protein complex deactivation and substantial posttranscriptional enhancement of
wc-1
RNA lifetime. Measuring the
wc-1
mRNA lifetime provides a critical test of the genetic networks.
VEGF kinoid vaccine, a therapeutic approach against tumor angiogenesis and metastases
Authors: Rad Farhad Haghighi , Le Buanec Hélène , Paturance Sébastien , Larcier Patrick , Genne Philippe , Ryffel Bernhard , Bensussan Armand , Bizzini Bernard , Gallo Robert C. , Zagury Daniel , Uzan Georges
Published: February 2007

Tumor growth depends on blood supply, requiring the development of new vessels, and vascular endothelial growth factor (VEGF) plays a central role in neoangiogenic processes. For this reason, VEGF represents a target for the development of new therapeutic antiangiogenic molecules. Clinical trials using anti-VEGF mAbs such as bevacizumab have validated the efficacy of this therapeutic approach but have also revealed adverse effects. Here we report that a VEGF-derived immunogen, consisting of a heterocomplex of a murine (m)VEGF and keyhole limpet hemocyanin, called “mVEGF kinoid,” triggered a strong Ab immune response in mice. The anti-VEGF Abs inhibited both the proliferation of human umbilical vein endothelial cells cultured in the presence of mVEGF and the binding of mVEGF to its receptor-2 Flk-1. In mVEGF kinoid-immunized BALB/c mice challenged with syngeneic CT26 colorectal tumor cells, the number and size of lung metastases were significantly decreased. In human (h)VEGF kinoid-immunized BALB/c mice, high levels of serum Abs to hVEGF were present, and purified IgG from these mice decreased by ≥50% the tumor growth of human A673 rhabdomyosarcoma cells and HT29 colon carcinoma xenografted in Swiss nude and NOD/SCID mice, respectively. Tumor cell growth inhibition was similar to that observed in mice receiving therapeutic doses of bevacizumab. These experiments suggest that a therapeutic vaccine containing VEGF kinoid may represent a strategy for safely combating VEGF-dependent neovascularization and metastases occurring in malignant tumors.
Adaptive climatic molecular evolution in wild barley at the
Isa
defense locus
Authors: Cronin James K. , Bundock Peter C. , Henry Robert J. , Nevo Eviatar
Published: February 2007

Wild barley (
Hordeum spontaneum
) represents a significant genetic resource for crop improvement in barley (
Hordeum vulgare
) and for the study of the evolution and domestication of plant populations. The
Isa
gene from barley has a putative role in plant defense. This gene encodes a bifunctional α-amylase/subtilisin inhibitor that inhibits the bacterial serine protease subtilisin, fungal xylanase, and the plant's own α-amylase. The inhibition of plant α-amylases suggests this protein may also be important for grain quality from a human perspective. We identified 16 SNPs in the coding region of the
Isa
locus of 178 wild barley accessions from eight climatically divergent sites across Israel. The pattern of SNPs suggested a large number of recombination events within this gene, indicating that the low-outcrossing rate of wild barley is not a barrier to recombinant haplotypes becoming established in the population. Seven amino acid substitutions were present in the coding region. Genetic diversity for each population was calculated by using Nei's diversity index, and a Spearman rank correlation was carried out to test the association between gene diversity and 16 ecogeographical factors. Highly significant correlations were found between diversity at the
Isa
locus and key water variables, evaporation, rainfall, humidity, and latitude. The pattern of association suggests selective sweeps in the wetter climates, with resulting low diversity and weaker selection or diversifying selection in the dryer climates resulting in much higher diversity.
The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain
Authors: Ugolini Gabriele , Marinelli Sara , Covaceuszach Sonia , Cattaneo Antonino , Pavone Flaminia
Published: February 2007

Nerve growth factor (NGF) is involved in pain transduction mechanisms and plays a key role in many persistent pain states, notably those associated with inflammation. On this basis, both the NGF ligand and its receptor TrkA (tyrosine kinase A) represent an eligible target for pain therapy. Although the direct involvement of NGF in pain modulation is well established, the effect of a direct functional block of the TrkA receptor is still unknown. In this study, we have demonstrated that MNAC13, the only anti-TrkA monoclonal antibody for which function neutralizing properties have been clearly shown both
in vitro
and
in vivo
, induces analgesia in both inflammatory and neuropathic pain models, with a surprisingly long-lasting effect in the latter. The formalin-evoked pain licking responses are significantly reduced by the MNAC13 antibody in CD1 mice. Remarkably, treatment with the anti-TrkA antibody also produces a significant antiallodynic effect on neuropathic pain: repeated i.p. injections of MNAC13 induce significant functional recovery in mice subjected to sciatic nerve ligation, with effects persisting after administration. Furthermore, a clear synergistic effect is observed when MNAC13 is administered in combination with opioids, at doses that are not efficacious
per se
. This study represents a direct demonstration that neutralizing antibodies directed against the TrkA receptor may display potent analgesic effects in inflammatory and chronic pain.
DDB1 is essential for genomic stability in developing epidermis
Authors: Cang Yong , Zhang Jianxuan , Nicholas Sally A. , Kim Arianna L. , Zhou Pengbo , Goff Stephen P.
Published: February 2007

