bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA^+Pro^: an Improved Progressive Multiple Sequence Alignment Algorithm for Evolutionary Analysis Using Combined DNA-Protein Sequences
Authors: Wang Xiaolong , Xu Shuang-yong , Gou Deming
Published: July 2019

Alignment of DNA and protein sequences is a basic tool in the study of evolutionary, structural and functional relationship among macromolecules. Present sequence alignment methods are somewhat error-prone, often producing systematic bias. Errors in sequence alignments sometimes lead to subsequent misinterpretation of evolutionary, structural and functional information in genes, proteins and genomes. In traditional sequence alignment algorithms, alignments of DNA and protein sequences are conducted separately. It has been long believed that the phylogenetic signal disappears more rapidly from DNA sequences than from encoded proteins. It is therefore generally preferable to align sequences at the amino acid level. Here we present a new method—DNA^+Pro^, which aggregates DNA and protein sequences into combined DNA-protein sequences and align them in a combined fashion. We demonstrate that combining sequences improve the quality of multiple sequence alignment and solve practical evolutionary problems in primate immunodeficiency virus proteins and bacterial restriction enzymes. In addition to increased theoretical information contents, the distance estimations are more biological significant in combined alignment than in protein only or DNA only alignments. By integrating information buried separately in DNA and protein sequences, DNA^+Pro^ improves the accuracy of multiple sequence alignment of closely-related proteins and prevents certain errors that may occur in phylogeny analysis using protein only approaches. The DNA^+Pro^ software and the supplementary data are downloadable free of charge from "our website, http://www.dnapluspro.com":http://www.dnapluspro.com.
Tracing blastomere fate choices of early embryos in single cell culture
Authors: Li Mingyou , Song Jianxin , Yan Yan , Yuan Yongming , Li Chang Ming , Hong Yunhan , Zhao Haobin , Hong Ni , Li Zhendong , Yi Meisheng , Ge Ruowen , Liu Rong
Published: July 2019

Blastomeres of early vertebrate embryos undergo numerous fate choices for division, motility, pluripotency maintenance and restriction culminating in various cell lineages. Tracing blastomere fate choices at the single cell level in vitro has not been possible because of the inability to isolate and cultivate early blastomeres as single cells. Here we report the establishment of single cell culture system in the fish medaka, enabling the isolation and cultivation of individual blastomeres from 16- to 64-cell embryos for fate tracing at the single cell level in vitro. Interestingly, these blastomeres immediately upon isolation exhibit motility, lose synchronous divisions and even stop dividing in &8805;50% cases, suggesting that the widely accepted nucleocytoplasmic ratio controlling synchronous divisions in entire embryos does not operate on individual blastomeres. We even observed abortive division, endomitosis and cell fusion. Strikingly, ~5% of blastomeres in single cell culture generated extraembryonic yolk syncytial cells, embryonic stem cells and neural crest-derived pigment cells with timings mimicking their appearance in embryos. We revealed the maternal inheritance of key lineage regulators and their differential expression in cleavage embryos. Therefore, medaka blastomeres possess the accessibility for single cell culture, previously unidentified heterogeneity in motility, division, gene expression and intrinsic ability to generate major extraembryonic and embryonic lineages without positioning cues. Our data demonstrate the fidelity and potential of the single cell culture system for tracking blastomere fate decisions under defined conditions in vitro.
Chronic Morbilliviral Encephalitis in a Young Striped Dolphin from Italy
Authors: Eleni Claudia , Di Guardo Giovanni , Cocumelli Cristiano , Scholl Francesco , Di Francesco Cristina Esmeralda , Speranza Roberto , Pennelli Massimiliano
Published: July 2019

A young male striped dolphin (Stenella coeruleoalba) found stranded in November 2009 was affected by a chronic non-suppurative encephalitis, with prominent mononuclear cell perivascular cuffs, neuronal degeneration, microgliosis, neuronophagia and occasional presence of multinucleate syncytia. Immunohistochemical and biomolecular investigations for Morbillivirus were positive exclusively from the brain, but not from the cerebellum nor from any other tissue, with morbilliviral antigen being detected in neurons and astrocytes. A low neutralizing antibody titer (1:10) against Morbillivirus (CDV) was also found, with no simultaneous presence of anti-Brucella antibodies.The main reason why the present case appears to be of interest is provided by its peculiar neuro-histopathologic, immunohistochemical and biomolecular features, with Morbillivirus antigenic and genomic positivity being exclusively confined to the brain of this dolphin, which may have developed a transplacentally-acquired infection.
Genome-wide comparison of cyanobacterial transposable elements, potential genetic diversity indicators
Authors: Lin Shen , Haas Stefan , Zemojtel Tomasz , Xiao Peng , Vingron Martin , Li Renhui
Published: July 2019

Background:

Transposable elements are widely distributed in archaea, bacteria and eukarya domains. Considerable discrepancies of transposable elements in eukaryotes have been reported; however, the studies focusing on the diversity of transposable systems in prokaryotes were scarce. Understanding the transposable element system in cyanobacteria by the genome-wide analysis will greatly improve the knowledge of cyanobacterial diversity.

