Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures.

Networks of tryptophan (Trp)─an aromatic amino acid with strong fluorescence response─are ubiquitous in biological systems, forming diverse architectures in transmembrane proteins, cytoskeletal filaments, subneuronal elements, photoreceptor complexes, virion capsids, and other cellular structures. We analyze the cooperative effects induced by ultraviolet (UV) excitation of several biologically relevant Trp mega-networks, thus giving insights into novel mechanisms for cellular signaling and control. Our theoretical analysis in the single-excitation manifold predicts the formation of strongly superradiant states due to collective interactions among organized arrangements of up to >105 Trp UV-excited transition dipoles in microtubule architectures, which leads to an enhancement of the fluorescence quantum yield (QY) that is confirmed by our experiments. We demonstrate the observed consequences of this superradiant behavior in the fluorescence QY for hierarchically organized tubulin structures, which increases in different geometric regimes at thermal equilibrium before saturation, highlighting the effect's persistence in the presence of disorder. Our work thus showcases the many orders of magnitude across which the brightest (hundreds of femtoseconds) and darkest (tens of seconds) states can coexist in these Trp lattices.

Impact of foliar application of fungicides on tomato leaf fungal community structure revealed by metagenomic analysis.

Fungicides are commonly used to manage plant pathogens. However, little is known about their effects on the non-target fungal communities that inhabit inside and outside the plant. These fungicides may have adverse effects on beneficial microbial communities with possible consequences for plant health and productivity. Hence, a metagenomic approach, based on the ITS2 region of fungal rDNA, was used to study the impact of foliar application of two fungicides (propineb and iprodione + carbendazim) on non-target tomato leaf fungal communities, in the context of early blight disease management. Metagenomic analysis revealed that the richness and diversity of tomato leaf fungal populations were adversely affected by the chemical treatments tested. Among the two fungicides, propineb (contact fungicide) imparted less non-targeted microorganisms than iprodione + carbendazim (systemic fungicide). In addition, all samples showed association of pathogenic genera Cladosporium, Corynespora, Pseudocercospora along with early blight pathogen Alternaria on tomato leaves that otherwise were undetected. Metagenomic studies also revealed a new mode of action for fungicides and bioagents besides their direct effect that is shifting the microbial community structure so that it provides greater resistance against the pathogen.

Complete genome sequence of Alteromonas pelagimontana 5.12T, a marine exopolysaccharide-producing bacterium isolated from hydrothermally influenced deep-sea sediment of eastern Southwest Indian Ridge.

The whole genome of Alteromonas pelagimontana 5.12T, a psychrotolerant deep-sea bacterium isolated from the sediment sample of eastern Southwest Indian Ridge, was sequenced and analysed for understanding its metabolic capacities and biosynthesis potential of natural products. The circular genome contained 4.3 Mb with a GC content of 42.6 mol%. Genomic data mining revealed a gene cluster for heavy metal resistance (czcABC, acrB, arsR1, copA, nikA, mntH, mntP), exopolysaccharides (EPS; epsCDEFHLM) and polyhydroxyalkanoates (PHA; phbC) production, as well as genes involved in complex polysaccharide degradation. Genes that could allow strain 5.12T to cope with acid stress (ibaG) and heat shock (ibpA, hslR) were observed along with ten chaperone-encoding genes which could possibly play vital role in adaptability of this strain to the hydrothermally influenced environment. Gene clusters for secondary metabolite production such as bacteriocin and arylpolyene were also predicted. Thus, genome sequencing and data mining provided insights into the molecular mechanisms involved in the adaptation to hydrothermally influenced deep-sea environment that could promote further experimental exploration.

Complete genome sequence and comparative genome analysis of Alcanivorax sp. IO_7, a marine alkane-degrading bacterium isolated from hydrothermally-influenced deep seawater of southwest Indian ridge.

