bluuebunny/crossref_metadata_2025 huggingface dataset:
Networks, Extinction and Paleocommunity Food Webs
Authors: Roopnarine Peter
Published: July 2019

Food webs represent trophic interactions among species in communities. Those interactions both structure and are structured by species richness, ecological diversity, and evolutionary processes. Geological and macroevolutionary timescales are therefore important to the understanding of food web dynamics, and there is a need for the consideration of paleocommunity food webs. The fossil record presents challenges in this regard, but the problem can be approached with combinatoric analysis and network theory. This paper is an introduction to the aspects of those disciplines relevant to the study of paleo-food webs, and explores a probabilistic and numerical approach.
Effect of Non-Coding RNA on Post-Transcriptional Gene Silencing of Alzheimer Disease
Authors: Namboori Krishnan , Mohan Arun , K.U. Radhagayathri , Gopal Varun , C.S. Vasavi , P Premkumar , Gopakumar Deepa , K.I. Ramachandran
Published: July 2019

A large amount of hidden biological information is contained in the human genome, which is not expressed or revealed in the form of proteins; the usual end product form of gene expression. Instead, most of such information is in the form of non-coding RNAs (ncRNAs). ncRNAs correspond to genes that are transcribed, but do not get translated into proteins. This part of the genome was, till recently, considered as ‘junk’. The term ‘junk’ implied lack of any discernible function of these RNA. More than 98% of the human genomic size encompasses these non-coding RNAs. But, recent research has evidently brought out the indispensible contribution of non-coding RNA in controlling and regulating gene expression. ncRNA such as siRNAs and microRNAs have been reported to greatly help in causing post-transcriptional gene silencing (PTGS) in cells through RNA interference (RNAi) pathway. In this work, we have investigated the possibility of using siRNAs and microRNAs to aid in gene silencing of early onset Alzheimer’s disease genes. Alzheimer’s disease specific mutations and their corresponding positions in mRNA have been identified for six genes; Presenilin-1, Presenilin-2, APP (amyloid beta precursor protein), APBB3, BACE-1 and PSENEN. Small interfering RNAs (siRNAs) that can cause PTGS through RNA interference pathway have been designed. RNA analysis has been done to verify complementarity of antisense siRNA sequence with target mRNA sequence. Interaction studies have been done computationally between these antisense siRNA strands and seven Argonaute proteins. From the interaction studies, only one of the seven Argonaute proteins; 1Q8K, was found to have interaction with the siRNAs indicating the importance and uniqueness of this particular protein in RISC (RNA induced silencing complex). The interaction studies have been carried out for the microRNAs also. Out of the 700 mature human microRNAs collected, 394 microRNAs have been identified to show partial complementarity with their target sequence on PSEN-1 mRNA. Of these 394, five microRNAs have shown partial complementarity to early onset Alzheimer’s disease specific mutations in PSEN-1 mRNA. Interaction studies have been done between these microRNAs and Argonaute proteins. Thus, design, characterization and analysis of ncRNAs that contribute to post transcriptional gene silencing of Alzheimer’s disease have been achieved.
Death of human tumor endothelial cells in vitro through a probable calcium-associated mechanism induced by bevacizumab and detected via a novel method
Authors: Weisenthal Larry , Liu Haddy , Rueff-Weisenthal Constance
Published: July 2019

We isolated three dimensional cell clusters from fresh human solid tumors and also isolated human neoplastic and normal lymphatic cells. Cells were cultured for 96 hours with and without bevacizumab and other agents. At concentrations of bevacizumab which completely removed VEGF from the culture medium, dead microvascular cells were detected through Fast Green/H&E staining as previously described. These peculiar staining characteristics suggested the involvement of calcium, and this was confirmed through staining with Alizarin red S. Using Alizarin staining as a marker for endothelial cell death permitted the use of public domain image analysis software which resulted in a sensitive and specific system for identifying active pharmaceuticals which target the tumor microvasculature at the same time direct antitumor cell effects are determined. Our results suggest an important role for calcium in endothelial cell death mediated by bevacizumab and other agents and further suggest that agents promoting calcium influx may potentiate the activity of antiangiogenic agents.
Multi-Cancer Computational Analysis Reveals Metastasis-Associated Variant of Desmoplastic Reaction Involving INHBA and THBS2
Authors: Kim Hoon , Watkinson John , Varadan Vinay , Anastassiou Dimitris
Published: July 2019

Despite extensive research, the details of the metastasis-associated biological mechanisms are largely unknown. Here, we analyze data from multiple cancers using a novel computational method identifying sets of genes whose coordinated overexpression indicates the presence of a particular phenotype. We conclude that there is one shared “core” metastasis-associated gene expression signature corresponding to a specific variant of desmoplastic reaction, present in a large subset of samples that have exceeded a threshold of invasive transition specific to each cancer, indicating that the biological mechanism is triggered at that point. For example this threshold is reached at stage IIIc in ovarian cancer and at stage II in colorectal cancer. It has several features, such as coordinated expression of particular collagens, mainly COL11A1 and other genes, mainly THBS2 and INHBA. The universally prominent presence of INHBA in all cancers strongly suggests a biological mechanism centered on activin A induced TGF-β signaling, because activin A is a member of the TGF-β superfamily consisting of an INHBA homodimer. It is accompanied by the expression of several transcription factors related to epithelial-mesenchymal transition, but not of SNAI1, and expression of E-cadherin is not downregulated. It is reversible, as evidenced by its absence in many matched metastasized samples, but its presence indicates that metastasis has occurred. Therefore, these results can be used for developing high-specificity biomarkers, as well as potential multi-cancer metastasis-inhibiting therapeutics targeting the corresponding biological mechanism.
Vestibular stimulation reduces unrealistic optimism
Authors: Tamagni Corinne , Palla Antonella , Krummenacher Peter , Vitacco Deborah , Huberle Elisabeth , Straumann Dominik , Hegemann Stefan , McKay Ryan , Brugger Peter
Published: July 2019

