Myosin VI contributes to synaptic transmission and development at the Drosophila neuromuscular junction

Abstract Background Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ) development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles. Results Our experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse. Conclusions Altogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission

Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications. Keywords: biomaterials; chronic wounds; immunomodulation; intrinsic immune cell signals; regenerative medicine; skin substitutes; skin tissue engineering; wound healing

Observation of long ionizing tracks with the ICARUS T600 first half-module

F. Arneodo, B. Bade"ek, A. Badertscher, B. Baiboussinov, M. Baldo Ceolin, G. Battistoni, B. Bekman, P. Benetti, E. Bernardini, M. Bischofberger, A. Borio di Tigliole, R. Brunetti, A. Bueno, E. Calligarich, M. Campanelli, C. Carpanese, D. Cavalli, F. Cavanna, P. Cennini, S. Centro, A. Cesana, C. Chen, D. Chen, D.B. Chen, Y. Chen, D. Cline, Z. Dai, C. De Vecchi, A. Dabrowska, R. Dolfini*, M. Felcini, A. Ferrari, F. Ferri, Y. Ge, A. Gigli Berzolari, I. Gil-Botella, K. Graczyk, L. Grandi, K. He, J. Holeczek, X. Huang, C. Juszczak, D. Kie"czewska, J. Kisiel, T. Koz"owski, H. Kuna-Ciska", M. Laffranchi, J. Łagoda, Z. Li, F. Lu, J. Ma, M. Markiewicz, A. Martinez de la Ossa, C. Matthey, F. Mauri, D. Mazza, G. Meng, M. Messina, C. Montanari, S. Muraro, S. Navas-Concha, M. Nicoletto, G. Nurzia, S. Otwinowski, Q. Ouyang, O. Palamara, D. Pascoli, L. Periale, G. Piano Mortari, A. Piazzoli, P. Picchi, F. Pietropaolo, W. P ! o"ch"opek, T. Rancati, A. Rappoldi, G.L. Raselli, J. Rico, E. Rondio, M. Rossella, A. Rubbia, C. Rubbia, P. Sala, D. Scannicchio, E. Segreto, F. Sergiampietri, J. Sobczyk, J. Stepaniak, M. Szeptycka, M. Szleper, M. Szarska, M. Terrani, S. Ventura, C. Vignoli, H. Wang, M. W ! ojcik, J. Woo, G. Xu, Z. Xu, A. Zalewska, J. Zalipska, C. Zhang, Q. Zhang, S. Zhen, W. Zipper a INFN Laboratori Nazionali del Gran Sasso, s.s. 17bis Km 18+910, Assergi (L'Aquila), Italy b Institute of Experimental Physics, Warsaw University, Warszawa, Poland c Institute for Particle Physics, ETH H . onggerberg, Z . urich, Switzerland Dipartimento di Fisica e INFN, Universit " a di Padova, via Marzolo 8, Padova, Italy Dipartimento di Fisica e INFN, Universit " a di Milano, via Celoria 16, Milano, Italy f Institute of Physics, University of Silesia, Katowice, Poland Dipartimento di Fisica e INFN, Universit " a di Pavia, via Bassi 6, Pavia, Italy Dpto de F!isica Te ! orica y del Cosmos & C.A.F.P.E., Universidad de Granada, Avda. Severo Ochoa s/n, Granada, Spain Dipartimento di Fisica e INFN, Universit " a dell'Aquila, via Vetoio, L'Aquila, Italy CERN, CH-1211 Geneva 23, Switzerland Politecnico di Milano (CESNEF), Universit " a di Milano, via Ponzio 34/3, Milano, Ital

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Myosin VI contributes to synaptic transmission and development at the <it>Drosophila </it>neuromuscular junction

Abstract Background Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ) development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles. Results Our experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse. Conclusions Altogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission.</p

Hydrogen Gas Inhalation Attenuates Acute Impulse Noise Trauma : A Preclinical In Vivo Study

Objective: Molecular hydrogen (H2) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H2 when inhaled immediately after impulse noise exposure. Methods: Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H2 inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H2 group), or to H2 inhalation (n = 5; the H2 group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H2 exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells. Results: Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H2 group; P &lt; .05) but significantly less so in the Noise + H2 group (P &lt; .05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H2 group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H2 group. The difference between the groups was significant in the basal region for OHCs (P = .003) and apical (P = .033) and basal (P = .048) regions for IHCs. Conclusions: Acute acoustic trauma can be reduced by H2 when inhaled immediately after impulse noise exposure

Predicting Return to Work after Head and Neck Cancer Treatment Is Challenging Due to Factors That Affect Work Ability

Striving to return to work is of great importance to many cancer survivors. The purpose of the study is to prospectively investigate the factors that hinder and facilitate return to work (RTW) at 3 and 12 months after the end of treatment in head and neck cancer (HNC) survivors and whether these factors influence the ability to continue working after treatment. Participants (n = 227) aged ≤ 65 years at diagnosis with HNC were included. Data were collected before the start of treatment and at 3 and 12 months after the end of treatment. The Rubin causal model was used for statistical analysis. Within the 3-month follow-up period, 92 participants had RTW and 30 had retired. At the 12-month follow-up, 80 of these participants were still working, another 51 participants had RTW, and five participants working still suffered from cancer. The hindrance to RTW within 3 months was advanced tumour stage (stage III and IV) (p = 0.0038). Hindrances to RTW at the 12-month follow-up were oral cancer (p = 0.0210) and larynx cancer (p = 0.0041), and facilitators were living in a relationship (p = 0.0445) and a white-collar job (p = 0.00267). Participants with early tumour stage (stage I and II) (p = 0.0019) and a white-collar job (p = 0.0185) had earlier RTW. The conclusion is that disease factors were the most important hindrances to RTW, and type of work and living with a spouse or partner were nonclinical factors influencing RTW