Autoimmune processes after long-term low-level exposure to electromagnetic fields (experimental results) part 3. The effect of long-term nonthermal RF EMF exposure on complement-fixation antibodies against homologenous tissue

The effect of long-term nonthermal EMF exposure of 2450 MHz (500 μW/cm²) on the level of antibodies against brain and liver tissues is studied on rats by the complement-fixation test (CFT) in the cold. It is found that a statistically significant increase in the level of antibodies against aqueous extracts of brain and liver tissues in blood serum is detected only on the 14th day after exposure is ended.     

Autoimmune processes after long-term low-level exposure to electromagnetic fields part 4. Oxidative intracellular stress response to the long-term rat exposure to nonthermal RF EMF

Forty eight male Wistar rats with initial weight of 200–220 g were exposed to EMF of 2450 MHz frequency and 500 μW/cm² intensity for 7 h daily over a period of 30 days. On the seventh and 14th days after completion of exposure to the long-term EMF, enzyme immunoassay revealed a significant increase in the amount of specific antibodies of the IgM and IgG classes against the compounds yielded by interaction of amino acids with nitric oxide and its derivatives; tryptophan metabolites; azelaic acid; small-chain fatty acids; small-chain hydroxylated fatty acids; and palmitic, myristic, and oleic acids.     

Changes in belowground carbon in Acacia crassicarpa and Eucalyptus urophylla plantations after tree girdling

Limitations in the techniques used to separate root-derived and soil-organic-matter (SOM)-derived respiration have hampered the understanding of forest carbon cycling. Tree girdling is considered to be a robust approach with little disturbance to the root–soil system. Using this approach, we tried to separate root-derived respiration from SOM-derived respiration under Acacia crassicarpa and Eucalyptus urophylla plantations in South China. We found that girdling reduced soil respiration and temperature sensitivity of respiration (Q ₁₀) under both plantations compared to controls, but the intensity of girdling effects was species specific. Six months after girdling, live fine root biomass was lower than the control in A. crassicarpa but not in E. urophylla. Soil microbial biomass (C _mic) under A. crassicarpa was increased by girdling 17 days after treatment, but decreased thereafter. In contrast, there was no difference in C _mic between girdled and control treatments under E. urophylla. Girdling significantly decreased soil organic carbon (SOC) and dissolved organic carbon (DOC) under A. crassicarpa, but not under E. urophylla. We ascribe differences in girdling effects on belowground carbon between the two species to differences in resprouting traits.     

Bafilomycin A1 is a potassium ionophore that impairs mitochondrial functions

Novel activities of bafilomycin A1, a macrolide antibiotic known as an inhibitor of V-ATPases, were discovered. Bafilomycin A1 induced uptake of potassium ions by energized mitochondria and caused mitochondrial swelling, loss of membrane potential, uncoupling of oxidative phosphorylation, inhibition of the maximal respiration rates, and induced pyridine nucleotide oxidation. The mitochondrial effects provoked by nanomolar concentrations of bafilomycin A1 were connected to its activity as a potent, K⁺-specific ionophore. The K⁺ ionophoric activity of bafilomycin A1 was observed also in black lipid membranes, indicating that it was an inherent property of the bafilomycin A1 molecule. It was found that bafilomycin A1 is a K⁺ carrier but not a channel former. Bafilomycin A1 is the first and currently unique macrolide antibiotic with K⁺ ionophoric properties. The novel properties of bafilomycin A1 may explain some of the biological effects of this plecomacrolide antibiotic, independent of V-ATPase inhibition.     

Allosteric communication in dihydrofolate reductase: signaling network and pathways for closed to occluded transition and back

Escherichia coli dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate. During the catalytic cycle, DHFR undergoes conformational transitions between the closed (CS) and occluded (OS) states that, respectively, describe whether the active site is closed or occluded by the Met20 loop. The CS→OS and the reverse transition may be viewed as allosteric transitions. Using a sequence-based approach, we identify a network of residues that represents the allostery wiring diagram. Many of the residues in the allostery wiring diagram, which are dispersed throughout the adenosine-binding domain as well as the loop domain, are not conserved. Several of the residues in the network have been previously shown by NMR experiments, mutational studies, and molecular dynamics simulations to be linked to equilibration conformational fluctuations of DHFR. To further probe the nature of events that occur during conformational fluctuations, we use a self-organized polymer model to monitor the kinetics of the CS→OS and the reverse transitions. During the CS→OS transition, coordinated changes in a number of residues in the loop domain enable the Met20 loop to slide along the α-helix in the adenosine-binding domain. Sliding is triggered by pulling of the Met20 loop by the βG-βH loop and the pushing action of the βG-βH loop. The residues that facilitate the Met20 loop motion are part of the network of residues that transmit allosteric signals during the CS→OS transition. Replacement of M16 and G121, whose C^α atoms are about 4.3 Å in the CS, by a disulfide cross-link impedes that CS→OS transition. The order of events in the OS→CS transition is not the reverse of the forward transition. The contact Glu18-Ser49 in the OS persists until the sliding of the Met20 loop is nearly complete. The ensemble of structures in the transition state in both the allosteric transitions is heterogeneous. The most probable transition-state structure resembles the OS (CS) in the CS→OS (OS→CS) transition, which is in accord with the Hammond postulate. Structures resembling the OS (CS) are present as minor (∼ 1-3%) components in equilibrated CS (OS) structures.     

