Origin of symbol-using systems: speech, but not sign, without the semantic urge

Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint

The map-1 Gene Family in Root-Knot Nematodes, Meloidogyne spp.: A Set of Taxonomically Restricted Genes Specific to Clonal Species

Taxonomically restricted genes (TRGs), i.e., genes that are restricted to a limited subset of phylogenetically related organisms, may be important in adaptation. In parasitic organisms, TRG-encoded proteins are possible determinants of the specificity of host-parasite interactions. In the root-knot nematode (RKN) Meloidogyne incognita, the map-1 gene family encodes expansin-like proteins that are secreted into plant tissues during parasitism, thought to act as effectors to promote successful root infection. MAP-1 proteins exhibit a modular architecture, with variable number and arrangement of 58 and 13-aa domains in their central part. Here, we address the evolutionary origins of this gene family using a combination of bioinformatics and molecular biology approaches. Map-1 genes were solely identified in one single member of the phylum Nematoda, i.e., the genus Meloidogyne, and not detected in any other nematode, thus indicating that the map-1 gene family is indeed a TRG family. A phylogenetic analysis of the distribution of map-1 genes in RKNs further showed that these genes are specifically present in species that reproduce by mitotic parthenogenesis, with the exception of M. floridensis, and could not be detected in RKNs reproducing by either meiotic parthenogenesis or amphimixis. These results highlight the divergence between mitotic and meiotic RKN species as a critical transition in the evolutionary history of these parasites. Analysis of the sequence conservation and organization of repeated domains in map-1 genes suggests that gene duplication(s) together with domain loss/duplication have contributed to the evolution of the map-1 family, and that some strong selection mechanism may be acting upon these genes to maintain their functional role(s) in the specificity of the plant-RKN interactions

Reading between Eye Saccades

Background: Skilled adult readers, in contrast to beginners, show no or little increase in reading latencies as a function of the number of letters in words up to seven letters. The information extraction strategy underlying such efficiency in word identification is still largely unknown, and methods that allow tracking of the letter information extraction through time between eye saccades are needed to fully address this question. Methodology/Principal Findings: The present study examined the use of letter information during reading, by means of the Bubbles technique. Ten participants each read 5,000 five-letter French words sampled in space-time within a 200 ms window. On the temporal dimension, our results show that two moments are especially important during the information extraction process. On the spatial dimension, we found a bias for the upper half of words. We also show for the first time that letter positions four, one, and three are particularly important for the identification of five-letter words. Conclusions/Significance: Our findings are consistent with either a partially parallel reading strategy or an optimal serial reading strategy. We show using computer simulations that this serial reading strategy predicts an absence of a wordlength effect for words from four- to seven letters in length. We believe that the Bubbles technique will play an importan

A New Basal Sauropod Dinosaur from the Middle Jurassic of Niger and the Early Evolution of Sauropoda

The early evolution of sauropod dinosaurs is poorly understood because of a highly incomplete fossil record. New discoveries of Early and Middle Jurassic sauropods have a great potential to lead to a better understanding of early sauropod evolution and to reevaluate the patterns of sauropod diversification.A new sauropod from the Middle Jurassic of Niger, Spinophorosaurus nigerensis n. gen. et sp., is the most complete basal sauropod currently known. The taxon shares many anatomical characters with Middle Jurassic East Asian sauropods, while it is strongly dissimilar to Lower and Middle Jurassic South American and Indian forms. A possible explanation for this pattern is a separation of Laurasian and South Gondwanan Middle Jurassic sauropod faunas by geographic barriers. Integration of phylogenetic analyses and paleogeographic data reveals congruence between early sauropod evolution and hypotheses about Jurassic paleoclimate and phytogeography.Spinophorosaurus demonstrates that many putatively derived characters of Middle Jurassic East Asian sauropods are plesiomorphic for eusauropods, while South Gondwanan eusauropods may represent a specialized line. The anatomy of Spinophorosaurus indicates that key innovations in Jurassic sauropod evolution might have taken place in North Africa, an area close to the equator with summer-wet climate at that time. Jurassic climatic zones and phytogeography possibly controlled early sauropod diversification

Antimonial Resistance in Leishmania donovani Is Associated with Increased In Vivo Parasite Burden

Leishmania donovani is an intracellular protozoan parasite that causes visceral leishmaniasis (VL). Antimonials (SSG) have long been the first-line treatment against VL, but have now been replaced by miltefosine (MIL) in the Indian subcontinent due to the emergence of SSG-resistance. Our previous study hypothesised that SSG-resistant L. donovani might have increased in vivo survival skills which could affect the efficacy of other treatments such as MIL. The present study attempts to validate these hypotheses. Fourteen strains derived from Nepalese clinical isolates with documented SSG-susceptibility were infected in BALB/c mice to study their survival capacity in drug free conditions (non-treated mice) and in MIL-treated mice. SSG-resistant parasites caused a significant higher in vivo parasite load compared to SSG-sensitive parasites. However, this did not seem to affect the strains' response to MIL-treatment since parasites from both phenotypes responded equally well to in vivo MIL exposure. We conclude that there is a positive association between SSG-resistance and in vivo survival skills in our sample of L. donovani strains which could suggest a higher virulence of SSG-R strains compared to SSG-S strains. These greater in vivo survival skills of SSG-R parasites do not seem to directly affect their susceptibility to MIL. However, it cannot be excluded that repeated MIL exposure will elicit different adaptations in these SSG-R parasites with superior survival skills compared to the SSG-S parasites. Our results therefore highlight the need to closely monitor drug efficacy in the field, especially in the context of the Kala-azar elimination programme ongoing in the Indian subcontinent