Unrealistic optimism (UO) refers to the tendency of healthy people to underestimate their risk of future misfortune. Just as left-ear caloric irrigation attenuates anosognosia (denial of manifest illness) in clinical patients, we found that it also reduces UO about future health risks in healthy individuals. This finding demonstrates asymmetric hemispheric involvement in emotion regulation and self-evaluation, and suggests that a similar neuropsychological process underpins anosognosia and healthy optimism.
Living unicellular eukaryote Tetrahymena pyriformis as a model for study of mitochondrial energetics in mammalian cells under conditions of reduced oxidative metabolism.
Authors: Mokhova Elena
Published: July 2019

Some “animal-like” protozoa are used instead of mammalian cells in diverse investigations. Tetrahymena pyriformis cells in stationary phase of growth and washed from oxidative substrates (T.pyriformis) function under conditions of reduced oxidative metabolism. To elucidate if T.pyriformis can be applied as a model for mitochondrial energetics study in mammalian cells during hibernation, the features of T.pyriformis mitochondria were compared with that of liver mitochondria isolated from hibernating animals; the published earlier data were used. Based on the respiration recording and observation of Mito Tracker Red fluorescence in living T.pyriformis we tentatively concluded that the mitochondrial electrical membrane potential, Δψ, is low, and that the most part of the proton motive force is stored as the difference of pH between the sides of inner mitochondrial membrane. A sharp decrease of the maximal uncoupler-stimulated respiration rates was observed in the liver mitochondria isolated from hibernating animals. These and other data are explained by hypothesis that remodeling the liver mitochondria to a condense configuration is prerequisite for reduction of the oxidative metabolism. The rearrangement possibly resembles the apoptosis with the initial Δψ decrease induced by the respiratory activity suppression; the process has been earlier studied by E. Gotlieb and coauthors. The data suggest that T.pyriformis are suitable to study of some aspects of mitochondrial role in cellular adaptation to metabolic depression; that the evolutionary ancient mechanisms are conserved in a modified form in the ciliate and mammalian cells.
Computational Prediction and Analysis of the NAPP - DR6 Interaction: Implications for Alzheimer's Research
Authors: Audie Josheph , Ponomarev Sergei
Published: July 2019

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that involves a devastating clinical course and lacks an effective treatment. A biochemical model for neuronal development that might have implications for AD, recently proposed by Nikolaev and co-workers, hinges on a novel protein-protein interaction between the death cell receptor six (DR6) ectodomain and an N-terminal fragment of amyloid precursor protein (NAPP). The model provides a coherent and satisfying framework for better understanding AD pathophysiology. Moreover, the DR6-NAPP interaction offers a tempting target for novel pharmacological intervention. Given all of this, we constructed a structural model of the DR6-NAPP interaction using the neurotrophin p75 receptor as a template. Importantly, crucial steps in the modeling pipeline were independently validated using the p75 receptor. The final docked model shows excellent agreement with a variety of biophysical and theoretical data sets. Particularly worth noting is the excellent observed agreement between the theoretically calculated DR6-NAPP binding free energy and the corresponding experimental quantity. In brief, the balance of the evidence suggests that the DR6-NAPP model proposed here should prove useful in future studies, modeling work and efforts aimed at structure-based drug design.
CDAO-Store: A New Vision in Data Integration
Authors: Chisham Brandon , Le Trung , Pontelli Enrico , Son Tran , Wright Ben
Published: July 2019

The Comparative Data Analysis Ontology (CDAO) 1 is an ontology developed, as part of the EvoInfo2 and EvoIO3 groups supported by NESCent4, to provide semantics to the descriptions of data and transformations commonly found in the domain of phylogenetic inference. The core concepts of the ontology enables the description of phylogenetic trees and associated character data matrices.
Diffusion Approximations for Demographic Inference: DaDi
Authors: Gutenkunst Ryan , Hernandez Ryan , Williamson Scott , Bustamante Carlos
Published: July 2019

Models of demographic history (population sizes, migration rates, and divergence times) inferred from genetic data complement archeology and serve as null models in genome scans for selection. Most current inference methods are computationally limited to considering simple models or non-recombining data. We introduce a method based on a diffusion approximation to the joint frequency spectrum of genetic variation between populations. Our implementation, DaDi, can model up to three interacting populations and scales well to genome-wide data. We have applied DaDi to human data from Africa, Europe, and East Asia, building the most complex statistically well-characterized model of human migration out of Africa to date.
Waist Circumference predicting Cardiovascular Disease in Korean Men and Women
Authors: Jee Sun Ha , Park Sat Byul
Published: July 2019

Objective:

Obesity and cardiovascular disease (CVD) are closely related and have become increasingly prevalent in Korea. Asians are more prone to obesity-related co-morbidities than Caucasians, even at lower body mass index (BMI) and/or smaller waist circumference (WC) values. Nevertheless, little is known regarding the association of WC with the risk of CVD in non-Caucasian populations. The authors conducted a prospective cohort study of WC and the risk of CVD in the Korean Heart Study.