Genome of Alcanivorax sp. IO_7, an alkane degrading deep-sea bacteria isolated from hydrothermally-influenced Southwest Indian Ridge was sequenced and analysed. Genomic data mining revealed gene clusters for degrading n-alkane and cycloalkanes, including biosurfactant production. The strain was shown to grow on hexadecane as its sole carbon source, supporting the findings of genomic analysis. Presence of cyclohexanone monooxygenase among genomic islands suggest that this strain may have used gene transfer to enhance its hydrocarbon degradation ability. Genes encoding for heavy metal resistance, multidrug resistance and multiple natural product biosynthesis crucial for survival in the hydrothermally influenced deep sea environment were detected. In our comparative genome analysis, it was evident that marine Alcanivorax strains contain a suite of enzymes for n-alkane and haloalkanoate degradation. Comparative genome and genomic synteny analysis provided insights into the physiological features and adaptation strategies of Alcanivorax sp. IO_7 in the deep-sea hydrothermal environment.

Stem Cell Differentiation Stage Factors and their Role in Triggering Symmetry Breaking Processes during Cancer Development: A Quantum Field Theory Model for Reprogramming Cancer Cells to Healthy Phenotypes.

A long history of research has pursued the use of embryonic factors isolated during cell differentiation processes for the express purpose of transforming cancer cells back to healthy phenotypes. Recent results have clarified that the substances present at different stages of cell differentiation-which we call stem cell differentiation stage factors (SCDSFs)-are proteins with low molecular weight and nucleic acids that regulate genomic expression. The present review summarizes how these substances, taken at different stages of cellular maturation, are able to retard proliferation of many human tumor cell lines and thereby reprogram cancer cells to healthy phenotypes. The model presented here is a quantum field theory (QFT) model in which SCDSFs are able to trigger symmetry breaking processes during cancer development. These symmetry breaking processes, which lie at the root of many phenomena in elementary particle physics and condensed matter physics, govern the phase transitions of totipotent cells to higher degrees of diversity and order, resulting in cell differentiation. In cancers, which share many genomic and metabolic similarities with embryonic stem cells, stimulated redifferentiation often signifies the phenotypic reversion back to health and nonproliferation. In addition to acting on key components of the cellular cycle, SCDSFs are able to reprogram cancer cells by delicately influencing the cancer microenvironment, modulating the electrochemistry and thus the collective electrodynamic behaviors between dipole networks in biomacromolecules and the interstitial water field. Coherent effects in biological water, which are derived from a dissipative QFT framework, may offer new diagnostic and therapeutic targets at a systemic level, before tumor instantiation occurs in specific tissues or organs. Thus, by including the environment as an essential component of our model, we may push the prevailing paradigm of mutation-driven oncogenesis toward a closer description of reality.

Water-mediated correlations in DNA-enzyme interactions.

In this paper we consider dipole-mediated correlations between DNA and enzymes in the context of their water environment. Such correlations emerge from electric dipole-dipole interactions between aromatic ring structures in DNA and in enzymes. We show that there are matching collective modes between DNA and enzyme dipole fields, and that a dynamic time-averaged polarization vanishes in the water dipole field only if either DNA, enzyme, or both are absent from the sample. This persistent field may serve as the electromagnetic image that, in popular colloquialisms about DNA biochemistry, allows enzymes to "scan" or "read" the double helix. Topologically nontrivial configurations in the coherent ground state requiring clamplike enzyme behavior on the DNA may stem, ultimately, from spontaneously broken gauge symmetries.

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease.

Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood. Classically, mitochondrial dysfunction has been viewed as the major source of oxidative stress and has been shown to precede tau and amyloid pathology in various dementias, but the exact mechanisms are not clear. It is known that the production of ROS by mitochondria can result in ultraweak photon emission (UPE) within cells. While of low intensity, surrounding proteins within the cytosol can still absorb these energetic photons via aromatic amino acids (e.g., tryptophan and tyrosine). One likely absorber of these photons is the microtubule cytoskeleton, as it forms a vast network spanning neurons, is highly co-localized with mitochondria, and shows a high density of aromatic amino acids. Functional microtubule networks may traffic this ROS-generated endogenous photon energy for cellular signaling, or they may serve as dissipaters/conduits of such energy to protect the cell from potentially harmful effects. Experimentally, after in vitro exposure to exogenous photons, microtubules have been shown to reorient and reorganize in a dose-dependent manner with the greatest effect being observed around 280nm, in the tryptophan and tyrosine absorption range. In this paper, recent modeling efforts based on ambient temperature experiment are presented, showing that tubulin polymers can feasibly absorb and channel these photoexcitations via resonance energy transfer, on the order of dendritic length scales and neuronal fine structure. Since microtubule networks are compromised in tauopathic diseases such as Alzheimer's and Parkinson's dementias, patients with these illnesses would be unable to support effective channeling of these photons for signaling or dissipation. Consequent emission surplus due to increased UPE production or decreased ability to absorb and transfer may lead to increased cellular oxidative damage, thus hastening the neurodegenerative process.

