bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymerase-endonuclease amplification reaction for large-scale enzymatic production of antisense oligonucleotide
Authors: Wang Xiaolong , Gou Deming
Published: July 2019

Synthetic oligonucleotides are contaminated with highly homologous failure sequences. Oligonucleotide synthesis is difficult to scale up because it requires expensive equipments, hazardous chemicals, and tedious purification process. Here we report a novel thermocyclic reaction, polymerase-endonuclease amplification reaction (PEAR), for the amplification of oligonucleotides. A target oligonucleotide and a tandem repeated antisense probe are subjected to repeated cycles of denaturing, annealing, elongation and cleaving, in which thermostable DNA polymerase elongation and strand slipping generate duplex tandem repeats, and thermostable endonuclease (PspGI) cleavage releases monomeric duplex oligonucleotides. Each round of PEAR achieves >100-fold amplification. The product can be used in one more round of PEAR directly, and the process can be further repeated. In addition to avoiding dangerous materials and improved product purity, this reaction is easy to scale up and amenable to full automation, so it has the potential to be a useful tool for large-scale production of antisense oligonucleotide drugs.
Mammalian cells in culture actively export specific microRNAs
Authors: Wang Kai , Zhang Shile , Weber Jessica , Baxter David , Galas David
Published: July 2019

The discovery of microRNAs (miRNAs) as a new class of regulators of gene expression has triggered an explosion of research, but has left many unanswered questions about how this regulation works and how it is integrated with other regulatory mechanisms. A number of miRNAs have been found to be present in blood plasma and other body fluids of humans and mice in surprisingly high concentrations. This observation was unexpected in two respects: first, the fact that these molecules are present at all outside the cell at significant concentrations; and second, that these molecules appear to be stable outside of the cell. In light of this it has been suggested that the biological function of miRNAs may also extend outside of the cell and mediate cell-cell communication^[1-5]^. Such a system would be expected to export specific miRNAs from cells in response to specific biological stimuli. We report here that after serum deprivation several human cell lines tested do export a spectrum of miRNAs into the culture medium. The export response is substantial and prompt. The exported miRNAs are found both within and outside of microvesicles and exosomes. We have identified some candidate protein components of this system outside the cell, and found one exported protein that plays a role in protecting miRNA from degradation. Our results point to a hitherto unrecognized and uncharacterized miRNA trafficking system in mammalian cells that may involve cell-cell communication.
The modulation of alpha-wave amplitude in human EEG by the intention to act with a motor response
Authors: Kirschfeld Kuno
Published: July 2019

The most conspicuous signal in the human EEG is the so-called alpha wave, oscillations in the frequency range of 8 to 12 Hz. Visual stimulation of the retina suppresses the amplitude of alpha waves (Berger effect), and increased attention can reduce them. Here I show that one more parameter significantly affects the amplitudes of alpha waves: the intention to act by a motor response. Together with data from the literature, these results show that alpha waves are not part of the visual processing network but rather part of a long-range neuromodulatory network. The modulation modifies latencies in perception or motor response. The relevant mechanisms are located in early cortical visual areas; their activity may contribute to hemodynamic changes in these areas and thus explain dissociations between Bold signals and spike activities mentioned in the literature.
In silico microRNA identification from paprika (Capsicum annuum) ESTs
Authors: Manila T. M. , Riju A. , Lakshmi Priya Darshini K. , Chandrasekar A. , Eapen S. J.
Published: July 2019

A total of 33,311 Expressed Sequence Tags (EST) of paprika were mined from the GenBank EST database. The redundancy of the EST sequences was removed using CAP3 and it resulted 4,541 contigs 8,539 singletons as nonredundant data sets. The microRNAs were predicted using the program miRNAfinder. This program predicted a total of 85 miRNAs miRNAs. Another study was carried out to find the homologes miRNA using blast based tool named “miRseeK’ A total of 13 miRNAs with significant similarity with the plant miRNAs were obtained from paprika ESTs. The targets of the predicted miRNAs were found using the program miRU2. Findings suggest that most miRNAs play an important role in plant development, signal transduction, protein degradation and in response to environmental stress. The miRNAs were found to be perfectly or nearly complementary to its target mRNAs.
Choice reveals that rats are majoritarily resilient to cocaine addiction
Authors: Cantin Lauriane , Lenoir Magalie , Dubreucq Sarah , Serre Fushia , Vouillac Caroline , Ahmed Serge
Published: July 2019

