Analysis of genetic diversity in Eucalyptus grandis (Hill ex Maiden) seed sources using inter simple sequence repeats (ISSR) molecular markers

Eucalyptus grandis is an economically important tree species that is native to the Australian continent and its northern neighbours, where it is grown primarily for its hard wood timber and pulp for paperindustries. It is widely grown in tropical countries such as South Africa, Kenya, Angola, Ghana, and Zimbabwe. Five ISSR primers generated 41 scorable polymorphic bands which were used to analyse genetic diversity between and within the seed sources and for construction of neighbour-joining phenogram. Mean Genetic Diversity per each primer loci based on Nei (1987) statistics indicated significant genetic variation between seed sources with 26.4%, (Gst = 0.264) of the total variation attributed to differences between seed sources. The variation between populations could be due to ecological, geographical association and gene flow rates and hence they should be conserved to retain the full breadth of genetic variation of the species. Thus, ISSR-PCR technology is a reliable, rapid (high throughput) and cost effective marker system that can be used to study genetic variation and genetic relationships among E. grandis seed sources

Interferon-ß regulates the production of IL-10 by toll-like receptor-activated microglia

Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression. In this context, the anti-inflammatory cytokine interleukin (IL)-10 appears as an attractive target. In this study, we investigated how activation of microglia by TLRs with distinct roles in MS impacts on IL-10 production. We found that activation of TLR2, TLR4, and TLR9 induced the production of IL-10 to a greater extent than activation of TLR3. This was surprising as both TLR3 and IL-10 play protective roles in animal models of MS. Interestingly, combination of TLR3 triggering with the other TLRs, enhanced IL-10 through the modulation of its transcription, via interferon (IFN)-beta, but independently of IL-27. Thus, in addition to the modulation of inflammatory responses of the periphery described for the axis TLR3/IFN-beta, we now report a direct modulation of microglial responses. We further show that the presence of IFN-gamma in the microenvironment abrogated the modulation of IL-10 by TLR3, whereas that of IL-17 had no effect. Considering the therapeutic application of IFN-beta in MS, our study bears important implications for the understanding of the cytokine network regulating microglia responses in this setting.Portuguese Foundation for Science and Technology (FCT), Grant/Award Numbers: SFRH/BD/88081/2012 and SFRH/BPD/72710/2010; FEDER - Competitiveness Factors Operational Programme (COMPETE), Grant/Award Numbers: POCI-01-0145-FEDER-007038 and NORTE-01-0145-FEDER-000013; Norte Portugal Regional Operational Programme, PORTUGAL 2020, European Regional Development Fund (ERDF), Grant/Award Number: NORTE 2020; FCT-ANR, Grant/Award Number: FCT-ANR/BIM-MEC/0007/2013; FEDER - Fundo Europeu de Desenvolvimento Regional; COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; Institute for Research and Innovation in Health Sciences, Grant/Award Number: POCI-01-0145-FEDER-007274info:eu-repo/semantics/publishedVersio

Ethical leadership as antecedent of job satisfaction, affective organizational commitment and intention to stay among volunteers of non-profit organizations

The aim of this paper is to investigate among a group of non-profit organizations: (a) the effect of ethical leadership (EL) on volunteers\u2019 satisfaction, affective organizational commitment and intention to stay in the same organization; (b) the role played by job satisfaction as a mediator in the relationship between EL and volunteers\u2019 intentions to stay in the same organization, as well as between EL and affective commitment. An anonymous questionnaire was individually administered to 198 Italian volunteers of different non-profit organizations. The questionnaire contained the Ethical Leadership Scale, the Volunteers Satisfaction Index, the Affective organization Scale, as well as questions regarding the participants\u2019 age, sex, type of work, level of education, length of their volunteer works, intention to volunteer in the following months in the same organization. The construct as well the effects of EL on volunteers is approached in light of the Social Exchange Theory and the Social Learning Theory. Structural equation models were used to test hypothesized relationships. The results confirm the role of mediation of volunteer satisfaction in the relationships between the variables studied. In particular, EL was found to be positively associated both with volunteers\u2019 intention of staying and with their affective commitment. In the first case this relationship is fully explained by the mediation of the volunteers\u2019 satisfaction, while the latter is explained by both direct and indirect factors. To the authors\u2019 knowledge, this the first attempt to understand the role played by EL on volunteers\u2019 behavior and, more in general, in the management of non-profit organizations. Findings are relevant both for practitioners and managers of non-profit organization, since they suggest the relevance of the perception of EL by volunteers, as well as for scholars, since they further deepen the knowledge on EL and its effects on the followers. Limits of the study: the questionnaire was administered only among a group of non-statistical sample of volunteers. Furthermore, the study reached only volunteers from Italian non-profit organization

Balancing Feed-Forward Excitation and Inhibition via Hebbian Inhibitory Synaptic Plasticity

It has been suggested that excitatory and inhibitory inputs to cortical cells are balanced, and that this balance is important for the highly irregular firing observed in the cortex. There are two hypotheses as to the origin of this balance. One assumes that it results from a stable solution of the recurrent neuronal dynamics. This model can account for a balance of steady state excitation and inhibition without fine tuning of parameters, but not for transient inputs. The second hypothesis suggests that the feed forward excitatory and inhibitory inputs to a postsynaptic cell are already balanced. This latter hypothesis thus does account for the balance of transient inputs. However, it remains unclear what mechanism underlies the fine tuning required for balancing feed forward excitatory and inhibitory inputs. Here we investigated whether inhibitory synaptic plasticity is responsible for the balance of transient feed forward excitation and inhibition. We address this issue in the framework of a model characterizing the stochastic dynamics of temporally anti-symmetric Hebbian spike timing dependent plasticity of feed forward excitatory and inhibitory synaptic inputs to a single post-synaptic cell. Our analysis shows that inhibitory Hebbian plasticity generates ‘negative feedback’ that balances excitation and inhibition, which contrasts with the ‘positive feedback’ of excitatory Hebbian synaptic plasticity. As a result, this balance may increase the sensitivity of the learning dynamics to the correlation structure of the excitatory inputs

The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats

Clinical evidence indicates that positive allosteric modulators (PAMs) of GABAA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABAA receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABAA receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvulsant, and antinociceptive effects in rodents with reduced motoric side effects. The present study evaluated the potential of KRM-II-81 as a novel analgesic. Oral administration of KRM-II-81 attenuated formalin-induced flinching; in contrast, diazepam was not active. KRM-II-81 attenuated nociceptive-associated behaviors engendered by chronic spinal nerve ligation (L5/L6). Diazepam decreased locomotion of rats at the dose tested in the formalin assay (10 mg/kg) whereas KRM-II-81 produced small decreases that were not dose-dependent (10–100 mg/kg). Plasma and brain levels of KRM-II-81 were used to demonstrate selectivity for α2/3- over α1-associated GABAA receptors and to define the degree of engagement of these receptors. Plasma and brain concentrations of KRM-II-81 were positively-associated with analgesic efficacy. GABA currents from isolated rat dorsal-root ganglion cultures were potentiated by KRM-II-81 with an ED50 of 32 nM. Measures of respiratory depression were reduced by alprazolam whereas KRM-II-81 was either inactive or produced effects with lower potency and efficacy. These findings add to the growing body of data supporting the idea that α2/3-selective GABAA receptor PAMs will have efficacy and tolerability as pain medications including those for neuropathic pain. Given their predicted anxiolytic effects, α2/3-selective GABAA receptor PAMs offer an additional inroad into the management of pain