New Caledonian crows plan for specific future tool use.

The ability to plan for future events is one of the defining features of human intelligence. Whether non-human animals can plan for specific future situations remains contentious: despite a sustained research effort over the last two decades, there is still no consensus on this question. Here, we show that New Caledonian crows can use tools to plan for specific future events. Crows learned a temporal sequence where they were (a) shown a baited apparatus, (b) 5 min later given a choice of five objects and (c) 10 min later given access to the apparatus. At test, these crows were presented with one of two tool-apparatus combinations. For each combination, the crows chose the right tool for the right future task, while ignoring previously useful tools and a low-value food item. This study establishes that planning for specific future tool use can evolve via convergent evolution, given that corvids and humans shared a common ancestor over 300 million years ago, and offers a route to mapping the planning capacities of animals.

Publisher Correction: Mental template matching is a potential cultural transmission mechanism for New Caledonian crow tool manufacturing traditions.

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Mental template matching is a potential cultural transmission mechanism for New Caledonian crow tool manufacturing traditions.

Cumulative cultural evolution occurs when social traditions accumulate improvements over time. In humans cumulative cultural evolution is thought to depend on a unique suite of cognitive abilities, including teaching, language and imitation. Tool-making New Caledonian crows show some hallmarks of cumulative culture; but this claim is contentious, in part because these birds do not appear to imitate. One alternative hypothesis is that crows' tool designs could be culturally transmitted through a process of mental template matching. That is, individuals could use or observe conspecifics' tools, form a mental template of a particular tool design, and then reproduce this in their own manufacture - a process analogous to birdsong learning. Here, we provide the first evidence supporting this hypothesis, by demonstrating that New Caledonian crows have the cognitive capacity for mental template matching. Using a novel manufacture paradigm, crows were first trained to drop paper into a vending machine to retrieve rewards. They later learnt that only items of a particular size (large or small templates) were rewarded. At test, despite being rewarded at random, and with no physical templates present, crows manufactured items that were more similar in size to previously rewarded, than unrewarded, templates. Our results provide the first evidence that this cognitive ability may underpin the transmission of New Caledonian crows' natural tool designs.

Does absolute brain size really predict self-control? Hand-tracking training improves performance on the A-not-B task.

Large-scale, comparative cognition studies are set to revolutionize the way we investigate and understand the evolution of intelligence. However, the conclusions reached by such work have a key limitation: the cognitive tests themselves. If factors other than cognition can systematically affect the performance of a subset of animals on these tests, we risk drawing the wrong conclusions about how intelligence evolves. Here, we examined whether this is the case for the A-not-B task, recently used by MacLean and co-workers to study self-control among 36 different species. Non-primates performed poorly on this task; possibly because they have difficulty tracking the movements of a human demonstrator, and not because they lack self-control. To test this, we assessed the performance of New Caledonian crows on the A-not-B task before and after two types of training. New Caledonian crows trained to track rewards moved by a human demonstrator were more likely to pass the A-not-B test than birds trained on an unrelated choice task involving inhibitory control. Our findings demonstrate that overlooked task demands can affect performance on a cognitive task, and so bring into question MacLean's conclusion that absolute brain size best predicts self-control.

Thermodynamic characterization of human telomere quadruplex unfolding.

The 3'-terminal extensions of eukaryotic chromosomes are unique examples of functional single-stranded DNA. Human telomeres are constructed of the repeated DNA sequence 5'-d(TTAGGG). Four-repeats of human telomeric DNA have been characterized by high-resolution techniques to be capable of forming at least five distinct monomeric conformations. The predominant solution topology is influenced by solution conditions and the presence of 3'- or 5'-flanking residues. This study describes the unfolding mechanisms for human telomeric quadruplexes formed by eight sequence variants that form three unique antiparallel topologies in K(+) solution. Thermal unfolding monitored by circular dichroism is analyzed by singular value decomposition to enumerate the number of significant spectral species required to model the unfolding process. Thermal denaturation of all quadruplexes studied is found to be best modeled by a four-state sequential mechanism with two populated intermediates. The thermal unfolding was also investigated in 50% (v/v) acetonitrile in which a parallel topology is favored. Under these dehydrating conditions, quadruplex thermal denaturation is best modeled by a three-state sequential unfolding mechanism with one populated intermediate. Dehydrated parallel quadruplexes demonstrate increased thermal stability. The spectral properties of the unfolding intermediate suggest that it is most likely a triple-helical structure.

