bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling reaction-diffusion of molecules on surface and in volume spaces with the E-Cell System
Authors: Arjunan Satya , Tomita Masaru
Published: July 2019

The-Cell System is an advanced open-source simulation platform to model and analyze biochemical reaction networks. The present algorithm modules of the system assume that the reacting molecules are all homogeneously distributed in the reaction compartments, which is not the case in some cellular processes. The MinCDE system in Escherichia coli, for example, relies on intricately controlled reaction, diffusion and localization of Min proteins on the membrane and in the cytoplasm compartments to inhibit cell division at the poles of the rod-shaped cell. To model such processes, we have extended the E-Cell System to support reaction-diffusion and dynamic localization of molecules in volume and surface compartments. We evaluated our method by modeling the in vivo dynamics of MinD and MinE and comparing their simulated localization patterns to the observations in experiments and previous computational work. In both cases, our simulation results are in good agreement.
Desiderata for an ontology of diseases for the annotation of biological datasets.
Authors: Bodenreider Olivier , Burgun Anita
Published: July 2019

There is a plethora of disease ontologies available, all potentially useful for the annotation of biological datasets. We define seven desirable features for such ontologies and examine whether or not these features are supported by eleven disease ontologies. The four ontologies most closely aligned with our desiderata are Disease Ontology, SNOMED CT, NCI thesaurus and UMLS.
The RNA Ontology (RNAO): An ontology for integrating RNA sequence and structure data
Authors: Batchelor Colin , Bittner Thomas , Eilbeck Karen , Mungall Chris , Richardson Jane , Knight Rob , Stombaugh Jesse , Zirbel Craig , Westhof Eric , Leontis Neocles
Published: July 2019

Biomedical Ontologies are intended to integrate diverse biomedical data to enable intelligent data-mining and facilitate translation of basic research into useful clinical knowledge. We present the first version of RNAO, an ontology for integrating RNA 3D structural, biochemical and sequence data. While each 3D data file depicts the structure of a specific molecule, such data have broader significance as representatives of classes of homologous molecules, which, while differing in sequence, generally share core structural features of functional importance. Thus, 3D structure data gain value by being linked to homologous sequences in genomic data and databases of sequence alignments. Likewise genomic data can increase in value by annotation of shared structural features, especially when these can be linked to specific functions. The RNAO is being developed in line with the developing standards of the Open Biomedical Ontologies (OBO) Consortium.
Interspecific differences in single nucleotide polymorphisms (SNPs) and indels in expressed sequence tag libraries of oil palm Elaeis guineensis and E. oleifera
Authors: Riju Aikkal , Arunachalam Vadivel
Published: July 2019

Oil palm is the second largest source of edible oil, which meets one-fifth of global demands of oils and fats. Expressed sequence tag (EST) sequencing programs have provided a wealth of information, identifying novel genes from a broad range of organisms and providing an indication of gene expression level in particular tissues. It also provides the richest source of biologically useful SNPs due to the relatively high redundancy of gene sequence, the diversity of genotypes represented within databases. EST based SNPs are potential molecular markers and aid in genetic improvement. A total of 21062 and 2053 polymorphic (SNP and Indel) sites in E. guineensis species and in E. oleifera, 4955 SNPs and 1172 Indels were detected. SNP(17.5/kbp) and Indel(4.1/kbp) frequency was higher in E. oleifera than E. guineensis species (16.8/kbp, 1.6/kbp). E. oleifera showed higher transition to transversion ratio (1.40) than in E. guineensis (1.02). The ratio of Ts vs Tv showed, the genetic divergence is occurring in this crops in different fashion and E. guineensis had diverged more than E. oleifera. We provide the results of the study as online database ("http://riju.byethost31.com/oilpalm/":http://riju.byethost31.com/oilpalm/) for use by oil palm breeders.
Using Ontology Fingerprints to evaluate genome-wide association study results
Authors: Tsoi Lam , Boehnke Michael , Klein Richard , Zheng W. Jim
Published: July 2019

We describe an approach to characterize genes or phenotypes via ontology fingerprints which are composed of Gene Ontology (GO) terms overrepresented among those PubMed abstracts linked to the genes or phenotypes. We then quantify the biological relevance between genes and phenotypes by comparing their ontology fingerprints to calculate a similarity score. We validated this approach by correctly identifying genes belong to their biological pathways with high accuracy, and applied this approach to evaluate GWA study by ranking genes associated with the lipid concentrations in plasma as well as to prioritize genes within linkage disequilibrium (LD) block. We found that the genes with highest scores were: ABCA1, LPL, and CETP for HDL; LDLR, APOE and APOB for LDL; and LPL, APOA1 and APOB for triglyceride. In addition, we identified some top ranked genes linking to lipid metabolism from the literature even in cases where such knowledge was not reflected in current annotation of these genes. These results demonstrate that ontology fingerprints can be used effectively to prioritize genes from GWA studies for experimental validation.
Development and Characterization of Eudragit RS 100 Loaded Microsponges and its Colonic Delivery Using Natural Polysaccharides
Authors: Jain Vikas , Singh Ranjit
Published: July 2019