Results:

In this study, the transposable elements of seventeen cyanobacterial genomes were analyzed. The abundance of insertion sequence (IS) elements differs significantly among the cyanobacterial genomes examined. In particular, water bloom forming Microcystis aeruginosa NIES843 was shown to have the highest abundance of IS elements reaching 10.95% of the genome. IS family is a widely acceptable IS classification unit, and IS subfamily, based on probe sequences, was firstly proposed as the basic classification unit for IS element system. Both of IS family and IS subfamily were set as the two hierarchical units for evaluating the IS element system diversity. Totally, 1982 predicted IS elements, within 21 IS families and 133 subfamilies were identified in the examined cyanobacterial genomes. Families IS4, IS5, IS630 and IS200-605 are widely distributed, and therefore supposed to be the ancestral IS families. Analysis on the intactness of IS elements showed that the percentage of the intact IS differs largely among these cyanobacterial strains. Higher percentage of the intact IS detected in the two hot spring cyanobacterial strains implied that the intactness of IS elements may be related to the genomic stabilization of cyanobacteria inhabiting in the extreme environments. The frequencies between IS elements and miniature inverted-repeat transposable elements (MITEs) were shown to have a linear positive correlation.

Conclusions:

The transposable element system in cyanobacterial genomes is of hypervariabilty. With characterization of easy definition and stability, IS subfamily is considered as a reliable classification unit in IS element system. The abundance of intact IS, the composition of IS families and subfamilies, the sequence diversity of IS element nucleotide and transposase amino acid are informative and suitable as the indicators for studies on cyanobacterial diversity. Practically, the transposable system may provide us a new perspective to realize the diversity and evolution of populations of water bloom forming cyanobacterial species.
Finding scientific articles in a large digital archive: BioStor and the Biodiversity Heritage Library
Authors: Page Roderic
Published: July 2019

The Biodiversity Heritage Library (BHL) is a large digital archive of legacy biological literature, comprising over 31 million pages scanned from books, monographs, and journals. During the digitisation process basic metadata about the scanned items is recorded, but not article-level metadata. Given that the article is the standard unit of citation, this makes it difficult to locate cited literature in BHL. Adding the ability to easily find articles in BHL would greatly enhance the value of the archive. A service was developed to locate articles in BHL based on matching article metadata to BHL metadata using approximate string matching, regular expressions, and string alignment. This article finding service is exposed as a standard OpenURL resolver on the BioStor web site "http://biostor.org/openurl/":http://biostor.org/openurl/. This resolver can be used on the web, or called by bibliographic tools that support OpenURL. BioStor provides tools for extracting, annotating, and visualising articles from the Biodiversity Heritage Library. BioStor is available from "http://biostor.org/":http://biostor.org/.
Ambiguous Dependence Of Minimal Plant Generation Time On Nuclear DNA Content
Authors: Ivanov Victor
Published: July 2019

AMBIGUOUS DEPENDENCE OF MINIMAL PLANT GENERATION TIME ON NUCLEAR DNA CONTENT Victor B. Ivanov The minimum generation time (MGT) of plant development was suggested to depend on nuclear DNA content, which varies in plants over wide limits1. In ephemeral species with the shortest MGT, the average C values were significantly lower than in annual species, whereas the average C values in annual species were lower than those in perennial plants. However, nobody has paid attention to the ratio of annual to perennial species number as a function of C values. Here I show that with increasing C the ratio of annual to perennial species increases to C values equal to 7-8 pg (monocots) and 6-7 pg (eudicots) and then decreases and that the fraction of annuals is abundant not at the lowest, but at some higher C levels. Hence, C value increase exerts an ambiguous effect on MGT. The C value is not the only factor, which determines the duration of the plant development. Nevertheless, the nuclear DNA content exerts a pronounced effect on MGT together with other diverse factors affecting the rate of plant development, especially at higher C values.
The Nuclear Imaging Uncertainty Principle. Do Nuclear Cameras Really Work?
Authors: Fleming Richard , Harrington Gordon
Published: July 2019

The introduction of the Heisenberg Uncertainty principle and Nuclear Cardiology occurred simultaneously in 1925-1927. Thirty years later the Anger gamma camera would allow for a more sophisticated radioactive isotope counting to determine the presence or absence of disease. When employed with technetium-99m isotopes, ischemic heart disease can be inferred by differences in visual appearance of cardiac images. These gestalts of imaging results have been separated from the quantitative information recorded by the cameras computer. We investigated whether current camera and computer systems are sophisticated enough to quantify differences between images to be clinically relevant. Our study demonstrated that efforts to "sharpen" image appearance does so at a reduction in "accuracy". Like Heisenberg, this work shows that one cannot know the exact location AND the amount of activity simultaneously and that a decision must be made for accuracy over image sharpness if one is to truly quantify differences in isotope concentration between images.
Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions
Authors: Koyama Hiroyuki , Kagaya Hideo , Oba Makoto , Miura Yutaka , Ishii Takehiko , Takato Tsuyoshi , Kataoka Kazunori , Miyata Tetsuro
Published: July 2019