Assessing the relative reward value of cocaine and how it changes with repeated use represents a long-standing goal in addiction research. Surprisingly, recent experimental research in rats – the most frequently used animal model in the field – suggests that the reward value of cocaine may in fact be relatively weak at least in the majority of individuals. Here, we provide strong additional evidence that confirms and extends the validity and generality of this research. Specifically, we demonstrate that no matter how heavy is past cocaine self-administration, most rats value cocaine poorly and readily decide to quit when offered the opportunity of making a different choice (i.e., drinking water sweetened with saccharin, an otherwise biologically inessential rewarding behavior). On average, rats estimate that cocaine is worth about 10 times less than the alternative reward. Only a small minority of rats prefer to continue taking cocaine when offered the choice. These findings reveal the existence of a genuine resilience to cocaine addiction in the majority of rats, a phenomenon that has long been suspected, though not firmly demonstrated, in humans. Only a minority would be prone to develop this disorder. We propose that choice should serve as a behavioral screening assay to identify vulnerable individuals, among the resilient majority, in future experimental research on the determinants of cocaine addiction.
Polymorphisms of TSER and MTHFR are associated with prognosis of fluoropyrimidine-based therapy in colorectal cancer patients
Authors: Kim Jong Woo , Lee Jae Ho , Hong Seung Ho , Bae Su Jin , Kwon Young Do , Oh Doyeun , Kim Nam Keun
Published: July 2019

This study was designed to investigate the influence of TSER and MTHFR polymorphisms on the clinical outcomes of patients with colorectal cancer receiving 5-FU-based chemotherapy. Genomic DNA was isolated from 103 frozen or paraffin-embedded tissues of colorectal cancer patients. The genotypes of two common polymorphisms were determined by PCR-RFLP. Patient prognoses were compared with genotype groups and analyzed according to tumor location. Polymorphisms of TSER and MTHFR 677C>T were not significantly associated with clinicopathological factors. There were no differences in prognosis between genotypes or functional groups when the TSER and MTHFR groups were considered separately. However, analysis of combined genotypes of the TSER and the MTHFR 677C>T polymorphisms were associated with the survival rate of colorectal cancer patients who received 5-FU-based chemotherapy (p=0.028). Prognosis of colorectal cancer patients was significantly different between proximal colon and distal colon cancers (p=0.002). However, prognosis did not receive any effect of the combined genotype when analyzed according to tumor location, such as proximal and distal colon cancer. The combined TSER and MTHFR 677C>T genotypes can be prognostic factors in colorectal cancer, where gene-gene interactions between the genotypes may occur.
Frequency-dependent selection predicts patterns of radiations and biodiversity
Authors: Melian Carlos , Alonso David , Vazquez Diego , Regetz James , Allesina Stefano
Published: July 2019

Most empirical studies support a decline in speciation rates through time, although evidence for constant speciation rates also exists. Declining rates have been explained by invoking niche-filling processes, whereas constant rates have been attributed to non-adaptive processes such as sexual selection, mutation, and dispersal. Trends in speciation rate and the processes underlying it remain unclear, representing a critical information gap in understanding patterns of global diversity. Here we show that the speciation rate is driven by frequency dependent selection. We used a frequency-dependent and DNA sequence-based model of populations and genetic-distance-based speciation, in the absence of adaptation to ecological niches. We tested the frequency-dependent selection mechanism using cichlid fish and Darwin's finches, two classic model systems for which speciation rates and richness data exist. Using negative frequency dependent selection, our model both predicts the declining speciation rate found in cichlid fish and explains their species richness. For groups like the Darwin's finches, in which speciation rates are constant and diversity is lower, the speciation rate is better explained by a model without frequency-dependent selection. Our analysis shows that differences in diversity are driven by larger incipient species abundance (and consequent lower extinction rates) with frequency-dependent selection. These results demonstrate that mutations, genetic-distance-based speciation, sexual and frequency-dependent selection are sufficient not only for promoting rapid proliferation of new species, but also for maintaining the high diversity observed in natural systems.
Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?
Authors: Moloughney Joseph , Thomas Janice , Costa Christie , Bullon Karla , Spencer James , Toney Jeffrey
Published: July 2019

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today.
Cost effective mass multiplication of Gymnema sylvestre in hydroponic system
Authors: Karthic Raju , Seshadri Sundaram
Published: July 2019

Present experiment was designed with an objective to develop a cost efficient mass multiplication method for Gymnema sylvestre using hydroponic system. A plastic tub, with polyethylene cover, containing 1/10 strength of MS salts supplemented with Indole butyric acid (IBA) at different concentrations (0.5, 1.0, 2.5 mg/L) was studied. Medium containing 0.5mg/L of IBA produced highest rooting (66%) with 96 % survival. This protocol will serve as an alternative to the existing in vitro and clonal multiplication protocols.
Aven and Survivin Expression in Egyptian Acute Leukemia and Their Relation to Apoptosis
Authors: Assem Magda , Abedel- ALhameid Thorraya , A-Basset Gihan , Hilal Amany , Kamel Mahmoud , Khalil Iman , Alsharkawey Nahla , Metwally Ayman
Published: July 2019

Background:

Several anti apoptotic signals have been recently identified. Aven and Survivin are broadly expressed and are conserved in mammalian species. Patients and Methods: 39 AML and 25 ALL were tested. Aven and Survivin expression were detected by RT-PCR. DNA fragmentation was carried out daily after treatment..

