Sex‐specific mitonuclear epistasis and the evolution of mitochondrial bioenergetics,ageing, and life history in seed beetles

The role of mitochondrial DNA for the evolution of life‐history traits remains debated. We examined mitonuclear effects on the activity of the multisubunit complex of the electron transport chain (ETC) involved in oxidative phosphorylation (OXPHOS) across lines of the seed beetle Acanthoscelides obtectus selected for a short (E) or a long (L) life for more than >160 generations. We constructed and phenotyped mitonuclear introgression lines, which allowed us to assess the independent effects of the evolutionary history of the nuclear and the mitochondrial genome. The nuclear genome was responsible for the largest share of divergence seen in ageing. However, the mitochondrial genome also had sizeable effects, which were sex‐specific and expressed primarily as epistatic interactions with the nuclear genome. The effects of mitonuclear disruption were largely consistent with mitonuclear coadaptation. Variation in ETC activity explained a large proportion of variance in ageing and life‐history traits and this multivariate relationship differed somewhat between the sexes. In conclusion, mitonuclear epistasis has played an important role in the laboratory evolution of ETC complex activity, ageing, and life histories and these are closely associated. The mitonuclear architecture of evolved differences in life‐history traits and mitochondrial bioenergetics was sex‐specific.     

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction. Because there is no diagnostic test yet available for preeclampsia, we used a proteomic approach to identify novel serum/plasma biomarkers for this condition. We conducted case control studies comparing nulliparous women who developed preeclampsia at 36-38 weeks of gestation with healthy nulliparous women matched by gestational age at sampling. Serum/plasma was depleted of six abundant proteins and analyzed by two-dimensional gel electrophoresis (n = 12 per group) and difference gel electrophoresis (n = 12 per group). Differences in abundance of protein spots were detected by univariate and multivariate statistical analyses. Proteins were identified by mass spectrometry and expression of selected proteins was validated by immunoblotting. Proteins whose concentrations were selectively associated with preeclampsia included apolipoprotein E (apoE), apoC-II, complement factor C3c, fibrinogen, transthyretin, and complement factor H-related protein 2. An increase in a deglycosylated isoform of apoE3 and concomitantly decreased amounts of one apoE3 glycoisoform were identified in preeclamptic plasma and confirmed by immunoblotting. Altered production of these preeclampsia-related apoE3 isoforms might impair reverse cholesterol transport, contributing to arterial damage. These findings point to a novel mechanistic link between preeclampsia and subsequent cardiovascular disease.     

Upregulation and phosphorylation of HspB1/Hsp25 and HspB5/αB-crystallin after transient middle cerebral artery occlusion in rats

Ischemic stroke leads to cellular dysfunction, cell death, and devastating clinical outcomes. The cells of the brain react to such a cellular stress by a stress response with an upregulation of heat shock proteins resulting in activation of endogenous neuroprotective capacities. Several members of the family of small heat shock proteins (HspBs) have been shown to be neuroprotective. However, yet no systematic study examined all HspBs during cerebral ischemia. Here, we performed a comprehensive comparative study comprising all HspBs in an animal model of stroke, i.e., 1 h transient middle cerebral artery occlusion followed by 23 h of reperfusion. On the mRNA level out of the 11 HspBs investigated, HspB1/Hsp25, HspB3, HspB4/αA-crystallin, HspB5/αB-crystallin, HspB7/cvHsp, and HspB8/Hsp22 were significantly upregulated in the peri-infarct region of the cerebral cortex of infarcted hemispheres. HspB1 and HspB5 reached the highest mRNA levels and were also upregulated at the protein level, suggesting that these HspBs might be functionally most relevant. Interestingly, in the infarcted cortex, both HspB1 and HspB5 were mainly allocated to neurons and to a lesser extent to glial cells. Additionally, both proteins were found to be phosphorylated in response to ischemia. Our data suggest that among all HspBs, HspB1 and HspB5 might be most important in the neuronal stress response to ischemia/reperfusion injury in the brain and might be involved in neuroprotection.     