Alteromonas pelagimontana sp. nov., a marine exopolysaccharide-producing bacterium isolated from the Southwest Indian Ridge.

A novel exopolysaccharide-producing strain, designated as 5.12T, was isolated from a sediment sample from the Southwest Indian Ridge, Indian Ocean. The strain was Gram-stain-negative, motile, strictly aerobic, and oxidase- and catalase-positive. It grew optimally at 35 °C, at pH 6.0 and in the presence of 3.5 % (w/v) NaCl. Its major isoprenoid quinone was ubiquinone-8 (Q-8) and summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c), C16 : 0 and C18 : 1ω7c were the major cellular fatty acids. The DNA G+C content was 46.1 mol%. 16S rRNA gene sequence analysis suggested that strain 5.12T is a member of the genus Alteromonas. Strain 5.12T exhibited close 16S rRNA gene sequence similarity to Alteromonas lipolytica JW12T (96.1 %), Alteromonas hispanica F-32T (95.9 %), Alteromonas confluentis DSSK2-12T (95.9 %), Alteromonas litorea TF-22T (95.6 %) and Alteromonas mediterranea DET (95.5 %). Strain 5.12T contained phosphatidylethanolamine and phosphatidylglycerol as the major polar lipids. Owing to significant differences in the 16S rRNA gene sequences, as well as the phenotypic and chemotaxonomic characteristics, the novel isolate described here merits classification as a representative of a novel species of the genus Alteromonas, for which the name Alteromonas pelagimontana sp. nov. is proposed. The type strain of this species is 5.12T (LMG 29661T= MCC 3250T).

Draft Genome Sequence of Idiomarina sp. Strain 5.13, a Highly Stress-Resistant Bacterium Isolated from the Southwest Indian Ridge.

Idiomarina sp. strain 5.13, able to produce biopolymer and exopolysaccharide, was isolated from a sediment sample collected from the Southwest Indian Ridge, Indian Ocean. Analysis of its draft genome sequence provides insights into its remarkable stress tolerance and offers the genetic basis for harnessing the biotechnological potential of this strain.

Ultrasound-Guided Parasternal Block Allows Optimal Pain Relief and Ventilation Improvement After a Sternal Fracture.

INTRODUCTION: Sternal fractures are a painful condition which can result in pulmonary morbidity if not treated promptly. The management of isolated fractures has changed from hospital to home-based treatment, provided other major injuries have been excluded. Pain management is the mainstay of treatment. In this case report, we describe how a parasternal block under ultrasound guidance for sternal fracture provided better analgesia thereby improving ventilation. CASE REPORT: A 26-year-old man was admitted to the emergency department following a road traffic accident. His initial evaluation revealed a radio-cubital displaced fracture at the elbow level with severe tenderness over the sternum. Chest X-ray on admission did not reveal any abnormality. On preoperative checkup he was found to have altered chest mechanics with severe pain and tenderness over the sternum. Arterial blood gas (ABG) analysis showed respiratory acidosis. Pulmonary electrical impedance tomography showed hypoventilation of anterior portions of both lungs. An ultrasound examination of the sternum showed a fractured sternum with complete disjunction. An ultrasound-guided bilateral parasternal block was performed which resulted in efficient analgesia and thereby improved his ventilation as indicated by the improvement in ABG. CONCLUSION: Timely and proper analgesia can reduce the pulmonary morbidity in sternal fractures. Of the various analgesic techniques, parasternal block under ultrasound guidance is a relatively simple, safe, and target-specific procedure that can provide efficient pain relief.

