bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C
Authors: Inuzuka Takayuki , Fujioka Yoichiro , Tsuda Masumi , Fujioka Mari , Satoh Aya O. , Horiuchi Kosui , Nishide Shinya , Nanbo Asuka , Tanaka Shinya , Ohba Yusuke 
Published: February 2016

AbstractAngiotensin II (AII) type 2 receptor (AT2R) negatively regulates type 1 receptor (AT1R) signaling. However, the precise molecular mechanism of AT2R-mediated AT1R inhibition remains poorly understood. Here, we characterized the local and functional interaction of AT2R with AT1R. AT2R colocalized and formed a complex with AT1R at the plasma membrane, even in the absence of AII. Upon AII stimulation, the spatial arrangement of the complex was modulated, as confirmed by Förster resonance energy transfer (FRET) analysis, followed by AT2R internalization along with AT1R. AT2R internalization was specifically observed only in the presence of AT1R; AT2R alone could not be internalized. The AT1R-specific inhibitor losartan completely inhibited both the conformational change and the internalization of AT2R with AT1R, whereas the AT2R-specific inhibitor PD123319 partially hindered these phenomena, demonstrating that the activation of both receptors was indispensable for these effects. In addition, treatment with the protein kinase C (PKC) inhibitors inhibited the ligand-dependent accumulation of AT2R but not that of AT1R in the endosomes. A mutation in the putative phosphorylation sites of AT2R also abrogated the co-internalization of ATR2 with AT1R and the inhibitory effect of ATR2 on AT1R. These data suggest that AT2R inhibits ligand-induced AT1R signaling through the PKC-dependent pathway.
Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus
Authors: Lopez-Rojas Jeffrey , Heine Martin , Kreutz Michael R. 
Published: February 2016

AbstractThe dentate gyrus is the main entry gate for cortical input to the hippocampus and one of the few brain areas where adult neurogenesis occurs. Several studies have shown that it is relatively difficult to induce synaptic plasticity in mature but not in newborn dentate granule cells. In the present work we have systematically addressed how classical protocols to induce synaptic plasticity affect action potential firing and intrinsic excitability in mature granule cells. We found that stimulation paradigms considered to be relevant for learning processes consistently modified the probability to generate action potentials in response to a given synaptic input in mature cells, in some paradigms even without any modification of synaptic strength. Collectively the results suggest that plasticity of intrinsic dendritic excitability has a lower induction-threshold than synaptic plasticity in mature granule cells and that this form of plasticity might be an important mechanism by which mature granule cells contribute to hippocampal function.
NATpipe: an integrative pipeline for systematical discovery of natural antisense transcripts (NATs) and phase-distributed nat-siRNAs from de novo assembled transcriptomes
Authors: Yu Dongliang , Meng Yijun , Zuo Ziwei , Xue Jie , Wang Huizhong 
Published: February 2016

AbstractNat-siRNAs (small interfering RNAs originated from natural antisense transcripts) are a class of functional small RNA (sRNA) species discovered in both plants and animals. These siRNAs are highly enriched within the annealed regions of the NAT (natural antisense transcript) pairs. To date, great research efforts have been taken for systematical identification of the NATs in various organisms. However, developing a freely available and easy-to-use program for NAT prediction is strongly demanded by researchers. Here, we proposed an integrative pipeline named NATpipe for systematical discovery of NATs from de novo assembled transcriptomes. By utilizing sRNA sequencing data, the pipeline also allowed users to search for phase-distributed nat-siRNAs within the perfectly annealed regions of the NAT pairs. Additionally, more reliable nat-siRNA loci could be identified based on degradome sequencing data. A case study on the non-model plant Dendrobium officinale was performed to illustrate the utility of NATpipe. Finally, we hope that NATpipe would be a useful tool for NAT prediction, nat-siRNA discovery, and related functional studies. NATpipe is available at www.bioinfolab.cn/NATpipe/NATpipe.zip.
Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Schlauch K A , Khaiboullina S F , De Meirleir K L , Rawat S , Petereit J , Rizvanov A A , Blatt N , Mijatovic T , Kulick D , Palotás A , Lombardi V C 
Published: February 2016

AbstractMyalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone. The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested. In the present study, we used a DNA single-nucleotide polymorphism (SNP) chip representing over 906,600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls. To the best of our knowledge, this study represents the most comprehensive genome-wide association study (GWAS) of an ME/CFS cohort conducted to date. Here 442 SNPs were identified as candidates for association with ME/CFS (adjustedP-value<0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene. Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing protein. We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci. Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies.
Use of machine learning for behavioral distinction of autism and ADHD
Authors: Duda M , Ma R , Haber N , Wall D P 
Published: February 2016

