Molecular signatures of divergence and selection in closely related pine taxa

Efforts to detect loci under selection in plants have mostly focussed on single species. However, assuming that intraspecific divergence may lead to speciation, comparisons of genetic variation within and among recently diverged taxa can help to locate such genes. In this study, coalescent and outlier detection methods were used to assess nucleotide polymorphism and divergence at 79 nuclear gene fragments (1212 SNPs) in 16 populations (153 individuals) of the closely related, but phenotypically and ecologically distinct, pine taxa Pinus mugo, P. uliginosa and P. uncinata across their European distributions. Simultaneously, mitochondrial DNA markers, which are maternally inherited in pines and distributed by seeds at short geographic distance, were used to assess genetic relationships of the focal populations and taxa. The majority of nuclear loci showed homogenous patterns of variation between the taxa due to a high number of shared SNPs and haplotypes, similar levels of polymorphism, and low net divergence. However, against this common genetic background and an overall low population structure within taxa at mitochondrial markers, we identified several genes showing signatures of selection, accompanied by significant intra- and interspecific divergence. Our results indicate that loci involved in species divergence may be involved in intraspecific local adaptation.     

Regulation of Vascular Tone,Angiogenesis and Cellular Bioenergetics by the 3-Mercaptopyruvate Sulfurtransferase/H2S Pathway: Functional Impairment by Hyperglycemia and Restoration by dl-α-Lipoic Acid

Hydrogen sulfide (H₂S), as a reducing agent and an antioxidant molecule, exerts protective effects against hyperglycemic stress in the vascular endothelium. The mitochondrial enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is an important biological source of H₂S. We have recently demonstrated that 3-MST activity is inhibited by oxidative stress in vitro and speculated that this may have an adverse effect on cellular homeostasis. In the current study, given the importance of H₂S as a vasorelaxant, angiogenesis stimulator and cellular bioenergetic mediator, we first determined whether the 3-MST/H₂S system plays a physiological regulatory role in endothelial cells. Next, we tested whether a dysfunction of this pathway develops during the development of hyperglycemia and μmol/L to diabetes-associated vascular complications. Intraperitoneal (IP) 3-MP (1 mg/kg) raised plasma H₂S levels in rats. 3-MP (10 1 mmol/L) promoted angiogenesis in vitro in bEnd3 microvascular endothelial cells and in vivo in a Matrigel assay in mice (0.3–1 mg/kg). In vitro studies with bEnd3 cell homogenates demonstrated that the 3-MP-induced increases in H₂S production depended on enzymatic activity, although at higher concentrations (1–3 mmol/L) there was also evidence for an additional nonenzymatic H₂S production by 3-MP. In vivo, 3-MP facilitated wound healing in rats, induced the relaxation of dermal microvessels and increased mitochondrial bioenergetic function. In vitro hyperglycemia or in vivo streptozotocin diabetes impaired angiogenesis, attenuated mitochondrial function and delayed wound healing; all of these responses were associated with an impairment of the proangiogenic and bioenergetic effects of 3-MP. The antioxidants dl-α-lipoic acid (LA) in vivo, or dihydrolipoic acid (DHLA) in vitro restored the ability of 3-MP to stimulate angiogenesis, cellular bioenergetics and wound healing in hyperglycemia and diabetes. We conclude that diabetes leads to an impairment of the 3-MST/H₂S pathway, and speculate that this may contribute to the pathogenesis of hyperglycemic endothelial cell dysfunction. We also suggest that therapy with H₂S donors, or treatment with the combination of 3-MP and lipoic acid may be beneficial in improving angiogenesis and bioenergetics in hyperglycemia.     

Genomic analysis of Campylobacter fetus subspecies: identification of candidate virulence determinants and diagnostic assay targets

Background  

Campylobacter fetus subspecies venerealis is the causative agent of bovine genital campylobacteriosis, asymptomatic in bulls the disease is spread to female cattle causing extensive reproductive loss. The microbiological and molecular differentiation of C. fetus subsp. venerealis from C. fetus subsp. fetus is extremely difficult. This study describes the analysis of the available C. fetus subsp. venerealis AZUL-94 strain genome (~75–80%) to identify elements exclusively found in C. fetus subsp. venerealis strains as potential diagnostic targets and the characterisation of subspecies virulence genes.     