Results:

Survivin was expressed (P=0.06) more in AML (74%) than in ALL (52%). While, Aven was equally expressed in both leukemias. Patients were categorized into 3 groups based on DNA fragmentation. Absence of Aven significantly (p&x2039;0.001) contributed to DNA fragmentation,but Survivin did not contribute as much. None of the concordant both positive Survivin and Aven were in group III (the good 5 day fragmentation, (P< 0.001). Survivin was statistically related to CD7 expression (P<0.001) in AML only. There was a significant dissociation between Aven and Survivin in AML (p=0.03) and near significant dissociation in ALL (p=0.07). Conclusion: Aven seems to be more important as an inhibitor of apoptosis than survivin in acute leukemia. The presence of both confers a survival disadvantage and a significantly worse DNA fragmentation pattern suggesting a synergistic inhibition of apoptosis. The highly significant relation between CD7 and survivin expression might suggest their involvement in a common signal transduction pathway.
Pandemic (H1N1) 2009 Cluster Analysis: A Preliminary Assessment
Authors: Wick Charles , Stanford Michael , Jabbour Rabih , Deshpande Samir , McCubbin Patrick , Skowronski Evan , Zulich Alan
Published: July 2019

Pandemic (H1N1) 2009 virus has been causing major concerns around the world because of its epidemic potential, rapid dissemination, rate of mutations, and the number of fatalities. One way to gain an advantage over this virus is to use existing rapid bioinformatics tools to examine easily and inexpensively generated genetic sequencing data. We have used the protein sequences deposited with the National Center for Biotechnology Information (NCBI) for data mining to study the relationship among the Pandemic (H1N1) 2009 proteins. There are 11 proteins in the Pandemic (H1N1) 2009 virus, and analysis of sequences from 65 different locations around the globe has resulted in two major clusters. These clusters illustrate the Pandemic H1N1 2009 virus is already experiencing significant genetic drift and that rapid worldwide travel is affecting the distribution of genetically distinct isolates.
Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers
Authors: Huang Shi
Published: July 2019

Interpretations of molecular data by the modern evolution theory are often sharply inconsistent with paleontological results. This is to be expected since the theory is only true for microevolution and yet fossil records are mostly about macroevolution. The maximum genetic diversity (MGD) hypothesis is a more coherent and complete account of evolution that has yet to meet a single contradiction. Here, molecular data were analyzed based on the MGD to resolve key questions of primate phylogeny. A new method was developed from a novel result predicted by the MGD: genetic non-equidistance to a simpler taxon only in slow but not in fast evolving sequences given non-equidistance in time. This ‘slow clock’ method showed that humans are genetically more distant to orangutans than African apes are and separated from the pongid clade (containing orangutan and African apes) 17.3 million years ago. Also, tarsiers are genetically closer to lorises than simian primates are, suggesting a tarsier-loris clade to the exclusion of simian primates. The validity and internal coherence of the primate phylogeny here were independently verified. The molecular split time of human and pongid calibrated from the fossil record of gorilla, or the fossil times for the radiation of anthropoids/mammals at the K/T boundary and for the Eutheria-Metatheria split in the Early Cretaceous, were independently confirmed from molecular dating calibrated using the fossil split times of tarsier-loris and two other pairs of mammals (mouse-rat and opossum-kangaroo). This remarkable and unprecedented concordance between molecules and fossils provides the latest confirmation of the inseparable unity of genotype and phenotype and the unmatched value of MGD in a coherent interpretation of life history.
Factors influencing impala distribution patterns in Nairobi National Park, Kenya
Authors: Obade Vincent , Clercq Eva
Published: July 2019

Monitoring the distribution of wild animals using appropriate methods and survey techniques is essential not only for sustainable management but also to avoid wastage of resources. This study applied remote sensing to investigate the factors influencing the distribution of herbivores in Nairobi National Park, Kenya. Impala was selected as indicator specie for the herbivores within the park, because the population of impala had drastically reduced over time. The influence of food availability, water and disturbance on herbivore presence was investigated. A positive significant statistical relationship between impala population density and feed availability was observed. However, the correlation between impala population density and water distance was negative, indicating less impalas as the distance from water sources increase. An interesting finding was the expectation of greater impala population presence next to roads. The study demonstrated a rapid method for gaining information useful for conservation and land use planning practices, such as in the determination of the carrying capacity or even for redistributing animals within the park.
A novel strategy for the targeted analysis of protein and peptide metabolites
Authors: Williamson Nicholas , Reilly Charles , Tan Chor-Teck , Ramarathinam Sri-Harsha , Jones Alun , Hunter Christie , Rooney Francis , Purcell Anthony
Published: July 2019