The mammalian epidermis is maintained by proliferation and differentiation of epidermal progenitor cells in a stereotyped developmental program. Here we report that tissue-specific deletion of the UV-damaged DNA-binding protein 1 (DDB1) in mouse epidermis led to dramatic accumulation of c-Jun and p21Cip1, arrest of cell cycle at G
2
/M, selective apoptosis of proliferating cells, and as a result, a nearly complete loss of the epidermis and hair follicles. Deletion of the p53 tumor suppressor gene partially rescued the epithelial progenitor cells from death and allowed for the accumulation of aneuploid cells in the epidermis. Our results suggest that DDB1 plays an important role in development by controlling levels of cell cycle regulators and thereby maintaining genomic stability.
Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities
Authors: Moore David F. , Krokhin Oleg V. , Beavis Ronald C. , Ries Markus , Robinson Chevalia , Goldin Ehud , Brady Roscoe O. , Wilkins John A. , Schiffmann Raphael
Published: February 2007

Fabry disease is inherited as an X-linked disorder secondary to deficiency of α-galactosidase A, resulting in abnormal metabolism of substances containing α-
d
-galactosyl moieties. As a consequence, a multisystem disorder develops, culminating in strokes, progressive renal, and cardiac dysfunction. Signs and symptoms of Fabry disease become manifest in childhood, but diagnosis is often delayed. Thirteen children with Fabry disease (age range, 6.5–17 years) were studied as part of a 6-month open-label study of enzyme replacement therapy (ERT) with agalsidase alfa. Paired serum samples were drawn at the start of the study and after 6 months of ERT. Global protein changes in paired samples were compared by using differential stable isotope labeling of peptide lysine residues with
O
-methylisourea and subsequent nanoHPLC–tandem MS. Statistically significant decreases were observed for five proteins following ERT: α
2
-HS glycoprotein, vitamin D-binding protein, transferrin, Ig-α-2 C chain, and α-2-antiplasmin. The presence of low levels of α-2-antiplasmin and plasminogen was confirmed by alternate means in 34 consecutive patients, including four of five ERT-naïve subjects. Decreased α-2-antiplasmin was associated with a parallel increase in circulating VEGF. Soluble VEGF receptor-2 was significantly elevated in plasma of patients compared with pediatric controls and decreased with ERT. These results suggest previously unknown abnormalities of fibrinolysis and angiogenesis factors in Fabry disease. We demonstrated the feasibility of identifying treatment-specific alterations in a small number of subjects that point to previously unsuspected disease-related biological abnormalities.
Munc18-1 binds directly to the neuronal SNARE complex
Authors: Dulubova Irina , Khvotchev Mikhail , Liu Siqi , Huryeva Iryna , Südhof Thomas C. , Rizo Josep
Published: February 2007

Both SM proteins (for Sec1/Munc18-like proteins) and SNARE proteins (for soluble NSF-attachment protein receptors) are essential for intracellular membrane fusion, but the general mechanism of coupling between their functions is unclear, in part because diverse SM protein/SNARE binding modes have been described. During synaptic vesicle exocytosis, the SM protein Munc18-1 is known to bind tightly to the SNARE protein syntaxin-1, but only when syntaxin-1 is in a closed conformation that is incompatible with SNARE complex formation. We now show that Munc18-1 also binds tightly to assembled SNARE complexes containing syntaxin-1. The newly discovered Munc18-1/SNARE complex interaction involves contacts of Munc18-1 with the N-terminal H
abc
domain of syntaxin-1 and the four-helical bundle of the assembled SNARE complex. Together with earlier studies, our results suggest that binding of Munc18-1 to closed syntaxin-1 is a specialization that evolved to meet the strict regulatory requirements of neuronal exocytosis, whereas binding of Munc18-1 to assembled SNARE complexes reflects a general function of SM proteins involved in executing membrane fusion.
Toward understanding phosphoseryl-tRNA
Cys
formation: The crystal structure of
Methanococcus maripaludis
phosphoseryl-tRNA synthetase
Authors: Kamtekar Satwik , Hohn Michael J. , Park Hee-Sung , Schnitzbauer Michael , Sauerwald Anselm , Söll Dieter , Steitz Thomas A.
Published: February 2007

A number of archaeal organisms generate Cys-tRNA
Cys
in a two-step pathway, first charging phosphoserine (Sep) onto tRNA
Cys
and subsequently converting it to Cys-tRNA
Cys
. We have determined, at 3.2-Å resolution, the structure of the
Methanococcus maripaludis
phosphoseryl-tRNA synthetase (SepRS), which catalyzes the first step of this pathway. The structure shows that SepRS is a class II, α
4
synthetase whose quaternary structure arrangement of subunits closely resembles that of the heterotetrameric (αβ)
2
phenylalanyl-tRNA synthetase (PheRS). Homology modeling of a tRNA complex indicates that, in contrast to PheRS, a single monomer in the SepRS tetramer may recognize both the acceptor terminus and anticodon of a tRNA substrate. Using a complex with tungstate as a marker for the position of the phosphate moiety of Sep, we suggest that SepRS and PheRS bind their respective amino acid substrates in dissimilar orientations by using different residues.
Properties of glutamate receptors of Alzheimer's disease brain transplanted to frog oocytes
Authors: Bernareggi Annalisa , Dueñas Zulma , Reyes-Ruiz Jorge Mauricio , Ruzzier Fabio , Miledi Ricardo
Published: February 2007

