Elucidating the molecular mechanisms conferred by the histone chaperone FACT

The conserved and essential histone chaperone FACT (Facilitates Chromatin Transcription) reorganises nucleosomes during DNA transcription, replication and repair and ensures both, efficient elongation of polymerases and nucleosome integrity. In mammalian cells, FACT is a heterodimer, consisting of SSRP1 and SUPT16. Although the genetics and biochemistry of FACT are relatively well understood, it is not known whether it confers cell-type dedicated functions. However, genome-wide expression analyses across cell and tissue types implicate a role of FACT in maintaining an undifferentiated state. Here, we show that in mouse embryonic stem cells (mESCs), depletion of FACT leads to up-regulation and alternative splicing of pro-proliferative genes and key pluripotency factors concomitantly with hyper-proliferation of mES cells. Additionally, genes involved in neurogenesis are de-repressed in the absence of FACT, leading to faster progression of neuronal differentiation. To understand the role of FACT in regulating transcription at these loci, we performed MNase digestion of chromatin coupled to deep sequencing (MNase-seq) and Nascent Elongating Transcript Sequencing (NET-seq). Genes up-regulated upon FACT depletion, are characterised by loss of MNase-resistance just upstream of the transcription start site, suggesting that nucleosome deposition by FACT dampens gene expression. Finally, in combination with the NET-seq data, we show that this FACT-dependent nucleosome distribution at the promoter region is closely associated with strong uni-directionality of RNA Polymerase II towards the coding region. Taken together, FACT promotes Pol II governing through nucleosome deposition and thus enables maintenance of an undifferentiated state

Αλλαγές στον ρυθμό εφαρμογή δύναμης των κάτω άκρων από την προπαρασκευαστική στην αγωνιστική περίοδο σε αθλητές ρίψεων

Τις αθλητικές ρίψεις αποτελούν τα αγωνίσματα του ακοντισμού, της δισκοβολίας, της σφαιροβολίας και της σφυροβολίας. Η προπόνηση των αθλητών ρίψεων βασίζεται στις αρχές του περιοδισμού, που με βάση τη θεωρία αυτή, η αθλητική χρονιά χωρίζεται σε τρείς κύριες περιόδους μέσα στις οποίες υπάρχουν αυξομειώσεις της έντασης και του όγκου της προπόνησης με στόχο την κορύφωση της επίδοσης στην περίοδο των αγώνων. Για τη μεγιστοποίηση της ριπτικής επίδοσης πέρα της τεχνικής κατάρτισης των αθλητών και άλλων παραμέτρων ένας εκ των οποίων διαδραματίζει σημαντικότατο ρόλο είναι η αύξηση της παραγόμενης μυϊκής ισχύος των ριπτών. Σκοπός της παρούσας μελέτης ήταν να εξετάσει τις αλλαγές στο ρυθμό εφαρμογής δύναμης (ΡΕΔ) από την προπαρασκευαστική στην αγωνιστική περίοδο σε αθλητές των ρίψεων. Στην έρευνα συμμετείχαν 7 αθλητές μέσου έως υψηλού επιπέδου και των τεσσάρων ριπτικών αγωνισμάτων, οι οποίοι αξιολογήθηκαν στην ισχύ των κάτω άκρων μέσω του ΡΕΔ στη φάση 2 της προπαρασκευαστικής περιόδου (Τ1) και στη φάση 3 της αγωνιστικής περιόδου (Τ2). Τα αποτελέσματα έδειξαν ότι ο ΡΕΔ αυξήθηκε από την T1 στην T2 περίοδο σε όλα τα χρονικά σημεία που αυτός αξιολογήθηκε. Συγκεκριμένα, στα 150ms υπήρξε ποσοστιαία αύξηση κατά 3.363±1.7 (p=0.024, η2=0.599, power=0.705), στα 200ms υπήρξε ποσοστιαία αύξηση κατά 2.225±1.7 (p=0.009, η2=0.710, power=0.888) και στα 250ms υπήρξε ποσοστιαία αύξηση κατά 1,978±1,7 (από p=0.003, η2=0.799, power=0.980). Σύμφωνα με τα αποτελέσματα υπήρξε στατιστικά σημαντική βελτίωση του ΡΕΔ από την πρώτη στην δεύτερη αξιολόγηση, που συνεπάγεται την αύξηση της μυϊκής ισχύος των κάτω άκρων των αθλητών με σκοπό την βελτίωση της ριπτικής τους επίδοσης.ΟΧ

