Dolutegravir-based regimen maintains virological success in a patient with archived mutations to integrase inhibitors

no abstract availabl

Indole-3-butyric acid induces ectopic formation of metaxylem in the hypocotyl of Arabidopsis thaliana without conversion into indole-3-acetic acid and with a positive interaction with ethylene

The role of the auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) and of the auxin-interacting phytohormone ethylene, on the ectopic formation of primary xylem (xylogenesis in planta) is still little known. In particular, auxin/ethylene-target tissue(s), modality of the xylary process (trans-differentiation vs. de novo formation), and the kind of ectopic elements formed (metaxylem vs. protoxylem) are currently unknown. It is also unclear whether IBA may act on the process independently of conversion into IAA. To investigate these topics, histological analyses were carried out in the hypocotyls of Arabidopsis wild type seedlings and ech2ibr10 and ein3eil1 mutants, which are blocked in IBA-to-IAA conversion and ethylene signalling, respectively. The seedlings were grown under darkness with either IAA or IBA, combined or not with the ethylene precursor 1-aminocyclopropane-1-carboxylic acid. Adventitious root formation was also investigated because this process may compete with xylogenesis. Our results show that ectopic formation of protoxylem and metaxylem occurred as an indirect process starting from the pericycle periclinal derivatives of the hypocotyl basal part. IAA favoured protoxylem formation, whereas IBA induced ectopic metaxylem with ethylene cooperation through the EIN3EIL1 network. Ectopic metaxylem differentiation occurred independently of IBA-to-IAA conversion as mediated by ECH2 and IBR10, and in the place of IBA-induced adventitious root formation

Recognition and Phagocytosis of Apoptotic Cells

Physiological elimination of unwanted cells within the organism occurs via cell death by apoptosis and phagocytosis of these cells represents a key event in the apoptotic process. Macrophages, which are the dedicated phagocytes, and other occasionally phagocytic cells ingest the apoptotic cells while they are still intact, thus preventing the leakage of potentially harmful materials from the dying cells. Although evidence has been presented that the elimination of apoptotic bodies from the tissue operates by means of specific recognition systems, the molecular mechanisms by which an apoptotic cell is recognized are poorly understood. Recent data indicate that phagocyte recognition of apoptotic cells involves at least four classes of receptors on the phagocyte surface. On the other side, dying cells may display different signals to signal their status. Exposure of phosphatidyl serine (PS) on the surface of apoptotic lymphocytes triggers their specific recognition and removal by macrophages. Apoptotic thymocytes are also identified by altered lipid packing on their surface. Different populations of macrophages use either the vitronectin receptor or the PS receptor to recognize and remove apoptotic cells. It has been suggested that the asialoglycoprotein and the galactose-specific receptors of healthy hepatocytes and sinusoidal liver cells are implicated in the engulfment of apoptotic hepatocytes, likely in cooperation with other hepatic carbohydrate-specific receptor systems. The purpose of this review is to examine current knowledge of the mechanisms by which phagocytes recognize and ingest apoptotic cells

Percepciones de los alumnos acerca de las evaluaciones integrales de desempeño: hacia un modelo de evaluación eficaz enfocado en las destrezas comunicativas