Methods:

We examined the association of WC to CVD incidence among 53,026 Korean adults (30,152 men, 22,874 women) with no history of CVD and/or cancer. During a mean follow-up of 8.6 years, 2,722 incident cases of atherosclerotic cardiovascular disease (ASCVD) including 1,383 cases of ischemic heart disease (IHD) and 1,012 cases of stroke were documented. Results: Average WC at baseline was 84.0&177;8.2 cm in men and 75.2&177;8.9 cm in women. After adjustment for age and BMI, WC was significantly associated with cardiovascular risk factors (P <.001). In men, a WC of &8805;91 cm was associated with an ASCVD hazard ratio (HR) of 1.62 (95% confidence interval (CI): 1.25, 2.10) and an IHD HR of 1.70 (95% CI: 1.19, 2.42) in comparison with a WC of <78 cm even after further adjustment for BMI and traditional risk factors (P for trend = 0.0118, 0.0139 respectively). In women, the progressive associations of WC with ASCVD, IHD and stroke were observed. These associations were however attenuated after further adjustment for BMI and traditional risk factors. The multivariable HRs for ASCVD, IHD, and stroke increased with higher WC in both men and women.

Conclusions:

Central obesity significantly and independently contributes to cardiovascular outcomes in Korean men and women.
The Inhibitory Fc[gamma] Receptor is Unnecessary for IVIG Efficacy
Authors: Leontyev Danila , Katsman Yulia , Ma Xue-Zhong , Branch Donald
Published: July 2019

Intravenous gamma globulin (IVIG) is used as an effective therapy for many different autoimmune and inflammatory diseases. The current paradigm for the mechanism underpinning anti-inflammatory effects links IVIG administration to increased expression and activity of the inhibitory Fc[gamma] receptor (Fc[gamma]RIIB) on splenic macrophages. This hypothesis has been disputed in the literature. Here we show that IVIG administered in the context of passive antibody-mediated thrombocytopenia to be therapeutically efficacious in both splenectomized and unmanipulated Balb/c mice despite no upregulation of Fc[gamma]RIIB mRNA in the spleen. Moreover, IVIG effectively ameliorated immune thrombocytopenia (ITP) in Fc[gamma]RIIB-deficient Balb/c mice, but not in Fc[gamma]RIIB-/- or Fc[gamma]RIIB+/+ control mice with a C57BL6/129S background. Our results demonstrate that Fc[gamma]RIIB is not relevant to the beneficial effects of IVIG. We anticipate that investigators will now shift their research focus away from Fc[gamma]RIIB and seek out other possible mechanism(s) to explain the plethora of diseases and conditions treatable with IVIG.
The Gramene Genetic Diversity Module: a resource for genotype-phenotype association analysis in grass species
Authors: Chen Charles , DeClerck Genevieve , Casstevens Terry , Youens-Clark Ken , Zhang Jon , Ware Doreen , Jaiswal Pankaj , McCouch Susan , Buckler Edward
Published: July 2019

The Genetic Diversity module of the Gramene database ("http://www.gramene.org/diversity":http://www.gramene.org/diversity) is specifically designed to handle data from high-throughput sequencing and array-based genotyping plateforms. Empowered by the Genomic Diversity and Phenotype Data Model, Gramene Genetic Diversity module provides live database connectivities of RFLP, SSR and SNP allele data, information about QTL, passport data for wild and cultivated germplasm from rice, maize, wheat, and Arabidopsis, and quantitative phenotypic data for some of these accessions. Large datasets of SNP variation are searchable via genomic positions of interest by SNP Query tool on a sequenced genome; and, trait associations, patterns of linkage disequilibrium and diversity can be evaluated using TASSEL. The Gramene database is updated twice a year, with the most recent release (Build 31) completed in May 2010.
Solving the protein folding problems
Authors: Bywater Robert
Published: July 2019

The protein folding problem persists in being the major unsolved problem in biophysics and molecular biology. The most immediate obstacle to its solution is said to be the immense combinatorial difficulty of finding the global minimum energy structure, due to the galactic number of possible rotamer states for the polypeptide backbone and its sidechains, the so-called Levinthal paradox1. Much attention has been paid to the topography of the free energy surface that the folding polypeptide has to negotiate in order to find this minimum and the notion of a funnel-shaped topography has been proposed2. While this has achieved wide acceptance, providing insight into the possible shape of the free energy surface, it still does not solve the problem. In this work it is suggested that, in order to proceed further with this line of enquiry, it would be useful to focus on not one but, rather, two of the free energy minima accessible to the folding polypeptide. These two minima are considered to represent the active and inactive, or resting, states of the protein. There is experimental evidence for this model and a well populated database of structures that is analysed in detail in this work.
Single gene-based distinction of individual microbial genomes from a mixed population of microbial cells
Authors: Tamminen Manu , Virta Marko
Published: July 2019

Background:

Recent progress in environmental microbiology has revealed vast populations of microbes in any given habitat that cannot be detected by conventional culturing strategies. The use of sensitive genetic detection methods such as CARD-FISH and in situ PCR have been limited by the cell wall permeabilization requirement that cannot be performed similarly on all cell types without lysing some and leaving some unpermeabilized. Furthermore, the detection of low copy targets such as genes present in single copies in the microbial genomes, has remained problematic.