The detection and quantitation of exogenously administered biological macromolecules (e.g. vaccines, peptide and protein therapeutics) and their metabolites is frequently complicated by the presence of a complex endogenous mixture of closely related compounds. We describe a method that incorporates stable isotope labeling of the compound of interest allowing the selective screening of the intact molecule and all metabolites using a modified precursor ion scan. This method involves monitoring the low molecular weight fragment ions produced during MS/MS that distinguish isotopically labelled material from related endogenous compounds. All isotopically labelled substances can be selected using this scanning technique for further analysis whilst other unlabelled and irrelevant substances are ignored. The potential for this technique to be used in metabolism and pharmacokinetic experiments is discussed with specific examples looking at the metabolism of &x03B1;-synuclein in serum and the brain.
New methods for analyzing serological data with applications to influenza surveillance
Authors: Ndifon Wilfred
Published: July 2019

Two important challenges to the use of serological assays for influenza surveillance include the substantial amount of experimental effort involved, and the inherent noisiness of serological data. Here, informed by the observation that log-transformed serological data (obtained from the hemagglutination-inhibition assay) exist in an effectively one-dimensional space, computational methods are developed for accurately and efficiently recovering unmeasured serological data from a sample of measured data, and systematically minimizing noise found in the measured data. Careful application of these methods would enable the collection of better-quality serological data on a greater number of circulating influenza viruses than is currently possible, and improve the ability to identify potential epidemic/pandemic viruses before they become widespread. Although the focus here is on influenza surveillance, the described methods are more widely applicable.
A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation
Authors: Arjunan Satya , Tomita Masaru
Published: July 2019

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium Escherichia coli, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the in vivo MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally.
A Comparative Study of the Magnitude, Frequency and Distribution of Intense Rainfall in the United Kingdom
Authors: Rodda John , Little Max , Rodda Harvey , McSharry Patrick
Published: July 2019

During the 1960s, a study was made of the magnitude, frequency and distribution of intense rainfall over the UK, employing data from more than 120 daily-read rain gauges covering the period 1911 to 1960. Using the same methodology, that study was recently updated utilizing data for the period 1961 to 2006 for the same gauges, or from those nearby. This paper describes the techniques applied to ensure consistency of data and statistical modelling. It presents a comparison of patterns of extreme rainfalls for the two periods and discusses the changes that have taken place. Most noticeably, increases up to 20% have occurred in the north west of the country and in parts of East Anglia. There have also been changes in other areas, including decreases of the same magnitude over central England. The implications of these changes are considered.
Genome-scale approach proves that the lungfish-coelacanth sister group is the closest living relative of tetrapods with the BEST program
Authors: Shan Yunfeng , Gras Robin
Published: July 2019

The origin of tetrapods has not been resolved for decades. Three principal hypotheses (lungfish-tetrapod, coelacanth-tetrapod, or lungfish-coelacanth sister group) have been proposed. We used the Bayesian method under the coalescence model with the latest program (BEST) to perform a phylogenetic analysis for seven relevant taxa and 43 nuclear genes encoding amino acid residues with the jackknife method for taxon sub-sampling. The results, combined with those of other three genome-scale approaches, successfully prove the hypothesis that lungfishes and coelacanths form a monophyletic sister group and are equally related to tetrapods supported by high Bayesian posterior probabilities of the branch (a lungfish-coelacanth clade) and high taxon jackknife supports.
Towards a genome-wide transcriptogram: the Saccharomyces cerevisiae case
Authors: Rybarczyk José Luiz , Castro Mauro , Dalmolin Rodrigo , Moreira José , Brunnet Leonardo , de Almeida Rita
Published: July 2019

A genome modular classification that associates cellular processes to modules could lead to a method to quantify the differences in gene expression levels in different cellular stages or conditions: the transcriptogram, a powerful tool for assessing cell performance, would be at hand. Here we present a computational method to order genes on a line that clusters strongly interacting genes, defining functional modules associated with gene ontology terms. The starting point is a list of genes and a matrix specifying their interactions, available at large gene interaction databases. Considering the Saccharomyces cerevisiae genome we produced a succession of plots of gene transcription levels for a fermentation process. These plots discriminate the fermentation stage the cell is going through and may be regarded as the first versions of a transcriptogram. This method is useful for extracting information from cell stimuli/responses experiments, and may be applied with diagnostic purposes to different organisms.
Regulated peristalsis into the acidic region of the Drosophila larval midgut is controlled by a novel component of the Autonomic Nervous System
Authors: LaJeunesse Dennis Richard , Johnson Brooke Ann , Presnell Jason , Catignas Kathleen , Zapotoczny Grzegorz
Published: July 2019