Influence of glyco-oxidation on complexes between fibrin(ogen) and insulin-like growth factor-binding protein-1 in patients with diabetes mellitus type 2

Fibrinogen and insulin-like growth factor-binding protein-1 (IGFBP-1) are tightly connected to metabolic changes and complications in patients with diabetes mellitus (DM), and since they mutually interact to form complexes in plasma, we investigated whether and to what extent IGFBP-1/fibrinogen complexes change due to glyco-oxidative processes in DM and whether they participate in fibrin clot formation. These complexes were determined by immunoblotting in plasma samples from healthy adults and patients with DM type 2 (DM2). The influence of glyco-oxidation in vitro on the complexes was also investigated. Amounts of IGFBP-1/fibrinogen complexes in plasma from patients with DM2 were slightly but not significantly lower than in healthy persons. Such complexes in patients’ samples participated in fibrin clot formation to a significantly decreased extent. In vitro experiments with glucose or methylglyoxal (MGO) as reactive agents demonstrated that the complexes underwent glyco-oxidative modification leading to reduced formation and/or stability. Extensively oxidized fibrinogen almost completely lost its ability to bind IGFBP-1. The reduced affinity of fibrinogen for IGFBP-1 accompanying diabetes may potentially shift the equilibrium to liberate more IGFBP-1 (and possibly insulin-like growth factor (IGF)-I) able to activate platelets during coagulation, so contributing to the hypercoagulation state together with other factors. This hypothesis, however, needs further examination.     

Application of wound dressing Molndal technique in clean and potentially contamined postoperative wounds--initial comparative study

Because of a possible delayed wound healing, critical colonization and infection of wounds present a problem for surgeons, particularly in patients with compromised immune system or in case where the wound is heavy contaminated or poorly perfused. Molndal technique of wound dressing has proven to be effective in prevention of infection. In our study we wanted to describe the benefits of the application of Molndal technique wound dressing compared to traditional wound dressing technique at potentially contaminated and clean postoperative wounds. We examined postoperative wound after radical excision of pilonidal sinus and after implantation of partial endoprosthesis in hip fracture. Molndal technique consisted of wound dressing with Aquacel Ag - Hydrofiber. Traditional technique was performed using gauze compresses and hypoallergic adhesives. We analyzed the results of 50 patients after radical excision of pilonidal sinus. 25 patients were treated by Molndal technique and 25 patients by the traditional technique of wound dressing. In the group treated by Molndal technique only 1 (4%) patient has revealed a wound infection, proven by positive microbiological examination and suppuration. In the traditional technique group 4 (16%) patients developed wound infection as inflammation and secretion as a sign of superficial infection. In the other group we analyzed the results of 50 patients after implantation of partial endoprosthesis after hip fracture. 20 patients were treated by Molndal technique and 30 patients by the traditional technique of wound dressing. In the group treated by Molndal technique no patient has revealed a wound infection (0%). In the traditional technique group 4 (13%) patients developed wound infection. All complication in both group were superficial incisional surgical infection (according to HPSC). There was no deep incisional surgical site infection or organ/space surgical site infection. Our results are clearly showing that Molndal technique is effective in preventing the postoperative wound infection.     

Inhibition of Rho‐kinase protects cerebral barrier from ischaemia‐evoked injury through modulations of endothelial cell oxidative stress and tight junctions

Ischaemic strokes evoke blood–brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho‐kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho‐kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil‐ versus vehicle‐treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post‐ischaemia or 4 h post‐ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress‐ and tight junction‐related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen–glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin‐5. Cotreatment of cells with Y‐27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho‐kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions.

     

Hippocampal expression of cell‐adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Cell‐adhesion glycoprotein neuroplastin (Np) is involved in the regulation of synaptic plasticity and balancing hippocampal excitatory/inhibitory inputs which aids in the process of associative memory formation and learning. Our recent findings show that neuroplastin expression in the adult human hippocampus is specifically associated with major hippocampal excitatory pathways and is related to neuronal calcium regulation. Here, we investigated the hippocampal expression of brain‐specific neuroplastin isoform (Np65), its relationship with amyloid and tau pathology in Alzheimer's disease (AD), and potential involvement of neuroplastin in tissue response during the disease progression. Np65 expression and localization was analysed in six human hippocampi with confirmed AD neuropathology, and six age‐/gender‐matched control hippocampi by imunohistochemistry. In AD cases with shorter disease duration, the Np65 immunoreactivity was significantly increased in the dentate gyrus (DG), Cornu Ammonis 2/3 (CA2/3), and subiculum, with the highest level of Np expression being located on the dendrites of granule cells and subicular pyramidal neurons. Changes in the expression of neuroplastin in AD hippocampal areas seem to be related to the progression of disease. Our study suggests that cell‐adhesion protein neuroplastin is involved in tissue reorganization and is a potential molecular marker of plasticity response in the early neurodegeneration process of AD.     

Modelling of endothelial cell migration and angiogenesis in microfluidic cell culture systems

Biomechanics and Modeling in Mechanobiology - Tumour-induced angiogenesis is a complex biological process that involves growth of new blood vessels within the tumour microenvironment and is an...