Soft-Tissue Techniques in Sports Injuries Prevention and Rehabilitation

Participation in sports, in addition to its positive effects, leads to injuries caused by contact with the opponent or the high loads that develop on the musculoskeletal structures during the sports activities. Sports injuries mainly include (a) acute injuries such as muscle strains and ligament sprains, tendon injuries, dislocations and subluxations, fractures, and skin injuries but also (b) overuse injuries such as tendinopathies and painful myofascial syndromes. Many therapeutic techniques are used to treat these injuries, such as therapeutic exercise, various electrotherapy procedures and soft tissue techniques. Soft tissue techniques aim to promote health and well-being through their mechanical effects on the body’s soft tissues such as friction, compression, tissues sliding and myofascial release. Sports soft-tissue procedures are applied either directly with the hands of therapists such as classical massage or with the use of special equipment such as tools made of stainless steel (ERGON instrument-assisted soft tissue mobilization), elastic ischemic bandages (Kinetic flossing technique) and cups (cupping therapy). The following chapter analyzes the therapeutic effects of the above therapeutic interventions by presenting recent scientific evidence that supports their effects on the soft tissue’s dysfunctions of the human body and various pathological conditions

Blood Flow Restriction Training in Cardiovascular Disease Patients

Over the past two decades, blood flow restriction training (BFRT) has gained popularity not only in athletic performance training, but also with many researchers and physical therapists as an innovative rehabilitation tool. Blood flow restriction (BFR) exercise is a novel exercise modality in clinical settings, which induces muscle hypertrophy and increases strength with low to moderate training intensity through increased anabolic processes mediated by BFR (usually with cuff inflation). BFR limits arterial and venous blood flow and leads to blood pooling, which could increase the effects of exercise-induced training. Strength training at lower intensities (20–40% of maximum strength) in combination with BFR showed similar effects on muscle hypertrophy as training at 70% strength level without BFR. In this context, considering that periods of immobilization (or reduced functionality) due to pathology, injury, or surgery cause harmful effects on muscle mass and strength in both young and old people, muscular adaptations of occlusion exercise could be beneficial to the elderly and post-operative patients in rehabilitation regarding muscle regeneration. Furthermore, as this type of exercise does not require high loads, it might be a feasible method in cardiac rehabilitation. Therefore, this chapter aims to review all recent literature regarding the impact of low-load BFR resistance training in patients with cardiovascular pathologies on muscle strength and hypertrophy, vascular function, safety, cardiovascular responses, and inflammatory markers

A Game Theoretical Method for Cost-Benefit Analysis of Malware Dissemination Prevention

Copyright © Taylor & Francis Group, LLC. Literature in malware proliferation focuses on modeling and analyzing its spread dynamics. Epidemiology models, which are inspired by the characteristics of biological disease spread in human populations, have been used against this threat to analyze the way malware spreads in a network. This work presents a modified version of the commonly used epidemiology models Susceptible Infected Recovered (SIR) and Susceptible Infected Susceptible (SIS), which incorporates the ability to capture the relationships between nodes within a network, along with their effect on malware dissemination process. Drawing upon a model that illustrates the network’s behavior based on the attacker’s and the defender’s choices, we use game theory to compute optimal strategies for the defender to minimize the effect of malware spread, at the same time minimizing the security cost. We consider three defense mechanisms: patch, removal, and patch and removal, which correspond to the defender’s strategy and use probabilistically with a certain rate. The attacker chooses the type of attack according to its effectiveness and cost. Through the interaction between the two opponents we infer the optimal strategy for both players, known as Nash Equilibrium, evaluating the related payoffs. Hence, our model provides a cost-benefit risk management framework for managing malware spread in computer networks

Surgical Outcomes in Syndromic Tetralogy of Fallot: A Systematic Review and Evidence Quality Assessment

Tetralogy of Fallot (ToF) is one of the most common cyanotic congenital heart defects. We sought to summarize all available data regarding the epidemiology and perioperative outcomes of syndromic ToF patients. A PRISMA-compliant systematic literature review of PubMed and Cochrane Library was performed. Twelve original studies were included. The incidence of syndromic ToF was 15.3% (n = 549/3597). The most prevalent genetic syndromes were 22q11.2 deletion (47.8%; 95% CI 43.4–52.2) and trisomy 21 (41.9%; 95% CI 37.7–46.3). Complete surgical repair was performed in 75.2% of the patients (n = 161/214; 95% CI 69.0–80.1) and staged repair in 24.8% (n = 53/214; 95 CI 19.4–30.9). Relief of RVOT obstruction was performed with transannular patch in 64.7% (n = 79/122; 95% CI 55.9–72.7) of the patients, pulmonary valve-sparing technique in 17.2% (n = 21/122; 95% CI 11.5–24.9), and RV-PA conduit in 18.0% (n = 22/122; 95% CI 12.1–25.9). Pleural effusions were the most common postoperative complications (n = 28/549; 5.1%; 95% CI 3.5–7.3). Reoperations were performed in 4.4% (n = 24/549; 95% CI 2.9–6.4) of the patients. All-cause mortality rate was 9.8% (n = 51/521; 95% CI 7.5–12.7). Genetic syndromes are seen in approximately 15% of ToF patients. Long-term survival exceeds 90%, suggesting that surgical management should be dictated by anatomy regardless of genetics

Splenic trauma : WSES classification and guidelines for adult and pediatric patients

Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.Peer reviewe