Quantum entanglement in photoactive prebiotic systems

This paper contains the review of quantum entanglement investigations in living systems, and in the quantum mechanically modelled photoactive prebiotic kernel systems. We define our modelled self-assembled supramolecular photoactive centres, composed of one or more sensitizer molecules, precursors of fatty acids and a number of water molecules, as a photoactive prebiotic kernel systems. We propose that life first emerged in the form of such minimal photoactive prebiotic kernel systems and later in the process of evolution these photoactive prebiotic kernel systems would have produced fatty acids and covered themselves with fatty acid envelopes to become the minimal cells of the Fatty Acid World. Specifically, we model self-assembling of photoactive prebiotic systems with observed quantum entanglement phenomena. We address the idea that quantum entanglement was important in the first stages of origins of life and evolution of the biospheres because simultaneously excite two prebiotic kernels in the system by appearance of two additional quantum entangled excited states, leading to faster growth and self-replication of minimal living cells. The quantum mechanically modelled possibility of synthesizing artificial self-reproducing quantum entangled prebiotic kernel systems and minimal cells also impacts the possibility of the most probable path of emergence of protocells on the Earth or elsewhere. We also examine the quantum entangled logic gates discovered in the modelled systems composed of two prebiotic kernels. Such logic gates may have application in the destruction of cancer cells or becoming building blocks of new forms of artificial cells including magnetically active ones.     

HSP70 polymorphisms in first psychotic episode drug-naïve schizophrenic patients

Aims

The aim of this study is to investigate differences in HSPA8 polymorphisms between first-episode psychotic (FEP) schizophrenic patients and healthy participants after adjustment for temperamental personality traits.

Main methods

This study included fifty drug-naive schizophrenic patients with an FEP and fifty healthy participants who served as controls. Genotyping of HSPA8 polymorphisms was performed in patients and healthy subjects as well. Personality characteristics were assessed using the standardized Greek version of the Alternative Five-Factor Zuckerman–Kuhlman Personality Questionnaire (ZKPQ).

Key findings

Our results showed that FEP patients presented a polymorphism differentiation related to the HSPA8 gene (rs1136141), and a higher frequency of T carriers compared to healthy controls was observed. The HSP8A polymorphism and the levels of Neuroticism as measured by the Alternative Five-Factor ZKPQ were the variables most closely and independently associated with FEP in multiple logistic regression analysis, and the odds of being assessed with a FEP was 2.8 times greater in T carriers compared to non-carriers.

Significance

Present findings indicate a role of HSP8A in FEP and underline the importance of including personality traits in the study of the factors associated with the development of schizophrenia.     

BDNF serum concentrations in first psychotic episode drug-naïve schizophrenic patients: Associations with personality and BDNF Val66Met polymorphism

AimsTo investigate the relationship among brain derived neurotrophic factor (BDNF) serum concentrations, BDNF Val66Met polymorphism and personality profile in drug-naïve schizophrenic patients with first-episode psychosis (FEP) and healthy participants.Main methodsThis cross-sectional study included fifty FEP patients and fifty healthy participants who served as controls. To study their personality profile the standardized Greek version of the Alternative Five-Factor Zuckerman–Kuhlman Personality Questionnaire (ZKPQ) was administered. Serum BDNF levels were measured and genotyping of BDNF Val66Met polymorphism was performed in patients and healthy subjects.Key findingsFEP patients presented lower BDNF serum concentrations (P = 0.002) and higher scores in ZKPQ Neuroticism (P = 0.001) and Aggression–Hostility (P = 0.002) scales while lower scores in the ZKPQ Sociability scale (P < 0.001) than healthy participants. Multivariate analysis revealed that the odds of being assessed with FEP were 0.4 times lower in those with higher BDNF values (P < 0.001) and 1.8 times greater in those with higher Neuroticism scores (P < 0.001). There were no significant differences with respect to the Val66Met polymorphism between patients and healthy participants.SignificanceReduced BDNF serum concentrations along with higher Neuroticism scores might be associated with FEP. A complex interplay between BDNF serum concentrations, personality traits, BDNF Val66Met polymorphism, and psychotic symptomatology has been arisen but further investigation is needed to better clarify the observed associations.     