AbstractAlthough autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) continue to rise in prevalence, together affecting >10% of today’s pediatric population, the methods of diagnosis remain subjective, cumbersome and time intensive. With gaps upward of a year between initial suspicion and diagnosis, valuable time where treatments and behavioral interventions could be applied is lost as these disorders remain undetected. Methods to quickly and accurately assess risk for these, and other, developmental disorders are necessary to streamline the process of diagnosis and provide families access to much-needed therapies sooner. Using forward feature selection, as well as undersampling and 10-fold cross-validation, we trained and tested six machine learning models on complete 65-item Social Responsiveness Scale score sheets from 2925 individuals with either ASD (n=2775) or ADHD (n=150). We found that five of the 65 behaviors measured by this screening tool were sufficient to distinguish ASD from ADHD with high accuracy (area under the curve=0.965). These results support the hypotheses that (1) machine learning can be used to discern between autism and ADHD with high accuracy and (2) this distinction can be made using a small number of commonly measured behaviors. Our findings show promise for use as an electronically administered, caregiver-directed resource for preliminary risk evaluation and/or pre-clinical screening and triage that could help to speed the diagnosis of these disorders.
New photosensitizers for photodynamic therapy
Authors: Abrahamse Heidi , Hamblin Michael R. 
Published: February 2016

Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.
Polyphosphate as a haemostatic modulator
Authors: Mutch Nicola J. 
Published: February 2016

Platelets are small anuclear cells that play a central role in haemostasis. Platelets become activated in response to various stimuli triggering release of their granular contents into the surrounding milieu. One of these types of granules, termed dense granules, have been found to contain polyphosphate (polyP) in addition to other inorganic biomolecules, such as serotonin, ADP, ATP, PPi. Individuals deficient in dense granules exhibit bleeding tendencies, emphasizing their importance in haemostasis. Platelet polyP is of a relatively defined size, approximately 60–100 phosphate monomers in length. These linear polymers act at various points in the coagulation and fibrinolytic systems thereby modulating the haemostatic response. Due to its highly anionic nature, polyP lends itself to being a natural activator of the contact system. The contact system functions in multiple pathways including coagulation, fibrinolysis, inflammation and complement. Activation of the contact system accelerates thrombin generation, the terminal enzyme in the coagulation cascade. PolyP also modulates factors further downstream in the coagulation cascade to augment thrombin generation. The net effect is increased fibrin formation and platelet activation resulting in faster clot formation. PolyP is incorporated into the forming clot thereby modifying the structure of the resulting fibrin network and its susceptibility to degradation by certain plasminogen activators. In conclusion, release of platelet polyP at the site of injury may facilitate clot formation and augment clot stability thereby promoting wound healing.
The new world of inorganic polyphosphates
Authors: Azevedo Cristina , Saiardi Adolfo 
Published: February 2016

Post-translational modifications (PTMs) add regulatory features to proteins that help establish the complex functional networks that make up higher organisms. Advances in analytical detection methods have led to the identification of more than 200 types of PTMs. However, some modifications are unstable under the present detection methods, anticipating the existence of further modifications and a much more complex map of PTMs. An example is the recently discovered protein modification polyphosphorylation. Polyphosphorylation is mediated by inorganic polyphosphate (polyP) and represents the covalent attachment of this linear polymer of orthophosphate to lysine residues in target proteins. This modification has eluded MS analysis as both polyP itself and the phosphoramidate bonds created upon its reaction with lysine residues are highly unstable in acidic conditions. Polyphosphorylation detection was only possible through extensive biochemical characterization. Two targets have been identified: nuclear signal recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1). Polyphosphorylation occurs within a conserved N-terminal polyacidic serine (S) and lysine (K) rich (PASK) cluster. It negatively regulates Nsr1–Top1 interaction and impairs Top1 enzymatic activity, namely relaxing supercoiled DNA. Modulation of cellular levels of polyP regulates Top1 activity by modifying its polyphosphorylation status. Here we discuss the significance of the recently identified new role of inorganic polyP.
Inorganic polyphosphate in cardiac myocytes: from bioenergetics to the permeability transition pore and cell survival
Authors: Dedkova Elena N. 
Published: February 2016