Methodology/Principal Findings:

We describe an emulsion-based procedure to trap individual microbial cells into picoliter-volume polyacrylamide droplets that provide a support for genetic material and therefore allow degradation of cellular material to expose the individual genomes. The polyacrylamide droplets are subsequently converted into picoliter-scale reactors for genome amplification. The amplified genomes are labelled based on the presence of a target gene and differentiated from those that do not contain the gene by flow cytometry. Using the Escherichia coli strains XL1 and MC1061, which differ with respect to the presence (XL1) or absence (MC1061) of a single copy of a tetracycline resistance gene per genome, we demonstrate that XL1 genomes present at 0.01% of MC1061 genomes can be differentiated using this method. Using a spiked sediment microbial sample, we demonstrate that the method is applicable to complex environmental microbial communities as a target gene-based screen for individual microbes.

Conclusions/Significance:

The genomic support for complete cell degradation allows an exposure of individual genomes of environmental bacteria. The genome exposure followed by genome amplification and labelling combines the benefits of in situ-PCR and FISH methods and permits the detection cells with single copy chromosomal targets in complex mixtures of microbial cells. The method could be optimized for fluorescence-activated cell sorting to enrich genetic material of interest from complex environmental samples.
From Blood Oxygenation Level Dependent (BOLD) signals to brain temperature maps
Authors: Sotero Roberto C , Iturria-Medina Yasser
Published: July 2019

A theoretical framework is presented for converting Blood Oxygenation Level Dependent (BOLD) images to temperature maps, based on the idea that disproportional local changes in cerebral blood flow (CBF) as compared with cerebral metabolic rate of oxygen consumption (CMRO2) during functional brain activity, lead to both brain temperature changes and the BOLD effect. Using an oxygen limitation model and a BOLD signal model we obtain a transcendental equation relating CBF and CMRO2 changes with the corresponding BOLD signal, which is solved in terms of the Lambert W function. Inserting this result in the dynamic bio-heat equation describing the rate of temperature changes in the brain, we obtain a non autonomous ordinary differential equation that depends on the BOLD response, which is solved numerically for each brain voxel. In order to test the method, temperature maps obtained from a real BOLD dataset are calculated showing temperature variations in the range: (-0.15, 0.1) which is consistent with experimental results. The method could find potential clinical uses as it is an improvement over conventional methods which require invasive probes and can record only few locations simultaneously. Interestingly, the statistical analysis revealed that significant temperature variations are more localized than BOLD activations. This seems to exclude the use of temperature maps for mapping neuronal activity as areas where it is well known that electrical activity occurs (such as V5 bilaterally) are not activated in the obtained maps. But it also opens questions about the nature of the information processing and the underlying vascular network in visual areas that give rise to this result.
Host Genetics and Viral Diversity: Report from a Global HIV Vaccine Enterprise Working Group
Authors: McMichael Andrew , McCutchan Francine , Working Group convened by the Globa the
Published: July 2019

The Global HIV Vaccine Enterprise convened a workshop in September 2009 to discuss human and viral genetic variation and its impact on future directions for HIV vaccine research and development. The formidable challenges presented by virus and host genetic variability are interrelated and complicate vaccine development. HIV vaccine researchers need to develop innovative approaches that will facilitate addressing these questions in novel ways.
Inactivation of the Retinoblastoma Protein by Mutant B-Raf in Malignant Melanoma
Authors: Kusano Eiji , Murata Satoru , Ohtsuki Mamitaro , Furukawa Yusuke , Kobayashi Yukiko , Kobayashi Takahisa , Kikuchi Jiro , Wada Taeko , Futaki Ken
Published: July 2019

Although activating mutations of B-Raf are the most common genetic abnormalities in human melanomas, the mechanism by which mutant B-Raf transforms melanocytes is poorly understood. Here we show that the retinoblastoma tumor suppressor protein (pRB) is a direct target of B-Raf and is inactivated by phosphorylation in melanomas carrying B-Raf mutations. In contrast, pRB is undetectable in melanomas with wild-type B-Raf. Mutant B-Raf directly interacts with pRB and induces its phosphorylation at serine-249 and threonine-252 (S249/T252). Inhibition of B-Raf activity results in dephosphorylation of pRB at S249/T252 along with other sites in melanoma cells. S249/T252 are phosphorylated earlier than other sites during cell cycle entry of normal melanocytes. Blocking B-Raf activation precluded S249/T252 phosphorylation in mitogen-stimulated melanocytes, which was accompanied by the impaired phosphorylation of pRB at other sites. B-Raf enhanced CDK2-mediated pRB phosphorylation in an in vitro kinase assay. These results suggest that B-Raf is an initiating RB kinase, which triggers inactivation of pRB at the earliest step in the cell cycle entry of normal melanocytes, and its activating mutations cause deregulated growth, leading to the development of melanoma.
A theory for the tissue specificity of BRCA1/2 related and other hereditary cancers
Authors: Friedenson Bernard
Published: July 2019