Genome-wide survey and analysis of microsatellites in nematodes, with a focus on the plant-parasitic species Meloidogyne incognita

<p>Abstract</p> <p>Background</p> <p>Microsatellites are the most popular source of molecular markers for studying population genetic variation in eukaryotes. However, few data are currently available about their genomic distribution and abundance across the phylum Nematoda. The recent completion of the genomes of several nematode species, including <it>Meloidogyne incognita</it>, a major agricultural pest worldwide, now opens the way for a comparative survey and analysis of microsatellites in these organisms.</p> <p>Results</p> <p>Using MsatFinder, the total numbers of 1-6 bp perfect microsatellites detected in the complete genomes of five nematode species (<it>Brugia malayi</it>, <it>Caenorhabditis elegans</it>, <it>M. hapla</it>, <it>M. incognita</it>, <it>Pristionchus pacificus</it>) ranged from 2,842 to 61,547, and covered from 0.09 to 1.20% of the nematode genomes. Under our search criteria, the most common repeat motifs for each length class varied according to the different nematode species considered, with no obvious relation to the AT-richness of their genomes. Overall, (AT)_<it>n</it>, (AG)_{<it>n </it>}and (CT)_{<it>n </it>}were the three most frequent dinucleotide microsatellite motifs found in the five genomes considered. Except for two motifs in <it>P. pacificus</it>, all the most frequent trinucleotide motifs were AT-rich, with (AAT)_{<it>n </it>}and (ATT)_{<it>n </it>}being the only common to the five nematode species. A particular attention was paid to the microsatellite content of the plant-parasitic species <it>M. incognita</it>. In this species, a repertoire of 4,880 microsatellite loci was identified, from which 2,183 appeared suitable to design markers for population genetic studies. Interestingly, 1,094 microsatellites were identified in 801 predicted protein-coding regions, 99% of them being trinucleotides. When compared against the InterPro domain database, 497 of these CDS were successfully annotated, and further assigned to Gene Ontology terms.</p> <p>Conclusions</p> <p>Contrasted patterns of microsatellite abundance and diversity were characterized in five nematode genomes, even in the case of two closely related <it>Meloidogyne </it>species. 2,245 di- to hexanucleotide loci were identified in the genome of <it>M. incognita</it>, providing adequate material for the future development of a wide range of microsatellite markers in this major plant parasite.</p

Changing Human Visual Field Organization from Early Visual to Extra-Occipital Cortex

BACKGROUND: The early visual areas have a clear topographic organization, such that adjacent parts of the cortical surface represent distinct yet adjacent parts of the contralateral visual field. We examined whether cortical regions outside occipital cortex show a similar organization. METHODOLOGY/PRINCIPAL FINDINGS: The BOLD responses to discrete visual field locations that varied in both polar angle and eccentricity were measured using two different tasks. As described previously, numerous occipital regions are both selective for the contralateral visual field and show topographic organization within that field. Extra-occipital regions are also selective for the contralateral visual field, but possess little (or no) topographic organization. A regional analysis demonstrates that this weak topography is not due to increased receptive field size in extra-occipital areas. CONCLUSIONS/SIGNIFICANCE: A number of extra-occipital areas are identified that are sensitive to visual field location. Neurons in these areas corresponding to different locations in the contralateral visual field do not demonstrate any regular or robust topographic organization, but appear instead to be intermixed on the cortical surface. This suggests a shift from processing that is predominately local in visual space, in occipital areas, to global, in extra-occipital areas. Global processing fits with a role for these extra-occipital areas in selecting a spatial locus for attention and/or eye-movements

Nelfinavir, an HIV-1 Protease Inhibitor, Induces Oxidative Stress–Mediated, Caspase-Independent Apoptosis in Leishmania Amastigotes

Visceral leishmaniasis is the most severe form of disease caused by the parasite Leishmania. It is a major concern in South America, Africa, India and the Middle East. Additionally, it has now emerged as an important opportunistic disease in patients coinfected with HIV-1. This is due, in part, to the increasing overlap between urban centers and rural areas endemic for Leishmania. Although more efficient combinatorial antiviral drug regimens for treating HIV-1 infection have been developed, the impact of such therapies on HIV-1/Leishmania coinfection is yet to be explored. In this study, we investigated the effect of nelfinavir, a well-characterized anti-HIV-1 drug, on Leishmania. Treating the parasite with nelfinavir activates events that are hallmarks of programmed cell death (also called apoptosis). Among these are oxidative stress, changes in DNA replication and fragmentation, and release of mitochondrial enzymes. Furthermore, these events occur without the participation of caspases, which are classically linked to apoptosis; however, this atypical apoptosis requires the translocation of endonuclease G from mitochondria to the cytoplasm. These findings provide insights for the design of new anti-parasitic therapies, particularly in the case of Leishmania/HIV-1 coinfections

Pan-RAF and MEK vertical inhibition enhances therapeutic response in non-V600 BRAF mutant cells

BACKGROUND: Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines. METHODS: Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model. RESULTS: All cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment. CONCLUSIONS: Our data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors