bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous timing of asexual cycles in Plasmodium falciparum quantified by extended time-lapse microscopy
Authors: Park Heungwon , Huang Shuqiang , Walzer Katelyn A. , You Lingchong , Chi Jen-Tsan Ashley , Buchler Nicolas E. 
Published: June 2018

ABSTRACTMalarial fever arises from the synchronous bursting of human red blood cells by the Plasmodium parasite. The released parasites re-infect neighboring red blood cells and undergo another asexual cycle of differentiation and proliferation for 48 hours, before again bursting synchronously. The synchrony of bursting is lost during in vitro culturing of the parasite outside the human body, presumably because the asexual cycle is no longer entrained by host-specific circadian cues. Therefore, most in vitro malaria studies have relied on the artificial synchronization of the parasite population. However, much remains unknown about the degree of timing heterogeneity of asexual cycles and how artificial synchronization may affect this timing. Here, we combined time-lapse fluorescence microscopy and long-term culturing to follow single cells and directly measure the heterogeneous timing of in vitro asexual cycles. We first demonstrate that unsynchronized laboratory cultures are not fully asynchronous and the parasites exhibit a bimodal distribution in their first burst times. We then show that synchronized and unsynchronized cultures had similar asexual cycle periods, which indicates that artificial synchronization does not fundamentally perturb asexual cycle dynamics. Last, we demonstrate that sibling parasites descended from the same schizont exhibited significant variation in asexual cycle period, although smaller than the variation between non-siblings. The additional variance between non-siblings likely arises from the variable environments and/or developmental programs experienced in different host cells.
Coherent feedforward regulation of gene expression byCaulobacterσTand GsrN during hyperosmotic stress
Authors: Tien Matthew Z. , Stein Benjamin J. , Crosson Sean 
Published: June 2018

AbstractGsrN is a conserved small RNA that is under transcriptional control of the general stress sigma factor, σT, and that functions as a post-transcriptional regulator ofCaulobacter crescentussurvival under multiple stress conditions. We have defined features of GsrN structure that determine survival under hyperosmotic stress, and have applied transcriptomic and proteomic methods to identify regulatory targets of GsrN under hyperosmotic conditions. The 5’ end of GsrN, which includes a conserved cytosine-rich stem loop structure, is necessary for cell survival after osmotic upshock. GsrN both activates and represses gene expression in this stress condition. Expression of an uncharacterized open reading frame predicted to encode a glycine-zipper protein,osrP, is strongly activated by GsrN. Our data support a model in which GsrN physically interacts withosrPmRNA through its 5’ C-rich stem loop to enhance OsrP protein expression. We conclude thatsigT,gsrN, andosrPform a coherent feedforward loop in which σTactivatesgsrNandosrPtranscription during stress, and GsrN activates OsrP protein expression at the post-transcriptional level. This study delineates transcriptional and post-transcriptional layers ofCaulobactergene expression control during hyperosmotic stress, uncovers a new regulatory target of GsrN, and defines a coherent feedforward motif in theCaulobacterGSR regulatory network.ImportanceBacteria inhabit diverse niches, and must adapt their physiology to constant environmental fluctuations. A major response to environmental perturbation is to change gene expression.Caulobacterand other alphaproteobacteria initiate a complex gene expression program known as the general stress response (GSR) under conditions including oxidative stress, osmotic stress, and nutrient limitation. The GSR enables cell survival in these environments. Understanding how bacteria survive stress requires that we dissect gene expression responses, such as the GSR, at the molecular level. This study is significant as it defines transcriptional and post-transcriptional layers of gene expression regulation in response to hyperosmotic stress. We further provide evidence that coherent feedforward motifs influence the system properties of theCaulobacterGSR pathway.
Interleukin-17 regulates neuron-glial communications, inhibitory synaptic transmission and neuropathic pain after chemotherapy
Authors: Luo Hao , Liu Hui-Zhu , Luo Xin , Bang Sangsu , Wang Zi-Long , Chen Gang , Ji Ru-Rong , Zhang Yu-Qiu 
Published: June 2018

AbstractThe proinflammatory cytokine Interleukin-17 (IL-17) is produced mainly by Th17 cells and has been implicated in pain regulation. However, synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We observed respective expression of IL-17 and its receptor IL-17R in spinal cord astrocytes and neurons. Patch clamp recording in spinal cord slices revealed that IL-17 not only enhanced EPSCs but also suppressed IPSCs and GABA-induced currents in lamina IIo somatostatin-expressing neurons. Spinal IL-17 was upregulated after paclitaxel treatment, and intrathecal IL-17R blockade reduced paclitaxel-induced neuropathic pain. In dorsal root ganglia, respective IL-17 and IL-17R expression in satellite glial cells and neurons was sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate both central and peripheral neuron-glial interactions in chemotherapy-induced peripheral neuropathy.
Multiway Canonical Correlation Analysis of Brain Signals
Authors: de Cheveigné Alain , Di Liberto Giovanni M. , Arzounian Dorothée , Wong Daniel D.E. , Hjortkjær Jens , Fuglsang Søren , Parra Lucas C. 
Published: June 2018