Women who inherit a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. All these suggestions share the assumption that some disabled function of normal tumor suppressor genes leads to a tissue specific cancer response. Here the idea is proposed and tested that major determinants of where BRCA1/2 hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to an inflammatory process or to a carcinogen such as during digestion, metabolism or elimination. An innate genomic deficit in a tumor suppressor gene impairs normal responses to these extrinsic challenges and exacerbates the susceptibility to disease in organ targets. This hypothesis also fits data for several tumor suppressors beyond BRCA1/2. A major advantage of this model is that it suggests there may be some options in addition to prophylactic surgery.
Membrane repair against H. pylori promotes cancer cell proliferation
Authors: Lin Li-Ling , Huang Hsuan-Cheng , Ogihara Satoshi , Wang Jin-Town , Chen Chiung-Nien , Juan Hsueh-Fen
Published: July 2019

Membrane repair is a universal response against physical and biological insults and enables cell survival. Helicobacter pylori is one of the most common human pathogens and the first formally recognized bacterial carcinogen associated with gastric cancer. However, little is known about host membrane repair in the context of H. pylori infection. Here we show that H. pylori disrupts the host plasma membrane and induces Ca2+ influx, which triggers the translocation of annexin family members A1 and A4 to the plasma membrane. This in turn activates a membrane repair response through the recruitment of lysosomal membranes and the induction of downstream signaling transduction pathways that promote cell survival and proliferation. Based on our data, we propose a new model by which H. pylori infection activates annexin A1 and A4 for membrane repair and how annexin A4 over-expression induced signaling promotes cell proliferation. Continual activation of this membrane repair response signaling cascade may cause abnormal cellular states leading to carcinogenesis. This study links H. pylori infection to membrane repair, providing insight into potential mechanisms of carcinogenesis resulting from membrane damage.
Universal fractal scaling of self-organized networks
Authors: Laurienti Paul , Joyce Karen , Telesford Qawi , Burdette Jonathan , Hayasaka Satoru
Published: July 2019

There is an abundance of literature on complex networks describing a variety of relationships among units in social, biological, and technological systems. Such networks, consisting of interconnected nodes, are often self-organized, naturally emerging without any overarching designs on topological structure yet enabling efficient interactions among nodes. Here we show that the number of nodes and the density of connections in such self-organized networks exhibit a power law relationship. We examined the size and connection density of 46 self-organizing networks of various biological, social, and technological origins, and found that the size-density relationship follows a fractal relationship spanning over 6 orders of magnitude. This finding indicates that there is an optimal connection density in self-organized networks following fractal scaling regardless of their sizes.
Isolation And Characterization Of Soil Microbes Of Shekhawati Region, Rajasthan
Authors: Tyagi Abhinav , Bajpai Vivek , Gupta V.K. , Gautam H.K.Gautam , Gaur Rajarshi Kumar
Published: July 2019

Bacteria are widely distributed and abundant in soils, but their ecological roles are poorly understood, owing in part to a paucity of cultured representatives. In a molecular survey at the Mody institute of Technology and science, Lakshmangarh, Sikar we isolated two microbes from soils using a biochemical and molecular methods. The isolates were sequenced by 16S rDNA, and designated as Pseudomonas sp. RK05 (HQ009799) and Uncultured gamma proteobacterium clone RK 04 (HQ009800). Results confirmed the hazardous effects of pollution on the distribution and biodiversity of soil microorganisms where most of the native beneficial microorganisms were disappeared or non-cultured under these stressed conditions compared to the normal non-polluted soils in the same governorate which is certainly affecting soil fertility and productivity. Results also proved the efficiency of molecular characterization as precise and fast techniques for determining soil biodiversity compared to the traditional cultivation methods.
Essay: On the close relationship between speciation, inbreeding and recessive mutations.
Authors: Joly Etienne
Published: July 2019

Whilst the principle of adaptive evolution is unanimously recognised as being caused by the process of natural selection favouring the survival and/or reproduction of individuals having acquired new advantageous traits, a consensus has proven much harder to find regarding the actual origin of species. Indeed, since speciation corresponds to the establishment of reproductive barriers, it is difficult to see how it could bring a selective advantage because it amounts to a restriction in the opportunities to breed with as many and/or as diverse partners as possible. In this regard, Darwin himself did not believe that reproductive barriers could be selected for, and today most evolutionary biologists still believe that speciation can only occur through a process of separation allowing two populations to diverge sufficiently to become infertile with one another. I do, however, take the view that, if so much speciation has occurred, and still occurs around us, it cannot be a consequence of passive drift but must result from a selection process, whereby it is advantageous for groups of individuals to reproduce preferentially with one another and reduce their breeding with the rest of the population.In this essay, I propose a model whereby new species arise by “budding” from an ancestral stock, via a process of inbreeding among small numbers of individuals, driven by the occurrence of advantageous recessive mutations. Since the phenotypes associated to such mutations can only be retained in the context of inbreeding, it is the pressure of the ancestral stock which will promote additional reproductive barriers, and ultimately result in complete separation of a new species. I thus contend that the phenomenon of speciation would be driven by mutations resulting in the advantageous loss of certain functions, whilst adaptive evolution would correspond to gains of function that would, most of the time be dominant.A very important further advantage of inbreeding is that it reduces the accumulation of recessive mutations in genomes. A consequence of the model proposed is that the existence of species would correspond to a metastable equilibrium between inbreeding and outbreeding, with excessive inbreeding promoting speciation, and excessive outbreeding resulting in irreversible accumulation of recessive mutations that could ultimately only lead to the species extinction.
Expanding the modern synthesis II: Formal perspectives on the inherent role of niche construction in fitness
Authors: Wallace Rodrick
Published: July 2019

