Antibody profile of pregnant women with antiphospholipid syndrome and pregnancy outcome after treatment with low dose aspirin and low-weight-molecular heparin

The aim of the research was to show our diagnostic and therapeutic experience with antiphospholipid syndrome (APS) in pregnant women. 36 pregnant women suspect on APS were included in the study: 32 with primary antiphospholipd syndrome (PAPS) and 4 with secondary antiphospholipid syndrome (SAPS). All pregnant women received low-molecular-weight-heparin (LMWH) and low dose aspirin (LDA) therapy. Control group represented 26 women with SAPS and previous bad reproductive anamnesis. Average pregnancy lasted 37.06 +/- 0.707 weeks. LMWH and LDA therapy was successful in 97.22%. Lupus anticoagulant (LA) was found to be more frequent in PAPS group (71.87%). Anticardiolipin antibodies (aCL) were found to be more frequent in SAPS (26.66%). For three patients (3.37%), PAPS was diagnosed due to a fact that they had positive antibeta2-glycoproteinl (antibeta-GP1). To make APS diagnosis, it is of great importance to search for all antiphospholipid antibodies. LMWH and low dose of acetylsalicylic acid should be the first choice therapy.     

Atherosclerotic lesions of supra-aortic arteries in diabetic patients

The aim of this prospective study was to determine the prevalence and localization of stenotic atherosclerotic lesions of supra-aortic arteries in diabetic patients according to age and sex. Angiograms obtained by digital subtraction angiography were analyzed in 150 diabetic patients (study group) and 150 non-diabetic patients (control group) with symptoms of cerebral ischemia. Diabetic patients were found to have a significantly higher prevalence of stenotic atherosclerotic lesions of the internal carotid artery. Lesions of the large supra-aortic arteries were significantly more common in the left than in the right side of the neck (p < 0.001), but the difference between the diabetic and the non-diabetic group did not reach statistical significance. Hemodynamic conditions were found to be more important than diabetes for the occurrence of atherosclerotic lesions in these arteries. Changes in the proximal segment of the left common carotid artery were the most common finding in diabetic patients, hence attention should be paid to this localization on control examinations.     

Pheochromocytoma presenting as a pancreatic mass: Avoiding a dangerous pitfall in endoscopic ultrasound-guided fine needle aspiration biopsy using GATA3 immunostain

Pheochromocytomas and sympathetic paragangliomas are rare tumours arising from chromaffin cells, producing catecholamines in various amounts. Fatal hypertensive episodes may occur perioperatively, which are preventable by alpha adrenergic receptor blockers. The perioperative mortality rate of diagnosed versus undiagnosed catecholamine-producing tumours is significant, considering that only a minority of tumours develop metastasis. Herein we describe a case of a primary adrenal pheochromocytoma referred to as a pancreatic tumour, successfully diagnosed by endoscopic ultrasound-guided fine needle aspiration biopsy, with a distinct morphology (prominent nuclear anisonucleosis, intranuclear pseudoinclusions, and multinucleation) and immunohistochemical signature.     

Multi‐causality and spatial non‐stationarity in the determinants of groundwater crustacean diversity in Europe

The recognition of multi‐causality and spatial non‐stationarity in the determinants of large‐scale biodiversity patterns requires to consider the role of multiple mechanisms, their interactions, and how these mechanisms vary in strength relative to each other across geographical space. Here, we challenge the view that historical climate stability primarily drives European patterns of groundwater crustacean diversity by testing also the role of spatial heterogeneity and productive energy. First, we predicted that the three mechanisms would be equally important at continental scale when analyzed separately, but that the importance of historical climate variability would weaken in joint analyses due to co‐variation with the two other mechanisms. Second, we predicted that the three mechanisms would exhibit predictable latitudinal changes in their relative strength. To test these predictions, we selected predictors representing each mechanism and analyzed separately and jointly their effects and interactions using global regression models. We further mapped the independent and overlapping effects of mechanisms across Europe using partial geographically weighted regressions. When analyzed separately, the three mechanisms explained the same amount of variation in species richness, but in the joint analysis, the influence of historical climate stability became hidden in the variation shared with the other mechanisms. Topographic heterogeneity interacted synergistically with actual evapotranspiration and habitat heterogeneity on species richness. Spatial non‐stationarity in the independent and overlapping effects of the three mechanisms was the most plausible explanation for the hump‐shaped latitudinal pattern of crustacean species richness. Productive energy and spatial heterogeneity were important predictors at mid and southern latitudes, whereas historical climate stability overlapped with the two other mechanisms in northern Europe and productive energy in southern Europe. Multi‐causality and spatial non‐stationarity provide a broader perspective of groundwater biodiversity determinants that revives the importance of spatial heterogeneity and the strong dependence of subterranean communities on food supply from the surface.     

Coordinated activation of AMP‐activated protein kinase,extracellular signal‐regulated kinase,and autophagy regulates phorbol myristate acetate‐induced differentiation of SH‐SY5Y neuroblastoma cells

We explored the interplay between the intracellular energy sensor AMP‐activated protein kinase (AMPK), extracellular signal‐regulated kinase (ERK), and autophagy in phorbol myristate acetate (PMA)‐induced neuronal differentiation of SH‐SY5Y human neuroblastoma cells. PMA‐triggered expression of neuronal markers (dopamine transporter, microtubule‐associated protein 2, β‐tubulin) was associated with an autophagic response, measured by the conversion of microtubule‐associated protein light chain 3 (LC3)‐I to autophagosome‐bound LC3‐II, increase in autophagic flux, and expression of autophagy‐related (Atg) proteins Atg7 and beclin‐1. This coincided with the transient activation of AMPK and sustained activation of ERK. Pharmacological inhibition or RNA interference‐mediated silencing of AMPK suppressed PMA‐induced expression of neuronal markers, as well as ERK activation and autophagy. A selective pharmacological blockade of ERK prevented PMA‐induced neuronal differentiation and autophagy induction without affecting AMPK phosphorylation. Conversely, the inhibition of autophagy downstream of AMPK/ERK, either by pharmacological agents or LC3 knockdown, promoted the expression of neuronal markers, thus indicating a role of autophagy in the suppression of PMA‐induced differentiation of SH‐SY5Y cells. Therefore, PMA‐induced neuronal differentiation of SH‐SY5Y cells depends on a complex interplay between AMPK, ERK, and autophagy, in which the stimulatory effects of AMPK/ERK signaling are counteracted by the coinciding autophagic response.