In the field of foreign and second language teaching, current trends in curriculum development highlight the importance of creating performance-based assessment instruments focused on the three modes of communication: interpretive (aural or reading comprehension without the possibility of negotiating meaning with the creator of the message), presentational (written or oral communication without the possibility of negotiating meaning with the reader/interlocutor) and interpersonal (oral or written two-way communication with the possibility of negotiating meaning with the reader/interlocutor) (The National Standards Collaborative Board 2015). As previous studies (Adair-Hauck, Glisan et al. 2006, Davin, Troyan et al. 2011, Adair-Hauck & Troyan 2013, Zapata 2016, Levi Altstaedter & Krosl 2018; among others) have shown, Integrated Performance Assessments, are a viable option for this kind of assessment approach. A crucial aspect of the teaching-learning process are students’ perceptions, as these can impact their performance on tasks and assessments. Although previous studies have focused on students’ perceptions of IPAs, (Zapata 2016, Levi Altstaedter & Krosl 2018), more research is needed on this topic. Therefore, this study investigates the relationship among variables such as perceptions of effectiveness of IPAs, assessment anxiety, perceptions of instrument design, and students’ satisfaction, while offering a theoretical model that presents a connection among those variables and offers a theoretical model that includes the conections among those variables. En el campo de la enseñanza de lenguas segundas y extranjeras, las tendencias actuales en diseño curricular se enfocan en la importancia de crear instrumentos que evalúen el progreso del alumno en cuanto al desarrollo de sus destrezas comunicativas en tres modos de comunicación: interpretativo (comprensión auditiva o lectora sin posibilidad de negociación de sentido con el creador del mensaje), presentacional (comunicación escrita u oral sin posibilidad de negociación de sentido con el lector/interlocutor) e interpersonal (comunicación oral o escrita con posibilidad de negociación de sentido con el lector/interlocutor) (The National Standards Collaborative Board 2015). Un tipo de evaluación que permite este enfoque es la evaluación integral de desempeño, cuya efectividad ha sido analizada en estudios recientes (Adair-Hauck, Glisan et al. 2006, Davin, Troyan et al. 2011, Adair-Hauck & Troyan 2013, Zapata 2016, Levi Altstaedter & Krosl 2018, entre otros). Un aspecto de suma importancia en el proceso enseñanza-aprendizaje son las percepciones del alumno, ya que éstas pueden influir en su desempeño en tareas y evaluaciones. Si bien estudios anteriores se han enfocado en el análisis de las percepciones de los alumnos acerca de las evaluaciones integrales de desempeño (Zapata 2016, Levi Altstaedter & Krosl 2018), es necesario ahondar aún más esta línea de investigación. Así, el presente estudio propone un análisis de la relación de variables tales como las percepciones de efectividad de las evaluaciones, las percepciones de ansiedad frente a las evaluaciones, las percepciones del diseño de instrumentos y las percepciones de satisfacción del alumno y ofrece un modelo teórico que presenta la conexión entre dichas variables

Transglutaminase Type II Is a Key Element in the Regulation of the Anti-Inflammatory Response Elicited by Apoptotic Cell Engulfment

Abstract A key feature of the macrophage-dependent clearance of apoptotic cells is the down-regulation of proinflammatory cytokines. Deficiency in the phagocytosis of apoptotic cells is often associated with the development of inflammatory reactions, resulting in chronic inflammatory and autoimmune diseases. The molecular mechanisms that regulate the engulfment process and particularly the immunomodulatory factors involved are still largely unknown in mammals. We have previously reported that the ablation of transglutaminase type II (TG2) in mice results in the defective clearance of apoptotic cells associated with the development of splenomegaly, autoantibodies, and glomerulonephritis. In this study we have investigated the mechanisms at the basis of the development of inflammation/autoimmunity associated with the defective clearance of apoptotic cells characterizing TG2 knockout mice. To this aim we compared the macrophage response to apoptotic cell exposure in wild-type vs TG2-null mice. We demonstrated that the lack of TG2 results in an impaired capacity of macrophages to engulf, but not to bind, apoptotic cells, which is paralleled by an abnormal inflammatory response both in vivo and in vitro. We have identified a differential response in the release of several cytokines in TG2−/− vs wild-type mice. Particularly relevant is the finding that both TGF-β and IL-12 regulations were significantly altered in the absence of TG2. These results help explain the autoimmune phenotype developed by these mice and suggest that TG2 is a key regulatory element of the anti-inflammatory features of apoptosis

Jasmonate and nitric oxide roles in the control of xylary cell formation and identity in Arabidopsis seedlings