The shape and tempo of language evolution.

There are approximately 7000 languages spoken in the world today. This diversity reflects the legacy of thousands of years of cultural evolution. How far back we can trace this history depends largely on the rate at which the different components of language evolve. Rates of lexical evolution are widely thought to impose an upper limit of 6000-10,000 years on reliably identifying language relationships. In contrast, it has been argued that certain structural elements of language are much more stable. Just as biologists use highly conserved genes to uncover the deepest branches in the tree of life, highly stable linguistic features hold the promise of identifying deep relationships between the world's languages. Here, we present the first global network of languages based on this typological information. We evaluate the relative evolutionary rates of both typological and lexical features in the Austronesian and Indo-European language families. The first indications are that typological features evolve at similar rates to basic vocabulary but their evolution is substantially less tree-like. Our results suggest that, while rates of vocabulary change are correlated between the two language families, the rates of evolution of typological features and structural subtypes show no consistent relationship across families.

Sputum and serum calprotectin are useful biomarkers during CF exacerbation.

BACKGROUND: Adequate monitoring of cystic fibrosis lung disease is difficult. CF exacerbation offers a unique setting to test the utility of biomarkers in the assessment of changing airways inflammation. We hypothesised that levels of calprotectin in sputum (and serum) would change informatively following treatment of an exacerbation. METHODS: 27 patients with CF were recruited at onset of pulmonary exacerbation. Sputum and serum were collected at the start and end of anti-biotic therapy. Sputum calprotectin, interleukin-8 (IL8), and myeloperoxidase (MPO) were measured, as were serum calprotectin, CRP and vascular endothelial growth factor (VEGF). RESULTS: Sputum calprotectin decreased following treatment of an exacerbation (p<0.05), and was superior to other sputum markers. Serum calprotectin, CRP, and VEGF also decreased significantly (p=0.002, p=0.002, p=0.013 respectively). Serum calprotectin level following treatment had predictive value for time to next exacerbation (p=0.032). CONCLUSIONS: This study demonstrates the superiority of calprotectin (in sputum and serum) as a biomarker of CF exacerbation over better-established markers.

Language phylogenies reveal expansion pulses and pauses in Pacific settlement.

Debates about human prehistory often center on the role that population expansions play in shaping biological and cultural diversity. Hypotheses on the origin of the Austronesian settlers of the Pacific are divided between a recent "pulse-pause" expansion from Taiwan and an older "slow-boat" diffusion from Wallacea. We used lexical data and Bayesian phylogenetic methods to construct a phylogeny of 400 languages. In agreement with the pulse-pause scenario, the language trees place the Austronesian origin in Taiwan approximately 5230 years ago and reveal a series of settlement pauses and expansion pulses linked to technological and social innovations. These results are robust to assumptions about the rooting and calibration of the trees and demonstrate the combined power of linguistic scholarship, database technologies, and computational phylogenetic methods for resolving questions about human prehistory.

Do new caledonian crows solve physical problems through causal reasoning?

The extent to which animals other than humans can reason about physical problems is contentious. The benchmark test for this ability has been the trap-tube task. We presented New Caledonian crows with a series of two-trap versions of this problem. Three out of six crows solved the initial trap-tube. These crows continued to avoid the trap when the arbitrary features that had previously been associated with successful performances were removed. However, they did not avoid the trap when a hole and a functional trap were in the tube. In contrast to a recent primate study, the three crows then solved a causally equivalent but visually distinct problem--the trap-table task. The performance of the three crows across the four transfers made explanations based on chance, associative learning, visual and tactile generalization, and previous dispositions unlikely. Our findings suggest that New Caledonian crows can solve complex physical problems by reasoning both causally and analogically about causal relations. Causal and analogical reasoning may form the basis of the New Caledonian crow's exceptional tool skills.