It is known that Alzheimer's disease (AD) is a synaptic disease that involves various neurotransmitter systems, particularly those where synaptic transmission is mediated by acetylcholine or glutamate (Glu). Nevertheless, very little is known about the properties of neurotransmitter receptors of the AD human brain. We have shown previously that cell membranes, carrying neurotransmitter receptors from the human postmortem brain, can be transplanted to frog oocytes, and their receptors will still be functional. Taking advantage of this fact, we have now studied the properties of Glu receptors (GluRs) from the cerebral cortices of AD and non-AD brains and found that oocytes injected with AD membranes acquired GluRs that have essentially the same functional properties as those of oocytes injected with membranes from non-AD brains. However, the amplitudes of the currents elicited by Glu were always smaller in the oocytes injected with membranes from AD brains. Western blot analyses of the same membrane preparations used for the electrophysiological studies showed that AD membranes contained significantly fewer GluR2/3 subunit proteins. Furthermore, the corresponding mRNAs were also diminished in the AD brain. Therefore, the smaller amplitude of membrane currents elicited by Glu in oocytes injected with membranes from an AD brain is a consequence of a reduced number of GluRs in cell membranes transplanted from the AD brain. Thus, using the comparatively simple method of microtransplantation of receptors, it is now possible to determine the properties of neurotransmitter receptors of normal and diseased human brains. That knowledge may help to decipher the etiology of the diseases and also to develop new treatments.
Arabidopsis
intragenomic conserved noncoding sequence
Authors: Thomas Brian C. , Rapaka Lakshmi , Lyons Eric , Pedersen Brent , Freeling Michael
Published: February 2007

After the most recent tetraploidy in the
Arabidopsis
lineage, most gene pairs lost one, but not both, of their duplicates. We manually inspected the 3,179 retained gene pairs and their surrounding gene space still present in the genome using a custom-made viewer application. The display of these pairs allowed us to define intragenic conserved noncoding sequences (CNSs), identify exon annotation errors, and discover potentially new genes. Using a strict algorithm to sort high-scoring pair sequences from the bl2seq data, we created a database of 14,944 intragenomic
Arabidopsis
CNSs. The mean CNS length is 31 bp, ranging from 15 to 285 bp. There are ≈1.7 CNSs associated with a typical gene, and
Arabidopsis
CNSs are found in all areas around exons, most frequently in the 5′ upstream region. Gene ontology classifications related to transcription, regulation, or “response to …” external or endogenous stimuli, especially hormones, tend to be significantly overrepresented among genes containing a large number of CNSs, whereas protein localization, transport, and metabolism are common among genes with no CNSs. There is a 1.5% overlap between these CNSs and the 218,982 putative RNAs in the
Arabidopsis
Small RNA Project database, allowing for two mismatches. These CNSs provide a unique set of noncoding sequences enriched for function. CNS function is implied by evolutionary conservation and independently supported because CNS-richness predicts regulatory gene ontology categories.
Cytokine Stimulation Promotes Glucose Uptake via Phosphatidylinositol-3 Kinase/Akt Regulation of Glut1 Activity and Trafficking
Authors: Wieman Heather L. , Wofford Jessica A. , Rathmell Jeffrey C.
Published: February 2007

Cells require growth factors to support glucose metabolism for survival and growth. It is unclear, however, how noninsulin growth factors may regulate glucose uptake and glucose transporters. We show that the hematopoietic growth factor interleukin (IL)3, maintained the glucose transporter Glut1 on the cell surface and promoted Rab11a-dependent recycling of intracellular Glut1. IL3 required phosphatidylinositol-3 kinase activity to regulate Glut1 trafficking, and activated Akt was sufficient to maintain glucose uptake and surface Glut1 in the absence of IL3. To determine how Akt may regulate Glut1, we analyzed the role of Akt activation of mammalian target of rapamycin (mTOR)/regulatory associated protein of mTOR (RAPTOR) and inhibition of glycogen synthase kinase (GSK)3. Although Akt did not require mTOR/RAPTOR to maintain surface Glut1 levels, inhibition of mTOR/RAPTOR by rapamycin greatly diminished glucose uptake, suggesting Akt-stimulated mTOR/RAPTOR may promote Glut1 transporter activity. In contrast, inhibition of GSK3 did not affect Glut1 internalization but nevertheless maintained surface Glut1 levels in IL3-deprived cells, possibly via enhanced recycling of internalized Glut1. In addition, Akt attenuated Glut1 internalization through a GSK3-independent mechanism. These data demonstrate that intracellular trafficking of Glut1 is a regulated component of growth factor-stimulated glucose uptake and that Akt can promote Glut1 activity and recycling as well as prevent Glut1 internalization.
Making good choices with variable information: a stochastic model for nest-site selection by honeybees
Authors: Perdriau Benjamin S , Myerscough Mary R
Published: February 2007