     

Conclusion: applying South East Asia Rainforest Research Programme science to land-use management policy and practice in a changing landscape and climate

The context and challenges relating to the remaining tropical rainforest are briefly reviewed and the roles which science can play in addressing questions are outlined. Key messages which articles in the special issue, mainly based on projects of the Royal Society South East Asia Rainforest Research Programme (SEARRP), have raised of relevance to policies on land use, land management and REDD+ are then considered. Results from the atmospheric science and hydrology papers, and some of the ecological ones, demonstrate the very high ecosystem service values of rainforest (compared with oil palm) in maintaining high biodiversity, good local air quality, reducing greenhouse emissions, and reducing landslide, flooding and sedimentation consequences of climate change-and hence provide science to underpin the protection of remaining forest, even if degraded and fragmented. Another group of articles test ways of restoring forest quality (in terms of biodiversity and carbon value) or maintaining as high biodiversity and ecological functioning levels as possible via intelligent design of forest zones and fragments within oil palm landscapes. Finally, factors that have helped to enhance the policy relevance of SEARRP projects and dissemination of their results to decision-makers are outlined.     

Plasma profiling reveals human fibulin-1 as candidate marker for renal impairment

There is a need for reliable and sensitive biomarkers for renal impairments to detect early signs of kidney toxicity and to monitor progression of disease. Here, antibody suspension bead arrays were applied to profile plasma samples from patients with four types of kidney disorders: glomerulonephritis, diabetic nephropathy, obstructive uropathy, and analgesic abuse. In total, 200 clinical renal-associated cases and control plasma samples from different cohorts were profiled. Parallel plasma protein profiles were obtained using biotinylated and nonfractionated samples and a selected set of 94 proteins targeted by 129 antigen-purified polyclonal antibodies. Out of the analyzed target proteins, human fibulin-1 was detected at significantly higher levels in the glomerulonephritis patient group compared to the controls and with elevated levels in patient samples for all other renal disorders investigated. Two polyclonal antibodies and one monoclonal antibody directed toward separate, nonoverlapping epitopes showed the same trend in the discovery cohorts. A technical verification using Western blot analysis of selected patient plasma confirmed the trends toward higher abundance of the target protein in disease samples. Furthermore, a verification study was carried out in the context of glomerulonephritis using an independent case and control cohort, and this confirmed the results from the discovery cohort, suggesting that plasma levels of fibulin-1 could serve as a potential indicator to monitor kidney malfunction or kidney damage.     

Human plasma glycome in attention-deficit hyperactivity disorder and autism spectrum disorders

Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction.     

Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats

The purpose of this study was to examine the effects of ghrelin on protein kinase B (Akt) and mitogen-activated protein kinase p42/44 (ERK1/2) activation as well as ghrelin effects on inducible nitric oxide (NO) synthase (iNOS; for gene Nos2) activity/expression in rat hearts. Male Wistar rats were treated with ghrelin (0.3 nmol/5 μl) or an equal volume of phosphate-buffered saline, injected every 24 h into the lateral cerebral ventricle for 5 days and 2 h after the last treatment the animals were sacrificed. Serum NO, L-arginine (L-Arg), and arginase activity were measured spectrophotometrically. For phosphorylation of Akt, ERK1/2, and iNOS protein expression, Western blot method was used. The expression of Nos2 mRNA was measured by the quantitative real-time polymerase chain reaction (qRT-PCR). Treatment with ghrelin significantly increased NO production in serum by 1.4-fold compared with control. The concentration of L-Arg was significantly higher in ghrelin-treated rats than in control while arginase activity was significantly lower in ghrelin-treated than in control hearts. Ghrelin treatment increased phosphorylation of Akt by 1.9-fold and ERK1/2 by 1.6-fold and increased iNOS expression by 2.5-fold compared with control. In addition, ghrelin treatment increased Nos2 gene expression by 2.2-fold as determined by qRT-PCR. These results indicate that ghrelin regulation of iNOS expression/activity is mediated via Akt/ERK1/2 signaling pathway. These results may be relevant to understanding molecular mechanisms underlying direct cardiovascular actions of ghrelin.     

Sponge non-metastatic Group I Nme gene/protein - structure and function is conserved from sponges to humans

Background  

Nucleoside diphosphate kinases NDPK are evolutionarily conserved enzymes present in Bacteria, Archaea and Eukarya, with human Nme1 the most studied representative of the family and the first identified metastasis suppressor. Sponges (Porifera) are simple metazoans without tissues, closest to the common ancestor of all animals. They changed little during evolution and probably provide the best insight into the metazoan ancestor's genomic features. Recent studies show that sponges have a wide repertoire of genes many of which are involved in diseases in more complex metazoans. The original function of those genes and the way it has evolved in the animal lineage is largely unknown. Here we report new results on the metastasis suppressor gene/protein homolog from the marine sponge Suberites domuncula, NmeGp1Sd. The purpose of this study was to investigate the properties of the sponge Group I Nme gene and protein, and compare it to its human homolog in order to elucidate the evolution of the structure and function of Nme.