AbstractBrain signals recorded with electroencephalography (EEG), magnetoencephalography (MEG) and related techniques often have poor signal-to-noise ratio due to the presence of multiple competing sources and artifacts. A common remedy is to average over repeats of the same stimulus, but this is not applicable for temporally extended stimuli that are presented only once (speech, music, movies, natural sound). An alternative is to average responses over multiple subjects that were presented with the same identical stimuli, but differences in geometry of brain sources and sensors reduce the effectiveness of this solution. Multiway canonical correlation analysis (MCCA) brings a solution to this problem by allowing data from multiple subjects to be fused in such a way as to extract components common to all. This paper reviews the method, offers application examples that illustrate its effectiveness, and outlines the caveats and risks entailed by the method.
Serotonergic and catecholaminergic (dopaminergic) oscillations in the reproductive regulation of Japanese quail
Authors: Yadav Suneeta , Chaturvedi Chandra Mohini 
Published: June 2018

AbstractSpecific temporal phase relation of serotonergic and dopaminergic oscillations alters reproductive responses in many species. Aim of the study was to confirm whether effect of serotonergic drug (5-HTP) and dopaminergic drug (L-DOPA) is due to their conversion into serotonin and dopamine respectively or other products. For this study, PCPA (p-chlorophenylalanine, a long lasting inhibitor of serotonin synthesis), DDC (Diethyldithiocarbamate, which inhibits biosynthesis of nor-adrenaline), α-MT (Methyl-p-tyrosine, an inhibitor for the conversion of tyrosine to DOPA) and DOPS (Dihydroxyphenylserine, a specific precursor for noradrenaline) were used in different groups in addition to 5-HTP and L-DOPA given at specific time interval. Reproductive responses monitored at 10 weeks post treatment indicate that gonadal activity was significantly low in HTP:DOPA (8-hr quail), HTP+PCPA:DOPA and HTP:DOPA+DDC quail compare to control (S:S). However, gonadal activity of HTP:S(HTP control), S:DOPA(DOPA control) and HTP: α-MT+DOPS was not different from S:S control and remained in active condition. These findings indicate that it is not the dose of neurotransmitter precursor drugs (5-HTP and L-DOPA) and the neurotransmitters (serotonin and dopamine itself) that cause the effect, instead it is the function of interval between the drug administration which induces or entrains specific phase relation between serotonergic and dopaminergic oscillations. Further, gonadal suppression observed in HTP:DOPA, HTP+PCPA:DOPA and HTP:DOPA+DDC group three groups is not due to injection of 5-HTP or L-DOPA (alone) but due to conversion of administered 5-HTP into serotonin and conversion of L-DOPA (administered) into dopamine; not due to their further conversion into catecholamines other than dopamine i.e. noradrenaline or adrenaline.
An efficient and robust laboratory workflow and tetrapod database for larger scale eDNA studies
Authors: Axtner Jan , Crampton-Platt Alex , Hörig Lisa A. , Mohamed Azlan , Xu Charles C.Y. , Yu Douglas W. , Wilting Andreas 
Published: June 2018

AbstractBackgroundThe use of environmental DNA, ‘eDNA,’ for species detection via metabarcoding is growing rapidly. We present a co-designed lab workflow and bioinformatic pipeline to mitigate the two most important risks of eDNA: sample contamination and taxonomic mis-assignment. These risks arise from the need for PCR amplification to detect the trace amounts of DNA combined with the necessity of using short target regions due to DNA degradation.FindingsOur high-throughput workflow minimises these risks via a four-step strategy: (1) technical replication with two PCRreplicatesand twoextraction replicates; (2) using multi-markers (12S,16S, CytB); (3) a ‘twin-tagging,’ two-step PCR protocol;(4) use of the probabilistic taxonomic assignment methodPROTAX, which can account for incomplete reference databases.As annotation errors in the reference sequences can result in taxonomic mis-assignment, we supply a protocol for curating sequence datasets. For some taxonomic groups and some markers, curation resulted in over 50% of sequences being deleted from public reference databases, due to (1) limited overlap between our target amplicon and reference sequences; (2) mislabelling of reference sequences; (3) redundancy.Finally, we provide a bioinformatic pipeline to process amplicons and conductPROTAXassignment and tested it on an ‘invertebrate derived DNA’ (iDNA) dataset from 1532 leeches from Sabah, Malaysia. Twin-tagging allowed us to detect and exclude sequences with non-matching tags. The smallest DNA fragment (16S) amplified most frequently for all samples, but was less powerful for discriminating at species rank. Using a stringent and lax acceptance criteria we found 162 (stringent) and 190 (lax) vertebrate detections of 95 (stringent) and 109 (lax) leech samples.ConclusionsOur metabarcoding workflow should help research groups increase the robustness of their results and therefore facilitate wider usage of e/iDNA, which is turning into a valuable source of ecological and conservation information on tetrapods.
cDeepbind: A context sensitive deep learning model of RNA-protein binding
Authors: Gandhi Shreshth , Lee Leo J. , Delong Andrew , Duvenaud David , Frey Brendan J. 
Published: June 2018