Amyloid protofilaments from the calcium-binding protein equine lysozyme: formation of ring and linear structures depends on pH and metal ion concentration

The calcium-binding equine lysozyme has been found to undergo conversion into amyloid fibrils during incubation in solution at acidic pH. At pH 4.5 and 57 degrees C, where equine lysozyme forms a partially unfolded molten globule state, the protein forms protofilaments with a width of ca. 2 nm. In the absence of Ca(2+) the protofilaments are present as annular structures with a diameter of 40-50 nm. In the presence of 10 mM CaCl(2) the protofilaments of equine lysozyme are straight or curved; they can assemble into thicker threads, but they do not appear to undergo circularisation. At pH 2.0, where the protein is more destabilised compared to pH 4.5, fibril formation occurs at 37 degrees C and 57 degrees C. At pH 2.0, both ring-shaped and linear protofilaments are formed, in which periodic repeats of ca 35 nm can be distinguished clearly. The rings constitute about 10% of all fibrillar species under these conditions and they are characterised by a larger diameter of 70-80 nm. All the structures bind Congo red and thioflavine T in a manner similar to fibrils associated with a variety of amyloid diseases. At pH 2.0, fibril formation is accompanied by some acidic hydrolysis, producing specific fragmentation of the protein, leading to the accumulation of two peptides in particular, consisting of residues 1-80 and 54-125. At the initial stages of incubation, however, full-length equine lysozyme represents the dominant species within the fibrils. We propose that the ring-shaped structures observed here, and in the case of disease-associated proteins such as alpha-synuclein, could be a second generic type of amyloid structure in addition to the more common linear fibrils.     

Does the cytotoxic effect of transient amyloid oligomers from common equine lysozyme in vitro imply innate amyloid toxicity?

In amyloid diseases, it is not evident which protein aggregates induce cell death via specific molecular mechanisms and which cause damage because of their mass accumulation and mechanical properties. We showed that equine lysozyme assembles into soluble amyloid oligomers and protofilaments at pH 2.0 and 4.5, 57 degrees C. They bind thioflavin-T and Congo red similar to common amyloid structures, and their morphology was monitored by atomic force microscopy. Molecular volume evaluation from microscopic measurements allowed us to identify distinct types of oligomers, ranging from tetramer to octamer and 20-mer. Monomeric lysozyme and protofilaments are not cytotoxic, whereas the oligomers induce cell death in primary neuronal cells, primary fibroblasts, and the neuroblastoma IMR-32 cell line. Cytotoxicity was accessed by ethidium bromide staining, MTT reduction, and TUNEL assays. Primary cultures were more susceptible to the toxic effect induced by soluble amyloid oligomers than the neuroblastoma cell line. The cytotoxicity correlates with the size of oligomers; the sample incubated at pH 4.5 and containing larger oligomers, including 20-mer, appears to be more cytotoxic than the lysozyme sample kept at pH 2.0, in which only tetramers and octamers were found. Soluble amyloid oligomers may assemble into rings; however, there was no correlation between the quantity of rings in the sample and its toxicity. The cytotoxicity of transient oligomeric species of the ubiquitous protein lysozyme indicates that this is an intrinsic feature of protein amyloid aggregation, and therefore soluble amyloid oligomers can be used as a primary therapeutic target and marker of amyloid disease.     

Diurnal and Seasonal Changes in Prunus Amygdalus Gas Exchanges

Diurnal courses in net photosynthetic rate (PN), stomatal conductance (gs), leaf water potential (), internal CO2 concentration (ci), and water use efficiency (WUE) were studied as season progressed, in relation to environmental factors in field grown Prunus amygdalus. In sun leaves PN reached maximum between 09:00 to 11:00 h and subsequently declined when high temperature and low humidity occurred. An increase was observed late in the afternoon. A decrease in gs and was found as season progressed in both years of measurements. In periods of high evaporative demand, was very low, however, it did not explain the reductions of PN in all the three periods (spring, early and late summer). Midday depression of PN and gs seemed to be related with leaf temperature (Tl) and high irradiance. Increase in ci and F0 and decrease in Fv/Fm found between 12:00 and 14:00 h corresponded to the decrease in PN. Therefore, a transient modification of photosynthetic machinery might be considered. WUE was negatively correlated with vapour pressure difference of leaf to air, that decreased during the day. The September values, higher than in the previous months, were due to the lower seasonal decreases in PN than in gs.     