Gene therapy is expected to open a new strategy for the treatment of refractory vascular diseases, so the development of appropriate gene vectors for vascular lesions is needed. To realize this requirement with a non-viral approach, cyclo(RGDfK) peptide (cRGD) was introduced to block copolymer, poly(ethylene glycol)-block-polycation carrying ethylenediamine units (PEG-PAsp(DET)). cRGD recognizes &x03B1;v&x03B2;3 and &x03B1;v&x03B2;5 integrins, which are abundantly expressed in vascular lesions. cRGD-conjugated PEG-PAsp(DET) (cRGD-PEG-PAsp(DET)) formed polyplex micelles through complexation with plasmid DNA (pDNA), and the cRGD-PEG-PAsp(DET) micelles achieved significantly more efficient gene expression and cellular uptake as compared with PEG-PAsp(DET) micelles in endothelial cells and vascular smooth muscle cells. Intracellular tracking of pDNA showed that cRGD-PEG-PAsp(DET) micelles were internalized via caveolae-mediated endocytosis, which is associated with a pathway avoiding lysosomal degradation, and that PEG-PAsp(DET) micelles were transported to acidic endosomes and lysosomes via clathrin-mediated endocytosis. Further, in vivo evaluation in rat carotid artery with a neointimal lesion revealed that cRGD-PEG-PAsp(DET) micelles realized sustained gene expression, while PEG-PAsp(DET) micelles facilitated rapid but transient gene expression. These findings suggest that introduction of cRGD to polyplex micelles might create novel and useful functions for gene transfer and contribute to the establishment of efficient gene therapy for vascular diseases.
Antiviral activity of (E)-cinnamaldehyde revisited with nanoscience tools
Authors: Goswami Arunava , Rahman Ayesha
Published: July 2019

Contradictory results have been reported regarding the anti-viral activity of (E)-cinnamaldehyde, a major constituent (~69%) of cinnamon. Here we show that (E)-cinnamaldehyde alone has very low antiviral property contrary to the belief of commoners. There are early sporadic reports in ancient medicinal practices that fine sand was used for increasing the efficacy of antiviral drugs. Can we increase the efficacy of (E)-cinnamaldehyde marginally by using one of the major constituents of sand like silica? Yes, when nanosilica is used as a carrier during (E)-cinnamaldehyde administration, the antiviral efficacy of the resultant cocktail increases marginally. Therefore, (E)-cinnamaldehyde consumed for centuries in tribal therapy as well as in alternative medicine are largely belief based and does not yield good result till date, when subjected to rigorous scientific investigation.
Adsorption of uranium and thorium on new adsorbent prepared from Moroccan oil shale impregnated with phosphoric acid
Authors: Khouya El Hassane , Legrouri Khadija , Fakhi Said , Hannache Hassan
Published: July 2019

Attention has been focused recently on the production of new adsorbents from Moroccan oil shale of Tarfaya (layer R3) by chemical activation with phosphoric acid and its application in wastewaters treatment. The optimal conditions for the preparation were searched and the tests of adsorption of uranium and thorium ions were affected. The best product was obtained by used of the ratio of activated agent/precursor equal 3 and activation of the mixture in air at 250°C during two hours after prepocessing at 120°C in air. Under these conditions the maximal adsorption capacity of methylene blue and specific area (SBET) of the new adsorbent were 526 mg/g and 630 m2/g, respectively. A batch mode experiment was used to explore the performances of this adsorbent for the removal of the U and Th from aqueous solutions prepared from UO2(NO3)2.6H2O and Th(NO3)4.5H2O. The adsorption parameters for the two radioelements were determined by application of the Langmuir, Freundlich and Elovich models.
Rapid pre-gel visualization of proteins with mass spectrometry compatibility
Authors: Mata-Gomez Marco , Yasui Matthew , Winkler Robert
Published: July 2019

Despite all of the prophecies of doom, gel electrophoresis is still prevalent in modern proteomic workflows. However, the currently used protein staining methods represent a serious bottleneck for a quick subsequent protein analysis using mass spectrometry. Substituting traditional protein stains by pre-gel derivatization with visible and mass spectrometry compatible reagents eliminates several processing steps and drastically reduces the sample preparation time. A defined chemistry permits seamless integration of such covalent protein staining methods into standardized bioinformatic pipelines. Using Uniblue A we could covalently stain simple to complex protein samples within 1 minute. Protein profiles on the gels were not compromised and MS/MS based sequence coverages higher than 80% could be obtained. In addition, the visual tracking of covalently stained proteins and peptides facilitates method development and validation. Altogether, this new chemo-proteomic approach enables true "at-line" analysis of proteins.
High Perceptual Load Makes Monocular Attention Different
Authors: Tan Dingyuan
Published: July 2019

Attention is a fundamental function of the human which is important in our daily life. Perceptual load is thought to play an important role in selective attention^1,2^. When perceptual load is high, the distracting information will be kept out of perception and will not affect us. When perceptual load is low, the distracting information will be processed deeply by us and will influence us^3^. However, most of the past research was concerned with binocular attention instead of monocular attention. In spite of the differences such as visual acuity^4^, stereopsis^5,6^ between binocular and monocular vision, there were few reports of their difference regarding to perceptual load which means more items and features in our research. Here we show their difference with the application of perceptual load to a selective attention task adapted from Eriksen's flanker task^7^. According to our research, monocular subjects are more sensitive to perceptual load with a lower perceptual load keeping them from the distracting effect. The difference may be attributed to less perceptual capacity rather than better attention of monocular vision. The research revealed a difference between binocular and monocular perceptual capacity and provides a new perspective to study the neural mechanism of perceptual capacity.
Failure of Abeta(1-40) amyloid fibrils under tensile loading
Authors: Paparcone Raffaella , Buehler Markus
Published: July 2019

