Widening the lens: what the manual modality reveals about language,learning and cognition

The goal of this paper is to widen the lens on language to include the manual modality. We look first at hearing children who are acquiring language from a spoken language model and find that even before they use speech to communicate, they use gesture. Moreover, those gestures precede, and predict, the acquisition of structures in speech. We look next at deaf children whose hearing losses prevent them from using the oral modality, and whose hearing parents have not presented them with a language model in the manual modality. These children fall back on the manual modality to communicate and use gestures, which take on many of the forms and functions of natural language. These homemade gesture systems constitute the first step in the emergence of manual sign systems that are shared within deaf communities and are full-fledged languages. We end by widening the lens on sign language to include gesture and find that signers not only gesture, but they also use gesture in learning contexts just as speakers do. These findings suggest that what is key in gesture''s ability to predict learning is its ability to add a second representational format to communication, rather than a second modality. Gesture can thus be language, assuming linguistic forms and functions, when other vehicles are not available; but when speech or sign is possible, gesture works along with language, providing an additional representational format that can promote learning.     

Phyloproteomics: what phylogenetic analysis reveals about serum proteomics

Phyloproteomics is a novel analytical tool that solves the issue of comparability between proteomic analyses, utilizes a total spectrum-parsing algorithm, and produces biologically meaningful classification of specimens. Phyloproteomics employs two algorithms: a new parsing algorithm (UNIPAL) and a phylogenetic algorithm (MIX). By outgroup comparison, the parsing algorithm identifies novel or vanished MS peaks and peaks signifying up or down regulated proteins and scores them as derived or ancestral. The phylogenetic algorithm uses the latter scores to produce a biologically meaningful classification of the specimens.     

Brave new proteins: what evolution reveals about protein structure.

Synthetic proteins provide important information about the principles of protein structure. They illuminate the processes of natural protein evaluation, but are not limited by these processes. Here, we review studies of several mutant proteins and discuss the general principles that can be derived from them.     

A Turing test of a timing theory

A quantitative theory of timing or conditioning can be evaluated with a Turing test in which the behavioral results of an experiment can be compared with the predicted results from the theory. An example is described based upon an experiment in which 12 rats were trained on three fixed-interval schedules of reinforcement, and a simulation of the predicted results from a packet theory of timing. An objective classification rule was used to determine whether a sample from the data or a sample from the theory was more similar to another sample from the theory. With an ideal theory, the expected probability of a correct classification would be 0.5. The observed probability of a correct classification was 0.6, which was slightly, but reliably, greater than 0.5. A Turing test provides a graded metric for the evaluation of a quantitative theory.     

Deciphering the Leishmania exoproteome: what we know and what we can learn

Parasitic protozoa of the genus Leishmania are the causative agents of leishmaniasis. Survival and transmission of these parasites in their different hosts require membrane-bound or extracellular factors to interact with and modify their host environments. Over the last decade, several approaches have been applied to study all the extracellular proteins exported by an organism at a particular time or stage in its life cycle and under defined conditions, collectively termed the secretome or the exoproteome. In this review, we focus on emerging data shedding light on the secretion mechanisms involved in the production of the Leishmania exoproteome. We also describe other methodologies currently available that could be used to analyse the Leishmania exoproteome. Understanding the complexity of the Leishmania exoproteome is a key component to elucidating the mechanisms used by these parasites for exporting proteins to the extracellular space during its life cycle. Given the importance of extracellular factors, a detailed knowledge of the Leishmania exoproteome may provide novel targets for rational drug design and/or a source of antigens for vaccine development.     

Deciphering biased-agonism complexity reveals a new active AT1 receptor entity

Functional selectivity of G protein-coupled receptor (GPCR) ligands toward different downstream signals has recently emerged as a general hallmark of this receptor class. However, pleiotropic and crosstalk signaling of GPCRs makes functional selectivity difficult to decode. To look from the initial active receptor point of view, we developed new, highly sensitive and direct bioluminescence resonance energy transfer-based G protein activation probes specific for all G protein isoforms, and we used them to evaluate the G protein-coupling activity of [(1)Sar(4)Ile(8)Ile]-angiotensin II (SII), previously described as an angiotensin II type 1 (AT(1)) receptor-biased agonist that is G protein independent but β-arrestin selective. By multiplexing assays sensing sequential signaling events, from receptor conformations to downstream signaling, we decoded SII as an agonist stabilizing a G protein-dependent AT(1A) receptor signaling module different from that of the physiological agonist angiotensin II, both in recombinant and primary cells. Thus, a biased agonist does not necessarily select effects from the physiological agonist but may instead stabilize and create a new distinct active pharmacological receptor entity.     

Comparative social cognition: what can dogs teach us?