Expanding the modern synthesis requires elevating the role of interaction within and across various biological scales to the status of an evolutionary principle. One way to do this is to characterize genes, gene expression, and embedding environment as information sources linked by crosstalk, constrained by the asymptotic limit theorems of information theory (Wallace, 2010a). This produces an inherently interactive structure that escapes the straightjacket of mathematical population genetics or other replicator dynamics. Here, we examine fitness from that larger perspective, finding it intimately intertwined with niche construction. Two complementary models are explored: niche construction as mediating the connection between environmental signals and gene expression, and as a means of tuning the channel for the transmission of genetic information in a noisy environment. These are different views of the same elephant, in a sense, seen as simplified projections down from a larger dynamic system.
Effects of surface passivation on gliding motility assays
Authors: Maloney Andy , Herskowitz Lawrence , Koch Steven
Published: July 2019

In this study, we report differences in the observed gliding speed of microtubules dependent on the choice of bovine casein used as a surface passivator. We observed differences in both speed and support of microtubules in each of the assays. Whole casein, comprised of [alpha]~s1~, [alpha]~s2~, [beta], and [kappa] casein, supported motility and averaged speeds of966 ± 7 nm/s. Alpha casein can be purchased as a combination of s1 and s2 and supported gliding motility and average speeds of 949 ± 4 nm/s. Beta casein did not support motility very well and averaged speeds of 870 ± 30 nm/s. Kappa casein supported motility very poorly and we were unable to obtain an average speed. Finally,we observed that mixing alpha, beta, and kappa casein with the proportions found in bovine whole casein supported motility and averaged speeds of 966 ± 7 nm/s.
Study of Molecular Mechanism of Antibiotic susceptibility against Polymicrobial Oral infection
Authors: Dwivedi Deepak
Published: July 2019

Abstract Introduction- Antibiotic to treat dental caries infection are routinely prescribed. Bacteria have increased resistance to the currently recommended antibiotics. The purpose of this investigation was to perform antibiotic susceptibility on a panel pathogenic strain of bacteria isolated step by step from dental caries infection.

Materials and Methods

-Bacteria were isolated from caries site of patients and cultivated identified at the species level. Each of 150 species of bacteria was tested for antibiotics susceptibility to a five antibiotics using Etest. Antibiotic used were Amoxicillin, Cloxocillin, Erythromycin, Tetracycline, Penicillin-V.

Results

- The percentages of Resistance in treatment for each antibiotic in this study were penicillin V: 72/150 (48%), Tetracycline: 99/150 (66%), amoxicillin: 135/150 (90%), Cloxocillin: 117/150 (78%), and Erythromycin: 90/150 (60%) (Table 1). If combination antibiotic therapy had been used to treat the bacteria isolated from dental caries, the percentage of Resistance for the combination of penicillin V/Amoxicillin would have been 39/150 (26%), and the combination of amoxicillin/ Erythromycin would have been 45/150 (30%).

Conclusion

- This study demonstrated the Molecular Mechanism of antibiotic resistance and susceptibility pattern, of bacteria causing dental caries. The comprehensive results data obtained will allow in investigating spatial distribution of pathogenic antibiotic resistant bacteria in patients of dental caries. In turn this will allow the development of novel diagnostic and treatment methods.
Evolution as a language that speaks itself
Authors: Wallace Rodrick
Published: July 2019

The 'self-referential' character of evolutionary process noted by Goldenfeld and Woese (2010) can be restated through a 'language' model in which genes, gene expression, and environment are represented as interacting information sources. The larger, composite, source that characterizes the high probability evolutionary paths then becomes, in a real sense, a language that speaks itself. The approach represents a significant extension of nonequilibrium condensed matter formalism in which the asymptotic limit theorems of information theory beat back the mathematical thicket a full step, providing necessary, but not sufficient, conditions for punctuated evolutionary transitions that can themselves be expressed as highly structured large deviations having their own grammar and syntax.
A Note On The Denisova Cave mtDNA Sequence
Authors: Caldararo Niccolo
Published: July 2019

The recently published Altai fossil sequence from Denisova Cave was purported to be so different from anatomically modern humans, yet have the physiological landmarks of that species designation. When the published sequence was examined it was found that segments in the mtDNA hypervariable regions could be found to align with that of anatomically modern humans if one introduced an insertion at a position found in Neanderthals. Some other points of interest arise from a reconsideration of the sequences for other published samples and Neanderthals from the same perspective.
Allelic Frequency of ABO And Rh D Blood Group Among The Banjara Backward Caste of Yavatmal District, Maharashtra , India
Authors: Chavhan Aravind , Pawar Santosh , Baig Mumtaz
Published: July 2019