In the present work, paracetamol loaded eudragit based microsponges were prepared using quasi-emulsion solvent diffusion method. The compatibility of the drug with various formulation components was established. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The colon specific formulations were prepared by compression coating of microsponges with pectin:hydroxypropylmethylcellulose (HPMC) mixture followed by tabletting. The in vitro dissolution studies were done on all formulations and the results were evaluated kinetically and statically. The kinetics of release study showed that the release data followed Higuchi matrix and the main mechanism of drug release from microsponges was diffusion. In vitro studies exhibited that compression coated colon specific tablet formulations started the release the drug at the 6th hour corresponding to the arrival time to proximal colon.
The Sonic Hedgehog Pathway Stimulates Prostate Tumor Growth by Paracrine Signaling and Recaptures Embryonic Gene Expression in Tumor Myofibroblasts
Authors: Shaw Aubie , Gipp Jerry , Bushman Wade
Published: July 2019

The Hedgehog (Hh) pathway contributes to prostate cancer growth and progression. The presence of robust Shh expression in both normal prostate and localized cancer challenged us to explain the unique growth promoting effect in cancer. We show here that paracrine Hh signaling exerts a non-cell autonomous effect on xenograft tumor growth and that Hh pathway activation in myofibroblasts alone is sufficient to stimulate tumor growth. Nine genes regulated by Hh in the mesenchyme of the developing prostate were found to be regulated in the stroma of Hh over-expressing xenograft tumors. Correlation analysis of gene expression in matched specimens of benign and malignant human prostate tissue revealed a partial 5 gene fingerprint of Hh-regulated expression in stroma of all cancers and the complete 9 gene fingerprint in the subset of tumors exhibiting a reactive stroma. No expression fingerprint was observed in benign tissues. We conclude that changes in the prostate stroma due to association with cancer result in an altered transcriptional response to Hh that mimics the growth promoting actions of the fetal mesenchyme. Patients with an abundance of myofibroblasts in biopsy tissue may comprise a sub-group that will exhibit a particularly good response to anti-Hedgehog therapy.
Cosmetic Use of Botulinum Toxin-A Affects Processing of Emotional Language
Authors: Havas David , Glenberg Arthur , Gutowski Karol , Lucarelli Mark , Davidson Richard
Published: July 2019

Language can evoke powerful emotions and influence consequent actions in readers, but the mechanisms underlying interactions of language and emotion are largely unknown. Since Darwin, emotional expressions have been implicated in emotional cognition, experience and understanding, but the functional role of the affective periphery is difficult to test. In a first experiment, facial electromyography revealed that silent reading of emotional (angry, sad, and happy) sentences automatically elicits differential patterns of activity in facial muscles used in expression of corresponding emotions (smiling and frowning). In a second experiment, temporary paralysis of the facial muscle corrugator supercilli (responsible for producing a frown) hindered processing, relative to pre-injection baseline, for angry and sad sentences, while processing for happy sentences was unaffected. These findings suggest a bi-directional mechanism between emotion and language, offer new evidence for facial feedback theories of emotion, and report a novel effect of botulinum toxin-A on human cognition.
Evaluation of protein surface roughness index using its heat denatured aggregates
Authors: Mishra Hrishikesh , Lahiri Tapobrata
Published: July 2019

Recent research works on potential of different protein surface describing parameters to predict protein surface properties gained significance for its possible implication in extracting clues on protein's functional site. In this direction, Surface Roughness Index, a surface topological parameter, showed its potential to predict SCOP-family of protein. The present work stands on the foundation of these works where a semi-empirical method for evaluation of Surface Roughness Index directly from its heat denatured protein aggregates (HDPA) was designed and demonstrated successfully. The steps followed consist, the extraction of a feature, Intensity Level Multifractal Dimension (ILMFD) from the microscopic images of HDPA, followed by the mapping of ILMFD into Surface Roughness Index (SRI) through recurrent backpropagation network (RBPN). Finally SRI for a particular protein was predicted by clustering of decisions obtained through feeding of multiple data into RBPN, to obtain general tendency of decision, as well as to discard the noisy dataset. The cluster centre of the largest cluster was found to be the best match for mapping of Surface Roughness Index of each protein in our study. The semi-empirical approach adopted in this paper, shows a way to evaluate protein's surface property without depending on its already evaluated structure.
The efficacy of working memory training in improving crystallized intelligence
Authors: Alloway Tracy , Alloway Ross
Published: July 2019