The Emergence and Evolution of Life in a “Fatty Acid World” Based on Quantum Mechanics

Quantum mechanical based electron correlation interactions among molecules are the source of the weak hydrogen and Van der Waals bonds that are critical to the self-assembly of artificial fatty acid micelles. Life on Earth or elsewhere could have emerged in the form of self-reproducing photoactive fatty acid micelles, which gradually evolved into nucleotide-containing micelles due to the enhanced ability of nucleotide-coupled sensitizer molecules to absorb visible light. Comparison of the calculated absorption spectra of micelles with and without nucleotides confirmed this idea and supports the idea of the emergence and evolution of nucleotides in minimal cells of a so-called Fatty Acid World. Furthermore, the nucleotide-caused wavelength shift and broadening of the absorption pattern potentially gives these molecules an additional valuable role, other than a purely genetic one in the early stages of the development of life. From the information theory point of view, the nucleotide sequences in such micelles carry positional information providing better electron transport along the nucleotide-sensitizer chain and, in addition, providing complimentary copies of that information for the next generation. Nucleotide sequences, which in the first period of evolution of fatty acid molecules were useful just for better absorbance of the light in the longer wavelength region, later in the PNA or RNA World, took on the role of genetic information storage.     

Pancreatic aplasia in a fetus with asplenia-cardiovascular defect-heterotaxy (Ivemark syndrome)

BACKGROUND: Asplenia or polysplenia and complex cardiovascular defects, in association with disturbed body symmetry and malposition of internal organs, constitute the main corpus of malformations in the heterogeneous group of heterotaxy disorders. In affected pregnancies, prenatal diagnosis is possible by ultrasonography, while prognosis and counseling largely depend upon the severity of the cardiac defect. CASE: We present a 25 week gestation fetus with typical findings of asplenia–cardiovascular defect–heterotaxy (Ivemark syndrome) and aplasia of the pancreas. CONCLUSIONS: Pancreatic aplasia emerges as an additional phenotypic feature in Ivemark syndrome and raises the possibility of total pancreatic insufficiency of the affected neonate as an additional, although rare, clinical consideration. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.     

Fibrillation of carrier protein albebetin and its biologically active constructs. Multiple oligomeric intermediates and pathways

We showed that the genetically engineered carrier-protein albebetin and its biologically active constructs with interferon-alpha(2) octapeptide LKEKKYSP or differentiation factor hexapeptide TGENHR are inherently highly amyloidogenic at physiological pH. The kinetics of fibrillation were monitored by thioflavine-T (ThT) binding and the morphological changes by atomic force microscopy. Fibrillation proceeds via multiple pathways and includes a hierarchy of amyloid structures ranging from oligomers to protofilaments and fibrils. Comparative height and volume microscopic measurements allowed us to identify two distinct types of oligomeric intermediates: pivotal oligomers ca. 1.2 nm in height comprised of 10-12 monomers and on-pathway amyloid-competent oligomers ca. 2 nm in height constituted of 26-30 molecules. The former assemble into chains and rings with "bead-on-string morphology", in which a "bead" corresponds to an individual oligomer. Once formed, the rings and chains remain in solution simultaneously with fibrils. The latter give rise to protofilaments and fibrils, and their formation is concomitant with an increasing level of ThT binding. The amyloid nature of filamentous structures was confirmed by a pronounced ThT and Congo red binding and beta-sheet-rich far-UV circular dichroism. We suggest that transformation of the pivotal oligomers into the amyloid-prone ones is a limiting stage in amyloid assembly. Peptides, either fused to albebetin or added into solution, and an increased ionic strength promote fibrillation of albebetin (net charge of -12) by counterbalancing critical electrostatic repulsions. This finding demonstrates that the fibrillation of newly designed polypeptide-based products can produce multimeric amyloid species with a potentially "new" functionality, raising questions about their safety.     

A homolog of lariat-debranching enzyme modulates turnover of branched RNA

Turnover of the branched RNA intermediates and products of pre-mRNA splicing is mediated by the lariat-debranching enzyme Dbr1. We characterized a homolog of Dbr1 from Saccharomyces cerevisiae, Drn1/Ygr093w, that has a pseudo-metallophosphodiesterase domain with primary sequence homology to Dbr1 but lacks essential active site residues found in Dbr1. Whereas loss of Dbr1 results in lariat-introns failing broadly to turnover, loss of Drn1 causes low levels of lariat-intron accumulation. Conserved residues in the Drn1 C-terminal CwfJ domains, which are not present in Dbr1, are required for efficient intron turnover. Drn1 interacts with Dbr1, components of the Nineteen Complex, U2 snRNA, branched intermediates, and products of splicing. Drn1 enhances debranching catalyzed by Dbr1 in vitro, but does so without significantly improving the affinity of Dbr1 for branched RNA. Splicing carried out in in vitro extracts in the absence of Drn1 results in an accumulation of branched splicing intermediates and products released from the spliceosome, likely due to less active debranching, as well as the promiscuous release of cleaved 5′-exon. Drn1 enhances Dbr1-mediated turnover of lariat-intermediates and lariat-intron products, indicating that branched RNA turnover is regulated at multiple steps during splicing.