The underlying cellular and molecular mechanisms that regulate and coordinate critical physiological processes such as peristalsis are complex, often cryptic, and involve the integration of multiple tissues and organ systems within the organism. We have identified a completely novel component of the larval autonomic nervous system in the Drosophila larval midgut that is essential for the peristaltic movement of food from the anterior midgut into the acidic region of the midgut. We have named this region the Superior Cupric Autonomic Nervous System or SCANS. Located at the junction of the anterior and the acidic portions of the midgut, the SCANS is characterized by a cluster of a novel neuro-enteroendocrine cells that we call Lettuce Head Cells, a valve, and two anterior muscular tethers to the dorsal gastric caeca. Using cell ablation and ectopic activation via expression of the Chlamydomonas reinhardtii blue-light activated channelrhodopsin, we demonstrate that the SCANS and in particular the Lettuce Head Cells are both necessary and sufficient for peristalsis and perhaps serve a larger role by coordinating digestion throughout the anterior midgut with development and growth.
In vitro synergistic anti-prion effect of cholesterol ester modulators
Authors: Orrù Christina Doriana , Cannas Maria Dolores , Vascellari Sarah , Angius Fabrizio , Cocco Pier Luigi , Norfo Claudia , Mandas Antonella , La Colla Paolo , Dessì Sandra , Pani Alessandra
Published: July 2019

Background.

Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral cells of sheep susceptible to or suffering from Scrapie were characterized by an altered cholesterol homeostasis compared to animals with a scrapie-resistant genotype, and that drugs influencing cholesterol esterification were endowed with selective anti-prion activity in N2a cell lines infected with the 22L and RML prion strains. Results. In prion-infected N2a cell lines we now report increased anti-prion activity of dual-drug combinations consisting of cholesterol ester modulators associated with prion inhibitors Synergism was obtained with the cholesterol ester modulators everolimus, pioglitazone, progesterone, and verapamil associated with the anti-prion chlorpromazine, and with everolimus and pioglitazone associated with the anti-prion quinacrine. Comparative lipid analyses in prion-infected and non-infected N2a cells by colorimetric, enzymatic, and chemical means, clearly demonstrated a derangement of type and distribution of cholesterol esters, free cholesterol, and triglycerides in the infected N2a cells. Although single-drug treatments influenced lipid syntheses, only the combined-drug treatments appeared to restore a lipid profile similar to that of untreated-uninfected cells.

Conclusions.

We conclude that the anti-prion synergistic effect of cholesterol ester modulators with the cholesterol metabolism interfering anti-prion drugs chlorpromazine and quinacrine may arise from the ability of combined drugs to re-establish the intracellular lipid profile of untreated-uninfected cells. Overall, these data suggest that inhibition of prion replication can be readily potentiated by combinatorial drug treatments, and that steps of cholesterol/cholesterol ester metabolism may represent suitable targets.
The Origin and Evolution of Viruses as Molecular Organisms
Authors: Bandea Claudiu
Published: July 2019

Viruses are the most abundant life forms and the repertoire of viral genes is greater than that of cellular genes. It is also evident that viruses have played a major role in driving cellular evolution, and yet, viruses are not part of mainstream biology, nor are they included in the Tree of Life. A reason for this major paradox in biology is the misleading dogma of viruses as viral particles and their enigmatic evolutionary origin. This article presents an alternative view about the nature of viruses based on their properties during the intracellular stage of their life cycle, when viruses express features comparable to those of many parasitic cellular species. Supporting this view about the nature of viruses is a novel hypothetical evolutionary model for their origin from parasitic cellular species that fused with their host cells. By losing their membrane and cellular structure within the host cell, these new types of parasitic species gained full access to precursors for the synthesis of their specific molecules and to the host’s information processing machineries, such as translation, which created unique parasitic and evolutionary opportunities. To identify viruses during their intracellular stage of their life cycle, in which their specific molecules are free or dispersed within the host cell, this paper introduces the concept of “molecular structure” and labels viruses as “molecular organisms.” Among the extant viruses, the life cycle of poxviruses and other complex viruses that fuse with their host cells provides compelling evidence for the fusion model. One of the most remarkable implications of fusion model is that new viral lineages originated from parasitic cellular species throughout the history of life, and that this process might still be active. Surprisingly, it appears that several parasitic cellular species are currently evolving into molecular organisms. More remarkably though, according to this model, several parasites that are currently classified as cellular organisms are in fact genuine molecular organisms. The current evidence for the fusion hypothesis is strong and it is fully testable using both experimental and phylogenetic approaches. The academic and research implications of this model, which supports the inclusion of viruses in the Tree of Life, are highly significant. Some of these implications are discussed in more detail in two other articles of this series, which presents a unifying model for the origin and evolution of cellular and viral domains, including the origin of life.
The cultural epigenetics of psychopathology: The missing heritability of complex diseases found?
Authors: Wallace Rodrick
Published: July 2019