Crystallized intelligence (Gc) is thought to reflect skills acquired through knowledge and experience and is related to verbal ability, language development^1^ and academic success^2^. Gc, together with fluid intelligence (Gf), are constructs of general intelligence^3^. While Gc involves learning, knowledge and skills, Gf refers to our ability in tests of problem-solving, pattern matching, and reasoning. Although there is evidence that Gf can be improved through memory training in adults^4^, the efficacy of memory training in improving acquired skills, such as Gc and academic attainment, has yet to be established. Furthermore, evidence of transfer effects from gains made in the trained tasks is sparse^5^. Here we demonstrate improvements in Gc and academic attainment using working memory training. Participants in the Training group displayed superior performance in all measures of cognitive assessments post-training compared to the Control group, who received knowledge-based training. While previous studies have indicated that gains in intelligence are due to improvements in test-taking skills^6^, this study demonstrates that it is possible to improve crystallized skills through working memory training. Considering the fundamental importance of Gc in acquiring and using knowledge and its predictive power for a large variety of intellectual tasks, these findings may be highly relevant to improving educational outcomes in those who are struggling.
Overcoming high temperature inhibition of flower formation and fruit production without bees
Authors: Liptay Albert , Salzman Ron , Stoller Jerry , Orzolek Michael
Published: July 2019

Flower formation in the Cucurbitaceae family is compromised at high temperatures; both male and female flowers and therefore fruit productivity are greatly reduced as the growing temperatures for these vegetable crops are increased above 26C. This intractable phenomenon has been documented both with outdoor field experiments at various latitudes on the eastern seaboard in the USA and in a laboratory, temperature-regulated setting. We now report that an agricultural product, FP, which has been, and is used globally on many commercial crops to increase flower number and strength during blossom formation and development, overcomes the apparent refractory floral initiation and development at high temperatures. This is a new and unexpected finding. Additionally, in another facet of the experiments reported here, the parthenocarpic fruit development potential of FP was tested by eliminating bee pollination. This aspect of the study was addressed in part because of the recent concerns with bee colony collapse disorder. Flower formation, flower development and fruit yield were increased by FP over the bee-pollinated, untreated controls at high temperatures. FP was developed over a number of years of outdoor field trials as an approach to crop productivity that included hormonal regulation of floral strength and supported by mineral supplements through to the fruit production process.
Prediction of Evolutionarily important catalytic amino acid of Mycobacterium tuberculosis O-Succinylbenzoate synthase through in silico mutational analysis
Authors: B Babajan , M Chaitanya , CM Anuradha , Chitta Suresh Kumar
Published: July 2019

The emergence of tuberculosis resistant to multiple, first- and second-line antibiotics poses challenges to a global control strategy that relies on standard drug treatment regimens. The high drug-resistant strains of Mycobacterium tuberculosis (Mtb) have been implicated in outbreaks and have been found throughout the world; a comprehensive understanding, the magnitude of this threat requires an accurate assessment of the worldwide burden of resistance. In an attempt to design anti-TB drugs, the target chosen is a key enzyme of Mtb, O-Succinylbenzoate synthase (OSBS), which is an attractive target for its role in electron transport chain as OSBS is not available in humans. An attempt has been to built the 3-D structure of Mtb-OSBS using online Swiss model server. With sequence alignment and scan motif identification, the importance of evolutionarily significant residues that are of functional importance for ligand binding and that form active sites were well established. Molecular simulation calculations of Mtb-OSBS model indicated evolutionarily conserve residues (Lys110 and Lys212) are the best in molecular interaction with substrate 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). The in silico mutational analysis of Mtb-OSBS model showed the evolutionarily conserved residues that are essential for catalytic activity. It has been found that active site amino acids of Mtb-OSBS are very important to maintain activity of the enzyme, which provides a novel approach to design new pharmacophore SHCHC substrate analogs against Mtb-OSBS. A series of SHCHC substrate analogs (1–100) compounds have been docked with the amino acid residues at the active site of the Mtb-OSBS enzyme, using AutoDock 4.0, a program employed to perform automated molecular docking. The free energies of binding (∆G) and inhibition constants (Ki) of the docked compounds were calculated by the Lamarckian Genetic Algorithm (LGA). Excellent to good correlations between the calculated and experimental Ki values were reported.
Oxytocin makes us trusting but not gullible
Authors: Mikolajczak Moïra , Lane Anthony , Gross James , de Timary Philippe , Luminet Olivier
Published: July 2019

Originally known for its role in childbirth and lactation, oxytocin (OT) has recently proved to play a key role in social behavior. Deprived of OT, humans are unable to recognize and to bond to their peers. Inversely, once boosted with OT, people become more caring, trusting and generous. Effect-sizes on trust and generosity were sufficiently large that OT started to be perceived as a natural drug that would make people credulous. But could OT really impede judgment and lead individuals to trust untrustworthy peers? Here we show that oxytocin makes people trusting, but not gullible. Namely, OT did not have a trust-enhancing effect on people who interacted with seemingly unreliable peers. These results emphasize that the effect of OT is much more context-dependent than previously thought. This finding therefore invalidates some of the potential commercial or military applications of oxytocin.
Theoretical studies on the pK~a~ values of perfluoroalkyl carboxylic acids: Non-helical conformation acidity constants for n-perfluorooctanoic acid (n-PFOA)
Authors: Rayne Sierra , Forest Kaya
Published: July 2019

