Prior physical exertion modulates allocentric distance perception: a demonstration of task-irrelevant cross-modal transfer

Physical exertion has been previously shown to influence distance perception in the egocentric framework. In this study, we show that physical exertion influences allocentric distance perception. Twenty healthy volunteers made allocentric line length estimates following varying levels of physical exertion. Each participant was presented with 30 different line lengths ranging from 1 to 12 cm, and each length was presented three times. Each line presentation was preceded by the participant exerting one of the following three levels of their maximal voluntary force (MVF): 20, 50, or 80 % MVF using their hand in the pinch force task. Psychometric curves were obtained for the lines perceived as 'long' following each of the three force levels. Lines that were perceived as 'short' following 20 and 50 % MVF were perceived as 'long' following 80 % MVF; that is, there was a significant leftward shift in the psychometric curve following 80 % MVF when compared to 20 and 50 % MVF. Here, we demonstrate that physical exertion influences perception of distances in the allocentric framework. We discuss our findings with respect to cross-modal interactions, fatigue physiology, peri- and extra-personal space interactions

Impaired Interoceptive Accuracy in Semantic Variant Primary Progressive Aphasia

Background: Interoception (the perception of internal bodily sensations) is strongly linked to emotional experience and sensitivity to the emotions of others in healthy subjects. Interoceptive impairment may contribute to the profound socioemotional symptoms that characterize frontotemporal dementia (FTD) syndromes, but remains poorly defined. Methods: Patients representing all major FTD syndromes and healthy age-matched controls performed a heartbeat counting task as a measure of interoceptive accuracy. In addition, patients had volumetric MRI for voxel-based morphometric analysis, and their caregivers completed a questionnaire assessing patients’ daily-life sensitivity to the emotions of others. Results: Interoceptive accuracy was impaired in patients with semantic variant primary progressive aphasia relative to healthy age-matched individuals, but not in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Impaired interoceptive accuracy correlated with reduced daily-life emotional sensitivity across the patient cohort, and with atrophy of right insula, cingulate, and amygdala on voxel-based morphometry in the impaired semantic variant group, delineating a network previously shown to support interoceptive processing in the healthy brain. Conclusion: Interoception is a promising novel paradigm for defining mechanisms of reduced emotional reactivity, empathy, and self-awareness in neurodegenerative syndromes and may yield objective measures for these complex symptoms

Humans store about 1.5 megabytes of information during language acquisition

We introduce theory-neutral estimates of the amount of information learners possess about how language works. We provide estimates at several levels of linguistic analysis: phonemes, wordforms, lexical semantics, word frequency and syntax. Our best guess is that the average English-speaking adult has learned 12.5 million bits of information, the majority of which is lexical semantics. Interestingly, very little of this information is syntactic, even in our upper bound analyses. Generally, our results suggest that learners possess remarkable inferential mechanisms capable of extracting, on average, nearly 2000 bits of information about how language works each day for 18 years

Mitochondria are the main source and one of the targets of Pb (lead)-induced oxidative stress in the yeast Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is a useful model organism for studying lead (Pb) toxicity. Yeast cells of a laboratory S. cerevisiae strain (WT strain) were incubated with Pb concentrations up to 1,000 μmol/l for 3 h. Cells exposed to Pb lost proliferation capacity without damage to the cell membrane, and they accumulated intracellular superoxide anion (O2 .−) and hydrogen peroxide (H2O2). The involvement of the mitochondrial electron transport chain (ETC) in the generation of reactive oxygen species (ROS) induced by Pb was evaluated. For this purpose, an isogenic derivative ρ0 strain, lacking mitochondrial DNA, was used. The ρ0 strain, without respiratory competence, displayed a lower intracellular ROS accumulation and a higher resistance to Pb compared to the WT strain. The kinetic study of ROS generation in yeast cells exposed to Pb showed that the production of O2 .− precedes the accumulation of H2O2, which is compatible with the leakage of electrons from the mitochondrial ETC. Yeast cells exposed to Pb displayed mutations at the mitochondrial DNA level. This is most likely a consequence of oxidative stress. In conclusion, mitochondria are an important source of Pb-induced ROS and, simultaneously, one of the targets of its toxicity.The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance.

