bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid pre-gel visualization of proteins with mass spectrometry compatibility
Authors: Mata-Gomez Marco , Yasui Matthew , Winkler Robert 
Published: July 2019

AbstractDespite 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 &quot;at-line&quot; analysis of proteins.
High Perceptual Load Makes Monocular Attention Different
Authors: Tan Dingyuan 
Published: July 2019

AbstractAttention 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&apos;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

AbstractAmyloid 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

AbstractIn 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

AbstractWhile 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

AbstractAutophagy 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

AbstractTelmisartan, 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

AbstractThe 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

AbstractGrowing 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

AbstractThe 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

AbstractRegulation 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

AbstractIn 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

AbstractAs 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.
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

AbstractMutations 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

AbstractThe 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

AbstractWhether 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

AbstractAlthough 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

AbstractThe 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.