Effects of intranasal corticosteroid on nasal adenosine monophosphate challenge in persistent allergic rhinitis.

BACKGROUND: Response to a single dose nasal adenosine monophosphate challenge has been used as a surrogate inflammatory marker for allergic rhinitis. Attenuation of response following intranasal corticosteroid would further validate the challenge. OBJECTIVE: To assess the effect of 4 weeks of 200 mcg once daily mometasone furoate nasal spray on a simplified (single 160 mg dose) nasal adenosine monophosphate challenge. METHODS: Twenty participants with persistent allergic rhinitis completed a double blind placebo-controlled crossover study. Outcome measures were the peak nasal inspiratory flow and total nasal symptoms score responses to nasal adenosine monophosphate challenge, as well as domiciliary peak nasal inspiratory flow and patient symptom diary cards. RESULTS: Mometasone significantly (P < 0.05) attenuated response time profiles vs. placebo for peak nasal inspiratory flow but not total nasal symptom scores. For the maximum percentage fall this amounted to a mean difference of 9.6% (95% confidence interval 1.3-17.9%). The coefficient of variation for repeatability was 48.7%. Improvements were seen in prechallenge and domiciliary measurements of peak nasal inspiratory flow (both P < 0.05) and total nasal symptom scores (both P < 0.01). CONCLUSIONS: Mometasone attenuates the peak nasal inspiratory flow response to a single 160 mg nasal adenosine monophosphate challenge. Such challenges have been shown to be sensitive to the effects of antihistamines, antileukotrienes and now nasal steroids. This further supports their application as surrogate inflammatory markers for therapeutic trials in allergic rhinitis, potentially as 20 min challenges which can be conducted in a non-hospital setting.

The effect of beta2-adrenoceptor haplotypes on bronchial hyper-responsiveness in patients with asthma.

BACKGROUND: The beta2-adrenoceptor exhibits genetic polymorphism which may be clinically relevant in terms of treatment response or bronchial hyper-responsiveness (BHR). The combined effect of these genotypes, or the haplotype, has not been fully characterized in terms of BHR. METHODS: We performed a retrospective analysis of the effects of haplotypes of amino acid substitution at position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients. RESULTS: There was a significant (P < 0.05) overall effect for forced expiratory volume (FEV(1)) but not after correction for steroid dose and atopic status. There were no significant differences for BHR to methacholine or AMP between the different haplotypes and no difference between the numbers of patients with or without clinically relevant BHR. Methacholine PD20 geometric mean-fold difference was 1.63 (95% CI: 0.95-2.80) between Arg-Arg/Gln-Gln and Gly-Gly/Gln-Gln and 1.26 (95% CI: 0.75-2.11) between Gly-Gly/Gln-Gln and Gly-Gly/Glu-Glu. CONCLUSIONS: The degree of BHR to indirect and direct stimuli does not differ between beta2-adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients presenting with asthma. Although beta2-adrenoceptor haplotypes do not predict BHR they may be important in predicting response to bronchodilator therapy.

A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis.