Inorganic polyphosphate (polyP) is a linear polymer of Pi residues linked together by high-energy phosphoanhydride bonds as in ATP. PolyP is present in all living organisms ranging from bacteria to human and possibly even predating life of this planet. The length of polyP chain can vary from just a few phosphates to several thousand phosphate units long, depending on the organism and the tissue in which it is synthesized. PolyP was extensively studied in prokaryotes and unicellular eukaryotes by Kulaev's group in the Russian Academy of Sciences and by the Nobel Prize Laureate Arthur Kornberg at Stanford University. Recently, we reported that mitochondria of cardiac ventricular myocytes contain significant amounts (280±60 pmol/mg of protein) of polyP with an average length of 25 Pi and that polyP is involved in Ca2+-dependent activation of the mitochondrial permeability transition pore (mPTP). Enzymatic polyP depletion prevented Ca2+-induced mPTP opening during ischaemia; however, it did not affect reactive oxygen species (ROS)-mediated mPTP opening during reperfusion and even enhanced cell death in cardiac myocytes. We found that ROS generation was actually enhanced in polyP-depleted cells demonstrating that polyP protects cardiac myocytes against enhanced ROS formation. Furthermore, polyP concentration was dynamically changed during activation of the mitochondrial respiratory chain and stress conditions such as ischaemia/reperfusion (I/R) and heart failure (HF) indicating that polyP is required for the normal heart metabolism. This review discusses the current literature on the roles of polyP in cardiovascular health and disease.
Phosphoinositide signalling in type 2 diabetes: a β-cell perspective
Authors: Rameh Lucia E. , Deeney Jude T. 
Published: February 2016

Type 2 diabetes is a complex disease. It results from a failure of the body to maintain energy homoeostasis. Multicellular organisms have evolved complex strategies to preserve a relatively stable internal nutrient environment, despite fluctuations in external nutrient availability. This complex strategy involves the co-ordinated responses of multiple organs to promote storage or mobilization of energy sources according to the availability of nutrients and cellular bioenergetics needs. The endocrine pancreas plays a central role in these processes by secreting insulin and glucagon. When this co-ordinated effort fails, hyperglycaemia and hyperlipidaemia develops, characterizing a state of metabolic imbalance and ultimately overt diabetes. Although diabetes is most likely a collection of diseases, scientists are starting to identify genetic components and environmental triggers. Genome-wide association studies revealed that by and large, gene variants associated with type 2 diabetes are implicated in pancreatic β-cell function, suggesting that the β-cell may be the weakest link in the chain of events that results in diabetes. Thus, it is critical to understand how environmental cues affect the β-cell. Phosphoinositides are important ‘decoders’ of environmental cues. As such, these lipids have been implicated in cellular responses to a wide range of growth factors, hormones, stress agents, nutrients and metabolites. Here we will review some of the well-established and potential new roles for phosphoinositides in β-cell function/dysfunction and discuss how our knowledge of phosphoinositide signalling could aid in the identification of potential strategies for treating or preventing type 2 diabetes.
A cautionary (spectral) tail: red-shifted fluorescence by DAPI–DAPI interactions
Authors: Omelon Sidney , Georgiou John , Habraken Wouter 
Published: February 2016

The fluorescent dye DAPI is useful for its association with and consequent amplification of an ∼460 nm emission maximum upon binding to dsDNA. Labelling with higher DAPI concentrations is a technique used to reveal Pi polymers [polyphosphate (polyP)], with a red-shift to ∼520–550 nm fluorescence emission. DAPI–polyP emissions of ∼580 nm are also generated upon 415 nm excitation. Red-shifted DAPI emission has been associated with polyP and RNA and has more recently been reported with polyadenylic acid (polyA), specific inositol phosphates (IPs) and heparin. We find that amorphous calcium phosphate (ACP) also demonstrates red-shifted DAPI emission at high DAPI concentrations. This DAPI spectral shift has been attributed to DAPI–DAPI electrostatic interactions enabled by molecules with high negative charge density that increase the local DAPI concentration and favour DAPI molecular proximity, as observed by increasing the dye/phosphate ratio. Excitation of dry DAPI (∼360 nm) confirmed a red-shifted DAPI emission. Whereas enzymatic approaches to modify substrates can help define the nature of DAPI fluorescence signals, multiple approaches beyond red-shifted DAPI excitation/emission are advised before conclusions are drawn about DAPI substrate identification.
Low‐complexity 0.55‐V 2.5‐μW bandgap reference and power‐on reset hybrid circuit
Authors: Zhou Bo , Liu Shuli , Chiang Patrick 
Published: February 2016