A density-dependent Markov process model is constructed for information transfer among scouts during nest-site selection by honeybees (Apis mellifera). The effects of site quality, competition between sites and delays in site discovery are investigated. The model predicts that bees choose the better of two sites more reliably when both sites are of low quality than when both sites are of high quality and that delay in finding a second site has most effect on the final choice when both sites are of high quality. The model suggests that stochastic effects in honeybee nest-site selection confer no advantage on the swarm.
Green swordtails alter their age at maturation in response to the population level of male ornamentation
Authors: Walling Craig A , Royle Nick J , Metcalfe Neil B , Lindström Jan
Published: February 2007

Effects of the social environment on age at sexual maturation are assumed to require direct interactions, such as suppression of subordinates through aggression from dominants. Using green swordtails (
Xiphophorus helleri
), we demonstrate for the first time that females and males adjust their age at maturation in response to visual cues of male sexual ornamentation in the current environment: females matured earlier, whereas males matured later if all the mature males seen had large ornaments. Thus, age at maturation shifted in accordance with the perceived quality of mates (females) or mating competitors (males), demonstrating a capability to use visual cues from the environment to strategically adjust rates of sexual development.
A private allele ubiquitous in the Americas
Authors: Schroeder K.B , Schurr T.G , Long J.C , Rosenberg N.A , Crawford M.H , Tarskaia L.A , Osipova L.P , Zhadanov S.I , Smith D.G
Published: February 2007

The three-wave migration hypothesis of Greenberget al. has permeated the genetic literature on the peopling of the Americas. Greenberget al. proposed that Na-Dene, Aleut-Eskimo and Amerind are language phyla which represent separate migrations from Asia to the Americas. We show that a unique allele at autosomal microsatellite locus D9S1120 is present in all sampled North and South American populations, including the Na-Dene and Aleut-Eskimo, and in related Western Beringian groups, at an average frequency of 31.7%. This allele was not observed in any sampled putative Asian source populations or in other worldwide populations. Neither selection nor admixture explains the distribution of this regionally specific marker. The simplest explanation for the ubiquity of this allele across the Americas is that the same founding population contributed a large fraction of ancestry to all modern Native American populations.
Time-dependent spectral analysis of epidemiological time-series with wavelets
Authors: Cazelles Bernard , Chavez Mario , Magny Guillaume Constantin de , Guégan Jean-Francois , Hales Simon
Published: February 2007

In the current context of global infectious disease risks, a better understanding of the dynamics of major epidemics is urgently needed. Time-series analysis has appeared as an interesting approach to explore the dynamics of numerous diseases. Classical time-series methods can only be used for stationary time-series (in which the statistical properties do not vary with time). However, epidemiological time-series are typically noisy, complex and strongly non-stationary. Given this specific nature,wavelet analysisappears particularly attractive because it is well suited to the analysis of non-stationary signals. Here, we review the basic properties of the wavelet approach as an appropriate and elegant method for time-series analysis in epidemiological studies. The wavelet decomposition offers several advantages that are discussed in this paper based on epidemiological examples. In particular, the wavelet approach permits analysis of transient relationships between two signals and is especially suitable for gradual change in force by exogenous variables.
Chaos in Robert Hooke's inverted cone
Authors: Argentina Médéric , Coullet Pierre , Gilli Jean-Marc , Monticelli Marc , Rousseaux Germain
Published: February 2007

Robert Hooke is perhaps one of the first scientists to have met chaotic motions. Indeed, to invert a cone and let a ball move in it was a mechanical model used by him to mimic the motion of a planet around a centre of force like the Sun. However, as the cone is inclined with respect to the gravity field, the perfect rosace followed by the particle becomes chaotic meanderings. We revisit this classical experiment designed by Hooke with the modern tools of dynamical systems and chaos theory. By a combination of both numerical simulations and experiments, we prove that the scenario of transition to the chaotic behaviour is through a period-doubling instability.
Radial structure of the Internet
Authors: Holme Petter , Karlin Josh , Forrest Stephanie
Published: February 2007

The structure of the Internet at the autonomous system (AS) level has been studied by the physics, mathematics and computer science communities. We extend this work to include features of the core and the periphery, taking a radial perspective on AS network structure. New methods for plotting AS data are described, and they are used to analyse datasets that have been extended to contain edges missing from earlier collections. The average distance from one vertex to the rest of the network is used as the baseline metric for investigating radial structure. Common vertex-specific quantities are plotted against this metric to reveal distinctive characteristics of central and peripheral vertices. Two datasets are analysed using these measures as well as two common generative models (Barabási–Albert and Inet). We find a clear distinction between the highly connected core and a sparse periphery. We also find that the periphery has a more complex structure than that predicted by degree distribution or the two generative models.
Observations of wild hunting behaviour and bioluminescence of a large deep-sea, eight-armed squid,
Taningia danae
Authors: Kubodera Tsunemi , Koyama Yasuhiro , Mori Kyoichi
Published: February 2007