Amyloid fibrils and plaques are detected in the brain tissue of patients affected by Alzheimer’s disease, but have also been found as part of normal physiological processes such as bacterial adhesion. Due to their highly organized structures, amyloid proteins have also been used for the development of novel nanomaterials, for a variety of applications including biomaterials for tissue engineering, nanolectronics, or optical devices. Past research on amyloid fibrils resulted in advances in identifying their mechanical properties, revealing a remarkable stiffness. However, the failure mechanism under tensile loading has not been elucidated yet, despite its importance for the understanding of key mechanical properties of amyloid fibrils and plaques as well as the growth and aggregation of amyloids into long fibers and plaques. Here we report a molecular level analysis of failure of amyloids under uniaxial tensile loading. Our molecular modeling results demonstrate that amyloid fibrils are extremely stiff with a Young’s modulus in the range of 18-30 GPa, in good agreement with previous experimental and computational findings. The most important contribution of our study is our finding that amyloid fibrils fail at relatively small strains of 2.5% to 4%, and at stress levels in the range of 1.02 to 0.64 GPa, in good agreement with experimental findings. Notably, we find that the strength properties of amyloid fibrils are extremely length dependent, and that longer amyloid fibrils show drastically smaller failure strains and failure stresses. As a result, longer fibrils in excess of hundreds of nanometers to micrometers have a greatly enhanced propensity towards spontaneous fragmentation and failure. We use a combination of simulation results and simple theoretical models to define critical fibril lengths where distinct failure mechanisms dominate.
The chronotron: a neuron that learns to fire temporally-precise spike patterns
Authors: Florian Răzvan
Published: July 2019

In many cases, neurons process information carried by the precise timing of spikes. Here we show how neurons can learn to generate specific temporally-precise output spikes in response to input spike patterns, thus processing and memorizing information that is fully temporally coded, both as input and as output. We introduce two new supervised learning rules for spiking neurons with temporal coding of information (chronotrons), one that is analytically-derived and highly efficient, and one that has a high degree of biological plausibility. We show how chronotrons can learn to classify their inputs and we study their memory capacity.
AAD-2004, a potent spin trapping molecule and microsomal prostaglandin E synthase-1 inhibitor, shows safety and efficacy in a mouse model of ALS
Authors: Shin Jin , Lee Young , Lee Jae , Lee Yong , Cho Woong , Im Doo , Lee Jin , Yun Bok , Son Sun , Park Sun , Byun Soo , Springer Joe , Gwag Byoung
Published: July 2019

While free radicals and inflammation constitute major routes of neuronal injury occurring in neurodegenerative diseases, neither antioxidants nor nonsteroidal anti-inflammatory drugs (NSAIDs) have shown significant efficacy in human clinical trials. To explore the possibility that concurrent blockade of free radicals and PGE2-mediated inflammation might constitute a safe and effective therapeutic approach to certain neurodegenerative diseases, we have developed 2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobezoic acid (AAD-2004) as a derivative of aspirin. AAD-2004 completely removed free radicals at 50 nM as a potent spin trapping molecule and inhibited microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 230 nM. Oral administration of AAD-2004 blocked free radical formation, PGE2 formation, and microglial activation in the spinal motor neurons of SOD1G93A mice. As a consequence, AAD-2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD-2004 was superior to ibuprofen or riluzole. Gastric bleeding was not induced by AAD-2004 even at a dose 400-fold higher than that required to obtain maximal therapeutic efficacy in SOD1G93A mice. Targeting both mPGES-1 and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases.
PML-RAR&x03B1; enhances autophagic activity through inhibiting Akt/mTOR pathway
Authors: Chen Guo-Qiang , Huang Ying , Zhao Xu-Yun , Chen Ting-Ting , Hou Jia-Kai , Zhang Jing , Yang Jie , Kogan Scott
Published: July 2019

Autophagy is a highly conserved, closely-regulated homeostatic cellular activity that allows for the bulk degradation of long-lived proteins and cytoplasmic organelles. Its roles in cancer initiation and progression and in determining the response of tumor cells to anticancer therapy are complicated, and the potential significance of autophagy in the pathogenesis and therapeutic response of acute myeloid leukemia has a little investigation. Here, we demonstrate that induction of acute promyelocytic leukemia (APL)-specific PML-RAR&x03B1; but not PLZF-RAR&x03B1;/NPM-RAR&x03B1; fusion protein up-regulates constitutive autophagic activation in leukemic and non-leukemic cells. The significant increase of autophagic activity is also found in the leukemic cells infiltrated bone marrow, spleen and liver from PML-RAR&x03B1;-transgenic APL syngenic transplanted mice. The specific autophagy inhibitor 3-methyladenine significantly abrogates PML-RAR&x03B1;-increased autophagy, while the autophagic flux assay reveals that the fusion protein induces autophagy in the manner of on-rate increase. Furthermore, this autophagy modulation of PML-RAR&x03B1; is possibly mediated by decreased activation of Akt/mTOR pathway. Given the critical role of the PML-RAR&x03B1; oncoprotein in APL pathogenesis, this study would shed new sights for an important role of autophagy in the development and treatment of this disease.
Structural basis for the activation of peroxisome proliferator-activated receptor-gamma by telmisartan
Authors: Amano Yasushi , Yamaguchi Tomohiko , Ohno Kazuki , Niimi Tatsuya , Orita Masaya , Sakashita Hitoshi , Takeuchi Makoto
Published: July 2019