A near‐threshold low‐complexity bandgap reference (BGR) and power‐on reset (POR) hybrid circuit is implemented in 65 nm CMOS, with an ultra‐low supply voltage of 0.55 V and power consumption of 2.5 μW. The BGR employing amplifier offset voltage and current matching, and the POR based on offset voltage matching and loop settling feature, are proposed. The circuit‐level simulation results verify that the presented implementation, not only generates a stable reference voltage with the typical temperature coefficient of 120 ppm/°C and line‐regulation feature of 3.3%/V, but provides a robust reset signal with power‐on and brown‐out detection function. The proposed near‐threshold circuit has ultra‐low power supply and design complexity, both for BGR and POR modules, when compared to the reported.
Individual pitch controller based on fuzzy logic control for wind turbine load mitigation
Authors: Han Bing , Zhou Lawu , Yang Fan , Xiang Zeng 
Published: February 2016

With the increasing size of modern large wind turbine (WT), the effects of dynamic loading on the structures become an important influence factor. There are mitigation measures for WT control systems to reduce these imbalance structural loads and regulate power. It has motivated the development of blade individual pitch control (IPC) methodologies. This study focuses on the design of fuzzy logic controller (FLC) for IPC. The controllers are designed in order to optimise a trade‐off among several control objectives such as blade root moment and generator torque. Three different FLC had been used in the controllers, the first one related to blade pitch angle and electromagnetic torque control variables to meet specified objectives for operation region, the second control model and the third model related to d‐q axis blade moment in non‐rotating frame of reference. Likewise, the optimisation criteria of FLC consider for each controller objective to mitigate fatigue loads and regulate output power. Finally, the effectiveness of proposed method is verified by simulation results for three‐bladed NREL 2 MW WT. The results proved that the fatigue loads in the turbine are reduced obviously.
Biology, social science and history: interdisciplinarity in three directions
Authors: Renwick Chris 
Published: February 2016

AbstractThe relationship between biological and social science is a long-standing area of interest for researchers on both sides of the divide, as well as in the humanities, where historians, among others, have been fascinated by its wider social, political and cultural implications. Yet interdisciplinary work in this area has always been problematic, not least because researchers are understandably concerned about interdisciplinarity being a cover for importing ideas and methods wholesale from other fields. This article explores the lessons, both positive and negative, that can be drawn from an ongoing project focused on building links between biology, social science and history. The article argues that dialogue between different disciplines is a difficult process to get going but ultimately rewarding. However, the article also argues that interdisciplinary practice is a much more elusive goal. The key to developing such practices lies in identifying new spaces for cooperative work rather than areas that are already occupied by researchers. This article is published as part of a thematic collection on the concept of interdisciplinarity.
Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes
Authors: Murray Ben , Antonyuk Svetlana V. , Marina Alberto , Lu Shelly C. , Mato Jose M. , Hasnain S. Samar , Rojas Adriana L. 
Published: February 2016

Significance
X-ray crystallography provides a structural basis for enzyme mechanisms by elucidating information about the chemical reaction occurring within the active site. Crystallographic structures can also aid in rational drug design. A highly conserved family of methionine adenosyltranferases (MATs) produces S-adenosylmethionine (SAMe) via an ATP-driven process. Dysregulation of MAT enzymes has been tightly linked to liver and colon cancer. Here we present crystal structures of human MATα2 proteins containing different ligands within the active site, allowing for a step change in our understanding of how this enzyme uses its substrates, methionine and adenosine, to produce the product SAMe.
Cortical response to categorical color perception in infants investigated by near-infrared spectroscopy
Authors: Yang Jiale , Kanazawa So , Yamaguchi Masami K. , Kuriki Ichiro 
Published: February 2016

Significance
There has been much debate on the Sapir–Wharf hypothesis regarding whether language affects our perceptual world. Despite much research on this topic, there remains no clear consensus on whether and how language affects categorical color perception. Here, we provide the first evidence, to our knowledge, that categorical color perception has a universal starting point prior to language acquisition. We measured the neural correlates of categorical color perception in prelinguistic infants. We found increased brain activities to colors in different categories, but not to colors in the same category. These results indicated that different color categories are differently represented in the visual cortex of prelinguistic infants, which implies that color categories may develop in the visual system before language acquisition.