Our newly developed underwater high definition video camera system took the first live images of adults of the mesopelagic large squid,
Taningia danae
, between 240 and 940 m deep off Ogasawara Islands, western North Pacific. The resulting footage includes attacking and bioluminescence behaviours, and reveals that
T. danae
is far from the sluggish neutrally buoyant deep-sea squid previously suspected. It can actively swim both forward and backward freely by flapping its large muscular triangular fins and changes direction quickly through bending its flexible body. It can attain speeds of 2–2.5 m s
−1
(7.2–9 km h
−1
) when attacking bait rigs. They emitted short bright light flashes from their large arm-tip photophores before final assault, which might act as a blinding flash for prey as well as a means of measuring target distance in a dark deep-sea environment. They also emitted long and short glows separated by intervals while wandering around the double torch lights attached to the bait rig, suggestive of potential courtship behaviours during mating.
The mystery of Etruscan origins: novel clues fromBos taurusmitochondrial DNA
Authors: Pellecchia Marco , Negrini Riccardo , Colli Licia , Patrini Massimiliano , Milanesi Elisabetta , Achilli Alessandro , Bertorelle Giorgio , Cavalli-Sforza Luigi L , Piazza Alberto , Torroni Antonio , Ajmone-Marsan Paolo
Published: February 2007

The Etruscan culture developed in Central Italy (Etruria) in the first millennium BC and for centuries dominated part of the Italian Peninsula, including Rome. The history of the Etruscans is at the roots of Mediterranean culture and civilization, but their origin is still debated: local or Eastern provenance? To shed light on this mystery, bovine and human mitochondrial DNAs (mtDNAs) have been investigated, based on the well-recognized strict legacy which links human and livestock populations.

In the region corresponding to ancient Etruria (Tuscany, Central Italy), severalBos taurusbreeds have been reared since historical times. These breeds have a strikingly high level of mtDNA variation, which is found neither in the rest of Italy nor in Europe. The Tuscan bovines are genetically closer to Near Eastern than to European gene pools and this Eastern genetic signature is paralleled in modern human populations from Tuscany, which are genetically close to Anatolian and Middle Eastern ones.

The evidence collected corroborates the hypothesis of a common past migration: both humans and cattle reached Etruria from the Eastern Mediterranean area by sea. Hence, the Eastern origin of Etruscans, first claimed by the classic historians Herodotus and Thucydides, receives strong independent support. As the Latin philosopher Seneca wrote:Asia Etruscos sibi vindicat(Asia claims the Etruscans back).
The threat of punishment enforces peaceful cooperation and stabilizes queues in a coral-reef fish
Authors: Wong Marian Y.L , Buston Peter M , Munday Philip L , Jones Geoffrey P
Published: February 2007

Social queues, in which subordinates wait for their turn to inherit dominant breeding status, are a familiar feature of many animal societies. However, little is known about the mechanisms stabilizing social queues given the inevitable conflict over rank between group members. Here, we report the role of punishment and cooperation in promoting the stability of size-based queues in a coral-dwelling goby,
Paragobiodon xanthosomus
(Gobiidae). Quantitative analysis of the size-structure of queues revealed that individuals of adjacent rank differ in size by a specific size ratio, and comparisons of individual growth rates within queues demonstrated that specific size ratios are maintained over time via the regulation of subordinate growth rates. Furthermore, contest experiments demonstrated that the specific size ratio represents a threshold above which the subordinates become a threat to their immediate dominant, and as a result, dominants evict subordinates that exceed this size ratio from the group. We propose that threshold size ratios are maintained by subordinates as a form of peaceful cooperation whereby they avoid inflicting costs on dominants, and that such cooperation arises in response to the threat of punishment in the form of eviction by dominants. Societal stability is therefore achieved through the effects of punishment and cooperation acting in concert to promote the resolution of conflict over rank between group members.
The devil to pay: a cost of mutualism with
Myrmelachista schumanni
ants in ‘devil's gardens’ is increased herbivory on
Duroia hirsuta
trees
Authors: Frederickson Megan E , Gordon Deborah M
Published: February 2007

‘Devil's gardens’ are nearly pure stands of the myrmecophyte,
Duroia hirsuta
, that occur in Amazonian rainforests. Devil's gardens are created by
Myrmelachista schumanni
ants, which nest in
D. hirsuta
trees and kill other plants using formic acid as an herbicide. Here, we show that this ant–plant mutualism has an associated cost; by making devil's gardens,
M. schumanni
increases herbivory on
D. hirsuta.
We measured standing leaf herbivory on
D. hirsuta
trees and found that they sustain higher herbivory inside than outside devil's gardens. We also measured the rate of herbivory on nursery-grown
D. hirsuta
saplings planted inside and outside devil's gardens in ant-exclusion and control treatments. We found that when we excluded ants, herbivory on
D. hirsuta
was higher inside than outside devil's gardens. These results suggest that devil's gardens are a concentrated resource for herbivores.
Myrmelachista schumanni
workers defend
D. hirsuta
against herbivores, but do not fully counterbalance the high herbivore pressure in devil's gardens. We suggest that high herbivory may limit the spread of devil's gardens, possibly explaining why devil's gardens do not overrun Amazonian rainforests.
Gamma-ray bursts, QSOs and active galaxies
Authors: Burbidge Geoffrey
Published: February 2007