Telmisartan, a selective angiotensin receptor blocker, has been recently shown to act as a partial agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). To understand the activation mechanism of PPARγ by telmisartan, we determined the ternary complex structure of PPARγ, telmisartan and coactivator peptide from SRC1 at 2.25 Å resolution. The overall fold of PPARγ is almost identical to previously-determined complex structures with agonists. However, telmisartan exhibits an unexpected binding mode, devoid of some essential hydrogen bonds for full activation of PPARγ.
Astrobiological Perspectives on Consciousness
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, trajectory found on Earth. Are many of these life forms likely to be conscious in ways that we would recognize? Almost certainly. Will many conscious entities develop high order technology? Less likely. If so, will we be able to communicate with them? Only on a basic level, and only with profound difficulty. The argument is straightforward.
The inherent occurrence of complex intron-rich spliceosomal split genes, including regulatory and splicing elements, within pre-biotic random genetic sequences
Authors: Bhasi Ashwini , Balan Bipin , Kumar Brajendra , Senapathy Sudar , Senapathy Periannan
Published: July 2019

Growing evidence indicates that complex intron-rich split genes and an advanced spliceosome existed in the earliest eukaryote, and possibly the first life form. We sought to examine how these split genes could have originated in the prebiotic system. We previously found that split coding sequences for complex proteins occur in abundance in random DNA sequences (P. Senapathy, et al, accompanying paper). This study demonstrates that a full complement of exons, introns and regulatory and splicing elements could have also occurred inherently within pre-biotic chemistry by chance. By comparing the characteristics of split genes found in computer-generated random genetic sequences with those of several extant eukaryotes, we show that an abundance of intron-rich split genes akin to those present in modern eukaryotes could have existed in the prebiotic system. These findings answer the post-genomic question of why the earliest life form contained highly complex intron-rich split genes, and, in conjunction with our companion study, show how they could encode a complex spliceosome.
The Physical Mechanism in Epilepsy - Understanding the Transition to Seizure
Authors: Aur Dorian
Published: July 2019

The occurrence of seizures is a rare event with a very low probability of incidence. Therefore, a new paradigm is required to understand how epileptic seizures are generated. Specifically, analytical models and experimental data analysis show that the process underlying seizure generation is a severe dysfunctional regulation of neuronal activity inside the epileptogenic region. Translated into significant changes of endogenous electric field, this dysfunction acts at fundamental level of charge dynamics and leads to chaotic diffusion and electrical resonances within clustered regions with high frequency oscillations (HFO). Since the altered regulation can be modeled by perturbed Hamiltonian systems with many degrees of freedom that describe the motion of charged particles in electric field, the Kolmogorov Arnold Moser theory (KAM) provides a physical model for the mechanism of epileptogenesis. Contrary to common belief, either inhibitory or excitatory function models of chronic epilepsy are incomplete and inconsistent.
Control of cell division in the adult brain by heparan sulfates in fractones and vascular basement membranes
Authors: Mercier Frederic , Douet Vanessa
Published: July 2019

Regulation of cell division in adult tissues and organs requires the coordination of growth factors at the surface of potentially-dividing cells in specific anatomic loci named germinal niches. However, the biological components and physiological system that control growth factors in the germinal niches are unknown. In the adult brain, no function has been attributed to fractones, the fractal-shaped extracellular matrix structures located in the subventricular zone (SVZ) next to neural stem and progenitor cells. Here, we show that BMP-7 (bone morphogenetic protein-7) and FGF-2 (fibroblast growth factor-2) modulate cell division in the SVZ only if the growth factors bind to heparan sulfates localized in fractones and adjoined vascular basement membranes. Our results strongly suggest that fractones and specialized basement membranes function as stem cell niche structures, capturing and potentiating growth factors to regulate cell division in the adult brain.
A Meteorite Ablation Debris: Testing and Analysis
Authors: Kayani Saheeb Ahmed
Published: July 2019

In this research report, X-ray diffraction (XRD) and X-ray fluorescence (XRF) spectrometry have been used to determine the mineralogical and elemental composition of a stone sample recovered from a location near village Lehri in district Jhelum, Pakistan. The test data is compared with previous findings (as reported in literature and included in references) to identify this sample stone as part of a prehistoric meteorite ablation debris.Further to this, carbon content of a specimen of the meteorite debris has been determined through combustion analysis. This carbon abundance has been compared with carbon wt% value of a certain type of meteorites to establish the origin and nature of the parent body of this particular meteorite debris.
Underlying Mathematics in Diversification of Human Olfactory Receptors in Different Loci
Authors: Hassan Sk. Sarif , Pal Choudhury Pabitra , Goswami Arunava
Published: July 2019