BACKGROUND: There are presently no placebo-controlled data regarding the effects of butterbur (BB) on subjective and objective outcomes in patients with perennial allergic rhinitis. OBJECTIVE: We performed a placebo-controlled evaluation of the effects of BB and fexofenadine (FEX) on subjective and objective outcomes in patients with perennial allergic rhinitis. METHODS: Sixteen patients with perennial allergic rhinitis and house dust mite sensitization were randomized in double-blind cross-over fashion to receive for 1 week either BB 50 mg twice daily, FEX 180 mg once daily and placebo (PL) once daily, or PL twice daily. The peak nasal inspiratory flow (PNIF) response to adenosine monophosphate (AMP) challenge administered as a single 400 mg/mL dose was measured over a 60-min period after challenge, and domiciliary total nasal symptom score was recorded. RESULTS: Pre-challenge values for mean+/-SEM PNIF (L/min) were not significantly different comparing all groups; BB (138+/-8), FEX (140+/-9), and PL (138+/-8). The maximum % PNIF fall from baseline after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (46+/-3), with BB (34+/-3) and FEX (39+/-3). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (1734+/-156), with BB (1052+/-258) and FEX (1194+/-161). There was also a significant reduction (P<0.05) in total nasal symptom score with BB (1.8+/-0.4) and FEX (1.8+/-0.4), compared to PL (2.8+/-0.5). There were no significant differences between BB and FEX for any outcomes. CONCLUSION: BB and FEX, in comparison to PL, were equally effective in attenuating the nasal response to AMP and in improving nasal symptoms, highlighting a potential role for BB in the treatment of allergic rhinitis.

A leiomyosarcoma of the oesophagus presenting incidentally without dysphagia.

Leiomyosarcoma is a rare tumour that accounts for 0.5% oesophageal sarcomas. The most common presenting symptom is dysphagia. This report presents a case of oesophageal leiomyosarcoma in a 56-year-old Caucasian man found incidentally while being investigated for refractory cough. There was no history of dysphagia in spite of tumour mass occupying most of the oesophageal lumen. The leiomyosarcoma was managed successfully with surgical resection and adjuvant radiotherapy. The patient remains disease free after 15 months after surgical intervention. The unusual case presentation is discussed and the surgical management of this rare condition reviewed.

Animal behaviour: Laterality in tool manufacture by crows.

New Caledonian crows (Fig. 1) fashion tapered tools from either the left or the right edge of the long narrow leaves of pandanus trees or screw pines, which they use to extract invertebrates in rainforest vegetation. Although right-handedness is thought to be uniquely human, we show here that crows from different localities display a widespread laterality in making their tools, indicating that this behaviour is unlikely to be attributable to local social traditions or ecological factors. To our knowledge, this is the first demonstration of species-level laterality in manipulatory skills outside humans.

Crystal structure of a complex between Pseudomonas aeruginosa alkaline protease and its cognate inhibitor: inhibition by a zinc-NH2 coordinative bond.

Serralysins are a family of metalloproteases secreted by Gram-negative bacteria into the medium in the form of inactive zymogens. Usually, all serralysin secretors have on the same operon a gene coding for a periplasmic 10-kDa protein, which is an inhibitor of the secreted protease. The recent characterization of the inhibitor of the alkaline protease from Pseudomonas aeruginosa revealed a surprisingly low dissociation constant of 4 pm, contrary to earlier studies on homologous systems, where inhibition constants in the microm range were reported. To approach a more accurate understanding, the crystal structure of the complex between inhibitor and protease from P. aeruginosa was determined at 1.74 A resolution and refined to R(free) = 0.204. The structure reported here shows clearly that the N terminus of the inhibitor forms a coordinative bond to the catalytic Zn(2+) ion with a nitrogen-zinc distance of 2.17 A. We conclude that this interaction adds substantially to the complex stability and show also that similar interactions are found in other metzincin-inhibitor complexes.

Language trees support the express-train sequence of Austronesian expansion.

Languages, like molecules, document evolutionary history. Darwin observed that evolutionary change in languages greatly resembled the processes of biological evolution: inheritance from a common ancestor and convergent evolution operate in both. Despite many suggestions, few attempts have been made to apply the phylogenetic methods used in biology to linguistic data. Here we report a parsimony analysis of a large language data set. We use this analysis to test competing hypotheses--the "express-train" and the "entangled-bank" models--for the colonization of the Pacific by Austronesian-speaking peoples. The parsimony analysis of a matrix of 77 Austronesian languages with 5,185 lexical items produced a single most-parsimonious tree. The express-train model was converted into an ordered geographical character and mapped onto the language tree. We found that the topology of the language tree was highly compatible with the express-train model.

