Early Science with the Large Millimetre Telescope: Molecules in the Extreme Outflow of a proto-Planetary Nebula

Extremely high velocity emission likely related to jets is known to occur in some proto-Planetary Nebulae. However, the molecular complexity of this kinematic component is largely unknown. We observed the known extreme outflow from the proto-Planetary Nebula IRAS 16342-3814, a prototype water fountain, in the full frequency range from 73 to 111 GHz with the RSR receiver on the Large Millimetre Telescope. We detected the molecules SiO, HCN, SO, and $^{13}$CO. All molecular transitions, with the exception of the latter are detected for the first time in this source, and all present emission with velocities up to a few hundred km s$^{-1}$. IRAS 16342-3814 is therefore the only source of this kind presenting extreme outflow activity simultaneously in all these molecules, with SO and SiO emission showing the highest velocities found of these species in proto-Planetary Nebulae. To be confirmed is a tentative weak SO component with a FWHM $\sim$ 700 km s$^{-1}$. The extreme outflow gas consists of dense gas (n$_{\rm H_2} >$ 10$^{4.8}$--10$^{5.7}$ cm$^{-3}$), with a mass larger than $\sim$ 0.02--0.15 M$_{\odot}$. The relatively high abundances of SiO and SO may be an indication of an oxygen-rich extreme high velocity gas.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society Letter

Geminivirus replication protein decreases PCNA sumoylation at two acceptor sites

Geminiviruses are plant viruses with circular, single-stranded DNA (ssDNA) genomes that infect a broad range of plants causing substantial crop diseases worldwide. They replicate in nuclei of infected cells by using host DNA replication machinery and an essential protein encoded in their genome designated Rep (replication-associated protein). This multifunctional protein induces the accumulation of the host factors involved in replication and it is capable of interacting with a lot of plant proteins including PCNA (Proliferating Cell Nuclear Antigen), a processivity factor that coordinates a wide range of processes involved in maintenance, duplication and transmission of the genome, and the sumoylation enzyme that conjugates SUMO to target proteins (SUMO-conjugating enzyme- SCE). PCNA modification by SUMO, and also ubiquitin, has long been known to be of key importance for determining how DNA damage is processed by the replisome and for maintenance of overall genome integrity. In yeast, PCNA sumoylation has been associated to DNA repair involving homologous recombination (HR). Previously, we reported that Rep ectopic expression does not result in broad changes in the sumoylation pattern of plant cells, but it modifies the sumoylation state of selected host proteins. In this work, we show, using a reconstituted sumoylation system in Escherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the Rep protein suppresses PCNA sumoylation at these lysines. Finally, we confirm that PCNA is sumoylated and that Rep also interferes with PCNA sumoylation in planta.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Eudragit® L100/chitosan composite thin bilayer films for intravaginal pH-responsive release of Tenofovir

[EN] The high rate of HIV new infections and AIDS-related deaths each year make prevention tools still necessary today. Different dosage forms – including films – for vaginal administration of antiretroviral drugs have been developed for this purpose. Six batches of Tenofovir-loaded films were formulated based on Eudragit® L100 (EL100) and chitosan, containing triethyl citrate and glycerol. In all the cases films structured in two layers – the upper layer mainly attributed to EL100 and the lower layer to chitosan – were revealed by SEM. A higher content in EL100 and plasticizers improves the mechanical properties and control over drug release in the vaginal medium without affecting mucoadhesion. The EL100-based layer acts as a structuring agent that controls Tenofovir release for days in the vaginal medium while it occurs in a few hours in the presence of seminal fluid. Bilayer films with the highest tested content of EL100 and plasticizers would be the most suitable as vaginal microbicides as they are easier to administer due to their excellent mechanical properties and they offer more comfortable posology and enhanced protection against HIV during intercourse due to their pH-responsive release of Tenofovir.This work was supported by the Spanish Research Agency and the European Regional Development Fund (AEI/FEDER, UE) [MAT2016-76416-R]

Therapeutic doses of nonsteroidal anti-inflammatory drugs inhibit osteosarcoma MG-63 osteoblast-like celss maturation, viability, and biomineralization potential

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line) were incubated in culture medium with 1–10  M of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP) by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.This study was supported by the BIO277 research group (Junta de Andalucía), by the Department of Nursing, Faculty of Health Sciences, University of Granada and by the research group Brighton Studies in Tissue-mimicry and Aided Regeneration (BrightSTAR), School of Pharmacy & Biomolecular Sciences, University of Brighton

A Bayesian Multiple-Trait and Multiple-Environment Model Using the Matrix Normal Distribution

Genomic selection (GS) is playing a major role in plant breeding for the selection of candidate individuals (animal or plants) early in time. However, for improving GS better statistical models are required. For this reason, in this chapter book we provide an improved version of the Bayesian multiple-trait and multiple-environment (BMTME) model of Montesinos-López et al. that takes into account the correlation between traits (genetic and residual) and between environments since allows general covariance’s matrices. This improved version of the BMTME model was derived using the matrix normal distribution that allows a more easy derivation of all full conditional distributions required, allows a more efficient model in terms of time of implementation. We tested the proposed model using simulated and real data sets. According to our results we have elements to conclude that this model improved considerably in terms of time of implementation and it is better than a Bayesian multiple-trait, multiple-environment model that not take into account general covariance structure for covariance’s of the traits and environments

Surgical management of a diabetic calcaneal ulceration and osteomyelitis with a partial calcanectomy and a sural neurofasciocutaneous flap

The treatment of calcaneal osteomyelitis in diabetic patients poses a great challenge to the treating physician and surgeon. The use of a distally based sural neurofasciocutaneous flap after an aggressive debridement of non-viable and poorly vascularized tissue and bone that is combined with a thorough antibiotic regimen provides a great technique for adequate soft tissue coverage of the heel. In this case report, the authors describe the aforementioned flap as a versatile alternative to the use of local or distant muscle flaps for diabetic patients with calcaneal osteomyelitis and concomitant large wounds

Predicting the onset and persistence of episodes of depression in primary health care. The predictD-Spain study: Methodology

Background: The effects of putative risk factors on the onset and/or persistence of depression remain unclear. We aim to develop comprehensive models to predict the onset and persistence of episodes of depression in primary care. Here we explain the general methodology of the predictD-Spain study and evaluate the reliability of the questionnaires used. Methods: This is a prospective cohort study. A systematic random sample of general practice attendees aged 18 to 75 has been recruited in seven Spanish provinces. Depression is being measured with the CIDI at baseline, and at 6, 12, 24 and 36 months. A set of individual, environmental, genetic, professional and organizational risk factors are to be assessed at each follow-up point. In a separate reliability study, a proportional random sample of 401 participants completed the test-retest (251 researcher-administered and 150 self-administered) between October 2005 and February 2006. We have also checked 118,398 items for data entry from a random sample of 480 patients stratified by province. Results: All items and questionnaires had good test-retest reliability for both methods of administration, except for the use of recreational drugs over the previous six months. Cronbach's alphas were good and their factorial analyses coherent for the three scales evaluated (social support from family and friends, dissatisfaction with paid work, and dissatisfaction with unpaid work). There were 191 (0.16%) data entry errors. Conclusion: The items and questionnaires were reliable and data quality control was excellent. When we eventually obtain our risk index for the onset and persistence of depression, we will be able to determine the individual risk of each patient evaluated in primary health car