Pdsg1 and Pdsg2, novel proteins involved in developmental genome remodelling in Paramecium

The epigenetic influence of maternal cells on the development of their progeny has long been studied in various eukaryotes. Multicellular organisms usually provide their zygotes not only with nutrients but also with functional elements required for proper development, such as coding and non-coding RNAs. These maternally deposited RNAs exhibit a variety of functions, from regulating gene expression to assuring genome integrity. In ciliates, such as Paramecium these RNAs participate in the programming of large-scale genome reorganization during development, distinguishing germline-limited DNA, which is excised, from somatic-destined DNA. Only a handful of proteins playing roles in this process have been identified so far, including typical RNAi-derived factors such as Dicer-like and Piwi proteins. Here we report and characterize two novel proteins, Pdsg1 and Pdsg2 (Paramecium protein involved in Development of the Somatic Genome 1 and 2), involved in Paramecium genome reorganization. We show that these proteins are necessary for the excision of germline-limited DNA during development and the survival of sexual progeny. Knockdown of PDSG1 and PDSG2 genes affects the populations of small RNAs known to be involved in the programming of DNA elimination (scanRNAs and iesRNAs) and chromatin modification patterns during development. Our results suggest an association between RNA-mediated trans-generational epigenetic signal and chromatin modifications in the process of Paramecium genome reorganization.

RNA-Guided Genome Editing

Ciliates have evolved highly complex and intricately controlled pathways to ensure the precise and complete removal of all genomic sequences not required for vegetative growth. At the same time, they retain a reference copy of all their genetic information for future generations. This chapter describes how different ciliates use RNA-mediated DNA comparison processes to form new somatic nuclei from germline nuclei. While these processes vary in their precise mechanisms, they all use RNA to target genomic DNA sequences—either for retention or elimination. They also all consist of more than one individual pathway acting cooperatively—the two subsets of small RNAs in Paramecium and the guide RNAs and Piwi-interacting RNAs in Oxytricha—to ensure a strong belt-and-braces approach to consistent and precise somatic nucleus development. Nonetheless, this genome comparison approach to somatic nucleus development provides an elegant method for trans-generational environmental adaptation. Conceptually, it is easy to imagine how somatic changes that occur during vegetative growth could be transferred to meiotic offspring, while an unaltered germline genome is retained. Further research in this area will have far-reaching implications for the trans-generational adaptation of more distantly related eukaryotes, such as humans.

Detection of chest trauma with whole-body low-dose linear slit digital radiography: a multireader study

The objective of our study was to compare the performance of low-dose linear slit digital radiography (DR) with computed radiography (CR) for the detection of trauma sequelae in the chest including rib fractures, pneumothorax, and lung contusion.

Do we really need 24-h observation for patients with minimal brain injury and small intracranial bleeding? The Bernese Trauma Unit Protocol

Traumatic brain injury is one of the most common reasons for admission to hospital emergency departments. However, optimal diagnosis and treatment protocols remain controversial. The aim of this study is to assess whether a specific group of patients can be discharged from the hospital without 24-h neurological observation.

Permanent teeth with horizontal root fractures after dental trauma. A retrospective study

The purpose of the present retrospective study was to evaluate the post-traumatic healing of the pulp and periodontium of 32 permanent teeth with horizontal root fractures. Twenty-nine patients, 8-48 years old, who presented at our department with a root fracture between January 2001 and April 2007, participated in the study. Root-fractured teeth with a loosened or dislocated coronal fragment were repositioned and splinted for 14-49 days (average: 34 days). In cases of severe dislocation of the coronal fragment, prophylactic endodontic treatment was performed. Follow-up examinations were conducted routinely after 1,2,3,6, and 12 months. For this study, follow-up took place for up to 7 years post trauma. Of 32 root-fractured teeth, 29 (91%) survived. 10 teeth (31%) exhibited pulpal healing; 13 teeth (41%) were prophylactically endodontically treated within 2 weeks of injury. At the fracture line, interposition of calcified tissue was evident in 6 teeth (19%), and interposition of granulation tissue was observed in 8 teeth (25%). The prognosis of the root-fractured teeth was good, and one-third of the teeth with root fractures possessed a vital pulp at the final examination.

Trauma-induced coagulopathy in severely injured patients: knowledge lost in translation?

Many guidelines exist on how to treat patients with multiple injuries correctly in an accident and emergency setting. The aim of the present work was to find out how well patients are treated focusing on trauma induced coagulopathy (TIC), and what anaesthetists involved in trauma care think about their own experiences with TIC.

Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2

Acute promyelocytic leukaemia (APL) patients are successfully treated with all-trans retinoic acid (ATRA). However, concurrent chemotherapy is still necessary and less toxic therapeutic approaches are needed. Earlier studies suggested that in haematopoietic neoplasms, the green tea polyphenol epigallocatechin-3-gallate (EGCG) induces cell death without adversely affecting healthy cells. We aimed at deciphering the molecular mechanism of EGCG-induced cell death in acute myeloid leukaemia (AML). A significant increase of death-associated protein kinase 2 (DAPK2) levels was found in AML cells upon EGCG treatment paralleled by increased cell death that was significantly reduced upon silencing of DAPK2. Moreover, combined ATRA and EGCG treatment resulted in cooperative DAPK2 induction and potentiated differentiation. EGCG toxicity of primary AML blasts correlated with 67 kDa laminin receptor (67LR) expression. Pretreatment of AML cells with ATRA, causing downregulation of 67LR, rendered these cells resistant to EGCG-mediated cell death. In summary, it was found that (i) DAPK2 is essential for EGCG-induced cell death in AML cells, (ii) ATRA and EGCG cotreatment significantly boosted neutrophil differentiation, and 67LR expression correlates with susceptibility of AML cells to EGCG. We thus suggest that EGCG, by selectively targeting leukaemic cells, may improve differentiation therapies for APL and chemotherapy for other AML subtypes.

Trauma mechanisms, patterns of injury, and outcomes in a retrospective study of 71 burns from civil gas explosions

Although explosion injuries caused by terror attacks or in war are evaluated in many studies, limited information about civil explosion injuries can be found in the literature.

Posttraumatic stress disorder and soluble cellular adhesion molecules at rest and in response to a trauma-specific interview in patients after myocardial infarction

Posttraumatic stress disorder (PTSD) and circulating cellular adhesion molecules (CAMs) predict cardiovascular risk. We hypothesized a positive relationship between PTSD caused by myocardial infarction (MI) and soluble CAMs. We enrolled 22 post-MI patients with interviewer-rated PTSD and 22 post-MI patients with no PTSD. At 32±6months after index MI, all patients were re-scheduled to undergo the Clinician-Administered PTSD Scale (CAPS) interview and had blood collected to assess soluble CAMs at rest and after the CAPS interview. Relative to patients with no PTSD, those with PTSD had significantly higher levels of soluble vascular cellular adhesion molecule (sVCAM)-1 and intercellular adhesion molecule (sICAM)-1 at rest and, controlling for resting CAM levels, significantly higher sVCAM-1 and sICAM-1 after the interview. Greater severity of PTSD predicted significantly higher resting levels of sVCAM-1 and soluble P-selectin in patients with PTSD. At follow-up, patients with persistent PTSD (n=15) and those who had remitted (n=7) did not significantly differ in CAM levels at rest and after the interview; however, both these groups had significantly higher sVCAM-1 and sICAM-1 at rest and also after the interview compared to patients with no PTSD. Elevated levels of circulating CAMs might help explain the psychophysiologic link of PTSD with cardiovascular risk.

Momentary stress moderates procoagulant reactivity to a trauma-specific interview in patients with posttraumatic stress disorder caused by myocardial infarction

Hypercoagulability of the blood might partially explain the increased cardiovascular disease risk in posttraumatic stress disorder (PTSD) and is also triggered by anticipatory stress. We hypothesized exaggerated procoagulant reactivity in patients with PTSD in response to a trauma-specific interview that would be moderated by momentary stress levels. We examined 23 patients with interviewer-diagnosed PTSD caused by myocardial infarction (MI) and 21 post-MI patients without PTSD. A second diagnostic (i.e., trauma-specific) interview to assess posttraumatic stress severity was performed after a median follow-up of 26 months (range 12-36). Before that interview patients rated levels of momentary stress (Likert scale 0-10) and had blood collected before and after the interview. The interaction between PTSD diagnostic status at study entry and level of momentary stress before the follow-up interview predicted reactivity of fibrinogen (P=0.036) and d-dimer (P=0.002) to the PTSD interview. Among patients with high momentary stress levels, PTSD patients had greater fibrinogen (P=0.023) and d-dimer (P=0.035) reactivity than non-PTSD patients. Among patients with low momentary stress levels, PTSD patients had less d-dimer reactivity than non-PTSD patients (P=0.024); fibrinogen reactivity did not significantly differ between groups. Momentary stress levels, but not severity of posttraumatic stress, correlated with d-dimer reactivity in PTSD patients (r=0.46, P=0.029). We conclude that momentary stress levels moderated the relationship between PTSD and procoagulant reactivity to a trauma-specific interview. Procoagulant reactivity in post-MI patients with PTSD confronted with their traumatically experienced MI was observed if patients perceived high levels of momentary stress before the interview.

Pretreatment and outcome correlates of past sexual and physical trauma in 118 bipolar I disorder patients with a first episode of psychotic mania

To assess the prevalence and correlates of childhood and adolescent sexual and/or physical abuse (SPA) in bipolar I disorder (BDI) patients treated for a first episode of psychotic mania.

Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients

High prevalence of trauma has been reported in psychosis. While role of trauma as a risk factor for developing psychosis is still debated, its negative impact on outcome has been described. Few studies have explored this issue in first-episode psychosis (FEP) patients. We assessed rate of stressful events, as well as premorbid and outcome correlates of past sexual and/or physical abuse (SPA) in an epidemiological FEP patients cohort.