Schizosaccharomyces pombe pus1 mutants are temperature sensitive due to decay of tRNAIle(UAU) by the 5'-3' exonuclease Dhp1, primarily targeting the unspliced pre-tRNA.

The pseudouridylase Pus1 catalyzes pseudouridine (Ψ) formation at multiple uridine residues in tRNAs, and in some snRNAs and mRNAs. Although Pus1 is highly conserved, and mutations are associated with human disease, little is known about eukaryotic Pus1 biology. Here, we show that Schizosaccharomyces pombe pus1Δ mutants are temperature sensitive due to decay of tRNAIle(UAU), as tRNAIle(UAU) levels are reduced, and its overexpression suppresses the defect.

Lymphatic distribution considerations for subunit vaccine design and development.

Subunit vaccines are an important platform for controlling current and emerging infectious diseases. The lymph nodes are the primary site generating the humoral response and delivery of antigens to these sites is critical to effective immunization. Indeed, the duration of antigen exposure within the lymph node is correlated with the antibody response.

A connection between the ribosome and two S. pombe tRNA modification mutants subject to rapid tRNA decay.

tRNA modifications are crucial in all organisms to ensure tRNA folding and stability, and accurate translation. In both the yeast Saccharomyces cerevisiae and the evolutionarily distant yeast Schizosaccharomyces pombe, mutants lacking certain tRNA body modifications (outside the anticodon loop) are temperature sensitive due to rapid tRNA decay (RTD) of a subset of hypomodified tRNAs. Here we show that for each of two S.

A connection between the ribosome and two tRNA modification mutants subject to rapid tRNA decay.

tRNA modifications are crucial in all organisms to ensure tRNA folding and stability, and accurate translation in the ribosome. In both the yeast and the evolutionarily distant yeast , mutants lacking certain tRNA body modifications (outside the anticodon loop) are temperature sensitive due to rapid tRNA decay (RTD) of a subset of hypomodified tRNAs. Here we show that for each of two mutants subject to RTD, mutations in ribosomal protein genes suppress the temperature sensitivity without altering tRNA levels.

Modeling the kinetics of lymph node retention and exposure of a cargo protein delivered by biotin-functionalized nanoparticles.

Generation of protective immunity through vaccination arises from the adaptive immune response developed primarily in the lymph nodes drained from the immunization site. Relative to the intramuscular route, subcutaneous administration allows for direct and rapid access to the lymphatics, but accumulation of soluble protein antigens within the lymph nodes is limited. Subunit vaccines also require immune stimulating adjuvants which may not accumulate in the same lymph nodes simultaneously with antigen.

Prospects for the pharmacological prevention of post-traumatic stress in vulnerable individuals.

Biological studies of posttraumatic stress disorder (PTSD) have found alterations of physiological stress pathways [sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis] soon after trauma in individuals who have subsequently developed PTSD, leading researchers to hypothesize that pharmacological manipulation of stress hormone levels may aid in preventing the development of post-traumatic distress. The present paper first reviews the current understanding of the neurobiology of PTSD development and then provides the rationale and evidence for early pharmacological strategies to prevent/reduce post-traumatic distress in at-risk trauma victims. Emphasis is placed on those interventions targeting the SNS and the HPA axis.

Traumatic childhood experiences in the 21st century: broadening and building on the ACE studies with data from the National Child Traumatic Stress Network.

The study objectives were to (a) examine the association between total number of trauma types experienced and child/adolescent behavioral problems and (b) determine whether the number of trauma types experienced predicted youth behavioral problems above and beyond demographic characteristics, using a diverse set of 20 types of trauma. Data came from the National Child Traumatic Stress Network's (NCTSN) Core Data Set (CDS), which includes youth assessed and treated for trauma across the United States. Participants who experienced at least one type of trauma were included in the sample (N = 11,028; age = 1½-18 years; 52.

Do gender and age moderate the symptom structure of PTSD? Findings from a national clinical sample of children and adolescents.

A substantial body of evidence documents that the frequency and intensity of posttraumatic stress disorder (PTSD) symptoms are linked to such demographic variables as female sex (e.g., Kaplow et al.

The efficacy of initial hydrocortisone administration at preventing posttraumatic distress in adult trauma patients: a randomized trial.

Unlabelled: OBJECTIVE/INTRODUCTION: Secondary pharmacological interventions have shown promise at reducing the development of posttraumatic stress disorder symptoms (PTSS) in preclinical studies. The present study examined the preliminary efficacy of a 10-day low-dose (20 mg bid) course of hydrocortisone at preventing PTSS in traumatic injury victims.

Methods: Sixty-four traumatic injury patients (34% female) were randomly assigned in a double-blind protocol to receive either a 10-day course of hydrocortisone or placebo initiated within 12 hours of the trauma.

Psychometric properties of the UCLA PTSD reaction index. part II: investigating factor structure findings in a national clinic-referred youth sample.