In basal hypocotyls of dark-grown Arabidopsis seedlings, xylary cells may form from the pericycle as an alternative to another developmental program, i.e. adventitious roots. It is known that several hormones may induce xylogenesis, as jasmonic acid (JA), indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA), which also affect xylary cell identity. Recent studies with the ethylene (ET)-perception mutant ein3eil1 and the ET-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) have shown ET involvement in IBA induced ectopic metaxylem. Nitric oxide (NO) is a reactive free radical molecule, which acts as a messenger in several cell differentiation events, including programmed cell death, moreover it can be produced after IBA/IAA-treatments influencing JA signalling and interacting positively/negatively with ET. To date, NO involvement in ET/JA-mediated xylogenesis has never been investigated.The aim of the present research was to determine the involvement of JA, ET and NO in the control of endogenous/exogenous auxin-induced xylogenesis through a possible crosstalk mediated by EIN3/EIL1. To this aim, ectopic xylem formation was investigated in the hypocotyl of dark-grown Arabidopsis seedlings exposed to various concentrations of JA methyl-ester (JAMe) with/without ACC, IBA or IAA. The xylogenic response in the wild-type (wt) was compared with that of the ein3eil1 mutant, the NO signal was quantified and the its role evaluated by measuring the effects of treatments with a NO donor/scavenger (SNP/cPTIO). Results show that the ectopic formation of protoxylem was enhanced in the wt by JAMe when applied alone at a specific concentration (i.e. 10μM), whereas in ein3eil1 mutant it occurred with any JAMe concentration (i.e. 0.01, 1 and 10 μM). This stimulation of xylary elements mediated by JAMe suggests that a negative interaction between JA and ET-signalling is involved in this developmental program. The negative interaction was confirmed by the reduction in xylogenesis observed in the wt after the combined application of JAMe with ACC, in comparison with JAMe alone. Nitric oxide was detected at early stages of both xylogenesis and adventitious rooting in the hypocotyl pericycle cells and its production was highly enhanced by JAMe at the highest concentration, combined or not with IBA (10 μM). Histological analyses showed that the xylary identity changed when JAMe was applied with each auxin in comparison with treatments with auxin alone. In addition, the IBA/IAA-induced adventitious rooting was increased by the same JAMe concentration enhancing xylogenesis when applied alone. This suggests a role for JA in modulating both developmental programs (adventitious rooting and xylogenesis) in the same target cells (hypocotyl pericycle cells), through an interaction with NO, as summarized in the model proposed (Fig. 1)

Nitric oxide cooperates with auxin to mitigate the alterations in the root system caused by cadmium and arsenic

Oryza sativa L. is a worldwide food-crop frequently growing in cadmium (Cd)/arsenic (As) polluted soils, with its root-system as the first target of the pollutants. Root-system development involves the establishment of optimal indole-3-acetic acid (IAA) levels, also requiring the conversion of the IAA natural precursor indole-3-butyric acid (IBA) into IAA, causing nitric oxide (NO) formation. Nitric oxide is a stress-signaling molecule. In rice, a negative interaction of Cd or As with endogenous auxin has been demonstrated, as some NO protective effects. However, a synergism between the natural auxins (IAA and/or IBA) and NO was not yet determined and might be important for ameliorating rice metal(oid)-tolerance. With this aim, the stress caused by Cd/As toxicity in the root cells and the possible recovery by either NO or auxins (IAA/IBA) were evaluated after Cd or As (arsenate) exposure, combined or not with the NO-donor compound sodium-nitroprusside (SNP). Root fresh weight, membrane electrolyte leakage, and H2O2 production were also measured. Moreover, endogenous IAA/IBA contents, transcription-levels of OsYUCCA1 and OsASA2 IAA-biosynthetic-genes, and expression of the IAA-influx-carrier OsAUX1 and the IAA-responsive DR5::GUS construct were analyzed, and NO-epifluorescence levels were measured. Results showed that membrane injury by enhanced electrolyte leakage occurred under both pollutants and was reduced by the treatment with SNP only in Cd-presence. By contrast, no membrane injury was caused by either exogenous NO or IAA or IBA. Cd- and As-toxicity also resulted into a decreased root fresh weight, mitigated by the combination of each pollutant with either IAA or IBA. Cd and As decreased the endogenous NO-content, increased H2O2 formation, and altered auxin biosynthesis, levels and distribution in both adventitious (ARs) and mainly lateral roots (LRs). The SNP-formed NO counteracted the pollutants’ effects on auxin distribution/levels, reduced H2O2 formation in Cd-presence, and enhanced AUX1-expression, mainly in As-presence. Each exogenous auxin, but mainly IBA, combined with Cd or As at 10 µM, mitigated the pollutants’ effects by increasing LR-production and by increasing NO-content in the case of Cd. Altogether, results demonstrate that NO and auxin(s) work together in the rice root system to counteract the specific toxic-effects of each pollutant

Jasmonates, ethylene and brassinosteroids control adventitious and lateral rooting as stress avoidance responses to heavy metals and metalloids