A molecular mechanics force field method (MMFF94) systematic rotor conformational search was conducted on the well known environmental contaminant n-perfluorooctanoic acid (n-PFOA). The MMFF94 conformational search yielded 2915 separate low- through high-energy conformers of n-PFOA. Ranking of these structures gave the 94 lowest MMFF94 energy conformations that were subjected to subsequent density functional theory (DFT) computational investigations at the B3LYP/6-311++G(d,p) level of theory. Application of a thermodynamic cycle approach, coupled with aqueous and gas phase DFT calculations on the molecular and anionic forms for each of the 94 lowest energy n-PFOA conformers, gave estimated acidity constants (pK~a~ values) for a final converged set of twelve n-PFOA conformers, including the global minimum helical perfluoroalkyl chain geometry and eleven non-helical higher energy conformations. Collectively, the twelve lowest energy conformers appear to completely encompass the global conformational space for n-PFOA, indicating no higher energy conformations likely remain that could appreciably influence the observed composite aqueous pK~a~ of this compound. The estimated pK~a~ values of all eleven non-helical n-PFOA conformers were within 0.1 pK~a~ units of the helical conformer pK~a~. The findings support previous predictions and recent experimental evidence for an aqueous phase n-PFOA monomeric pK~a~ of about zero.
Chromosomal mutational algebra: a new algebra to manipulate chromosomal mutation
Authors: Mazumdar Dipankar
Published: July 2019

This study leads to a new algebra. An algebra is defined on the common mechanisms of chromosomal mutation. The algebra (S^[PSI](C)^, ~*~, ', [DELTA], D) is constructed for a given C and [PSI]. This algebra represents the most common chromosomal mutational mechanisms. This can lead to a new way to manipulate chromosomal mutation with higher structures of abstract mathematics. The first proposal of the algebra was reported in Mazumdar et al., 2007.
Endogenous Viral Etiology of Prion Diseases
Authors: Bandea Claudiu
Published: July 2019

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of incurable neurodegenerative disorders, including Kuru and Creutzfeldt-Jakob disease in humans, “mad cow” disease in cattle, and scrapie in sheep. This paper presents structural, genetic, and evolutionary evidence supporting an endogenous TSE virus model that integrates the three major traditional views on the nature of TSE pathogens, the conventional virus view, the prion hypothesis, and the virino concept, into a novel conceptual and evolutionary framework. According to this model, the TSE pathogens are symbiotic endogenous viruses that inadvertently produce transmissible viral particles that lack the viral genome and are composed primarily of the viral prion protein (PrP). Production of defective viral particles that contain a partial genome or lack the viral genome entirely is a relatively common event in the life cycle of many viruses. Similar to the normal viral particles, which contain a genome, these defective viral particles can be transmitted to new host cells. Obviously, in the absence of viral genome, these protein-only viral particles cannot establish a productive infection. However, if these viral particles enter a host cell that carries the parental or a related virus and induce the production of similar protein-only particles, then they would appear as self-replicating, protein-only infectious pathogens if mistakenly taken out from the context of the viral life cycle. This misconception, which is rooted into the current dogma of viruses as viral particles, led to the development of the prion theory. The endogenous TSE virus model is consistent with the TSE data and offers solutions to many enigmatic features associated with TSE, including the function of PrP that, despite more than two decades of TSE research conducted primarily within the framework of the prion hypothesis, is still not known. According to the TSE endogenous virus model, PrP is the protein of an endogenous virus that has co-evolved with their vertebrate hosts by providing a protective function against pathogenic viruses. The evidence for the endogenous TSE virus model and for the antiviral protective function of PrP is strong, and they are fully open to additional experimental testing. The endogenous virus model opens the TSE research field to new interpretations and directions, both in basic research and in associated biomedical and public health fields, and could lead to development of new diagnostic and therapeutic approaches.
Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD).
Authors: Proitsi Petroula , Lupton Michelle , Reeves Suzanne , Hamilton Gillian , Archer Nicola , Martin Belinda , hollingworth Paul , Lawlord Brian , Gill Michael , Owen Michael , Williams Julie , Lovestone Simon , Powell John
Published: July 2019

Although there is evidence for the involvement of genes of serotonergic and dopaminergic systems in the manifestation of the Behavioural and Psychological Symptoms in Dementia (BPSD), genetic association studies are contradictory. We used 1008 probable AD patients from the UK and applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of 11 polymorphisms in the serotonergic and dopaminergic systems, on four behavioural sub-phenotypes, namely "psychosis"," moods", "agitation" and "behavioural dyscontrol", as well as on 12 NPI items. Significant findings included the association of DRD1 A48G with "psychosis" (p=0.037), the association of DAT1 VNTR with "agitation" (p=0.006) and the association of DRD4 with "moods" sub-phenotype (p=0.008). In addition, associations were identified between DRD1 A48G and DAT1 VNTR with aberrant motor behaviour (AMB) symptoms (p=0.001 and p=0.015 respectively), between DRD4 and sleep disturbances (p=0.018) and between 5HTTLPR and apathy (p=0.033). Finally, significant interactions were observed between COMT Val158Met and 5HTTLPR with "psychosis" (p=0.026), between HTTLPR and STin2 with "psychosis" (p=0.005), between DAT1 3'UTR VNTR and COMT Val158Met with "agitation" (p=0.0001) and between DAT1 3'UTR VNTR and 5HTTLPR with the "moods" factor (p=0.0027). The complexity of the interrelations between genetic variation, behavioural symptoms and clinical variables was efficiently captured by this MIMIC model.
Robustness of self-organised systems to changes in individual level behaviour: an example from real and simulated self-organised snail aggregations
Authors: Stafford Richard , Davies Mark , Williams Gray
Published: July 2019