The distribution of ABO blood groups and Rh(D) factor has been studied among the Banjara of Backward population of Yavatmal (Maharashtra). The A, B, O and AB blood group percentage were recorded as 24.54%, 33.82%, 29.64% and 12% respectively. The allele frequencies of O, A, B and AB groups in the combined data were found to be 0.5354, 0.2022 and 0.2624 respectively. The distribution of Rh(D) group varies among the ABO blood groups. The Rh(D) positive allelic frequency was 0.8405 and the Rh(D) negative incidence was recorded as 02.55% in the studied population.
The proatherosclerotic function of indoleamine 2, 3-dioxygenase 1 in the developmental stage of atherosclerosis
Authors: Liang Heng , Chen Mantian , Qi Fangfei , Shi Lei , Duan Zhenzhen , Yang Ruoyu , He Jinchao , Lou Bin , Li Yigang , Yang Qing
Published: July 2019

The discrepancy of indoleamine 2, 3-dioxygenase 1 (IDO1) function in atherosclerosis has been noted. Compared to the protective effect of IDO1 against established atherogenesis, the role of IDO1 in the developmental process of atherosclerosis is still unclear. Here, the expression patterns and activities of IDO1 and its isoenzyme tryptophan 2,3-dioxygenase (TDO) in aortas and blood samples of patients with atherosclerosis were investigated. IDO1 and TDO were colocalized with CD3-positive lymphocytes and CD68-positive macrophages in atherosclerotic lesions. The expression and activity of IDO1 and TDO increased with the grade of the histological classification in early atherosclerosis (grade I, II), but the increase did not continue in advanced atherosclerosis (grade III). Treatment of THP-1 macrophages (THP-M) with oxidized low-density lipoprotein (oxLDL) induced the expression of IDO1 via the PI3K/Akt/NF-κB pathway, indicating the potential function of IDO1 in foam cells. Before and after treatment with oxLDL on THP-M, IFN-γ-induced IDO1 exhibited different degrees of promotion on foaming, inflammatory factor production and cell apoptosis. Finally, we found that the IDO1 inhibitor 1-methyl-tryptophan could elevate the high-density lipoprotein cholesterol level in serum and reduce the area of the aortic atherosclerotic lesions in high-fat diet-fed ApoE−/−mice. Our study indicated that IDO1 played a complicated and unfixed role in the entire process of atherogenesis, despite the atheroprotective role in established atherosclerosis. IDO1 also had proatherosclerotic functions in the developmental stages of atherosclerosis. Modulation of IDO1 could be a good method for alleviating atherosclerosis.
Hypoxia inducible factor 1α in vascular smooth muscle cells promotes angiotensin II-induced vascular remodeling via activation of CCL7-mediated macrophage recruitment
Authors: Qi Dan , Wei Ming , Jiao Shiyu , Song Yanting , Wang Xia , Xie Guomin , Taranto Joseph , Liu Ye , Duan Yan , Yu Baoqi , Li Huihua , Shah Yatrik M. , Xu Qingbo , Du Jie , Gonzalez Frank J. , Qu Aijuan
Published: July 2019

The process of vascular remodeling is associated with increased hypoxia. However, the contribution of hypoxia-inducible factor 1α (HIF1α), the key transcription factor mediating cellular hypoxic responses, to vascular remodeling is established, but not completely understood. In the angiotensin II (Ang II)-induced vascular remodeling model, HIF1α was increased and activated in vascular smooth muscle cells (VSMCs). Selective genetic disruption of Hif1a in VSMCs markedly ameliorated Ang II-induced vascular remodeling, as revealed by decreased blood pressure, aortic thickness, collagen deposition, inflammation, and aortic stiffness. VSMC Hif1a deficiency also specifically suppressed Ang II-induced infiltration of CD45+CD11b+F4/80+CD206− M1 macrophages into the vessel. Mechanistically, HIF1α deficiency in VSMCs dramatically suppressed the expression of CCL7, a chemokine critical for macrophage recruitment. Bioinformatic analysis and chromatin immunoprecipitation assays revealed three functional hypoxia-response elements in the Ccl7 promoter, indicating that Ccl7 is a direct HIF1α target gene. Blocking CCL7 with antibody in vivo alleviated Ang II-induced hypertension and vascular remodeling, coincident with decreased macrophage infiltration. This study provides direct evidence that HIF1α activation in VSMCs exacerbates Ang II-induced macrophage infiltration and resultant vascular remodeling via its target gene Ccl7, and thus may serve as a potential therapeutic target for remodeling-related vascular disease.
Amino acid-induced regulation of hepatocyte growth: possible role of Drosha
Authors: Fabris Gaia , Dumortier Olivier , Pisani Didier F. , Gautier Nadine , Van Obberghen Emmanuel
Published: July 2019