Research in comparative social cognition addresses how challenges of social living have formed the cognitive structures that control behaviours involved in communication, social learning and social understanding. In contrast to the traditional psychological approach, recent investigations take both evolutionary and functional questions into account, but the main emphasis is still on the mechanisms of behaviour. Although in traditional research ‘comparative’ meant mainly comparisons between humans and other primates, ethological influences have led to a broadening of the spectrum of species under study. In this review, we evaluated how the study of dogs broadens our understanding of comparative social cognition. In the early days of ethology, dogs enjoyed considerable interest from ethologists, but during the last 20 years, dogs have rarely been studied by ethological methods. Through a complex evolutionary process, dogs became adapted for living in human society; therefore, the human environment and social setting now represents a natural ecological niche for this species. We have evidence that dogs have been selected for adaptations to human social life, and that these adaptations have led to marked changes in their communicative, social, cooperative and attachment behaviours towards humans. Until now, the study of dogs was hindered by the view that they represent an ‘artificial’ species, but by accepting that dogs are adapted to their niche, as are other ‘natural’ species, comparative investigations can be put into new light.     

Animal cognition: chimpanzee alarm calls depend on what others know

After a wild chimpanzee encounters a model of a dangerous snake, whether or not he gives an alarm call depends on his perception of another individual's knowledge.     

Pluripotent human stem cell lines: what we can learn about cancer initiation

Although the cancer stem cell (CSC) hypothesis has become an attractive model to account for tumor recurrence, failure to define a cell of origin has created the need to explore alternative models for cancer initiation and maintenance. Recent studies have linked an embryonic stem cell (ESC)-like gene signature with poorly defined high-grade tumors. Here, we review advances in the ESC field with an emphasis on how human pluripotent stem cells (hPSCs) can be used to define early tumorigenic events, including potential miRNA and epigenetic targets, as well as proto-oncogene and tumor suppressor networks that might facilitate hierarchal transformation. These studies allow for investigation of cancer initiation in a manner that cannot be achieved using primary tumors, where only retrospective evaluation of CSC development is possible. By comparing transformed hPSCs with their normal counterparts, we hope to develop novel cell-specific therapies that selectively target CSCs.     

The counterbend phenomenon in dynein-disabled rat sperm flagella and what it reveals about the interdoublet elasticity

Rat sperm that have been rendered passive by disabling the dynein motors with 50 muM sodium metavanadate and 0.1 mM ATP exhibit an interesting response to imposed bending. When the proximal flagellum is bent with a microprobe, the portion of the flagellum distal to the probe contact point develops a bend in the direction opposite the imposed bend. This "counterbend" is not compatible with a simple elastic beam. It can be satisfactorily explained by the sliding tubule model of flagellar structure but only if there are permanent elastic connections between the outer doublets of the axoneme. The elastic component that contributes the bending torque for the counterbend does not reset to a new equilibrium position after an imposed bend but returns the flagellum to a nearly straight or slightly curved final position after release from the probe. This suggests it is based on fixed, rather than mobile, attachments. It is also disrupted by elastase or trypsin digestion, confirming that it is dependent on a protein linkage. Adopting the assumption that the elasticity is attributed to the nexin links that repeat at 96 nm intervals, we find an apparent elasticity for each link that ranges from 1.6 to 10 x 10(-5) N/m. However, the elasticity is nonlinear and does not follow Hooke's law but appears to decrease with increased stretch. In addition, the responsible elastic elements must be able to stretch to more than 10 times their resting length without breakage to account for the observed counterbend formation. Elasticity created by some type of protein unfolding may be the only viable explanation consistent with both the extreme capacity for extension and the nonlinear character of the restoring force that is observed.     

Culture-sensitive neural substrates of human cognition: a transcultural neuroimaging approach

Our brains and minds are shaped by our experiences, which mainly occur in the context of the culture in which we develop and live. Although psychologists have provided abundant evidence for diversity of human cognition and behaviour across cultures, the question of whether the neural correlates of human cognition are also culture-dependent is often not considered by neuroscientists. However, recent transcultural neuroimaging studies have demonstrated that one's cultural background can influence the neural activity that underlies both high- and low-level cognitive functions. The findings provide a novel approach by which to distinguish culture-sensitive from culture-invariant neural mechanisms of human cognition.     

ATP synthase: what we know about ATP hydrolysis and what we do not know about ATP synthesis

In ATP synthase, X-ray structures, demonstration of ATP-driven gamma-subunit rotation, and tryptophan fluorescence techniques to determine catalytic site occupancy and nucleotide binding affinities have resulted in pronounced progress in understanding ATP hydrolysis, for which a mechanism is presented here. In contrast, ATP synthesis remains enigmatic. The molecular mechanism by which ADP is bound in presence of a high ATP/ADP concentration ratio is a fundamental unknown; similarly P(i) binding is not understood. Techniques to measure catalytic site occupancy and ligand binding affinity changes during net ATP synthesis are much needed. Relation of these parameters to gamma-rotation is a further goal. A speculative model for ATP synthesis is offered.     

Language evolution and human history: what a difference a date makes

Historical inference is at its most powerful when independent lines of evidence can be integrated into a coherent account. Dating linguistic and cultural lineages can potentially play a vital role in the integration of evidence from linguistics, anthropology, archaeology and genetics. Unfortunately, although the comparative method in historical linguistics can provide a relative chronology, it cannot provide absolute date estimates and an alternative approach, called glottochronology, is fundamentally flawed. In this paper we outline how computational phylogenetic methods can reliably estimate language divergence dates and thus help resolve long-standing debates about human prehistory ranging from the origin of the Indo-European language family to the peopling of the Pacific.