Developmental and environmental signaling networks often converge during plant growth in response to changing conditions. Stress-induced hormones, such as jasmonates (JAs), can influence growth by crosstalk with other signals like brassinosteroids (BRs) and ethylene (ET). Nevertheless, it is unclear how avoidance of an abiotic stress triggers local changes in development as a response. It is known that stress hormones like JAs/ET and BRs can regulate the division rate of cells from the first asymmetric cell divisions (ACDs) in meristems, suggesting that stem cell activation may take part in developmental changes as a stress-avoidance-induced response. The root system is a prime responder to stress conditions in soil. Together with the primary root and lateral roots (LRs), adventitious roots (ARs) are necessary for survival in numerous plant species. AR and LR formation is affected by soil pollution, causing substantial root architecture changes by either depressing or enhancing rooting as a stress avoidance/survival response. Here, a detailed overview of the crosstalk between JAs, ET, BRs, and the stress mediator nitric oxide (NO) in auxin-induced AR and LR formation, with/without cadmium and arsenic, is presented. Interactions essential in achieving a balance between growth and adaptation to Cd and As soil pollution to ensure survival are reviewed here in the model species Arabidopsis and rice

Cortical Network Topology in Prodromal and Mild Dementia Due to Alzheimer\u2019s Disease: Graph Theory Applied to Resting State EEG

Graph theory analysis on resting state electroencephalographic rhythms disclosed topological properties of cerebral network. In Alzheimer\u2019s disease (AD) patients, this approach showed mixed results. Granger causality matrices were used as input to the graph theory allowing to estimate the strength and the direction of information transfer between electrode pairs. The number of edges (degree), the number of inward edges (in-degree), of outgoing edges (out-degree) were statistically compared among healthy controls, patients with mild cognitive impairment due to AD (AD-MCI) and AD patients with mild dementia (ADD) to evaluate if degree abnormality could involve low and/or high degree vertices, the so called hubs, in both prodromal and over dementia stage. Clustering coefficient and local efficiency were evaluated as measures of network segregation, path length and global efficiency as measures of integration, the assortativity coefficient as a measure of resilience. Degree, in-degree and out-degree values were lower in AD-MCI and ADD than the control group for non-hubs and hubs vertices. The number of edges was preserved for frontal electrodes, where patients\u2019 groups showed an additional hub in F3. Clustering coefficient was lower in ADD compared with AD-MCI in the right occipital electrode, and it was positively correlated with mini mental state examination. Local and global efficiency values were lower in patients\u2019 than control groups. Our results show that the topology of the network is altered in AD patients also in its prodromal stage, begins with the reduction of the number of edges and the loss of the local and global efficiency

Brassinosteroids interact with nitric oxide in the response of rice root systems to arsenic stress

Brassinosteroids (BRs), an emerging class of phytohormones, affect numerous plant physiological and metabolic processes and can improve plant defense systems to counteract metalloid phytotoxicity. Nitric oxide (NO), a reactive nitrogen species (RNS), behaves as a signalling molecule activating plant cellular responses to various environmental conditions. Brassinosteroids induce NO synthesis through nitrate reductase (NR) and NO synthase (NOS) activities. Arsenite and arsenate, inorganic forms of the metalloid arsenic (As), cause both soil pollution and many disorders in numerous plants, including important crops like rice, due to the oxidative stress generated by the imbalance between RNS and reactive oxygen species (ROS). Rice is very susceptible to As toxicity because both As availability and solubility are high in flooded paddy fields in many cultivated areas. The research aims to investigate the effects of BRs on the rice root systems exposed to 10-4 M Na2HAsO40.7 H2O [As(V)] or 2.5 × 10-5 M NaAsO2 [As(III)], highlighting the induced cyto-histological events and dissecting the NO role in the root response. A specific concentration (10-7 M) of 24-epibrassinolide (24-eBL), an exogenously applied BR, increases lateral root (LR) formation of more than 50% in the presence of As(III) or As(V). In addition, eBL attenuates the thickening of the cell walls induced by As in the outermost root cortical layers of LRs and in the adventitious roots (ARs) by reducing of ⁓ 50% the lignin deposition, while it restores the As(v)-altered NO levels by increasing OsNOS1 expression and the cellular NO distribution