The similarity of the absorption spectra of gamma-ray burst (GRB) sources or afterglows with the absorption spectra of quasars (QSOs) suggests that QSOs and GRB sources are very closely related. Since most people believe that the redshifts of QSOs are of cosmological origin, it is natural to assume that GRBs or their afterglows also have cosmological redshifts. For some years a few of us have argued that there is much optical evidence suggesting a very different model for QSOs, in which their redshifts have a non-cosmological origin, and are ejected from low-redshift active galaxies. In this paper I extend these ideas to GRBs. In 2003, Burbidge (Burbidge 2003
Astrophys. J.
183
, 112–120) showed that the redshift periodicity in the spectra of QSOs appears in the redshift of GRBs. This in turn means that both the QSOs and the GRB sources are similar objects ejected from comparatively low-redshift active galaxies. It is now clear that many of the GRBs of low redshift do appear in, or very near, active galaxies.

A new and powerful result supporting this hypothesis has been produced by Prochter
et al
. (Prochter
et al
. 2006
Astrophys. J. Lett
.
648
, L93–L96). They show that in a survey for strong MgII absorption systems along the sightlines to long-duration GRBs, nearly every sightline shows at least one absorber. If the absorbers are intervening clouds or galaxies, only a small fraction should show absorption of this kind. The number found by Prochter
et al
. is four times higher than that normally found for the MgII absorption spectra of QSOs. They believe that this result is inconsistent with the intervening hypothesis and would require a statistical fluctuation greater than 99.1% probability.

This is what we expect if the absorption is intrinsic to the GRBs and the redshifts are not associated with their distances. In this case, the absorption must be associated with gas ejected from the QSO. This in turn implies that the GRBs actually originate in comparatively low-redshift active galaxies and are ejected in the same way as are the QSOs. This relates these phenomena to a supernova origin for the GRBs. The current situation based on the latest observational data will be discussed.
Gamma-ray bursts and cosmology
Authors: Lamb D.Q
Published: February 2007

I review the current status of the use of gamma-ray bursts (GRBs) as probes of the early Universe and cosmology. I describe the promise of long GRBs as probes of the high redshift (
z
>4) and very high redshift (
z
>5) Universe, and several key scientific results that have come from observations made possible by accurate, rapid localizations of these bursts by Swift. I then estimate the fraction of long GRBs that lie at very high redshifts and discuss ways in which it may be possible to rapidly identify—and therefore study—a larger number of these bursts. Finally, I discuss the ways in which both long and short GRBs can be made ‘standard candles’ and used to constrain the properties of dark energy.
The late X-ray afterglow of gamma-ray bursts
Authors: Willingale Richard , O'Brien Paul T
Published: February 2007

We have developed a functional fit which can be used to represent the entire temporal decay of the X-ray afterglow of gamma-ray bursts (GRBs). The fit delineates and parameterizes well-defined phases for the decay: the prompt emission; an initial steep decay; a shallow plateau phase; and finally, a powerlaw afterglow. For 20% of GRBs, the plateau phase is weak, or not seen, and the initial powerlaw decay becomes the final afterglow.

We compare the temporal decay parameters and X-ray spectral indices for 107 GRBs discovered by Swift with the expectations of the standard fireball model including a search for possible jet breaks. For approximately 50% of GRBs, the observed afterglow is in accord with the model, but for the rest the temporal and spectral properties are not as expected. We identify a few possible jet breaks, but there are many examples where such breaks are predicted but are absent. We also find that the start time of the final afterglow decay,
T
a
, is associated with the peak of the prompt
γ
-ray emission spectrum,
E
peak
, just as optical
jet-break
times,
t
j
, are associated with
E
peak
in the Ghirlanda relation.
Understanding primate brain evolution
Authors: Dunbar R.I.M , Shultz Susanne
Published: February 2007

We present a detailed reanalysis of the comparative brain data for primates, and develop a model using path analysis that seeks to present the coevolution of primate brain (neocortex) and sociality within a broader ecological and life-history framework. We show that body size, basal metabolic rate and life history act as constraints on brain evolution and through this influence the coevolution of neocortex size and group size. However, they do not determine either of these variables, which appear to be locked in a tight coevolutionary system. We show that, within primates, this relationship is specific to the neocortex. Nonetheless, there are important constraints on brain evolution; we use path analysis to show that, in order to evolve a large neocortex, a species must first evolve a large brain to support that neocortex and this in turn requires adjustments in diet (to provide the energy needed) and life history (to allow sufficient time both for brain growth
and
for ‘software’ programming). We review a wider literature demonstrating a tight coevolutionary relationship between brain size and sociality in a range of mammalian taxa, but emphasize that the social brain hypothesis is not about the relationship between brain/neocortex size and group size
per se
; rather, it is about social complexity and we adduce evidence to support this. Finally, we consider the wider issue of how mammalian (and primate) brains evolve in order to localize the social effects.
Before and below ‘theory of mind’: embodied simulation and the neural correlates of social cognition
Authors: Gallese Vittorio
Published: February 2007

