Classification of Types of Stuttering Symptoms Based on Brain Activity

Among the non-fluencies seen in speech, some are more typical (MT) of stuttering speakers, whereas others are less typical (LT) and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT) whole-word repetitions (WWR) should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type

Updated Three-Stage Model for the Peopling of the Americas

Background: We re-assess support for our three stage model for the peopling of the Americas in light of a recent report that identified nine non-Native American mitochondrial genome sequences that should not have been included in our initial analysis. Removal of these sequences results in the elimination of an early (i.e.,40,000 years ago) expansion signal we had proposed for the proto-Amerind population. Methodology/Findings: Bayesian skyline plot analysis of a new dataset of Native American mitochondrial coding genomes confirms the absence of an early expansion signal for the proto-Amerind population and allows us to reduce the variation around our estimate of the New World founder population size. In addition, genetic variants that define New World founder haplogroups are used to estimate the amount of time required between divergence of proto-Amerinds from the Asian gene pool and expansion into the New World. Conclusions/Significance: The period of population isolation required for the generation of New World mitochondrial founder haplogroup-defining genetic variants makes the existence of three stages of colonization a logical conclusion. Thus, our three stage model remains an important and useful working hypothesis for researchers interested in the peopling of th

Description of the attachment geometry of the anteromedial and posterolateral bundles of the ACL from arthroscopic perspective for anatomical tunnel placement

The anterior cruciate ligament (ACL) consists of an anteromedial bundle (AMB) and a posterolateral bundle (PLB). A reconstruction restoring the functional two-bundled nature should be able to approximate normal ACL function better than the most commonly used single-bundle reconstructions. Accurate tunnel positioning is important, but difficult. The purpose of this study was to provide a geometric description of the centre of the attachments relative to arthroscopically visible landmarks. The AMB and PLB attachment sites in 35 dissected cadaver knees were measured with a 3D system, as were anatomical landmarks of femur and tibia. At the femur, the mean ACL centre is positioned 7.9 ± 1.4 mm (mean ± 1 SD) shallow, along the notch roof, from the most lateral over-the-top position at the posterior edge of the intercondylar notch and from that point 4.0 ± 1.3 mm from the notch roof, low on the surface of the lateral condyle wall. The mean AMB centre is at 7.2 ± 1.8 and 1.4 ± 1.7 mm, and the mean PLB centre at 8.8 ± 1.6 and 6.7 ± 2.0 mm. At the tibia, the mean ACL centre is positioned 5.1 ± 1.7 mm lateral of the medial tibial spine and from that point 9.8 ± 2.1 mm anterior. The mean AMB centre is at 3.0 ± 1.6 and 9.4 ± 2.2 mm, and the mean PLB centre at 7.2 ± 1.8 and 10.1 ± 2.1 mm. The ACL attachment geometry is well defined relative to arthroscopically visible landmarks with respect to the AMB and PLB. With simple guidelines for the surgeon, the attachments centres can be found during arthroscopic single-bundle or double-bundle reconstructions

Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies

Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite

Apicomplexan parasites are obligate intracellular parasites that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms of the parasites invade their host cells by gliding motility, an active process driven by parasite adhesion proteins and molecular motors. A crucial point during host cell invasion is the formation of a ring-shaped area of intimate contact between the parasite and the host known as a tight junction. As the invasive zoite propels itself into the host-cell, the junction moves down the length of the parasite. This process must be tightly regulated and signalling is likely to play a role in this event. One crucial protein for tight-junction formation is the apical membrane antigen 1 (AMA1). Here we have investigated the phosphorylation status of this key player in the invasion process in the human malaria parasite Plasmodium falciparum. We show that the cytoplasmic tail of P. falciparum AMA1 is phosphorylated at serine 610. We provide evidence that the enzyme responsible for serine 610 phosphorylation is the cAMP regulated protein kinase A (PfPKA). Importantly, mutation of AMA1 serine 610 to alanine abrogates phosphorylation of AMA1 in vivo and dramatically impedes invasion. In addition to shedding unexpected new light on AMA1 function, this work represents the first time PKA has been implicated in merozoite invasion