We extend a cognitive paradigm for gene expression to the epigenetic epidemiology of mental disorders, recognizing the fundamental role that culture plays in human biology as another heritage mechanism parallel to, and interacting with, the more familiar genetic and epigenetic systems. In the mathematical model, culture acts as another tunable epigenetic catalyst that both directs developmental trajectories and becomes convoluted with individual ontology via a mutually interacting crosstalk mediated by a social interaction that is itself culturally driven. We call for the incorporation of embedding culture as an essential component of the epigenetic regulation of human mental development and its dysfunctions, bringing what is perhaps the central reality of human biology into the center of biological psychiatry. The cultural and epigenetic systems of heritage may well provide the 'missing' heritability of complex diseases now under so much intense discussion.
16S rRNA based identification of Aeromonas sp. kumar by constructing phylogenetic tree and identification of regulatory elements from the harmful Red Tide bloom, Gulf of Mannar
Authors: Kumar P. , Ramakritinan C. M. , Kumaraguru A. K.
Published: July 2019

A bacterial strain, designated Aeromonas sp. kumar, was isolated from a water sample collected from Red tide Bloom occurred in the region of Gulf of Mannar region, Puthumadam Coast, India and the strain was identified using 16S rRNA based identification. During the sample collection, microbiology analysis was done to study the morphology of the bacteria. Pure culture of strain was maintained through out the study. DNA was isolated and sequenced using 16S rRNA primers. A length of 1452 nucleotide was sequenced and was put in public data base for obtaining accession number. The sequence was studied using MEGA 4, to estimate the evolutionary distances and to construct the Phylogenetic tree. Along with that Regulatory elements and Transcription factors were studied using BPROM tool. In genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream (towards the 5' region of the sense strand). The objective of the study is to predict the regulatory elements which are -10 box, -35box and three Transcription Factors (rpoD19, rpoD17 and araC) with their binding sites in the 16S rRNA gene of Aeromonas sp. kumar. The gene bank accession number for 16S rRNA gene of Aeromonas sp. kumar is FJ896014.
Natural Selection In Utero Contributes to the Male Longevity Deficit in Contemporary Human Populations
Authors: Catalano Ralph
Published: July 2019

Much literature invokes natural selection to explain the pervasive deficit in the average lifespan of men compared to women.^1^ The explanation assumes that mothers, not fathers, provisioned children over much of human existence, and that women who lived long enough to help their children and grand children survive to reproductive age had more grandchildren and great-grandchildren than did shorter-lived women.^2^ Although this argument implies that natural selection would conserve mutations that conferred longevity on mothers but not fathers,^3,4^ it offers no explanation of the considerable changes over historic time in the male longevity deficit thereby implying that these arise solely from culture.^5^ I show, however, that natural selection in utero empirically predicts variability over time in the deficit. This mechanism spontaneously aborts less fit fetuses during stressful times and reportedly selects more against males than females. My finding suggests that natural selection interacts with culture to predictably affect both the life span and sex ratio of contemporary human populations.
Voluntary universal testing and treatment is unlikely to lead to HIV elimination: a modeling analysis
Authors: Wagner Bradley , Blower Sally
Published: July 2019

Recently Granich et al. at the World Health Organization (WHO) concluded, using mathematical modeling, that HIV epidemics could be eliminated within a decade. They assumed all individuals would be tested annually and every infected individual (regardless of stage of infection) would be put on treatment. Based on this modeling study the WHO is considering using universal testing and treatment as an HIV elimination strategy. Here we examine the study by Granich et al. and assess its validity. We present new analyses of their model by varying assumptions and parameter values. We find that under certain very optimistic assumptions HIV elimination would be (theoretically) possible, but it would take at least 70 years. To obtain this result we assumed ~65% of symptomatic and ~20% of asymptomatic individuals would be treated per year; ARVs would reduce infectivity of treated individuals a hundred fold, and only 5% of symptomatic individuals would give up treatment per year. Even under optimistic assumptions we find elimination to be unlikely. For example, we show if ~65% of symptomatic individuals are treated per year and treated individuals are completely noninfectious, HIV will remain endemic with a prevalence of 34% and an incidence of 2% per year. We conclude that the model developed by Granich et al., when used with realistic parameter values, does not show HIV elimination is possible. However our modeling results show treatment could act as an effective prevention tool and significantly reduce transmission, even if only symptomatic individuals receive ARVs. Treatment should first, and foremost, be used for therapeutic purposes. Hence, we recommend – when resources are limited - targeting those in need of treatment. Such a strategy would be ethical, feasible and epidemiologically sound. We advise that models used as health policy tools should be carefully evaluated and their results interpreted with caution.
Comparative semiempirical, ab initio, and DFT study on the thermodynamic properties of linear and branched PFSA/Fs, PFCA/Fs, and perhydroalkyl sulfonic acids, alkanes, and alcohols
Authors: Rayne Sierra , Forest Kaya
Published: July 2019