As per conservative estimate, approximately (51-105) Olfactory Receptors (ORs) loci are present in human genome occurring in clusters. These clusters are apparently unevenly spread as mosaics over 21 pair of human chromosomes. Olfactory Receptor (OR) gene families which are thought to have expanded for the need to provide recognition capability for huge number of pure and complex odorants. ORs form the largest known multi-gene family in the human genome. Recent studies have shown that 388 full length and 414 OR pseudo-genes are present in these OR genomic clusters. In this paper, the authors report a classification method for all human ORs based on their sequential quantitative information like presence of poly strings of nucleotides bases, long range correlation and so on. An L-System generated sequence has been taken as an input into a star-model of specific subfamily members and resultant sequence has been mapped to a specific OR based on the classification scheme using fractal parameters like Hurst exponent and fractal dimensions.
Correction: 3-deazaneplanocin A protects against cisplatin-induced renal tubular cell apoptosis and acute kidney injury by restoration of E-cadherin expression
Authors: Ni Jun , Hou Xiying , Wang Xueqiao , Shi Yinfeng , Xu Liuqing , Zheng Xiaoqing , Liu Na , Qiu Andong , Zhuang Shougang
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The Cornelia de Lange Syndrome-associated factor NIPBL interacts with BRD4 ET domain for transcription control of a common set of genes
Authors: Luna-Peláez Noelia , March-Díaz Rosana , Ceballos-Chávez María , Guerrero-Martínez Jose A. , Grazioli Paolo , García-Gutiérrez Pablo , Vaccari Thomas , Massa Valentina , Reyes Jose C. , García-Domínguez Mario
Published: July 2019

Mutations in NIPBL are the major cause of Cornelia de Lange Syndrome (CdLS). NIPBL is the cohesin-loading factor and has recently been associated with the BET (bromodomains and extra-terminal (ET) domain) proteins BRD2 and BRD4. Related to this, a CdLS-like phenotype has been described associated to BRD4 mutations. Here, we show direct interaction of NIPBL with different BET members in yeast, and selective interaction with BRD4 in cells, being the ET domain involved in the interaction. To understand the relationship between NIPBL and BET proteins, we have performed RNA-Seq expression analysis following depletion of the different proteins. Results indicate that genes regulated by NIPBL largely overlap with those regulated by BRD4 but not with those regulated by BRD2. ChIP-Seq analysis indicates preferential NIPBL occupancy at promoters, and knockdown experiments show mutual stabilization of NIPBL and BRD4 on co-regulated promoters. Moreover, human fibroblasts from CdLS probands with mutations in NIPBL show reduced BRD4 at co-occupied promoters. Functional analysis in vivo, using mutants of Drosophila melanogaster, confirmed the genetic interaction between Nipped-B and fs(1)h, the orthologs of human NIPBL and BRD4, respectively. Thus, we provide evidence for NIPBL and BRD4 cooperation in transcriptional regulation, which should contribute to explain the recently observed CdLS-like phenotype associated with BRD4 mutations.
Single-cell reconstruction of follicular remodeling in the human adult ovary
Authors: Fan X. , Bialecka M. , Moustakas I. , Lam E. , Torrens-Juaneda V. , Borggreven N. V. , Trouw L. , Louwe L. A. , Pilgram G. S. K. , Mei H. , van der Westerlaken L. , Chuva de Sousa Lopes S. M.
Published: July 2019

The ovary is perhaps the most dynamic organ in the human body, only rivaled by the uterus. The molecular mechanisms that regulate follicular growth and regression, ensuring ovarian tissue homeostasis, remain elusive. We have performed single-cell RNA-sequencing using human adult ovaries to provide a map of the molecular signature of growing and regressing follicular populations. We have identified different types of granulosa and theca cells and detected local production of components of the complement system by (atretic) theca cells and stromal cells. We also have detected a mixture of adaptive and innate immune cells, as well as several types of endothelial and smooth muscle cells to aid the remodeling process. Our results highlight the relevance of mapping whole adult organs at the single-cell level and reflect ongoing efforts to map the human body. The association between complement system and follicular remodeling may provide key insights in reproductive biology and (in)fertility.
Plasticity versus stability across the human cortical visual connectome
Authors: Haak Koen V. , Beckmann Christian F.
Published: July 2019

Whether and how the balance between plasticity and stability varies across the brain is an important open question. Within a processing hierarchy, it is thought that plasticity is increased at higher levels of cortical processing, but direct quantitative comparisons between low- and high-level plasticity have not been made so far. Here, we address this issue for the human cortical visual system. We quantify plasticity as the complement of the heritability of resting-state functional connectivity and thereby demonstrate a non-monotonic relationship between plasticity and hierarchical level, such that plasticity decreases from early to mid-level cortex, and then increases further of the visual hierarchy. This non-monotonic relationship argues against recent theory that the balance between plasticity and stability is governed by the costs of the “coding-catastrophe”, and can be explained by a concurrent decline of short-term adaptation and rise of long-term plasticity up the visual processing hierarchy.
Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936
Authors: Hillary Robert F. , McCartney Daniel L. , Harris Sarah E. , Stevenson Anna J. , Seeboth Anne , Zhang Qian , Liewald David C. , Evans Kathryn L. , Ritchie Craig W. , Tucker-Drob Elliot M. , Wray Naomi R. , McRae Allan F. , Visscher Peter M. , Deary Ian J. , Marioni Riccardo E.
Published: July 2019