Perfect behaviours that are optimal to the environment an agent operates within rarely exist in real animals or in robotic systems. The costs (be they biological or economic) of building sensors and processing the information they capture become excessive compared to the small advantages that occur from the modifications of behaviour. Many self-organised systems are thought to change their properties as a result of changes in individual behaviour. Here, using both natural systems and computer simulations, we demonstrate that intertidal snail aggregations slightly decrease in size when individuals forage for shorter periods due to hotter and more desiccating conditions – a non-optimal behaviour for the snails since aggregation reduces desiccation stress. However, this decrease only occurs in simple experimental systems (and simulations of these systems). When studied in their more complex natural environment, and when simulated in such an environment, using the same information-processing behaviours, no difference in aggregation behaviour was found between hot and cool days. These results give an indication of the robustness of self-organised systems to changes in individual-level behaviour. They demonstrate that information processing capabilities of self-organised groups may not need to be as great as for agents that perform solitary tasks, and also that oversimplified tests of swarm intelligence may not give a true indication of how tasks may be performed in a more complex environment.
Organising metabolic networks: cycles in flux distributions
Authors: Kritz Maurício , dos Santos Marcelo , Urrita Sebastián , Schwartz Jean-Marc
Published: July 2019

Metabolic networks are among the most widely studied biological systems. The topology and interconnections of metabolic reactions have been well described for many species, but are not sufficient to understand how their activity is regulated in living organisms. The principles directing the dynamic organisation of reaction fluxes remain poorly understood. Cyclic structures are thought to play a central role in the homeostasis of biological systems and in their resilience to a changing environment. In this work, we investigate the role of fluxes of matter cycling in metabolic networks. First, we introduce a methodology for the computation of cyclic and acyclic fluxes in metabolic networks, adapted from an algorithm initially developed to study cyclic fluxes in trophic networks. Subsequently, we apply this methodology to the analysis of three metabolic systems, including the central metabolism of wild type and a deletion mutant of Escherichia coli, erythrocyte metabolism and the central metabolism of the bacterium Methylobacterium extorquens. The role of cycles in driving and maintaining the performance of metabolic functions upon perturbations is unveiled through these examples. This methodology may be used to further investigate the role of cycles in living organisms, their pro-activity and organisational invariance, leading to a better understanding of biological entailment and information processing.
Cortical activity modulation of language processing by dynamic optimization of task complexity and functional restrictions
Authors: Ghosh Shantanu , Basu Amrita , Khushu Subash , Kumaran Senthil
Published: July 2019

Language, regarded as a hierarchical cognitive code activated by functional operational modes of the brain by most neuropsychologists, is characterized by increased cognitive load in successively higher levels of processing. Language comprehension is posited to be executed through symbolic-iconic information being encoded neurally as modulated phenomena, and can be studied in vivo by functional brain imaging. Using a lexical decision-making task in conjunction with syntactic error correction that effectively isolated the regulatory neural substrate of processing structural-functional information, and minimizing the possible confounds of gender and proficiency, functional magnetic resonance imaging (fMRI) was performed on bilingual volunteers to ascertain the attentional modulation of second language lexical and sentence processing. Our results indicate that while a right posterior cingulate gyrus-precuneus-lingual gyrus-cerebellar loop processes lexical information, the left inferior and middle frontal cortices are critically involved in the implementation of a structural-functional decision-making procedural loop in mediating second language comprehension.
Magnetoencephalography May Allow the Electromagnetic 'Biopsy' of Central Nervous System Neoplastic Tissue
Authors: Pearlman Michael , Castillo Eduardo , Papanicolaou Andrew , Butler Ian , Slopis John , Frye Richard
Published: July 2019

Developing a non-invasive method for definitively diagnosing intracranial neoplasms would reduce the risks involved with diagnosis and improve the treatment of such tumors. We used magnetoencephalography to measure the power spectral densities of malignant brain tumor cells in vitro and found that meningioma and medulloblastoma cells produce unique electromagnetic signatures. Our results suggest that non-invasive identification of neoplastic tissue is possible through the use of magnetoencephalography.
Spherulites of A[beta]~42~ in vitro and in Alzheimer's disease
Authors: Exley Christopher , House Emily , Collingwood Joanna , Davidson Mark , Cannon Danielle , Donald Athene
Published: July 2019