Rotational knee laxity: Reliability of a simple measurement device in vivo

<p>Abstract</p> <p>Background</p> <p>Double bundle ACL reconstruction has been demonstrated to decrease rotational knee laxity. However, there is no simple, commercially-available device to measure knee rotation. The investigators developed a simple, non-invasive device to measure knee rotation. In conjunction with a rigid boot to rotate the tibia and a force/moment sensor to allow precise determination of torque about the knee, a magnetic tracking system measures the axial rotation of the tibia with respect to the femur. This device has been shown to have acceptable levels of test re-test reliability to measure knee rotation in cadaveric knees.</p> <p>Methods</p> <p>The objective of this study was to determine reliability of the device in measuring knee rotation of human subjects. Specifically, the intra-tester reliability within a single testing session, test-retest reliability between two testing sessions, and inter-tester reliability were assessed for 11 male subjects with normal knees.</p> <p>Results</p> <p>The 95% confidence interval for rotation was less than 5° for intra-tester, test-retest, and inter-tester reliability, and the standard error of measurement for the differences between left and right knees was found to be less than 3°.</p> <p>Conclusion</p> <p>It was found that the knee rotation measurements obtained with this device have acceptable limits of reliability for clinical use and interpretation.</p

Mechanical analysis of infant carrying in hominoids

In all higher nonhuman primates, species survival depends upon safe carrying of infants clinging to body hair of adults. In this work, measurements of mechanical properties of ape hair (gibbon, orangutan, and gorilla) are presented, focusing on constraints for safe infant carrying. Results of hair tensile properties are shown to be species-dependent. Analysis of the mechanics of the mounting position, typical of heavier infant carrying among African apes, shows that both clinging and friction are necessary to carry heavy infants. As a consequence, a required relationship between infant weight, hair–hair friction coefficient, and body angle exists. The hair–hair friction coefficient is measured using natural ape skin samples, and dependence on load and humidity is analyzed. Numerical evaluation of the equilibrium constraint is in agreement with the knuckle-walking quadruped position of African apes. Bipedality is clearly incompatible with the usual clinging and mounting pattern of infant carrying, requiring a revision of models of hominization in relation to the divergence between apes and hominins. These results suggest that safe carrying of heavy infants justify the emergence of biped form of locomotion. Ways to test this possibility are foreseen here

Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: Derivation of a clinical algorithm

Proadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI

Quantifying variation in the ability of yeasts to attract Drosophila melanogaster

Yeasts that invade and colonise fruit significantly enhance the volatile chemical diversity of this ecosystem. These modified bouquets are thought to be more attractive to Drosophila flies than the fruit alone, but the variance of attraction in natural yeast populations is uncharacterised. Here we investigate how a range of yeast isolates affect the attraction of female D. melanogaster to fruit in a simple two choice assay comparing yeast to sterile fruit. Of the 43 yeast isolates examined, 33 were attractive and seven repellent to the flies. The results of isolate-versus-isolate comparisons provided the same relative rankings. Attractiveness varied significantly by yeast, with the strongly fermenting Saccharomyces species generally being more attractive than the mostly respiring non-Saccharomyces species (P = 0.0035). Overall the habitat (fruit or other) from which the isolates were directly sampled did not explain attraction (P = 0.2352). However, yeasts isolated from fruit associated niches were more attractive than those from non-fruit associated niches (P = 0.0188) regardless of taxonomic positioning. These data suggest that while attractiveness is primarily correlated with phylogenetic status, the ability to attract Drosophila is a labile trait among yeasts that is potentially associated with those inhabiting fruit ecosystems. Preliminary analysis of the volatiles emitted by four yeast isolates in grape juice show the presence/absence of ethanol and acetic acid were not likely explanations for the observed variation in attraction. These data demonstrate variation among yeasts for their ability to attract Drosophila in a pattern that is consistent with the hypothesis that certain yeasts are manipulating fruit odours to mediate interactions with their Drosophila dispersal agent. © 2013 Palanca et al