The use of supramolecular structures as protein ligands

Congo red dye as well as other eagerly self-assembling organic molecules which form rod-like or ribbon-like supramolecular structures in water solutions, appears to represent a new class of protein ligands with possible wide-ranging medical applications. Such molecules associate with proteins as integral clusters and preferentially penetrate into areas of low molecular stability. Abnormal, partly unfolded proteins are the main binding target for such ligands, while well packed molecules are generally inaccessible. Of particular interest is the observation that local susceptibility for binding supramolecular ligands may be promoted in some proteins as a consequence of function-derived structural changes, and that such complexation may alter the activity profile of target proteins. Examples are presented in this paper.     

Lipopeptide Biosurfactant Pseudofactin II Induced Apoptosis of Melanoma A 375 Cells by Specific Interaction with the Plasma Membrane

In the case of melanoma, advances in therapies are slow, which raises the need to evaluate new therapeutic strategies and natural products with potential cancer cell inhibiting effect. Pseudofactin II (PFII), a novel cyclic lipopeptide biosurfactant has been isolated from the Arctic strain of Pseudomonas fluorescens BD5. The aim of this study was to investigate the effect of PFII on A375 melanoma cells compared with the effect of PFII on Normal Human Dermis Fibroblast (NHDF) cells and elucidate the underlying mechanism of PFII cytotoxic activity. Melanoma A375 cells and NHDF cells were exposed to PFII or staurosporine and apoptotic death was assessed by monitoring caspase 3-like activity and DNA fragmentation. From time-dependent monitoring of lactate dehydrogenase (LDH) release, Ca²⁺ influx, and a correlation between Critical Micelle Concentration (CMC) we concluded that cell death is the consequence of plasma membrane permeabilisation by micelles. This finding suggests that pro-apoptotic mechanism of PFII is different from previously described cyclic lipopeptides. The mechanism of PFII specificity towards malignant cells remains to be discovered. The results of this study show that PFII could be a new promising anti-melanoma agent.     

Possible Association between Suicide Committed under Influence of Ethanol and a Variant in the AUTS2 Gene

Background

rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide.

Methods

We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians.

Results

We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR  =  1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019).

Conclusions

In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.     

Population and community-level compositional patterns shape the realized niche of the rare arctic-alpine species Carex lachenalii Schkuhr

The ability for vegetative growth and development of generative organs often reflects an adaptation to the environment and may be a suitable proxy for understanding population dynamics of rare relict species. An example of such a plant is Carex lachenalii Schkuhr, an arctic-alpine species, in the temperate zone of Europe only occurring in isolated localities of high-elevation mountain ranges. We aimed to assess whether there were relationships between flower production and clonal growth of C. lachenalii, both at the tuft and plot level, and how co-occurring vegetation could modify this relationship. In the study we focused on population-level traits of C. lachenalii, vegetation traits and components of functional diversity. At the tuft level we found that the proportion of flowering ramets of C. lachenalii decreased with increasing diameter of the tuft. At the plot level, in snowbed vegetation C. lachenalii produced more flowering ramets. We suggest this is due to higher environmental stress, expressed by high importance of habitat filtering (low functional dispersion) in shaping species composition of co-occurring vegetation. In granite grasslands and milder environment (expressed by higher functional dispersion), C. lachenalii produced more vegetative ramets, which we suggest is a result of a more competitive environment. While in snowbeds investment in flowering ramets could promote successful persistence of C. lachenalii, survival of subpopulations occurring in the highly competitive conditions of granite grasslands may be uncertain due to potentially weak adaptation to competition with graminoids and dwarf shrubs.     

Fine root classification matters: nutrient levels in different functional categories,orders and diameters of roots in boreal Pinus sylvestris across a latitudinal gradient

Plant and Soil - Any grouping of tree species concerned with SOC sequestration should include trees that are as homogeneous as possible in their carbon sequestration. We propose a classification of...     

