Assessment of Blood Contamination in Biological Fluids Using MALDI-TOF MS

Biological fluid sample collection often includes the risk of blood contamination that may alter the proteomic profile of biological fluid. In proteomics studies, exclusion of contaminated samples is usually based on visual inspection and counting of red blood cells in the sample; analysis of specific blood derived proteins is less used. To fill the gap, we developed a fast and sensitive method for ascertainment of blood contamination in crude biological fluids, based on specific blood-derived protein, hemoglobin detection by MALDI-TOF MS. The MALDI-TOF MS based method allows detection of trace hemoglobin with the detection limit of 0.12 nM. UV-spectrometry, which was used as reference method, was found to be less sensitive. The main advantages of the presented method are that it is fast, effective, sensitive, requires very small sample amount and can be applied for detection of blood contamination in various biological fluids collected for proteomics studies. Method applicability was tested on human cerebrospinal and follicular fluid, which proteomes generally do not contain hemoglobin, however, which possess high risk for blood contamination. Present method successfully detected the blood contamination in 12 % of cerebrospinal fluid and 24 % of follicular fluid samples. High percentage of contaminated samples accentuates the need for initial inspection of proteomic samples to avoid incorrect results from blood proteome overlap.     

Identification,Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening

Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC₅₀ value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization.     

The role of SIRT2 in vascular-related and heart-related diseases: A review

At present, cardiovascular disease is one of the important factors of human death, and there are many kinds of proteins involved. Sirtuins family proteins are involved in various physiological and pathological activities of the human body. Among them, there are more and more studies on the relationship between sirtuin2 (SIRT2) protein and cardiovascular diseases. SIRT2 can effectively inhibit pathological cardiac hypertrophy. The effect of SIRT2 on ischaemia-reperfusion injury has different effects under different conditions. SIRT2 can reduce the level of reactive oxygen species (ROS), which may help to reduce the severity of diabetic cardiomyopathy. SIRT2 can affect a variety of cardiovascular diseases, energy metabolism and the ageing of cardiomyocytes, thereby affecting heart failure. SIRT2 also plays an important role in vascular disease. For endothelial cell damage used by oxidative stress, the role of SIRT2 is bidirectional, which is related to the degree of oxidative stress stimulation. When the degree of stimulation is small, SIRT2 plays a protective role, and when the degree of stimulation increases to a certain level, SIRT2 plays a negative role. In addition, SIRT2 is also involved in the remodelling of blood vessels and the repair of skin damage.     

Building Blocks of Temporal Filters in Retinal Synapses

Sensory systems must be able to extract features of a stimulus to detect and represent properties of the world. Because sensory signals are constantly changing, a critical aspect of this transformation relates to the timing of signals and the ability to filter those signals to select dynamic properties, such as visual motion. At first assessment, one might think that the primary biophysical properties that construct a temporal filter would be dynamic mechanisms such as molecular concentration or membrane electrical properties. However, in the current issue of PLOS Biology, Baden et al. identify a mechanism of temporal filtering in the zebrafish and goldfish retina that is not dynamic but is in fact a structural building block—the physical size of a synapse itself. The authors observe that small, bipolar cell synaptic terminals are fast and highly adaptive, whereas large ones are slower and adapt less. Using a computational model, they conclude that the volume of the synaptic terminal influences the calcium concentration and the number of available vesicles. These results indicate that the size of the presynaptic terminal is an independent control for the dynamics of a synapse and may reveal aspects of synaptic function that can be inferred from anatomical structure.     

Cultural longevity: Morin on cultural lineages

Morin has written a rich and valuable book. Its main aim is to isolate the factors involved in maintaining behavioural lineages over time, and to understand how these factors might interact. In doing so, it takes issue with the abstract and idealised models and arguments of dual-inheritance theorists, which are alleged in this account to rely on an overly simplistic notion of imitative learning. Morin’s book is full of ethnographic, anthropological, and psychological research, and there is much to commend in it. However, Morin’s arguments against the dual-inheritance theorists are less convincing when put under scrutiny, and his positive picture which includes appeals to ostensive communication, intrinsic appeal and cultural attraction has some difficulties. I argue that when we contrast dual-inheritance theorists and Morin, we find that there may be fewer differences and greater commonalities than Morin’s book might suggest.     

Xenotransplantation: Biotechnological Aspects and Current Attitudes

Xenotransplantation of organs from the large domestic species will only be successful if the donor animals have been genetically modified, in particular regarding the α-Gal epitope, certain human complements (CD55 and CD59) and/or H-transferase. This requires, among other things, major embryo-technological efforts, and the rate of success is still far from an acceptable level in the domestic species. It is currently poor, but the progress is very good. In this brief review certain embryo-technological problems will be addressed with the focus on the pig as potential organ donor. In addition, certain views of the Danish ad hoc Committee on Gene Technology on xenotransplantation will be presented in this context as they are supposed to mirror the concern and the views of the issues important for the public and each individual.     

A rare hybridization event in two common Caribbean wrasses (genus <Emphasis Type="Italic">Halichoeres</Emphasis>; family Labridae)

Molecular tools were used to evaluate the hybrid status of a specimen with intermediate colour pattern between Halichoeres bivittatus and Halichoeres garnoti from Belize. Phylogenetic analyses of the two species, eight Halichoeres species from new and old world lineages and two outgroups showed that the study species are closely related and that H. garnoti is the maternal contributor to the putative hybrid specimen, based on partial mitochondrial COI data. Direct sequencing of Intron 1 of the nuclear ribosomal protein S7 identified H. bivittatus as sister to H. garnoti with the putative hybrid specimen in an intermediate position, due to heterozygosity at nucleotides alternatively fixed in the two putative parent species. This is consistent with the hybrid status of the specimen, with parental contributions from both H. garnoti and H. bivittatus. These results, combined with no evidence of introgression between the two parent species (based on the mtDNA and the single investigated nuclear marker) and the biogeography and ecology of these species suggests that this is a rare event with minimal evolutionary implications.     

GIS-based Tools for Regional Assessments and Planning Processes Regarding Potential Environmental Effects of Poplar SRC

Based on regional stakeholder preferences and planning guidelines as allocation criteria for SRC, this study aims at providing a transparent approach to evaluate multiple environmental effects and the regional significance of SRC systems. Using the example of two poplar SRC-systems (4-year rotation, 9-year rotation) the potential effects on ground water supply, wind erosion, and biodiversity aspects are evaluated in comparison to arable land for two selected municipalities in the district of Uelzen, Germany. Building on fuzzy membership functions and simple fuzzy-logic rules, the qualitative multi-criteria assessment is transparent and easily to adapt. This approach is transferable to other regions and spatial levels, since it derives from commonly available data and scientific evidence. Results show that implementation of SRC could provide multiple beneficial environmental effects, especially in areas with low landscape heterogeneity. The tools provided allow for a multi-criteria evaluation of environmental effects, and reveal the sensitivity to distinct allocation patterns. Physiographical conditions of the study area implicate a preference for mini-SRC systems. This is supported by smaller decline of annual deep percolation water compared to maxi-SRC. On average, decline in groundwater recharge of mini-SRC (92mm a⁻¹) is comparable to irrigated arable land (80mm a⁻¹), which is common practice in the study area. Currently, the utilization of beneficial environmental SRC effects is quite limited, since only 3 % of arable land is suitable for SRC implementation regarding farmers’ preferences for SRC allocation. Allocation preferences could however change substantially with increasing incentives for SRC, e.g., due to regional bioenergy schemes or “Greening” initiatives within the European Common Agricultural Policy, which is to be reformed by 2013.