How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases.

Macroscopic quantum effects in living systems have been studied widely in pursuit of fundamental explanations for biological energy transport and sensing. While it is known that type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers remains unclear. We propose a quantum mechanical model for collective electronic behavior in the DNA helix, where dipole-dipole oscillations are quantized through boundary conditions imposed by the enzyme. Zero-point modes of coherent oscillations would provide the energy required for double-strand breakage. Such quanta may be preserved in the presence of thermal noise by the enzyme's displacement of water surrounding the DNA recognition sequence. The enzyme thus serves as a decoherence shield. Palindromic mirror symmetry of the enzyme-DNA complex should conserve parity, because symmetric bond-breaking ceases when the symmetry of the complex is violated or when physiological parameters are perturbed from optima. Persistent correlations in DNA across longer spatial separations-a possible signature of quantum entanglement-may be explained by such a mechanism.

The Becton Dickinson FocalPoint GS Imaging System: clinical trials demonstrate significantly improved sensitivity for the detection of important cervical lesions.

Location-guided screening in cervical cytology offers a potentially significant advance over routine manual screening. A prospective, 2-armed, masked clinical trial of the BD FocalPoint GS Imaging System using SurePath slides (BD Diagnostics-TriPath, Burlington, NC) compared routine manual screening and quality control rescreening with computer-assisted, field-of-view screening and device-directed quality control rescreening. The results obtained in the 2 arms were compared with adjudicated reference diagnoses for each slide. Sensitivity, specificity, and negative predictive value were calculated for the detection of atypical squamous cells of undetermined significance and greater (ASC-US+), low-grade squamous intraepithelial lesion and greater (LSIL+), and high-grade squamous intraepithelial lesion and greater (HSIL+) groups. We evaluated 12,313 slides. The detection sensitivities for HSIL+ were increased by 19.6% (P < .0001) and for LSIL+ were increased by 9.8% (P < .0001) in the computer-assisted arm, with small statistically significant decreases in specificity. For ASC-US+ sensitivity and specificity, the study arms were not statistically different. Use of this system might be expected to improve accuracy for clinically important entities without increasing equivocal case detection.

Synthesis, permeability and biocompatibility of tricomponent membranes containing polyethylene glycol, polydimethylsiloxane and polypentamethylcyclopentasiloxane domains.

The synthesis of "smart" tricomponent amphiphilic membranes containing poly(ethylene glycol) (PEG), polydimethylsiloxane (PDMS) and polypentamethylcyclopentasiloxane (PD(5)) domains is described. Contact angle hysteresis indicates that in air, the surfaces of such PEG/PD(5)/PDMS membranes are enriched by the hydrophobic components, PDMS and PD(5), while in water, the surfaces are rich in the hydrophilic PEG. The oxygen permeability of a series of membranes with varying M(c,hydrophilic) (M(n,PEG)=4600, 10,000 and 20,000 g/mol) and varying PEG/PD(5)/PDMS compositions was studied. Oxygen permeability increased with the amount of PDMS in the membrane. The molecular weight cut-off (MWCO) ranges and permeability coefficients of insulin through a series of PEG/PD(5)/PDMS(=29/14/57) membranes with varying M(c,hydrophilic) were determined. Insulin permeability is directly related to M(c,hydrophilic) of the membrane. MWCO studies show that the membranes are semipermeable to, i.e., allow the transport of smaller proteins such as insulin (M(n)=5733 g/mol, R(s)=1.34 nm) and cytochrome c (M(n)=12,400 g/mol, R(s)=1.63 nm), but are barriers to larger proteins such as albumin (M(n)=66,000 g/mol, R(s)=3.62 nm). Implantation of representative membranes in rats showed them to be biocompatible. According to these studies, PEG/PD(5)/PDMS membranes may be suitable for biological applications, e.g., immunoisolation of cells.

Effect of oral L-carnitine on serum myoglobin in hemodialysis patients.