In an adult healthy liver, hepatocytes are in a quiescent stage unless a physical injury, such as ablation, or a toxic attack occur. Indeed, to maintain their crucial organismal homeostatic role, the damaged or remaining hepatocytes will start proliferating to restore their functional mass. One of the limiting conditions for cell proliferation is amino-acid availability, necessary both for the synthesis of proteins important for cell growth and division, and for the activation of the mTOR pathway, known for its considerable role in the regulation of cell proliferation. The overarching aim of our present work was to investigate the role of amino acids in the regulation of the switch between quiescence and growth of adult hepatocytes. To do so we used non-confluent primary adult rat hepatocytes as a model of partially ablated liver. We discovered that the absence of amino acids induces in primary rat hepatocytes the entrance in a quiescence state together with an increase in Drosha protein, which does not involve the mTOR pathway. Conversely, Drosha knockdown allows the hepatocytes, quiescent after amino-acid deprivation, to proliferate again. Further, hepatocyte proliferation appears to be independent of miRNAs, the canonical downstream partners of Drosha. Taken together, our observations reveal an intriguing non-canonical action of Drosha in the control of growth regulation of adult hepatocytes responding to a nutritional strain, and they may help to design novel preventive and/or therapeutic approaches for hepatic failure.
Multilayered spraying and gradient dotting of nanodiamond–polycaprolactone guidance channels for restoration of immune homeostasis
Authors: Qian Yun , Cheng Yuan , Ouyang Yuanming , Yuan Wei-En , Fan Cunyi
Published: July 2019

The major problem in peripheral nerve repair is restoration of the microenvironment rather than traditional structural reconstruction. Nanodiamonds (NDs), highly biocompatible carbon nanoparticles, are widely applied in medical engineering. They may alleviate inflammatory insults in peripheral nerve injury because they can induce macrophage polarization from a proinflammatory to an anti-inflammatory state. Here we report a concentric multilayered spraying manufacturing process to fabricate microporous ND/polycaprolactone (PCL) nerve bridges. We investigated the proliferative, adhesive, and glioprotective role of these bridges in Schwann cells in vitro. We further evaluated their long-term in vivo performance in a 20-mm sciatic nerve defect rat model. ND/PCL nerve bridges are comparable to autografts in functional, electrophysiological, and morphological sciatic nerve repair. They ameliorate the immune milieu by inducing M1 to M2 macrophage polarization. In addition, they pose no harm to major organs after 4 months of implantation. These findings show the promising roles of ND-based nanotechnology in neuroengineering.
Publisher Correction: Claudin-3-deficient C57BL/6J mice display intact brain barriers
Authors: Dias Mariana Castro , Coisne Caroline , Lazarevic Ivana , Baden Pascale , Hata Masaki , Iwamoto Noriko , Francisco David Miguel Ferreira , Vanlandewijck Michael , He Liqun , Baier Felix A. , Stroka Deborah , Bruggmann Rémy , Lyck Ruth , Enzmann Gaby , Deutsch Urban , Betsholtz Christer , Furuse Mikio , Tsukita Shoichiro , Engelhardt Britta
Published: July 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Phase and amplitude imaging with quantum correlations through Fourier Ptychography
Authors: Aidukas Tomas , Konda Pavan Chandra , Harvey Andrew R. , Padgett Miles J. , Moreau Paul-Antoine
Published: July 2019

Extracting as much information as possible about an object when probing with a limited number of photons is an important goal with applications from biology and security to metrology. Imaging with a few photons is a challenging task as the detector noise and stray light are then predominant, which precludes the use of conventional imaging methods. Quantum correlations between photon pairs has been exploited in a so called ‘heralded imaging scheme’ to eliminate this problem. However these implementations have so-far been limited to intensity imaging and the crucial phase information is lost in these methods. In this work, we propose a novel quantum-correlation enabled Fourier Ptychography technique, to capture high-resolution amplitude and phase images with a few photons. This is enabled by the heralding of single photons combined with Fourier ptychographic reconstruction. We provide experimental validation and discuss the advantages of our technique that include the possibility of reaching a higher signal to noise ratio and non-scanning Fourier Ptychographic acquisition.
Speech, movement, and gaze behaviours during dyadic conversation in noise
Authors: Hadley Lauren V. , Brimijoin W. Owen , Whitmer William M.
Published: July 2019

How do people have conversations in noise and make themselves understood? While many previous studies have investigated speaking and listening in isolation, this study focuses on the behaviour of pairs of individuals in an ecologically valid context. Specifically, we report the fine-grained dynamics of natural conversation between interlocutors of varying hearing ability (n = 30), addressing how different levels of background noise affect speech, movement, and gaze behaviours. We found that as noise increased, people spoke louder and moved closer together, although these behaviours provided relatively small acoustic benefit (0.32 dB speech level increase per 1 dB noise increase). We also found that increased noise led to shorter utterances and increased gaze to the speaker’s mouth. Surprisingly, interlocutors did not make use of potentially beneficial head orientations. While participants were able to sustain conversation in noise of up to 72 dB, changes in conversation structure suggested increased difficulty at 78 dB, with a significant decrease in turn-taking success. Understanding these natural conversation behaviours could inform broader models of interpersonal communication, and be applied to the development of new communication technologies. Furthermore, comparing these findings with those from isolation paradigms demonstrates the importance of investigating social processes in ecologically valid multi-person situations.