Although plasma proteins may serve as markers of neurological disease risk, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. Therefore, we conduct genome- and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750 healthy older adults). We identify 41 independent genome-wide significant (P < 5.4 × 10−10) loci for 33 proteins and 26 epigenome-wide significant (P < 3.9 × 10−10) sites associated with the levels of 9 proteins. Using this information, we identify biological pathways in which putative neurological biomarkers are implicated (neurological, immunological and extracellular matrix metabolic pathways). We also observe causal relationships (by Mendelian randomisation analysis) between changes in gene expression (DRAXIN, MDGA1 and KYNU), or DNA methylation profiles (MATN3, MDGA1 and NEP), and altered plasma protein levels. Together, this may help inform causal relationships between biomarkers and neurological diseases.
Self-selective van der Waals heterostructures for large scale memory array
Authors: Sun Linfeng , Zhang Yishu , Han Gyeongtak , Hwang Geunwoo , Jiang Jinbao , Joo Bomin , Watanabe Kenji , Taniguchi Takashi , Kim Young-Min , Yu Woo Jong , Kong Bai-Sun , Zhao Rong , Yang Heejun
Published: July 2019

The large-scale crossbar array is a promising architecture for hardware-amenable energy efficient three-dimensional memory and neuromorphic computing systems. While accessing a memory cell with negligible sneak currents remains a fundamental issue in the crossbar array architecture, up-to-date memory cells for large-scale crossbar arrays suffer from process and device integration (one selector one resistor) or destructive read operation (complementary resistive switching). Here, we introduce a self-selective memory cell based on hexagonal boron nitride and graphene in a vertical heterostructure. Combining non-volatile and volatile memory operations in the two hexagonal boron nitride layers, we demonstrate a self-selectivity of 1010 with an on/off resistance ratio larger than 103. The graphene layer efficiently blocks the diffusion of volatile silver filaments to integrate the volatile and non-volatile kinetics in a novel way. Our self-selective memory minimizes sneak currents on large-scale memory operation, thereby achieving a practical readout margin for terabit-scale and energy-efficient memory integration.
Avian Influenza A (H7N9) and related Internet search query data in China
Authors: Chen Ying , Zhang Yuzhou , Xu Zhiwei , Wang Xuanzhuo , Lu Jiahai , Hu Wenbiao
Published: July 2019

The use of Internet-based systems for infectious disease surveillance has been increasingly explored in recent years. However, few studies have used Internet search query or social media data to monitor spatial and temporal trends of avian influenza in China. This study investigated the potential of using search query and social media data in detecting and monitoring avian influenza A (H7N9) cases in humans in China. We collected weekly data on laboratory-confirmed H7N9 cases in humans, as well as H7N9-related Baidu Search Index (BSI) and Weibo Posting Index (WPI) data in China from 2013 to 2017, to explore the spatial and temporal trends of H7N9 cases and H7N9-related Internet search queries. Our findings showed a positive relationship of H7N9 cases with BSI and WPI search queries spatially and temporally. The outbreak threshold time and peak time of H7N9-related BSI and WPI searches preceded H7N9 cases in most years. Seasonal autoregressive integrated moving average (SARIMA) models with BSI (β = 0.008, p < 0.001) and WPI (β = 0.002, p = 0.036) were used to predict the number of H7N9 cases. Regression tree model analysis showed that the average H7N9 cases increased by over 2.4-fold (26.8/11) when BSI for H7N9 was >  = 11524. Both BSI and WPI data could be used as indicators to develop an early warning system for H7N9 outbreaks in the future.
Mechanisms by Which Genotoxins Cause Micronuclei and Other Nuclear Anomalies
Authors: Fenech Michael
Published: July 2019

Normal eukaryotic cells contain a single nucleus. However, abnormal small nuclei known as micronuclei, additional to the main nucleus, may occur in cells that are exposed to genotoxic agents (chemicals and/or radiation) that cause structural or numerical chromosome aberrations. Micronuclei originate from chromosome fragments or whole chromosomes that lag behind during anaphase in mitosis. This occurs because most chromosome fragments lack centromeres or because some of the whole chromosomes have defective centromeres and/or kinetochores, which results in their inability to engage with the mitotic spindle. An alternative mechanism for these events is malfunction of the mitotic spindle. The molecular mechanisms that cause chromosome fragmentation can also result in the formation of asymmetrical chromosome rearrangements such as dicentric chromosomes. The centromeres of dicentric chromosomes are often pulled in opposite directions during anaphase leading to the formation of anaphase bridges that can be observed as nucleoplasmic bridges during the binucleated stage in telophase. The formation of nucleoplasmic bridges leads to hypermutation via breakage–fusion–bridge cycles causing gene amplification and ultimately to the extrusion of the amplified DNA via nuclear budding. Using the cytokinesis-block technique it is possible to identify micronuclei, nucleoplasmic bridges and nuclear buds simultaneously because the cells are halted at the binucleated stage in mitosis, which is the ideal stage to observe and measured these nuclear anomalies. Recent studies have also shown that entrapment of a chromosome within a micronucleus may result in the shattering of the chromosome (chromothripsis) followed by random rearrangement and ligation of the fragments leading to the formation of an abnormal chromosome (chromoanagenesis). Thus, formation of micronuclei and nucleoplasmic bridges are themselves events that generate further chromosomal instability.
The Cytokinesis-block Micronucleus Cytome Assay in Human Lymphocytes
Authors: Fenech Michael
Published: July 2019

