An in vivo control map for the eukaryotic mRNA translation machinery

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis

Magnetized Domain Walls in the Deconfined Sakai-Sugimoto Model at Finite Baryon Density

The magnetized pure pion gradient ($\mathcal{5}\phi$) phase in the deconfined Sakai-Sugimoto model is explored at zero and finite temperature. We found that the temperature has very small effects on the phase. The thermodynamical properties of the phase shows that the excitations behave like a scalar solitonic free particles. By comparing the free energy of the pion gradient phase to the competing multiquark-pion gradient (MQ-$\mathcal{5}\phi$) phase, it becomes apparent that the pure pion gradient is less thermodynamically preferred than the MQ-$\mathcal{5}\phi$ phase. However, in the parameter space where the baryonic chemical potential is smaller than the onset value of the multiquark, the dominating magnetized nuclear matter is the pion gradient phase.Comment: 20 pages, 9 figure

The impact of different DNA extraction kits and laboratories upon the assessment of human gut microbiota composition by 16S rRNA gene sequencing

Peer reviewedPublisher PD

Prospective, randomized evaluation of a personal digital assistant-based research tool in the emergency department

Background Personal digital assistants (PDA) offer putative advantages over paper for collecting research data. However, there are no data prospectively comparing PDA and paper in the emergency department. The aim of this study was to prospectively compare the performance of PDA and paper enrollment instruments with respect to time required and errors generated. Methods We randomized consecutive patients enrolled in an ongoing prospective study to having their data recorded either on a PDA or a paper data collection instrument. For each method, we recorded the total time required for enrollment, and the time required for manual transcription (paper) onto a computer database. We compared data error rates by examining missing data, nonsensical data, and errors made during the transcription of paper forms. Statistical comparisons were performed by Kruskal-Wallis and Poisson regression analyses for time and errors, respectively. Results We enrolled 68 patients (37 PDA, 31 paper). Two of 31 paper forms were not available for analysis. Total data gathering times, inclusive of transcription, were significantly less for PDA (6:13 min per patient) compared to paper (9:12 min per patient; p < 0.001). There were a total of 0.9 missing and nonsense errors per paper form compared to 0.2 errors per PDA form (p < 0.001). An additional 0.7 errors per paper form were generated during transcription. In total, there were 1.6 errors per paper form and 0.2 errors per PDA form (p < 0.001). Conclusion Using a PDA-based data collection instrument for clinical research reduces the time required for data gathering and significantly improves data integrity

Inverse magnetic catalysis in dense holographic matter

We study the chiral phase transition in a magnetic field at finite temperature and chemical potential within the Sakai-Sugimoto model, a holographic top-down approach to (large-N_c) QCD. We consider the limit of a small separation of the flavor D8-branes, which corresponds to a dual field theory comparable to a Nambu-Jona Lasinio (NJL) model. Mapping out the surface of the chiral phase transition in the parameter space of magnetic field strength, quark chemical potential, and temperature, we find that for small temperatures the addition of a magnetic field decreases the critical chemical potential for chiral symmetry restoration - in contrast to the case of vanishing chemical potential where, in accordance with the familiar phenomenon of magnetic catalysis, the magnetic field favors the chirally broken phase. This "inverse magnetic catalysis" (IMC) appears to be associated with a previously found magnetic phase transition within the chirally symmetric phase that shows an intriguing similarity to a transition into the lowest Landau level. We estimate IMC to persist up to 10^{19} G at low temperatures.Comment: 42 pages, 11 figures, v3: extended discussion; new appendix D; references added; version to appear in JHE

Study protocol for POSITIF, a randomised multicentre feasibility trial of a brief cognitive-behavioural intervention plus information versus information alone for the treatment of post-stroke fatigue

© 2020 The Author(s). Background: Approximately, half of stroke survivors experience fatigue. Fatigue may persist for many months and interferes with participation in everyday activities and has a negative impact on social and family relationships, return to work, and quality of life. Fatigue is among the top 10 priorities for 'Life after Stroke' research for stroke survivors, carers, and clinicians. We previously developed and tested in a small uncontrolled pilot study a manualised, clinical psychologist-delivered, face-to-face intervention, informed by cognitive behavioural therapy (CBT). We then adapted it for delivery by trained therapists via telephone. We now aim to test the feasibility of this approach in a parallel group, randomised controlled feasibility trial (Post Stroke Intervention Trial In Fatigue, POSITIF). Methods/design: POSITIF aims to recruit 75 stroke survivors between 3 months and 2 years post-stroke who would like treatment for their fatigue. Eligible consenting stroke survivors will be randomised to either a 7-session manualised telephone-delivered intervention based on CBT principles plus information about fatigue, or information only. The aims of the intervention are to (i) provide an explanation for post-stroke fatigue, in particular that it is potentially reversible (an educational approach), (ii) encourage participants to overcome the fear of taking physical activity and challenge negative thinking (a cognitive approach) and (iii) promote a balance between daily activities, rest and sleep and then gradually increase levels of physical activity (a behavioural approach). Fatigue, mood, quality of life, return to work and putative mediators will be assessed at baseline (just before randomisation), at the end of treatment and 6 months after randomisation. POSITIF will determine the feasibility of recruitment, adherence to the intervention and the resources required to deliver the intervention in a larger trial. Discussion: The POSITIF feasibility trial will recruit until 31 January 2020. Data will inform the utility and design of a future adequately powered randomised controlled trial. Trial registration: ClinicalTrials.gov, NCT03551327. Registered on 11 June 2018

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Cut Throat Injuries at a University Teaching Hospital in Northwestern Tanzania: A Review of 98 cases.

Cut throat injuries though rarely reported in literature pose a great therapeutic challenge because multiple vital structures are vulnerable to injuries in the small, confined unprotected area. A sudden increase in the number of cut throat patients in our centre in recent years prompted the authors to analyze this problem. This study was conducted in our local setting to describe the etiology, patterns and treatment outcome of these injuries. This was a combined retrospective and prospective study of cut throat injury patients who were managed at Bugando Medical Centre between February 2009 and January 2013. Statistical data analysis was done using SPSS software version 17.0. A total of 98 patients with cut throat injuries were studied. Males outnumbered females by a ratio of 2.4: 1. The median age of patients was 26 years (range 8 to 78 years). Majority of patients (79.6%) had no employment and most of them (65.3%) came from rural community. Homicide was the commonest (55.1%) cause, followed by suicidal attempts (34.7%) and accidental (10.2%) injuries. Interpersonal conflict (24.4%) was the most common motivating factor for homicidal injury whereas psychiatric illness (16.2%) and road traffic accidents (9.2%) were the most frequent motivating factors of suicidal attempt and accidental injuries respectively. The majority of injuries were in Zone II accounting for 65.3% of cases and most of them had laryngeal (57.1%) injury. Surgical debridement, laryngeal/hypopharynx repair and tracheostomy were the most common surgical procedures performed in 93.9%, 73.5% and 70.4% of patients respectively. Postoperative complication rate was 57.1%, the commonest being surgical site infections in 28.1% of patients and it was significantly associated with late presentation and anatomical zones (P < 0.001). The overall median duration of hospitalization was 12 days. Patients who had postoperative complications stayed longer in the hospital and this was statistically significant (p = 0.011). Mortality rate was 11.2% and was significantly associated with co-morbidities, delayed presentation and presence of complications (p < 0.001). The follow up of patients was poor. Cut throat injuries are a major cause of morbidity and mortality among young adult males in our setting. Addressing the root causes of violence such as poverty, unemployment, and substance abuse will reduce the incidence of these injuries in our environment