Oral L-carnitine has been reported to lower the elevated serum myoglobin of renal failure in chronic peritoneal dialysis patients, and intravenous L-carnitine can improve muscle fatigue and cramps in chronic hemodialysis patients. In this study oral L-carnitine, 1.98 g/day, was administered to 6 chronic hemodialysis patients for 8 weeks. Serum levels of myoglobin, creatine kinase, and aldolase, as well as skeletal muscle symptoms (cramps during dialysis, fatigue, and weakness) were monitored biweekly for 12 weeks. Mean baseline serum myoglobin level was 337 +/- 34 ng/mL. By 6 and 8 weeks mean serum myoglobin was 234 +/- 39 and 233 +/- 40 ng/mL, significantly lower by the Friedman test (p < 0.05). Four weeks after carnitine was discontinued, mean serum myoglobin had risen to 320 +/- 118 ng/mL. Serum creatine kinase and aldolase levels were normal throughout the study. All 6 patients noted improvement in muscular symptoms, with maximal effect at 8 weeks, although 2 patients did not improve until 2 to 4 weeks after carnitine was stopped. We conclude that oral L-carnitine may lower serum myoglobin and improve muscle cramps and weakness in hemodialysis patients. The maximal effect of carnitine on myoglobin occurs 2 weeks before the maximal improvement in muscular symptoms.

Cholinergic and serotonergic stimulation of phosphoinositide hydrolysis is decreased in Alzheimer's disease.

Agonist-stimulated phosphoinositide (PPI) hydrolysis is a major signal transduction pathway in brain. These studies investigated neurotransmitter stimulated PPI hydrolysis in postmortem human brain. Preliminary studies using rat brain suggested that moderate postmortem delay has little effect on PPI hydrolysis and that human tissue might be reliably studied for differences in receptor-PLC coupling. Studies in human brain membranes (frontal cortex) indicated that the time course for GTP gamma S and carbachol/GTP gamma S-stimulated PPI hydrolysis was linear for at least 20 min. GTP gamma S-stimulated [3H]inositol phosphate (InsP) formation was enhanced by carbachol (232%) and 5-Hydroxytryptamine (5HT-147%). SAX-HPLC separation of [3H]inositol polyphosphates indicated that the major isomer of inositol trisphosphate (InsP3) was Ins(1.4.5)P3, the expected product of PtdIns(4,5)P2 hydrolysis. Ca2+ increased PPI hydrolysis progressively from 100 nM through 50 microM and synergistically enhanced carbachol/GTP gamma S stimulation. Comparisons of age-matched controls with Alzheimer's patients indicated that GTP gamma S, carbachol/GTP gamma S, and 5HT/GTP gamma S-stimulation of PPI hydrolysis is reduced approximately 50% in membranes prepared from Alzheimer's patients. Ca2+ of PPI hydrolysis was not different between controls and Alzheimer's patients suggesting that muscarinic cholinergic and serotonergic receptors are uncoupled from PLC in Alzheimer's disease. These studies indicate that there are changes in cholinergic and serotonergic signal transduction in Alzheimer's disease. Further, this method can be used to study signal transduction events in postmortem human brain.

Activation of phosphatidylinositol 3-kinase and phosphatidylinositol 4-kinase during rat parotid acinar cell proliferation.