We examined the underlying factor structure of the UCLA PTSD Reaction Index (PTSD-RI) using data from 6,591 children/adolescents exposed to trauma, presenting for treatment at any of 54 National Child Traumatic Stress Network (NCTSN) centers. Using confirmatory factor analysis, we tested the 3-factor DSM-IV PTSD model, 2 separate 4-factor models (Dysphoria vs. Emotional Numbing) and a recently conceptualized 5-factor Dysphoric Arousal model.

Psychometric properties of the UCLA PTSD reaction index: part I.

This article presents psychometric characteristics of the UCLA PTSD Reaction Index for DSM IV (PTSD-RI) derived from a large sample of children and adolescents (N = 6,291) evaluated at National Child Traumatic Stress Network centers. Overall mean total PTSD-RI score for girls was significantly higher as compared with boys. Age-related differences were found in that overall mean total PTSD-RI scores and within sex groups were higher among those aged 7-9 years and 16-18 years.

Avoidant coping as a mediator between peritraumatic dissociation and posttraumatic stress disorder symptoms.

Peritraumatic dissociation consistently predicts posttraumatic stress disorder (PTSD). Avoidant coping may serve as a mechanism through which peritraumatic dissociation contributes to PTSD symptoms. Path analysis was used to examine whether avoidant coping assessed 6 weeks following a motor vehicle accident mediated the relationship between in-hospital peritraumatic dissociation and 6-month (n = 193) and 12-month (n = 167) chronic PTSD symptoms.

The impact of caregiver distress on the longitudinal development of child acute post-traumatic stress disorder symptoms in pediatric injury victims.

Objective: The present study prospectively examined the development of child PTSD symptoms (PTSS) and the impact of caregiver PTSS on child PTSS following injury.

Methods: One hundred and eighteen ED patients and their caregivers were interviewed in-hospital and 2- and 6-weeks posttrauma. Structural equation modeling and hierarchical linear regressions examined the development of PTSS.

The efficacy of early propranolol administration at reducing PTSD symptoms in pediatric injury patients: a pilot study.

Initial research supports the use of propranolol to prevent posttraumatic stress disorder (PTSD); research has not examined pharmacological prevention for children. Twenty-nine injury patients (ages 10-18 years old) at risk for PTSD were randomized to a double-blind 10-day trial of propranolol or placebo initiated within 12 hours postadmission. Six-week PTSD symptoms and heart rate were assessed.

DSM-V PTSD diagnostic criteria for children and adolescents: a developmental perspective and recommendations.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) should ensure systematic attention to age-specific manifestations and selective modifications of the diagnostic criteria for posttraumatic stress disorder (PTSD) among children and adolescents. The authors propose developmental refinements to the conceptual framework for PTSD based on an appreciation of the different neurosignatures of danger and safety, and maturational processes that underlie symptom presentation. This includes preliminary evidence for the developmental salience of additional dimensions for PTSD (e.

Trauma history characteristics and subsequent PTSD symptoms in motor vehicle accident victims.

The present study examined the relationship between trauma history characteristics (number and type of traumas, age at first trauma, and subjective responses to prior traumas) and the development of posttraumatic stress disorder (PTSD) symptoms following a motor vehicle accident (MVA). One hundred eighty-eight adult MVA victims provided information about prior traumatization and were evaluated for PTSD symptoms 6 weeks and one year following the MVA. Results indicated that after controlling for demographics and depression, prior trauma history characteristics accounted for a small, but significant amount of the variance in PTSD symptoms.

Acute child and mother psychophysiological responses and subsequent PTSD symptoms following a child's traumatic event.

This study examined the relationship between acute cortisol responses to trauma and subsequent PTSD symptoms (PTSS) in children and their biological mothers. Urinary cortisol levels were assessed in 54 children aged 8-18 upon admission to a level-1 trauma center. Six weeks posttrauma, 15-hour urine samples were collected from children and their mothers.

Parental posttraumatic stress symptoms as a moderator of child's acute biological response and subsequent posttraumatic stress symptoms in pediatric injury patients.

Objective: To examine how parental responses following pediatric injury may influence their child's posttraumatic stress symptoms (PTSS).

Methods: Heart rate (HR) from 82 pediatric injury patients was measured during emergency medical services (EMSs) transport and following hospital admission. Twelve-hour urinary cortisol levels were assessed upon admission.

Brief report: the impact of maternal posttraumatic stress disorder symptoms and child gender on risk for persistent posttraumatic stress disorder symptoms in child trauma victims.

Objective: To longitudinally examine the impact of maternal posttraumatic stress disorder symptoms (PTSS) on child adjustment following a child's traumatic injury, focusing on child gender differences.

Methods: Forty-one child traumatic injury victims aged 8-18 years and their biological mothers were interviewed over two follow-ups (6 weeks and 7 months). Children were administered the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale for Children and Adolescents (CAPS-CA), whereas mothers completed the CAPS.