Alkaline proteinase inhibitor of Pseudomonas aeruginosa. Interaction of native and N-terminally truncated inhibitor proteins with Pseudomonas metalloproteinases.

The apr locus of Pseudomonas aeruginosa encodes alkaline proteinase (APR), a member of the metzincin metalloendopeptidase superfamily, and an 11.4-kDa alkaline proteinase inhibitor (APRin). We describe here the expression in Escherichia coli and characterization of full-length and N-terminally truncated APRin proteins. Fluorescence and circular dichroism spectra indicated that the recombinant proteins were folded into native-like structures. Analytical ultracentrifugation showed that APRin was monomeric and formed a 1:1 complex with APR. Binding of wild-type APRin to APR occurred with association (k(on)) and dissociation (k(off)) rate constants of 0.29 +/- 0.06 x 10(6) m(-1) s(-1) and 1.15 +/- 0.08 x 10(-6) s(-1) to give an equilibrium dissociation constant (K(D)) of approximately 4 x 10(-12) m (25 degrees C, pH 7.0, ionic strength 2.4 m). The association rate decreased by approximately 2-fold in 20% glycerol and increased by approximately 3-fold in 0.1 m NaCl. The glycerol effect suggests a diffusion-limited reaction, and the small salt effect indicates that electrostatic interactions contribute little to binding. Deletion of residues 1-10, 1-6, or 6-10 abolished inhibition, and deletion of residues 1-2, 1-3, 1-4, and 1-5 resulted in a progressively decreased affinity of APRin for APR (K(D) = 0.12 micrometer the Delta(1-5) mutant). Substitution of APRin residues 6-10 with a (Gly)(5) or (Pro)(5) linker restored inhibitory activity of the Delta(6-10) mutant but with a 100- and 50-fold reduction in K(D). Log k(on) for the full-length and truncated inhibitors correlated with the solvent-accessible surface area of their N-terminal regions, suggesting that increased interactions and/or desolvation of these residues in the transition state for binding contribute to the enhanced association rate. Treatment of APRin with pseudolysin, also secreted by P. aeruginosa, resulted in removal of residues 1-5. APRin was neither an inhibitor nor a substrate of other metzincins, including collagenase or gelatinases A or B.

The phylogenetic relationships of the shags and cormorants: can sequence data resolve a disagreement between behavior and morphology?

Taxonomic arrangements for the cormorants and shags (Phalacrocoracidae) had varied greatly until two quite similar arrangements, one based on behavior and the other on osteological characters, became the basis for current thought on the evolutionary relationships of these birds. The terms cormorant and shag, which had previously been haphazardly applied to members of the group, became the vernacular terms for the two major subdivisions within this family. The two taxonomies differ in places, however, with the behavioral taxonomy placing several species within the shags and the osteological taxonomy and phylogeny grouping those species (as the marine cormorants) and placing them within the cormorants. In an attempt to resolve the differences in the relationships hypothesized by behavior and morphology, we sequenced three mitochondrial genes (12S, ATPase 6, and ATPase 8). Initial equally weighted parsimony trees differed slightly from our two weighted parsimony trees, one of which was also our maximum-likelihood tree. Many of the branches within our trees were well supported, but some sections of the phylogeny proved difficult to resolve with confidence. Our sequence trees differ substantially from the morphological phylogeny and show that neither the shags nor the cormorants are monophyletic, but form an intermingled group. Some of the groups supported by both the behavioral and the morphological taxonomies (e.g., the cliff shags, Stictocarbo) appear to be polyphyletic. Conversely, the monophyly of the blue-eyed shags, a traditional group that the osteological analysis had found to be paraphyletic, was supported by the sequence data. Until more taxa are sampled and a fully robust phylogeny is obtained, a conservative approach accepting a single genus, Phalacrocorax, for the shags and cormorants is recommended.