Studies on forest health and vegetation changes in Greece under the effects of climate changes

Greece, as part of the Mediterranean Basin, is projected to be among the most vulnerable countries to climate change. It is therefore quite urgent to adapt forest management to the changing climate in order to enhance biodiversity and to enable the conservation of healthy and productive forests. In the framework of the project LIFE+ AdaptFor (www.life-adaptfor.gr), an effort was made to understand the ecological responses and the vulnerability of forest ecosystems in the face of climate change; the overall aim of the project is the development and implementation of appropriate adaptation strategies. Four study areas were selected where changes in vegetation, quite likely attributed to climate change, have already been observed (dieback of Scots pine and Greek fir, intrusion of conifers in broadleaved forests). To investigate the synergism of climatic parameters’ alterations in the development of the occurring phenomena, time series of temperature and precipitation for the period 1950–2009 were produced and parameters of forest status were investigated, including mapping of vegetation changes through remote sensing. The findings support the hypothesis that climate change has an impact on forest health; the dieback of tree species can be attributed to outbreaks of pathogens (fungi and insects) which are associated with climatic parameters. However, the intrusion of conifer species into broadleaved forests showed no direct connection to climatic parameters, something that needs to be further investigated. In all cases, insufficient or inappropriate management practices applied in the areas exacerbated the occurring phenomena.     

Pituitary adenylate cyclase-activating peptide: a pivotal modulator of steroid-induced reproductive behavior in female rodents

Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates the secretion of GnRH into the hypothalamic hypophysial portal system and sensitizes the pituitary for release of hormones that trigger ovulation. Because reproductive behavior is synchronized with GnRH release, the present study was undertaken to determine whether PACAP in the ventromedial nucleus (VMN) plays a role in receptivity. To this end, we used rat and mouse reproductive behavioral models to determine the biological relationship between PACAP and steroid receptor function in females. We provide evidence for the requirement of PACAP in the VMN for progesterone (P)-dependent sexual behavior in estrogen (E)-primed females. We clarify the biological and molecular mechanisms of PACAP activity by showing 1) that inhibition of endogenous PACAP suppresses P receptor (PR)-dependent sexual behavior facilitated by the steroid P or D1-like agonist SKF38393 and 2) that PR, steroid receptor coactivators-1 and -2, and new protein synthesis are essential for ligand independent PACAP-facilitated behavior. These findings are consistent with convergence of PACAP-mediated cellular signals on PR for genomic activation and subsequent behavioral changes. Further, we show that steroids regulate both endogenous PACAP mRNA in the VMN and immunoreactive PACAP in the medial basal hypothalamus and cerebral spinal fluid for ligand-dependent, steroid receptor-dependent receptivity. The present findings delineate a novel, steroid-dependent mechanism within the female hypothalamus by which the neuropeptide PACAP acts as a feed-forward, paracrine, and/or autocrine factor for synchronization of behavior coordinate with hypothalamic control of ovulation.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Mesenchymal stem cells in autoimmune diseases: hype or hope?

Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases.     

Pentacycloundecane lactam vs lactone norstatine type protease HIV inhibitors: binding energy calculations and DFT study

Background

Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC₅₀ values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC₅₀) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.

Results

The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC₅₀ = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC₅₀ = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆G_solv) were also considered.

Conclusions

A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC₅₀ data.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users.     

Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into cardiomyocytes

Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors.     

RETRACTED ARTICLE: Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium

Introduction  

Mast cells have been implicated to play a functional role in arthritis, especially in autoantibody-positive disease. Among the cytokines involved in rheumatoid arthritis (RA), IL-17 is an important inflammatory mediator. Recent data suggest that the synovial mast cell is a main producer of IL-17, although T cells have also been implicated as prominent IL-17 producers as well. We aimed to identify IL-17 expression by mast cells and T cells in synovium of arthritis patients.     

In situ cooling in a lung hilar clamping model of ischemia-reperfusion injury

Experimental models for studying transplantation have up to now been unable to isolate reperfusion injury with minimal surgical manipulation and without the interference of graft rejection. Six pigs were subjected to left hilum preparation only (control group), and eight pigs were subjected to left hilum preparation plus in situ cooling ischemia and reperfusion of the lung (experimental group). The hilum was dissected free from other tissues in both groups. Lung preservation was achieved by antegrade flush perfusion via the left pulmonary artery. Pulmonary veins were clamped at the left atrium and a vent was created. The left main bronchus was clamped. Lung temperature was maintained at 4 degrees -8 degrees C, while core temperature was kept at 38 degrees C. After 3 hrs of cold ischemia the clamps were removed and the lung was reperfused. Elevated pulmonary vascular resistance and local and systemic aspects of ischemia-reperfusion syndrome were consistently reproduced. This large-animal model of in situ unilateral lung cold ischemia with warm reperfusion proved to be very reliable in reproducing all aspects of ischemia-reperfusion injury. It excludes the interference of rejection and extensive surgical manipulation. We therefore propose its use in experimental studies investigating pharmaceutical or cooling modifications affecting lung ischemia-reperfusion outcomes.