Plasmodium falciparum translational machinery condones polyadenosine repeats

Plasmodium falciparum is a causative agent of human malaria. Sixty percent of mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate polyA runs cause ribosome stalling and frameshifting, triggering mRNA surveillance pathways and attenuating protein synthesis. Here, we show that P. falciparum is an exception to this rule. We demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately translated in P. falciparum cells. We show that polyA runs do not elicit any response from No Go Decay (NGD) or result in the production of frameshifted proteins. This is in stark contrast to what we observe in human cells or T. thermophila, an organism with similar AT-content. Finally, using stalling reporters we show that Plasmodium cells evolved not to have a fully functional NGD pathway

Direct measurement and modeling of intraglottal, subglottal, and vocal fold collision pressures during phonation in an individual with a hemilaryngectomy

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, a rounded peak during the open phase, and a minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.Fil: Mehta, Daryush D.. Massachusetts General Hospital; Estados UnidosFil: Kobler, James B.. Massachusetts General Hospital; Estados UnidosFil: Zeitels, Steven M.. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados UnidosFil: Zañartu, Matías. Universidad Técnica Federico Santa María; ChileFil: Ibarra, Emiro J.. Universidad Técnica Federico Santa María; ChileFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Manriquez, Rodrigo. Universidad Técnica Federico Santa María; ChileFil: Erath, Byron D.. Clarkson University; Estados UnidosFil: Peterson, Sean D.. University of Waterloo; CanadáFil: Petrillo, Robert H.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados UnidosFil: Hillman, Robert E.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados Unidos. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unido

The effects of verbal information and approach-avoidance training on children's fear-related responses.

BACKGROUND AND OBJECTIVES This study examined the effects of verbal information and approach-avoidance training on fear-related cognitive and behavioural responses about novel animals. METHODS One hundred and sixty children (7-11 years) were randomly allocated to receive: a) positive verbal information about one novel animal and threat information about a second novel animal (verbal information condition); b) approach-avoidance training in which they repeatedly pushed away (avoid) or pulled closer (approach) pictures of the animals (approach-avoidance training), c) a combined condition in which verbal information was given prior to approach-avoidance training (verbal information + approach-avoidance training) and d) a combined condition in which approach-avoidance training was given prior to verbal information (approach-avoidance training + verbal information). RESULTS Threat and positive information significantly increased and decreased fear beliefs and avoidance behaviour respectively. Approach-avoidance training was successful in training the desired behavioural responses but had limited effects on fear-related responses. Verbal information and both combined conditions resulted in significantly larger effects than approach-avoidance training. We found no evidence for an additive effect of these pathways. LIMITATIONS This study used a non-clinical sample and focused on novel animals rather than animals about which children already had experience or established fears. The study also compared positive information/approach with threat information/avoid training, limiting specific conclusions regarding the independent effects of these conditions. CONCLUSIONS The present study finds little evidence in support of a possible causal role for behavioural response training in the aetiology of childhood fear. However, the provision of verbal information appears to be an important pathway involved in the aetiology of childhood fear

Co-rumination buffers the link between social anxiety and depressive symptoms in early adolescence

Objectives: We examined whether co-rumination with online friends buffered the link between social anxiety and depressive symptoms over time in a community sample. Methods: In a sample of 526 participants (358 girls; Mage = 14.05) followed at three time points, we conducted a latent cross-lagged model with social anxiety, depressive symptoms, and co-rumination, controlling for friendship stability and friendship quality, and adding a latent interaction between social anxiety and co-rumination predicting depressive symptoms. Results: Social anxiety predicted depressive symptoms, but no direct links between social anxiety and co-rumination emerged. Instead, co-rumination buffered the link between social anxiety and depressive symptoms for adolescents with higher but not lower levels of social anxiety. Conclusions: These findings indicate that co-rumination exerted a positive influence on interpersonal relationships by diminishing the influence from social anxiety on depressive symptoms over time

Peer Perceptions of Social Skills in Socially Anxious and Nonanxious Adolescents

Previous studies using adult observers are inconsistent with regard to social skills deficits in nonclinical socially anxious youth. The present study investigated whether same age peers perceive a lack of social skills in the socially anxious. Twenty high and 20 low socially anxious adolescents (13–17 years old) were recorded giving a 5-min speech. Unfamiliar peer observers (12–17 years old) viewed the speech samples and rated four social skills: speech content, facial expressions, posture and body movement, and way of speaking. Peer observers perceived high socially anxious adolescents as significantly poorer than low socially anxious adolescents on all four social skills. Moreover, for all skills except facial expressions, group differences could not be attributed to adolescents’ self-reported level of depression. We suggest that therapists take the perceptions of same age peers into account when assessing the social skills of socially anxious youth

Neurotrophic gene polymorphisms and response to psychological therapy

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR=0.60 (0.42–0.85), P=0.005). These effects remained even when other clinically relevant covariates were accounted for (OR=0.62 (0.41–0.92), P=0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions

Letter from J. B. Erath, Gatesville, Texas, to Honorable George E. Burny, May 1864

Letter written from the First Frontier District of Texas, of which Quayle was commander, providing information on Confederate military dispositions, 1862-64

Letter from J. B. Erath, Gatesville, Texas, to Honorable George E. Burny, May 7, 1864

Letter written from the First Frontier District of Texas, of which Quayle was commander, providing information on Confederate military dispositions, 1862-64