Synthesis of a protected trihydroxyindolizidine 3-carboxylate via a hetero-Diels–Alder addition of ethyl 2-nitrosoacrylate to a d-ribose-derived exo-glycal

A protected trihydroxyindolizidine 3-carboxylate was prepared by a 6-endo epoxide cleavage, which in turn was intermediately formed from the hetero-Diels–Alder adduct of ethyl 2-nitrosoacrylate to a d-ribose-derived exo-glycal.     

Four new depsides in Origanum dictamnus methanol extract

We herein describe the identification of four new depsides present in methanol extract of Origanum dictamnus. O. dictamnus’ (dittany) aerial parts methanol extract was subjected to semi-preparative RP-HPLC fractionation followed by identification of individual compounds in each fraction using 1D/2D NMR, MS approaches and DFT calculations. The structural data revealed that 4 of the compounds were novel hitherto unidentified molecules, whereas the other 6 corresponded to known structures belonging to the groups of monoterpenes, phenolic acids and depsides. We have additionally estimated the antioxidant capacity of the methanol extract and individual fractions using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) in vitro assay. Methanol extract exhibited significant scavenging activity, which was attributed predominantly to the depside group of phytochemicals. The scavenging activity of the new compounds is reported herein for first time. Moreover, the antimitotic activities of the methanol extract as well as that of rosmarinic acid were examined and appeared to be several fold weaker comparing to their scavenging capacity.     

Phase Synchronization of Hemodynamic Variables at Rest and after Deep Breathing Measured during the Course of Pregnancy

Background

The autonomic nervous system plays a central role in the functioning of systems critical for the homeostasis maintenance. However, its role in the cardiovascular adaptation to pregnancy-related demands is poorly understood. We explored the maternal cardiovascular systems throughout pregnancy to quantify pregnancy-related autonomic nervous system adaptations.

Methodology

Continuous monitoring of heart rate (R-R interval; derived from the 3-lead electrocardiography), blood pressure, and thoracic impedance was carried out in thirty-six women at six time-points throughout pregnancy. In order to quantify in addition to the longitudinal effects on baseline levels throughout gestation the immediate adaptive heart rate and blood pressure changes at each time point, a simple reflex test, deep breathing, was applied. Consequently, heart rate variability and blood pressure variability in the low (LF) and high (HF) frequency range, respiration and baroreceptor sensitivity were analyzed in resting conditions and after deep breathing. The adjustment of the rhythms of the R-R interval, blood pressure and respiration partitioned for the sympathetic and the parasympathetic branch of the autonomic nervous system were quantified by the phase synchronization index γ, which has been adopted from the analysis of weakly coupled chaotic oscillators.

Results

Heart rate and LF/HF ratio increased throughout pregnancy and these effects were accompanied by a continuous loss of baroreceptor sensitivity. The increases in heart rate and LF/HF ratio levels were associated with an increasing decline in the ability to flexibly respond to additional demands (i.e., diminished adaptive responses to deep breathing). The phase synchronization index γ showed that the observed effects could be explained by a decreased coupling of respiration and the cardiovascular system (HF components of heart rate and blood pressure).

Conclusions/Significance

The findings suggest that during the course of pregnancy the individual systems become increasingly independent to meet the increasing demands placed on the maternal cardiovascular and respiratory system.     

LepChorionDB,a database of Lepidopteran chorion proteins and a set of tools useful for the identification of chorion proteins in Lepidopteran proteomes

Chorion proteins of Lepidoptera have a tripartite structure, which consists of a central domain and two, more variable, flanking arms. The central domain is highly conserved and it is used for the classification of chorion proteins into two major classes, A and B. Annotated and unreviewed Lepidopteran chorion protein sequences are available in various databases. A database, named LepChorionDB, was constructed by searching 5 different protein databases using class A and B central domain-specific profile Hidden Markov Models (pHMMs), developed in this work. A total of 413 Lepidopteran chorion proteins from 9 moths and 1 butterfly species were retrieved. These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes. LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins. LepChorionDB is freely available at http://bioinformatics.biol.uoa.gr/LepChorionDB.     

Hypoxemic resuscitation from hemorrhagic shock prevents lung injury and attenuates oxidative response and IL-8 overexpression

We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.     

Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells

The Mig-10/RIAM/lamellipodin (MRL) family member Rap1-GTP-interacting adaptor molecule (RIAM) interacts with active Rap1, a small GTPase that is frequently activated in tumors such as melanoma and prostate cancer. We show here that RIAM is expressed in metastatic human melanoma cells and that both RIAM and Rap1 are required for BLM melanoma cell invasion. RIAM silencing in melanoma cells led to inhibition of tumor growth and to delayed metastasis in a severe combined immunodeficiency xenograft model. Defective invasion of RIAM-silenced melanoma cells arose from impairment in persistent cell migration directionality, which was associated with deficient activation of a Vav2-RhoA-ROCK-myosin light chain pathway. Expression of constitutively active Vav2 and RhoA in cells depleted for RIAM partially rescued their invasion, indicating that Vav2 and RhoA mediate RIAM function. These results suggest that inhibition of cell invasion in RIAM-silenced melanoma cells is likely based on altered cell contractility and cell polarization. Furthermore, we show that RIAM depletion reduces β1 integrin-dependent melanoma cell adhesion, which correlates with decreased activation of both Erk1/2 MAPK and phosphatidylinositol 3-kinase, two central molecules controlling cell growth and cell survival. In addition to causing inhibition of cell proliferation, RIAM silencing led to higher susceptibility to cell apoptosis. Together, these data suggest that defective activation of these kinases in RIAM-silenced cells could account for inhibition of melanoma cell growth and that RIAM might contribute to the dissemination of melanoma cells.     

Signals of Climate Change in Butterfly Communities in a Mediterranean Protected Area

The European protected-area network will cease to be efficient for biodiversity conservation, particularly in the Mediterranean region, if species are driven out of protected areas by climate warming. Yet, no empirical evidence of how climate change influences ecological communities in Mediterranean nature reserves really exists. Here, we examine long-term (1998–2011/2012) and short-term (2011–2012) changes in the butterfly fauna of Dadia National Park (Greece) by revisiting 21 and 18 transects in 2011 and 2012 respectively, that were initially surveyed in 1998. We evaluate the temperature trend for the study area for a 22-year-period (1990–2012) in which all three butterfly surveys are included. We also assess changes in community composition and species richness in butterfly communities using information on (a) species’ elevational distributions in Greece and (b) Community Temperature Index (calculated from the average temperature of species'' geographical ranges in Europe, weighted by species'' abundance per transect and year). Despite the protected status of Dadia NP and the subsequent stability of land use regimes, we found a marked change in butterfly community composition over a 13 year period, concomitant with an increase of annual average temperature of 0.95°C. Our analysis gave no evidence of significant year-to-year (2011–2012) variability in butterfly community composition, suggesting that the community composition change we recorded is likely the consequence of long-term environmental change, such as climate warming. We observe an increased abundance of low-elevation species whereas species mainly occurring at higher elevations in the region declined. The Community Temperature Index was found to increase in all habitats except agricultural areas. If equivalent changes occur in other protected areas and taxonomic groups across Mediterranean Europe, new conservation options and approaches for increasing species’ resilience may have to be devised.     

Butterfly and grasshopper diversity patterns in humid Mediterranean grasslands: the roles of disturbance and environmental factors

The present paper studies butterfly, grasshopper and vascular plant communities in ten seasonally flooded grasslands with different anthropogenic disturbance regimes (NW Greece). Disturbance intensity was assessed on the basis of disturbance frequency and type (grazing, mowing, trampling, constructions). The distribution patterns of butterflies are regulated by humidity and elevation (Redundancy Analysis). Elevation, flower-heads abundance, low disturbance intensity and plant species richness predict grasshopper species richness well, while the latter together with humidity predict plant species richness (Generalized Linear Models). Chorthippus lacustris, a critically endangered endemic grasshopper species, is positively associated with humid microhabitats with high flower-heads abundance. An indicator value procedure reveals four butterfly species as being typical species for habitats with a pronounced character of hedgerows and tree lines. Conservation management of grassland butterflies should focus on the maintenance of the humid character of the humid grasslands as well as on the maintenance of hedgerows and tree lines. The reduction of human-induced disturbance towards occasional grazing and mowing seems to benefit both butterfly and grasshopper communities. Finally, we suggest the use of grasshoppers as surrogates for vascular plants and vice versa, given their congruent species richness patterns.