Several amyloid-forming proteins and peptides, including insulin^1^, [beta]-lactoglobulin^2^ and albumin^3^, form spherulites in vitro under non-physiological solution conditions. These micrometer-sized, roughly spherical structures are composed of ordered arrays of [beta] sheets of amyloid fibrils in radial arrangements which, characteristically, show a typical Maltese cross pattern of light extinction under the polarizing microscope. The physiological significance, if any, of these amyloid super assemblies is unknown although in Alzheimer's disease there is the suggestion that senile plaques composed primarily of [beta] sheets of A[beta]~42~ are spherulitic^4^. Herein we describe the first observation of the formation in vitro of spherulites of A[beta]~42~. They were formed under near-physiological conditions in which the [beta] sheet conformation of pre-formed aggregates of A[beta]~42~ had been abolished following the addition of an excess of copper. Incubation of these preparations at 37^o^C for up to 9 months resulted in the formation of spherulites. These were globular in appearance, 5 - 20 microns in diameter, and exhibited the typical Maltese cross pattern of light extinction. Similarly to other amyloid spherulites formed in vitro they bound Congo red without giving apple-green birefringence^5^ while also being thioflavin T-positive when viewed by fluorescence microscopy^3^. Near-identical spherulitic structures were also observed in abundance in 30 micron thick sections of Alzheimer's disease brain tissue. Synchrotron x-ray fluorescence showed that the location of these spherulites in AD tissue coincided with locally elevated concentrations of tissue copper. The formation in vitro of spherulites of A[beta]~42~ which morphologically appeared analogous to spherulitic structures observed in vivo strongly supports the hypothesis that spherulites and senile plaques in AD tissue are one and the same structures and that their ultimate formation involves copper.
Antibody responses to a Cryptosporidium parvum rCP15/60 vaccine
Authors: Burton Alexandra , Nydam Daryl , Jones Gary , Zambriski Jennifer , Linden Thomas , Cox Graham , Davis Randy , Brown Alicia , Bowman Dwight
Published: July 2019

Cryptosporidium parvum is a zoonotic apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhoea in mammals worldwide. The organism is transmitted by ingestion of oocysts, which are shed in faeces, and completes its lifecycle in a single host.^1^ C. parvum is ubiquitous on dairy operations worldwide and is one of the leading causes of diarrhoea in calves on these farms.^2,3^ Here, for the first time, we describe the antibody response in a large group of cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine and the antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. Results of recent genotype surveys indicate that calves are the only major reservoir for C. parvum infections in humans.^4^ Human C. parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDs patients.^4^ Drug therapy against cryptosporidiosis is limited and not wholly efficacious in either humans or calves^5^, making development of an effective vaccine of paramount importance. To date, there is no commercially available effective vaccine against C. parvum, although passive immunization utilizing different zoite surface (glyco)proteins has showed promise.^6-9^ All cows we vaccinated produced an antibody response to the rCP15/60 vaccine and the magnitude of response correlated strongly with the subsequent level of antibody in their colostrum. All calves fed rCP15/60-immune colostrum showed a dose-dependent absorption of antibody. Our results demonstrate that vaccination of cows with rCP15/60 successfully induces antibodies against CP15/60 in their serum and colostrum and that these antibodies are then well absorbed when fed to neonatal calves. With further research, this C. parvum vaccine may well be a practical method of conferring passive protection to calves against cryptosporidiosis. Furthermore, a specifically targeted immune-colostrum may be valuable in protection and treatment of immunocompromised human patients with cryptosporidiosis.
A Bayesian Framework for Parameter Estimation in Dynamical Models with Applications to Forecasting
Authors: Coelho Flávio Codeço , Codeço Claudia
Published: July 2019

Mathematical models in Biology are powerful tools for the study and exploration of complex dynamics. Nevertheless, bringing theoretical results to an agreement with experimental observations involves acknowledging a great deal of uncertainty intrinsic to our theoretical representation of a real system.Proper handling of such uncertainties, is key to the successful usage of models to predict experimental or field observations. This problem has been addressed over the years by many tools for model calibration an parameter estimation. In this article we present a general framework for uncertainty analysis and parameter estimation which is designed to handle uncertainties associated with the modeling of dynamic biological systems while remaining agnostic as to the type of model used. We apply the framework to two Influenza transmission models: one deterministic and the other stochastic. The results show that the framework can be applied without modifications to the two types of models and that it performs equally well on both. We also discuss the application of the framework to calibrate models for forecasting purposes.
Origin of nanosized diamonds in interstellar space and low-pressure-temperature Earth rocks
Authors: Simakov Sergei
Published: July 2019

Nanosized diamond particles in the interstellar space and in the Earth rocks related with water presence. In the paper proposed the model of the nanosized diamond particle formation from oxidized water-carbon dioxide gaseous mixtures.
Association of autoimmune diseases to allele 2 of the 3' immuno-globulines HS1.2 enhancer bearing an NF-&x03BA;B binding site.
Authors: Frezza Domenico , Gremese Elisa , Giambra Vincenzo , Mattioli Claudia , Tolusso Barbara , Bosello Silvia , DeSantis Maria , Birshtein Barbara , Ferraccioli Gianfranco
Published: July 2019