A systematic and comprehensive semiempirical, Hartree-Fock (HF) ab initio, and B3LYP density functional theory (DFT) study was conducted on the relative thermodynamic properties of various linear and branched perfluorinated and perhydrogenated alkyl compounds. The semiempirical AM1, PM3, and PM6 methods all consistently and accurately predict that branched alkyl compounds will generally be more thermodynamically stable than their linear counterparts. In contrast, HF and B3LYP calculations with the 6-31G(d,p), 6-31++G(d,p), and 6-311++G(d,p) basis sets predict that linear isomers will be more stable than branched analogs. These different linear versus branched perfluoroalkyl/perhydroalkyl thermodynamic property trends between semiempirical and ab initio/DFT methods were evident in both gas and aqueous phase calculations. Comparison of experimentally determined thermodynamic properties for several classes of linear and branched alkanes and alcohols with values calculated at the PM6 and B3LYP/6-311++G(d,p) levels of theory supported the well known findings that such DFT and HF approaches incorrectly predict branched alkyl compounds will be less thermodynamically stable than linear isomers. Calculations at the MP2/6-311++G(d,p)//B3LYP/6-311++G(d,p) and M05-2X/6-311++G(d,p) levels of theory on a representative subset of the linear and branched perfluorinated compounds supported the thermodynamic conclusions from the PM6 method. Strong agreement between PM6 estimated thermodynamic properties and available experimental data supports use of this computational method for accurately calculating the well established higher thermodynamic stability of branched alkyl compounds. Branched perfluoroalkyl compounds are thus expected to be more thermodynamically stable than their linear analogs.
PSA Dynamics traditionally evaluated with an inadequate formula
Authors: Gerber Hans-Jürg
Published: July 2019

The PSA doubling time is usually calculated from measured PSA values with an inadequate formula that tacitly assumes the absence of that process, which it is supposed to reveal. We present a modified calculational procedure which is optimized to unveil a weak second exponential process in the presence of a strong first one, using early screening data. The notion of Break Even Time (BET) indicates the stages of the processes.
The NCBO OBOF to OWL Mapping
Authors: Moreira Dilvan , Mungall Christopher , Shah Nigam , Aitken Stuart , Richter John-Day , Redmond Timothy , Musen Mark
Published: July 2019

Two of the most significant formats for biomedical ontologies are the Open Biomedical Ontologies Format (OBOF) and the Web Ontology Language (OWL). To make it possible to translate ontologies between these two representation formats, the National Center for Biomedical Ontology (NCBO) has developed a mapping between the OBOF and OWL formats as well as inter-conversion software. The goal was to allow the sharing of tools, ontologies, and associated data between the OBOF and Semantic Web communities.OBOF does not have a formal grammar, so the NCBO had to capture its intended semantics to map it to OWL.This official NCBO mapping was used to make all OBO Foundry ontologies available in OWL. Availability: This mapping functionality can be embedded into OBO-Edit and Protégé-OWL ontology editors. This software is available at: http://bioontology.org/wiki/index.php/OboInOwl:Main_Page
High energy-charged cell factory for heterologous protein synthesis
Authors: Kim Pil , Kim Hye Jung , Kwon Yeong Deok , Lee Sang Yup
Published: July 2019

Overexpression of gluconeogenic phosphoenolpyruvate carboxykinase (PCK) under glycolytic conditions enables Escherichia coli to maintain a greater intracellular ATP concentration and, consequently, to up-regulate genes for amino acid and nucleotide biosynthesis. To investigate the effect of a high intracellular ATP concentration on heterologous protein synthesis, we studied the expression of a foreign gene product, enhanced green fluorescence protein (eGFP), under control of the T7 promoter in E. coli BL21(DE3) strain overexpressing PCK. This strain was able to maintain twice as much intracellular ATP and to express two times more foreign protein than the control strain. These results indicate that a high energy-charged cell can be beneficial as a protein-synthesizing cell factory. The potential uses of such a cell factory are discussed.
Rsp5 promotes Gene Activation mediated by 9aaTAD Transcription Factors Oaf1 and Gal4
Authors: Lipp Joachim , Koranda Manfred , Piskacek Martin
Published: July 2019