Micronuclei (MN) are small additional nuclei within human cells that contain chromosome fragments or whole chromosomes that have been excluded from the main nuclei during nuclear division because they could not engage the spindle and segregate properly to the daughter nuclei during the metaphase–anaphase–telophase transition in mitosis. The cytokinesis-block micronucleus (CBMN) assay, which measures MN exclusively in cells that have completed one nuclear division ex vivo or in vitro in cultured lymphocytes, is one of the best validated methods for measuring DNA damage in humans. However, over the past decade it has become increasingly evident that there are other nuclear anomalies that are indicative of other forms of DNA damage, such as nucleoplasmic bridges (NPB), and nuclear buds (NBUD), which originate from asymmetrically rearranged dicentric chromosomes and elimination of amplified DNA, respectively. In addition, the ratio of mono-, bi- and multinucleated cells provides a measure of the cell division rate. Furthermore, cell death can also be measured by enumerating the frequency of necrotic and apoptotic cells. Consequently, the CBMN assay has now evolved into the CBMN-cytome assay, which is the format that captures the full spectrum of the six biomarkers indicated above. This chapter describes the CBMN-cytome assay (including some new additional biomarkers) and its application in human lymphocytes for in vitro and in vivo genotoxicity studies.
Experiments with Micronucleus Assays Using Nasal, Urothelial and Cervical Human Cells
Authors: Nersesyan Armen , Setayesh Tahereh , Kundi Michael , Mišík Miroslav , Wultsch Georg , Knasmueller Siegfried
Published: July 2019

This chapter describes the use and methods of micronucleus (MN) experiments with exfoliated cells from the nasal epithelium, bladder and cervix. No standardized protocols are available for these assays, but scoring criteria that were developed for oral mucosa (buccal cells) can be used. The data that are available from studies with nasal cells indicate that MN formation reflects exposure of the respiratory tract to genotoxic carcinogens. Experiments with urothelial cells may be useful in detecting occupational exposures to genotoxic chemicals, in particular those which induce bladder cancer, for the diagnosis of this form of cancer and also for the surveillance of bladder cancer patients. However, further experimental work is required to prove this latter assumption. The results of MN experiments with cervical cells indicate that this method could be useful for the detection and prognosis of cervical cancer.
Micronucleus Experiments with Fish Cell Lines
Authors: Žegura B. , Filipič M.
Published: July 2019

Fish cell lines have been successfully introduced for the detection of genotoxic effects and can serve as an alternative to animal testing in preliminary eco-/genotoxicological studies. Recently, the micronucleus assay that was originally developed for mammalian cells has also been extensively used in fish cell lines for testing the genotoxic activity of chemicals and complex environmental matrices. The present chapter reviews the current literature data on studies using the micronucleus assay on fish cell lines and considers micronucleus protocols applied on permanent piscine cell cultures. Furthermore, the most used fish cell lines in the micronucleus assay are discussed.
Heavy Metals II (Arsenic, Chromium, Nickel, Vanadium) and Micronuclei
Authors: Annangi Balasubramanyam , Marcos Ricard , Hernández Alba
Published: July 2019

Different studies have demonstrated the in vitro/in vivo genotoxicity of different metals by using the micronucleus (MN) assay in different cell types and organisms, including humans. In this chapter, we summarize the data obtained when arsenic, chromium, nickel, and vanadium were evaluated using the MN assay. For each one of the selected metals, the obtained information has been categorized according to whether it was obtained using in vitro or in vivo approaches. In vivo data has also been classified taking into account if it was obtained from biomonitoring studies involving human exposed populations, or from other in vivo models.
Pesticide Exposure and Its Effects on Micronucleus Frequency
Authors: Bolognesi Claudia , Holland Nina
Published: July 2019

Millions of people are exposed to pesticides in occupational and environmental settings in different parts of the world. The assessment of the genotoxicity of pesticides is critical for better regulation and protections because of their known harmful effects on human health ranging from cancer to adverse birth outcomes. The micronucleus (MS) assay in human lymphocytes and exfoliated cells is an effective method of assessing DNA damage induced by clastogenic and aneuploidogenic mechanisms. The majority of available studies of the MN assay in human lymphocytes of pesticide-exposed workers, including chemical plant workers, pesticide sprayers, floriculturists, agricultural workers and non-occupationally exposed groups reported positive findings. Subjects working in greenhouses or during intensive spraying season and having acute exposure, showed consistent increases in MN frequency. A decreased level of pesticide-induced genotoxicity was associated with proper use of personal protection. Buccal cell MN assay also demonstrated good potential for the monitoring of effects of pesticide exposure in humans, but further standardization of the study protocols and staining procedures will allow more reliable comparison of the data among human populations and laboratories. Overall, the MN assay is a cost effective and reliable tool for the biomonitoring of pesticide-induced DNA damage, and can validate the effects of educational and intervention programs aimed at reducing exposure and genetic damage.