NPY regulates human endocardial endothelial cell function

Growing evidence suggests that endocardial endothelial cells (EECs) may play an important role in the regulation of cardiac function by releasing several cardioactive factors such as endothelin-1 (ET-1), Angiotensin II (Ang II) and nitric oxide (NO). In our laboratory, we demonstrated that similar to ET-1, EECs do possess different types of NPY receptors, specifically Y(1) and Y(2) receptors. Furthermore, activation of these receptors was found to increase the steady-state level of intracellular free Ca(2+) in EECs and the frequency of beating of cardiomyocytes. In addition, NPY was also found to be present in EECs, and an increase of steady-state intracellular free Ca(2+) induced the release of this peptide from these cells. Thus, similar to ET-1, NPY seems to be released from EECs and this peptide seems to regulate excitation-secretion of these cells as well as excitation-contraction coupling of ventricular cardiomyocytes.     

Problems in assessment of risks from exposures to microwaves of mobile communication

Since pioneering investigations published in the beginning of 1970th, various biological responses to non-thermal (NT) microwaves (MW), including adverse health effects, have been described by many research groups all over the world. There is strong evidence that the NT MW biological effects depend on several physical parameters and biological variables, which must be controlled in replication studies. Apart from the fundamental importance, the development of comprehensive mechanisms for the NT MW effects is socially important. The effects of MW of mobile communications are of major concern because of the increased exposure in many countries. It has been shown that adverse effects of NT MW from GSM/UMTS mobile phones on human lymphocytes from healthy and hypersensitive to EMF persons depend on carrier frequency and modulation. Further investigations with human primary cells, animals and volunteers are needed to elucidate possible adverse effects of MW signals that are used in wireless communication. Identification of those types and frequency channels/bands for mobile communication, which do not affect human cells, is urgently needed as the high priority task for the development of safe mobile communication. Numerous data on the NT MW effects clearly indicate that the SAR-concept alone cannot underlie the safety guidelines for chronic exposures to MW from mobile communication and other approaches are needed. However, there is not enough research information to set exposure MW standards. Various genetic and epigenetic effects of signals used in mobile communication should be studied. It has been shown that NT MW affect cells of various types including stem cells and reproductive organs. Stem cells represent especially important cellular model because recent data suggest that different cancer types, including leukemia, have a fundamentally common basis that is grounded on epigenetic changes in stem cells.     

Docking with PIPER and refinement with SDU in rounds 6-11 of CAPRI

Our approach to protein-protein docking includes three main steps. First we run PIPER, a new rigid body docking program. PIPER is based on the Fast Fourier Transform (FFT) correlation approach that has been extended to use pairwise interactions potentials, thereby substantially increasing the number of near-native structures generated. The interaction potential is also new, based on the DARS (Decoys As the Reference State) principle. In the second step, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the conformations are refined by a new medium-range optimization method SDU (Semi-Definite programming based Underestimation). SDU has been developed to locate global minima within regions of the conformational space in which the energy function is funnel-like. The method constructs a convex quadratic underestimator function based on a set of local energy minima, and uses this function to guide future sampling. The combined method performed reliably without the direct use of biological information in most CAPRI problems that did not require homology modeling, providing acceptable predictions for targets 21, and medium quality predictions for targets 25 and 26.     

Genetic isolation between two recently diverged populations of a symbiotic fungus

Fungi are an omnipresent and highly diverse group of organisms, making up a significant part of eukaryotic diversity. Little is currently known about the drivers of fungal population differentiation and subsequent divergence of species, particularly in symbiotic, mycorrhizal fungi. Here, we investigate the population structure and environmental adaptation in Suillus brevipes (Peck) Kuntze, a wind‐dispersed soil fungus that is symbiotic with pine trees. We assembled and annotated the reference genome for Su. brevipes and resequenced the whole genomes of 28 individuals from coastal and montane sites in California. We detected two clearly delineated coast and mountain populations with very low divergence. Genomic divergence was restricted to few regions, including a region of extreme divergence containing a gene encoding for a membrane Na⁺/H⁺ exchanger known for enhancing salt tolerance in plants and yeast. Our results are consistent with a very recent split between the montane and coastal Su. brevipes populations, with few small genomic regions under positive selection and a pattern of dispersal and/or establishment limitation. Furthermore, we identify a putatively adaptive gene that motivates further functional analyses to link genotypes and phenotypes and shed light on the genetic basis of adaptive traits.