Nine-amino-acid transactivation domain, 9aaTAD, defines a large superfamily of yeast and mammals transcription factors. The transactivation of the 9aaTAD has been addressed to multiple general co-activators TAF9, MED15, CBP and p300. We demonstrate for the 9aaTAD transcription factors Oaf1 and Gal4 functional and physical interaction with E3-Ubiquitin Ligase Rsp5. The Rsp5-associations with RNA polymerase II and TFIID were reported previously.
An apparent medieval stereogram incorporating a symbol for optical illusion
Authors: Cisne John
Published: July 2019

Stereograms mark a threshold in understanding visual perception. Modern study of stereopsis began with Wheatstone's invention of the stereogram and stereoscope (~ 1832), important tools in vision research and technical imagery ever since. Stereoscopic images formed with frieze and wallpaper patterns in illuminated Insular manuscripts such as the Book of Durrow (~ 680 CE), Lindisfarne Gospels (~ 700-720), and Book of Kells (~ 800) show that, long before spectacle-quality magnifying lenses (~ 1286), illuminators somehow copied multicolored, microscopically detailed designs freehand with an accuracy unsurpassed in scientific instruments until the Renaissance (but well within the power of normally sighted humans' stereoscopic discrimination). If the artists accomplished this feat by free fusion using the unaided eyes as a magnifying stereocomparator, as suggested, they should have been able to create autostereograms. Did they? Here I report two examples of an apparent stereopair from the Book of Durrow, which gives a sharp, strongly three-dimensional image that includes, among other symbols, an eye-shaped sign identified with mirages (Fig. 1). Apparently, precocious empirical knowledge of stereopsis played more than a technical role in the creation of some of the world's more famous graphic art.
Photometric properties of microfossil shells
Authors: Zarkogiannis Stergios , Henrich Ruediger
Published: July 2019

The chromatic characteristics of fossil planktonic foraminifera were measured with the use of an opticoelectric microscope and a new aspect of their nature has been revealed.
Water soluble carbon nanotubes affect growth of the common gram (Cicer arietinum)
Authors: Tripathi Shweta , Sonkar Sumit Kumar , Kumar Abhishek , Khan M.Y. , Sarkar Sabyasachi
Published: July 2019

Multi-walled Carbon nanotube, its role and implications in biological systems are currently under evaluation and became interesting for many researchers primarily working on the interface of chemistry, physics and biology. However, concerns about the potential toxicity of multi-walled carbon nanotubes have been raised. To carry such affords, herein we investigate the effects of carboxylic acid functionalized water soluble carbon nanotube (wsCNT) on the growth of gram Cicer arietinum plant. The growth of gram plants was observed with and without the presence of wsCNT to demonstrate that carboxylated functionalized multi-walled carbon nanotubes showed better growth and under more wsCNT, the growth was enhanced without showing apparent toxicity. Although this is a preliminary study with a small group of plants, our results encourage further confirmation studies with larger groups of plants.
Soil Carbon in Agroforestry Systems: An Unexplored Treasure?
Authors: Nair P. K. Ramachandran , Nair Vimala , Gama-Rodrigues Emanuela , Garcia Rasmo , Haile Solomon , Howlett David , Kumar B. Mohan , Mosquera-Losada M.-Rosa , Saha Subhrajit , Takimoto Asako , Tonucci Rafael
Published: July 2019

Soil organic matter (SOM), which contains more reactive organic carbon (C) than any other single terrestrial pool, plays a major role in determining C storage in ecosystems and regulating atmospheric concentrations of carbon dioxide (CO2)^1^. Agroforestry, the practice of growing trees and crops in interacting combinations on the same unit of land^2^, primarily by resource-poor smallholder farmers in developing countries, is recognized as a strategy for soil carbon sequestration (SCS) under the Clean Development Mechanism (CDM) of the Kyoto Protocol^3^. The understanding about C storage and dynamics under agroforestry systems (AFS), however, is minimal. Our studies under various AFS in diverse ecological conditions in five countries showed that tree-based agricultural systems, compared to treeless systems, stored more C in deeper soil layers up to 1 m depth under comparable conditions. More C is stored in soil near the tree than away from the tree; higher SOC content is associated with higher species richness and tree density; and C3 plants (trees) contribute to more C in the silt- + clay-sized (<53 &x00B5;m) fractions that constitute more stable C, than C4 plants, in deeper soil profiles4 - 8. These results provide clear indications of the possibilities for climate change mitigation through SCS in AFS, and opportunities for economic benefit - through carbon trading - to millions of smallholder farmers in developing countries.