BACKGROUND: Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. METHODS: To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. RESULTS: The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. CONCLUSIONS: Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance mutations to improve the design of tuberculosis control measures, such as diagnostics, and inform patient management

Niche as a determinant of word fate in online groups

Patterns of word use both reflect and influence a myriad of human activities and interactions. Like other entities that are reproduced and evolve, words rise or decline depending upon a complex interplay between {their intrinsic properties and the environments in which they function}. Using Internet discussion communities as model systems, we define the concept of a word niche as the relationship between the word and the characteristic features of the environments in which it is used. We develop a method to quantify two important aspects of the size of the word niche: the range of individuals using the word and the range of topics it is used to discuss. Controlling for word frequency, we show that these aspects of the word niche are strong determinants of changes in word frequency. Previous studies have already indicated that word frequency itself is a correlate of word success at historical time scales. Our analysis of changes in word frequencies over time reveals that the relative sizes of word niches are far more important than word frequencies in the dynamics of the entire vocabulary at shorter time scales, as the language adapts to new concepts and social groupings. We also distinguish endogenous versus exogenous factors as additional contributors to the fates of words, and demonstrate the force of this distinction in the rise of novel words. Our results indicate that short-term nonstationarity in word statistics is strongly driven by individual proclivities, including inclinations to provide novel information and to project a distinctive social identity.Comment: Supporting Information is available here: http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

Characterisation of a recombinant β-xylosidase (xylA) from Aspergillus oryzae expressed in Pichia pastoris

β-xylosidases catalyse the hydrolysis of short chain xylooligosaccharides from their non-reducing ends into xylose. In this study we report the heterologous expression of Aspergillus oryzae β-xylosidase (XylA) in Pichia pastoris under the control of the glyceraldehyde-3-phosphate dehydrogenase promoter. The recombinant enzyme was optimally active at 55°C and pH 4.5 with Km and Vmax values of 1.0 mM and 250 μmol min−1 mg−1 respectively against 4-nitrophenyl β-xylopyranoside. Xylose was a competitive inhibitor with a Ki of 2.72 mM, whereas fructose was an uncompetitive inhibitor reducing substrate binding affinity (Km) and conversion efficiency (Vmax). The enzyme was characterised to be an exo-cutting enzyme releasing xylose from the non-reducing ends of β-1,4 linked xylooligosaccharides (X2, X3 and X4). Catalytic conversion of X2, X3 and X4 decreased (Vmax and kcat) with increasing chain length

Children Use Statistics and Semantics in the Retreat from Overgeneralization

How do children learn to restrict their productivity and avoid ungrammatical utterances? The present study addresses this question by examining why some verbs are used with un- prefixation (e.g., unwrap) and others are not (e.g., *unsqueeze). Experiment 1 used a priming methodology to examine children's (3–4; 5–6) grammatical restrictions on verbal un- prefixation. To elicit production of un-prefixed verbs, test trials were preceded by a prime sentence, which described reversal actions with grammatical un- prefixed verbs (e.g., Marge folded her arms and then she unfolded them). Children then completed target sentences by describing cartoon reversal actions corresponding to (potentially) un- prefixed verbs. The younger age-group's production probability of verbs in un- form was negatively related to the frequency of the target verb in bare form (e.g., squeez/e/ed/es/ing), while the production probability of verbs in un- form for both age groups was negatively predicted by the frequency of synonyms to a verb's un- form (e.g., release/*unsqueeze). In Experiment 2, the same children rated the grammaticality of all verbs in un- form. The older age-group's grammaticality judgments were (a) positively predicted by the extent to which each verb was semantically consistent with a semantic “cryptotype” of meanings - where “cryptotype” refers to a covert category of overlapping, probabilistic meanings that are difficult to access - hypothesised to be shared by verbs which take un-, and (b) negatively predicted by the frequency of synonyms to a verb's un- form. Taken together, these experiments demonstrate that children as young as 4;0 employ pre-emption and entrenchment to restrict generalizations, and that use of a semantic cryptotype to guide judgments of overgeneralizations is also evident by age 6;0. Thus, even early developmental accounts of children's restriction of productivity must encompass a mechanism in which a verb's semantic and statistical properties interact