The automatic translation of folk psychology into newly formed brain modules specifically dedicated to mind-reading and other social cognitive abilities should be carefully scrutinized. Searching for the brain location of intentions, beliefs and desires—as such—might not be the best epistemic strategy to disclose what social cognition really is. The results of neurocognitive research suggest that in the brain of primates, mirror neurons, and more generally the premotor system, play a major role in several aspects of social cognition, from action and intention understanding to language processing. This evidence is presented and discussed within the theoretical frame of an embodied simulation account of social cognition. Embodied simulation and the mirror neuron system underpinning it provide the means to share communicative intentions, meaning and reference, thus granting the parity requirements of social communication.
Socially intelligent robots: dimensions of human–robot interaction
Authors: Dautenhahn Kerstin
Published: February 2007

Social intelligence in robots has a quite recent history in artificial intelligence and robotics. However, it has become increasingly apparent that social and interactive skills are necessary requirements in many application areas and contexts where robots need to interact and collaborate with other robots or humans. Research on human–robot interaction (HRI) poses many challenges regarding the nature of interactivity and ‘social behaviour’ in robot and humans. The first part of this paper addresses dimensions of HRI, discussing requirements on social skills for robots and introducing the conceptual space of HRI studies. In order to illustrate these concepts, two examples of HRI research are presented. First, research is surveyed which investigates the development of a cognitive robot companion. The aim of this work is to develop social rules for robot behaviour (a ‘robotiquette’) that is comfortable and acceptable to humans. Second, robots are discussed as possible educational or therapeutic toys for children with autism. The concept of interactive emergence in human–child interactions is highlighted. Different types of play among children are discussed in the light of their potential investigation in human–robot experiments. The paper concludes by examining different paradigms regarding ‘social relationships’ of robots and people interacting with them.
Palatability of angiotensin II antagonists among nephropathic children
Authors: Meier Chiara M. , Simonetti Giacomo D. , Ghiglia Silvia , Fossali Emilio , Salice Patrizia , Limoni Costanzo , Bianchetti Mario G. ,   CHIld Project
Published: February 2007

What is already known about this subject

• Among children, medication palatability is crucial for adherence to therapeutic regimen.

• Several studies have measured the palatability of antimicrobial suspensions in paediatric patients by means of a visual analogue scale palatability score.

What this study adds

• This is the first analysis comparing the taste and smell acceptability of angiotensin II receptor blockers among paediatric patients with kidney disease.

• From the perspective of the child with kidney disease, the taste of pulverized candesartan is significantly superior to that of pulverized irbesartan, losartan, telmisartan or valsartan.

Aim Angiotensin II receptor blockers are widely prescribed in kidney disease. Among children, medication palatability is crucial for adherence.

Methods Taste and smell acceptability of five angiotensin II receptor blockers were compared among 21 nephropathic children using a visual analogue scale palatability score.

Results The score assigned to pulverized tablets of candesartan cilexetil was significantly higher than that assigned to pulverized tablets of irbesartan, losartan, telmisartan and valsartan.

Conclusions From the perspective of the nephropathic child, the taste of pulverized candesartan cilexetil is superior to that of irbesartan, losartan, telmisartan or valsartan.
The obestatin receptor (GPR39) is expressed in human adipose tissue and is down‐regulated in obesity‐associated type 2 diabetes mellitus
Authors: Catalán V. , Gómez‐Ambrosi J. , Rotellar F. , Silva C. , Gil M. J. , Rodríguez A. , Cienfuegos J. A. , Salvador J. , Frühbeck G.
Published: February 2007

Objective  The G protein‐coupled receptor 39 (GPR39) has recently been identified as the receptor for obestatin, a peptidic hormone involved in energy homeostasis. However, the expression levels of this receptor in human adipose tissue in obesity and obesity‐associated type 2 diabetes mellitus (T2DM) remain unknown. Therefore, we evaluated the actual presence of GPR39 mRNA in human adipose tissue and whether GPR39 expression levels are altered in obesity and obesity‐associated T2DM.

Design  Omental adipose tissue biopsies obtained from 15 women were used in the study. Patients were classified as lean (body mass index 20·8 ± 1·0 kg/m2), obese normoglycaemic (body mass index 48·4 ± 2·1 kg/m2) and obese T2DM patients (body mass index 52·6 ± 4·9 kg/m2). Anthropometric measurements and biochemical profiles were assessed for each subject. Real‐time RT‐PCR analyses were performed to quantify transcript levels of GPR39 and adiponectin.

Results  Obese T2DM patients exhibited significantly lower GPR39 expression levels compared to lean (P = 0·016) and obese normoglycaemic subjects (P = 0·008), while no differences between lean and obese normoglycaemic patients were observed. The mRNA expression levels of GPR39 were negatively correlated to fasting glucose concentrations (r = −0·581, P = 0·023), while exhibiting a positive correlation to adiponectin mRNA expression levels (r = 0·674, P = 0·006).

Conclusion  GPR39 is expressed in human adipose tissue. The reduced expression levels of GPR39 in omental adipose tissue observed in obese patients with T2DM suggest an involvement of obestatin signalling in glucose homeostasis and T2DM development.
Viscerally obese women with normal body weight have greater brachial‐ankle pulse wave velocity than nonviscerally obese women with excessive body weight
Authors: Lee Ji‐Won , Lee Hye‐Ree , Shim Jae‐Yong , Im Jee‐Aee , Kim Sang‐Hwan , Choi Hyunah , Lee Duk‐Chul
Published: February 2007

Objective  To confirm the association of visceral obesity and brachial‐ankle pulse wave velocity (baPWV) and to compare metabolic indices and baPWV between individuals who have normal body weight but are viscerally obese and individuals with excessive body weight who are not viscerally obese.

Patients and Measurements  We recruited a total of 150 women, aged 22 to 67 years. We assessed body composition, measured by computed tomography (CT), and divided the study population into four groups, based on visceral adipose tissue area (normal, normal body weight but viscerally obese, excessive body weight but not viscerally obese, and excessive body weight and viscerally obese). The baPWV was measured, using a volume plethysmographic instrument.

Results  Despite lower levels of total body fat, the women who had a normal body weight but were viscerally obese had a higher plasma triglyceride level and baPWV measurement and greater subcutaneous fat area (SFA) and thigh SFA than the women with excessive body weight who were not viscerally obese. After adjustment for age, mean blood pressure (BP), body mass index (BMI), triglyceride levels, fasting insulin levels, and free fatty acid (FFA) levels, baPWV was independently correlated with abdominal visceral fat area, as measured by CT (P = 0·001).

Conclusions  Mean baPWV was higher in women with normal body weight who were viscerally obese than in women who had excessive body weight but were not viscerally obese, and abdominal visceral fat was an independent factor for baPWV. These results suggest that early detection and intervention in viscerally obese individuals, even those within a normal BMI range, could be needed to prevent atherosclerosis and cardiovascular disease (CVD).
Interferon‐γ regulates cathepsin G activity in microglia‐derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro
Authors: Burster Timo , Beck Alexander , Poeschel Simone , Øren Anita , Baechle Daniel , Reich Michael , Roetzschke Olaf , Falk Kirsten , Boehm Bernhard O. , Youssef Sawsan , Kalbacher Hubert , Overkleeft Herman , Tolosa Eva , Driessen Christoph
Published: February 2007

The serine protease cathepsin (Cat) G dominates the proteolytic processing of the multiple sclerosis (MS)‐associated autoantigen myelin basic protein (MBP) in lysosomes from primary human B cells and dendritic cells. This is in contrast to B‐lymphoblastoid cell lines, where the asparagine endopeptidase (AEP) is responsible for this task. We have analysed microglia‐derived lysosomal proteases for their ability to process MBP in vitro. In lysosomes derived from primary murine microglia, CatD, CatS, AEP and CatG were involved in the processing of MBP. Interestingly, when microglia were treated with interferon‐γ to mimic a T helper type 1‐biased cytokine milieu in MS, CatG was drastically down‐regulated, in contrast to CatS, CatB, CatL, CatD or AEP. This resulted in significantly increased stability of MBP and a selective lack of CatG‐derived proteolytic fragments; however, it did not affect the gross pattern of MBP processing. Inhibition of serine proteases eliminated the processing differences between lysosomal extracts from resting microglia compared to interferon‐stimulated microglia. Thus, the cytokine environment modulates lysosomal proteases in microglia by a selective down‐regulation of CatG, leading to decreased MBP‐processing by microglia‐derived lysosomal proteases in vitro.
The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes
Authors: Smith Korsholm Karen , Agger Else Marie , Foged Camilla , Christensen Dennis , Dietrich Jes , Andersen Claire Swetman , Geisler Carsten , Andersen Peter
Published: February 2007

Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes did not have an effect on the maturation of murine bone‐marrow‐derived dendritic cells (BM‐DCs) related to the surface expression of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86. We found that ovalbumin (OVA) readily associated with the liposomes (> 90%) when mixed in equal concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM‐DCs as assessed by flow cytometry and confocal fluorescence laser‐scanning microscopy. This was an active process, which was arrested at 4° and by an inhibitor of actin‐dependent endocytosis, cytochalasin D. In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen‐presenting cells because we only observed a minimal uptake by T cells in mixed splenocyte cultures. The adsorption of antigen onto the liposomes increased the efficiency of antigen presentation more than 100 times in a responder assay with MHC class II‐restricted OVA‐specific T‐cell receptor transgenic DO11.10 T cells. Our data therefore suggest that the primary adjuvant mechanism of cationic DDA liposomes is to target the cell membrane of antigen‐presenting cells, which subsequently leads to enhanced uptake and presentation of antigen.