We identified allele *2 in the HS1.2 enhancer of the Igh 3' regulatory region (3'RR-1) as a risk factor for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc) (scleroderma). An NF-&x03BA;B binding site specific to allele *2 may contribute to the association of this allele with chronic inflammatory autoimmune diseases.
An RNA cis-element upstream of the HMGA1a binding site affects exon exclusion caused by HMGA1a
Authors: Ohe Kenji , Manabe Takayuki , Katayama Taiichi , Tohyama Masaya , Mayeda Akila
Published: July 2019

In addition to its characteristics as a DNA binding transcription factor, HMGA1a is known to bind RNA, sequence specifically and regulate aberrant splicing of the Presenilin-2 gene in sporadic Alzheimer’s disease^1,2^. We show here that an RNA cis-element, immediately upstream the HMGA1a binding site, induces exon inclusion upon mutating a GU sequence to CA. Psoralen mediated UV crosslinking showed U1 snRNP did not bind this sequence but oligonucleotide-mediated RNase H digestion showed it important for U1 snRNP to recognize the authentic 5’ splice site. This sequence (5’-AAGUAC-3’) was tested for hnRNPA1 binding and function. Coimmunoprecipitation of endogenous HMGA1a and hnRNPA1 in HeLa nuclear extract, implicated hnRNPA1 to be involved in HMGA1a mediated dysfunction of U1 snRNP. Though hnRNPA1 binding was weak, there was decreased binding when GU was mutated to CA. hnRNPA1 alone had no effect of splicing of a 5’ splice site adjacently downstream the HMGA1a binding site, but significantly attenuated HMGA1a mediated splicing suppression of this 5’ splice site. Thus, hnRNPA1, known as the human homolog of hrp48 in the PSI model, attenuates HMGA1a mediated U1 snRNP dysfunction.
Application of a periodic table for the genetic code of the influenza A/H3N2 virus
Authors: Morimoto Susumu
Published: July 2019

The progress of life sciences would be greatly enhanced if biological data were available in a manner similar to the periodic table of the elements. Currently, the mutation rules for influenza viruses remain ambiguous. In light of the threat of Avian Influenza there is an urgent need to understand the governing principles behind influenza virus mutations. Here, the applicability of a periodic table for the genetic code of influenza A/H3N2 virus is explored. In addition, two rules regarding single point mutations of the hemagglutinin gene are presented. The first rule states that non-synonymous single point mutations are intimately associated with the first or second base replacements between two congener codons of four groups (5, 6, 9, and 10) in the proposed periodic table. The second rule involves the use of a new index (inversion number) that describes a mutation. This paper will take the first step toward developing an approach for indexing different types of mutations in the influenza genome.
Extending Astrobiology: Consciousness and Culture
Authors: Wallace Rodrick
Published: July 2019

The Stanley Miller experiment suggests that amino acid-based life is ubiquitous in our universe, although its varieties are not likely to have followed the particular, highly contingent and path-dependent, evolutionary trajectory found on Earth. Are many alien organisms likely to be conscious in ways that we would recognize? Almost certainly. Will some develop high order technology? Less likely, but still fairly probable. If so, will we be able to communicate with them? Only on a basic level, and only with profound difficulty. The argument is fairly direct.
Remote preconditioning by aortic constriction: affords cardioprotection as classical or other remote ischemic preconditioning? Role of iNOS
Authors: Sharma Ashish , Munajjam Arshee , Vaishnav Bhawna , Sharma Richa , Kishore Kunal , Sharma Ashok , Sharma Akash , Sharma Divya , Kumari Rita , Tiwari Ashish , Srinivasan B.P. , Agarwal Shyam
Published: July 2019

Dose remote preconditioning by aortic constriction (RPAC) affords cardioprotection similar to classical or other remote ischemic preconditioning stimulus? Moreover study was also designed to investigate role of inducible nitric oxide synthase in remote preconditioning by aortic constriction. There are sufficient evidences that "ischemic preconditioning" has surgical applications and afford clinically relevant cardioprotection. Transient occlusion of circumflex artery, renal artery, limb artery or mesenteric artery preconditions the myocardium against ischemia reperfusion injury in case of ischemic heart disease leading to myocardial infraction. Here abdominal aorta was selected to produce RPAC. Four episodes of Ischemia-reperfusion of 5 min each to abdominal aorta produced RPAC by assessment of infract size, LDH and CK. These studies suggest RPAC produced acute (FWOP) and delayed (SWOP) cardioprotective effect. RPAC demonstrated a significant decrease in Ischemia-reperfusion induced release of LDH, CK and extent of myocardial infract size. L-NAME (10 mg/Kg i.v.), Aminoguanidine (150 mg/Kg s.c.), Aminoguanidine (300 mg/Kg s.c.), S-methyl isothiourea (3 mg/Kg i.v.), 1400W (1 mg/Kg i.v.) administered 10 min. before global ischemia reperfusion produced no marked effect. Aminoguanidine (150 mg/Kg s.c.), Aminoguanidine (300 mg/Kg s.c.), S-methyl isothiourea (3 mg/Kg i.v.), 1400W (1 mg/Kg i.v.) pretreatment after RPAC produced no significant effect on acute RPAC induced decrease in LDH, CK and infract size, whereas L-NAME (10 mg/Kg i.v.) increased RPAC induced decrease in LDH, CK and infract size. Most interesting observation is in delayed RPAC, where all NOS inhibitors pretreatment attenuate RPAC induced decrease in LDH, CK and infract size. In conclusions, "Remote preconditioning by aortic constriction" (RPAC) affords cardioprotection similar to classical or other remote ischemic preconditioning stimulus. Moreover, late or delayed phase of RPAC has been mediated by inducible nitric oxide synthase (iNOS) whereas it has not involved in acute RPAC.
Fuzzy logic as a decision-making support system for the indication of bariatric surgery based on an index (OBESINDEX) generated by the association between body fat and body mass index
Authors: Azevedo Joao , Miyahira Susana , Leal Lucas , Azevedo Glicia , Azevedo Otavio , Azevedo Joao , Miguel Gustavo
Published: July 2019