An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling,inhibitory studies and molecular modeling

Neisseria meningitides is a gram-negative diplococcus bacterium and is the main causative agent of meningitis and other meningococcal diseases. Alanine aminopeptidase from N. meningitides (NmAPN) belongs to the family of metallo-exopeptidase enzymes, which catalyze the removal of amino acids from the N-terminus of peptides and proteins, and are found among all the kingdoms of life. NmAPN is suggested to be mostly responsible for proteolysis and nutrition delivery, similar to the orthologs from other bacteria.     

Short-term growth of meadow fescue with atmospheric CO2 enrichment decreases freezing tolerance, modifies photosynthetic apparatus performance and changes the expression of some genes during cold acclimation

The objective of this study was to assess the effect of an elevated atmospheric CO₂ molar ratio on freezing tolerance, photosynthetic apparatus performance and expression of CBF6, Cor14b and LOS2 in meadow fescue (Festuca pratensis Huds.). It was shown that cold acclimation under a CO₂ molar ratio of 800 μmol mol(air)^?1 decreased the freezing tolerance of meadow fescue when compared to the ambient CO₂ level. This effect was not related either to changes observed in PSII redox state or to photosynthetic acclimation to cold, which was in fact more effective at an elevated CO₂ level. The decrease in freezing tolerance was linked to changes in the expression of CBF6 and LOS2 genes, whereas the protective effect on photosynthetic apparatus was connected with the activation of a non-photochemical mechanism of photoprotection as well as upregulation of FpCOR14b expression.     

Systematic Characterization of Myocardial Inflammation,Repair, and Remodeling in a Mouse Model of Reperfused Myocardial Infarction

Mouse models of myocardial infarction are essential tools for the study of cardiac injury, repair, and remodeling. Our current investigation establishes a systematic approach for quantitative evaluation of the inflammatory and reparative response, cardiac function, and geometry in a mouse model of reperfused myocardial infarction. Reperfused mouse infarcts exhibited marked induction of inflammatory cytokines that peaked after 6 hr of reperfusion. In the infarcted heart, scar contraction and chamber dilation continued for at least 28 days after reperfusion; infarct maturation was associated with marked thinning of the scar, accompanied by volume loss and rapid clearance of cellular elements. Echocardiographic measurements of end-diastolic dimensions correlated well with morphometric assessment of dilative remodeling in perfusion-fixed hearts. Hemodynamic monitoring was used to quantitatively assess systolic and diastolic function; the severity of diastolic dysfunction following myocardial infarction correlated with cardiomyocyte hypertrophy and infarct collagen content. Expression of molecular mediators of inflammation and cellular infiltration needs to be investigated during the first 72 hr, whereas assessment of dilative remodeling requires measurement of geometric parameters for at least four weeks after the acute event. Rapid initiation and resolution of the inflammatory response, accelerated scar maturation, and extensive infarct volume loss are important characteristics of infarct healing in mice.     

Structural heterogeneity of linear habitats positively affects Barred Warbler Sylvia nisoria,Common Whitethroat Sylvia communis and Lesser Whitethroat Sylvia curruca in farmland of Western Poland

Capsule Structural heterogeneity was the most important factor influencing the distribution of Barred Warbler Sylvia nisoria, Common Whitethroat S. communis and Lesser Whitethroat S. curruca in linear habitats in farmland of Western Poland.

Aims To investigate the occurrence of three species of Sylvia warblers in relation to the spatial structure of linear habitats in the agricultural landscape of Western Poland where, in contrast to Western Europe, field boundaries are not managed in terms of their size or spatial structure.

Methods In 2008, the distribution of breeding territories of Sylvia warblers in linear habitats was estimated in farmland of Western Poland. Redundancy detrended analysis was used to assess the relationship between bird abundance and seven linear habitat variables in ninety-four 150?m sections.

Results Sylvia warblers differed in habitat requirements, however heterogeneity affected their distribution to the greatest extent. In addition, Barred Warbler preferred high shrub volume and wider sections, whereas Common Whitethroat was attracted by brambles and nettles and Lesser Whitethroat favoured shrubs. All species avoided a high proportion of low vegetation.

Conclusion Structural heterogeneity resulted in highly preferred linear habitats for Sylvia warblers. Thus, maintaining or increasing structural heterogeneity of linear habitats may be a very effective tool for the conservation of farmland bird populations.