Chaperoning the guardian of the genome. The two-faced role of molecular chaperones in p53 tumor suppressor action

Organized networks of heat shock proteins, which possess molecular chaperone activity, protect cells from abrupt environmental changes. Additionally, molecular chaperones are essential during stress-free periods, where they moderate housekeeping functions. During tumorigenesis, these chaperone networks are extensively remodeled in such a way that they are advantageous to the transforming cell. Molecular chaperones by buffering critical elements of signaling pathways empower tumor evolution leading to chemoresistance of cancer cells. Controversially, the same molecular chaperones, which are indispensable for p53 in reaching its tumor suppressor potential, are beneficial in adopting an oncogenic gain of function phenotype when TP53 is mutated. On the molecular level, heat shock proteins by unwinding the mutant p53 protein expose aggregation-prone sites leading to the sequestration of other tumor suppressor proteins causing inhibition of apoptosis and chemoresistance. Therefore, within this review therapeutic approaches combining classical immuno- and/or chemotherapy with specific inhibition of selected molecular chaperones shall be discussed.     

Haematological changes in rabbits (Oryctolagus cuniculus f. domesticus) in the course of pregnancy

The analysis of haematological parameters is an important element of the assessment of the physiological condition of animals. Haematological parameters may change both under the influence of various external factors, and in the course of normal pregnancy, which has been found in various species of mammals, including rabbits. Our study showed statistically significant (p<0.05) changes in basic haematological parameters: RBC (decrease; 5.87±0.48 at day 15 vs. 5.42±0.32 T/L at day 26), MCH (increase; 1.35±0.04 before matching vs. 1.41±0.03 fmol at day 26), RDW (decrease; 15.77±1.80 at day 15 vs. 14.27±1.57% at day 26) MPV (increase; 5.17±0.31 at day 15 vs. 5.92±0.70 fL at day 26), WBC (decrease; 8.60±2.57 at day 15 vs. 4.94±0.88 G/L at day 26) and PLT (decrease; 398.17±91.67 before matching vs. 271.67±61.72 G/L at day 26) in Termond White rabbits and RBC (decrease; 6.18±0.68 before matching vs. 5.68±0.54 T/L at day 26), Hb (decrease; 8.00±0.90 before matching vs. 7.32±0.71 mmol/L at day 26), MCH (decrease; 1.32±0.05 at day 15 vs. 1.29±0.04 fmol at day 26) and WBC (decrease; 9.62±1.81 before matching vs. 5.85±2.23 G/L at day 26 as well as 9.58±2.35 at day 15 vs. 5.85±2.23 G/L at day 26) in Popielno White rabbits. Moreover, in the Popielno White rabbits we recorded a significant (p<0.05) decrease in the percentage of irregular erythrocytes at the end of pregnancy (11.00±10.02 at day 15 vs. 3.00±4.94 at day 26). The changes appear to be physiological but should be considered in studies using rabbits as model organisms.     

Sulphur nutrition and iron plaque formation on roots of rice seedlings and their consequences for immobilisation and uptake of chromium in solution culture

Plant and Soil - The contribution of sulphur (S)-induced responses to chromium (Cr) tolerance of rice plants is not yet fully elucidated. It is hypothesised that S nutrition mitigates the...     

Molecular dynamics imaging in micropatterned living cells

Micropatterning approaches using self-assembled monolayers of alkyl thiols on gold are not optimal for important imaging modalities in cell biology because of absorption of light and scattering of electrons by the gold layer. We report here an anisotropic solid microetching (ASOMIC) procedure that overcomes these limitations. The method allows molecular dynamics imaging by wide-field and total internal reflection fluorescence (TIRF) microscopy of living mammalian cells and correlative platinum replica electron microscopy.