Background:

A Fuzzy Obesity Index (OBESINDEX) for use as an alternative in bariatric surgery indication (BSI) is presented. The search for a more accurate method to evaluate obesity and to indicate a better treatment is important in the world health context. BMI (body mass index) is considered the main criteria for obesity treatment and BSI. Nevertheless, the fat excess related to the percentage of Body Fat (%BF) is actually the principal harmful factor in obesity disease that is usually neglected. This paper presents a new fuzzy mechanism for evaluating obesity by associating BMI with %BF that yields a fuzzy obesity index for obesity evaluation and treatment and allows building up a Fuzzy Decision Support System (FDSS) for BSI.

Methods:

Seventy-two patients were evaluated for both BMI and %BF. These data are modified and treated as fuzzy sets. Afterwards, the BMI and %BF classes are aggregated yielding a new index (OBESINDEX) for input linguistic variable are considered the BMI and %BF, and as output linguistic variable is employed the OBESINDEX, an obesity classification with entirely new classes of obesity in the fuzzy context as well is used for BSI.

Results:

There is a gradual, smooth obesity classification and BSI when using the proposed fuzzy obesity index when compared with other traditional methods for dealing with obesity.

Conclusion:

The BMI is not adequate for surgical indication in all the conditions and fuzzy logic becomes an alternative for decision making in bariatric surgery indication based on the OBESINDEX.
The neural bases of distracter-resistant working memory
Authors: Wager Tor , Insler Rachel , Smith Edward
Published: July 2019

A major difference between humans and other animals is our capacity to maintain information in working memory (WM) while performing secondary tasks, which enables sustained, complex cognition. A common assumption is that the lateral prefrontal cortex (PFC) is critical for WM performance in the presence of distracters, but direct evidence is scarce. We assessed the relationship between fMRI activity and WM performance within-subjects, with performance matched across Distracter and No-distracter conditions. Activity in ventrolateral PFC during WM encoding and maintenance positively predicted performance in both conditions, whereas activity in the pre-supplementary motor area (pre-SMA) predicted performance only under distraction. Other parts of dorsolateral and ventrolateral PFC predicted performance only in the No-distracter condition. These findings challenge a lateral PFC-centered view of distracter-resistance, and suggest that the lateral PFC supports a type of WM representation that is efficient for dealing with task-irrelevant input but is nonetheless easily disrupted by dual-task demands.
Basic emotions: Differences in time sequence and functional imaging with low resolution brain electrical tomography (LORETA)
Authors: Costa Tommaso , Crini Manuella
Published: July 2019

The aim of the present study is to investigate the relationship between the time course of brain activation during the observation of pictures depicting scenes associated with the four basic emotion of happiness, sadness, fear and disgust. Twenty-nine right-handed volunteers (17 male, 12 female; mean age 24.6 years) took part in the study. To study the time course of the affective processing the low resolution brain electromagnetic tomography (LORETA) has been used. Each emotional condition has shown specific activation patterns in different brain regions, changing over time. Our findings are in good agreement with other brain-imaging studies (PET/fMRI) but with the advantage to investigate the temporal evolution of the emotional process in the millisecond range. The results showed that the time sequence of activations is different and characteristic for each emotion conditions.
A sorites paradox in the conventional definition of amount of substance
Authors: Wheatley Nigel
Published: July 2019

The conventional definition of amount of substance n is as a quantity proportional to number of entities N. This implies that n is discrete for small N while n is considered to be continuous at the macroscopic scale, leading to a sorites paradox. A practical criterion is proposed for distinguishing between amount of substance and number of entities, and the implications for the conventional definition of amount of substance are discussed.
Unnatural Selection: A new formal approach to punctuated equilibrium in economic systems
Authors: Wallace Rodrick
Published: July 2019

Generalized Darwinian evolutionary theory has emerged as central to the description of economic process (e.g., Aldrich et. al., 2008). Here we demonstrate that, just as Darwinian principles provide necessary, but not sufficient, conditions for understanding the dynamics of social entities, in a similar manner the asymptotic limit theorems of information theory provide another set of necessary conditions that constrain the evolution of socioeconomic process. These latter constraints can, however, easily be formulated as a statistics-like analytic toolbox for the study of empirical data that is consistent with a generalized Darwinism, and this is no small thing.