We have recently shown that beta-adrenergic agonist, isoproterenol-induced parotid acinar cell proliferation is in part mediated by elevated levels of surface galactosyltransferase which undergoes interaction with the EGF-R. The receptor subsequently undergoes autophosphorylation on the tyrosine residues in a manner similar to its 'receptor-ligand' interaction (Purushotham et al. (1992) Biochem. J. 284, 767-776). In this study, we provide evidence for phosphatidylinositol 3-kinase and 4-kinase as cytoplasmic signalling proteins involved in both the isoproterenol and EGF-stimulated signal transduction upon in vitro and in-vivo stimulation of parotid acinar cells. Total cell lysate activity for the PtdIns 4-kinase was 2- and 3-fold higher than unstimulated control cells, while the PtdIns 3-kinase was 1.4- and 2.8-fold higher following stimulation by isoproterenol or EGF, respectively. Increases of 6- and 2-fold in phosphatidylinositol 3-kinase were observed in anti-phosphotyrosine-antibody-immunoprecipitated cell lysates upon in-vitro growth stimulation with isoproterenol or EGF, respectively. There was an increase in tyrosine phosphorylation of the holoenzyme and association of the p85 subunit of phosphatidylinositol 3-kinase with EGF-R in response to both isoproterenol and EGF treatments. This corresponded with the mobilization of p85 from the cytoplasm to the plasma membrane upon growth stimulation. These results further implicate the phosphoinositide metabolites in the second messenger signalling pathways of isoproterenol-induced rat parotid cell proliferation. The parallel utilization of EGF indicate that the post-transductional mechanisms of isoproterenol-induced acinar cell proliferation are similar to the growth-factor-mediated activation of intracellular signalling pathways for cell growth.

Insulin stimulates phosphatidylinositol 3-kinase activity in rat neuronal primary cultures.

We investigated the effect of insulin on phosphatidylinositol (PtdIns) 3-kinase (PtdIns 3-kinase) activity in neuronal cultures to determine if this enzyme is involved with the neurotrophic actions of insulin. Insulin caused a concentration-dependent increase in PtdIns 3-kinase activity in anti-phosphotyrosine immunoprecipitates. The kinase activity was able to phosphorylate PtdIns, PtdIns 4-phosphate, and PtdIns 4,5-bisphosphate. In intact neurons, a 10-min 1 mM insulin treatment in the presence of [32P]orthophosphate increased the levels of both 3-[32P]PtdIns phosphate and 3,4-[32P]PtdIns bisphosphate by 55 and 193%, respectively. This increase was associated with an increase in neurite outgrowth mediated by insulin. Our results indicate that insulin treatment of neuronal cells in primary culture increases PtdIns 3-kinase activity and the formation of the unique D-3-phosphorylated phosphoinositides, suggesting that growth factor-mediated neuronal growth may include the formation of novel phosphoinositide 3-phosphate phospholipids.

Radio-label and mass determinations of inositol 1,3,4,5-tetrakisphosphate formation in rat cerebral cortical slices: differential effects of myo-inositol.

To investigate the effects of increasing concentrations of myo-inositol (inositol) on receptor stimulated [3H]inositol polyphosphate formation in the absence of lithium, slices of rat cerebral cortex were incubated with various concentrations of [3H]inositol (1 to 30 microM). Carbachol stimulated formation of [3H]inositol trisphosphate (InsP3) and [3H]inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) increased several fold when the inositol concentration was increased reaching a plateau at approximately 12 microM inositol. Time course studies revealed that in the presence of low concentrations of inositol (1 microM), [3H]InsP3 and [3H]Ins(1,3,4,5)P4 formation in response to carbachol stimulation increased slowly over a 10 to 20 min time period, whereas in the presence of 4 and 12 microM inositol, carbachol stimulated [3H]InsP3 and [3H]Ins(1,3,4,5)P4 formation was rapid and essentially complete within 3 to 5 min after carbachol addition. Although the carbachol dose response in 12 microM inositol had a much greater maximal efficacy, there was no change in potency. Similar to the effects of carbachol on [3H]Ins(1,3,4,5)P4 formation from prelabeled phosphoinositides, muscarinic receptor stimulation increased Ins(1,3,4,5)P4 mass formation by seven fold. Furthermore, Li+ (8 mM) completely inhibited carbachol stimulated increases in Ins(1,3,4,5)P4 mass formation. In contrast to the effects of increasing inositol on carbachol stimulated formation of radiolabeled inositol phosphates, increasing inositol had no effect upon mass formation of Ins(1,3,4,5)P4. These results show that when measuring inositol polyphosphate formation by the radiolabeling technique in the absence of Li+, increasing the inositol concentration greatly increases the stimulated component of [3H]InsP3 and [3H]Ins(1,3,4,5)P4 formation. However, this inositol induced increase in agonist stimulated Ins(1,3,4,5)P4 formation is not reflected as an increase in mass formation.