AbstractMotivationDetermining RNA binding protein(RBP) binding specificity is crucial for understanding many cellular processes and genetic disorders. RBP binding is known to be affected by both the sequence and structure of RNAs. Deep learning can be used to learn generalizable representations of raw data and has improved state of the art in several fields such as image classification, speech recognition and even genomics. Previous work on RBP binding has either used shallow models that combine sequence and structure or deep models that use only the sequence. Here we combine both abilities by augmenting and refining the original Deepbind architecture to capture structural information and obtain significantly better performance.ResultsWe propose two deep architectures, one a lightweight convolutional network for transcriptome wide inference and another a Long Short-Term Memory(LSTM) network that is suitable for small batches of data. We incorporate computationally predicted secondary structure features as input to our models and show its effectiveness in boosting prediction performance. Our models achieved significantly higher correlations on held out in-vitro test data compared to previous approaches, and generalise well to in-vivo CLIP-SEQ data achieving higher median AUCs than other approaches. We analysed the output from our model for VTS1 and CPO and provided intuition into its working. Our models confirmed known secondary structure preferences for some proteins as well as found new ones where secondary structure might play a role. We also demonstrated the strengths of our model compared to other approaches such as the ability to combine information from long distances along the input.AvailabilitySoftware and models are available at https://github.com/shreshthgandhi/cDeepbindContactljlee@psi.toronto.edu, frey@psi.toronto.edu
Comparison of stimulus-evoked BOLD responses in human and monkey visual cortex
Authors: Patel Gaurav H. , Cohen Alexander L. , Baker Justin T. , Snyder Lawrence H. , Corbetta Maurizio 
Published: June 2018

AbstractWe characterized the blood oxygenation level dependent (BOLD) signal in humans and macaque monkeys by comparing the response in visual cortex to a single checkerboard or two checkerboards, spaced 1.5, 3.0, or 4.5 s apart. We found that the magnitude and shape of the BOLD response to a single checkerboard was similar in the two species. In addition, we found that the BOLD responses summed similarly, and that at an inter-stimulus interval (ISI) of 4.5 sec BOLD summation was nearly linear in both species. When comparing the ratio of the amplitude of the response to the second checkerboard at the 4.5 sec ISI with that of the single checkerboard between subjects in both species, the results from both monkey subjects fell within one standard deviation of the mean human results (human mean (n=12): .95 +/− .31 second/single response amplitude; monkey 1: 1.16; monkey 2: .86). At the shorter ISIs, both species demonstrated increased suppression of the BOLD response to the second checkerboard. These findings indicate that the magnitude of the BOLD response to events separated by 4.5 seconds can be accurately measured in and compared between human and monkey visual cortex.
Saracatinib and Dasatinib Fail To Prevent Heritable Pulmonary Arterial Hypertension
Authors: D’Amico Reid W. , Gladson Santhi , Shay Sheila , Copeland Courtney , West James D. 
Published: June 2018

AbstractEvidence suggests that the deregulation of SRC Family Kinases may play a role in the development of heritable pulmonary arterial hypertension, associated with BMPR2 mutations. The truncated c-terminus of the BMPR2 protein is known to increase the phosphorylation and downstream activity of SRC tyrosine kinases. To test the hypothesis that the inhibition of SRC can prevent heritable PAH due to a BMPR2 mutation, we exposed BMPR2 mutant mice to SRC inhibitors, saracatinib and dasatinib, to block the SRC activation caused by the BMPR2 mutation. Saracatinib and dasatinib failed to prevent the development of PAH in BMPR2 mutant mice. Increased pressure in the right ventricle was not normalized and muscularization of large blood vessels was not reduced when compared to wild type mice. Inhibiting SRC’s phosphorylation does not prevent heritable PAH, and thus supports evidence that SRC’s aberrant localization and trafficking in PAH plays a more critical role in disease development.
A synthetic non-histone substrate provides insight into substrate targeting by the Gcn5 HAT and sirtuin HDACs
Authors: Rössl Anthony , Lin Mong-Shang , Downey Michael 
Published: June 2018

ABSTRACTGcn5 and sirtuins are highly conserved HAT and HDAC enzymes that were first characterised as regulators of gene expression. Although histone tails are important substrates of these enzymes, these proteins also target many non-histone substrates that participate in diverse biological processes. The mechanisms used by these enzymes to choose their non-histone substrates is unclear. In this work, we use a unique synthetic biology approach in S. cerevisiae to demonstrate that a shared target sequence can act as a determinant of substrate selection for Gcn5 and sirtuins. We also exploit this system to define specific subunits of the Gcn5-containing ADA complex as regulators of non-histone acetylations proteome-wide.
Integrated thinking leading to integrated reporting: case study insights from a global player
Authors: Al-Htaybat Khaldoon , von Alberti-Alhtaybat Larissa 
Published: June 2018

PurposeThe purpose of this paper is to investigate the link between integrated thinking (IT) and integrated reporting (IR) in a global player. It seeks to shed light on how IT develops organically, using their IR as a source. Bourdieu’s theory of practice is utilised to explain the concept of IT and how it is established in the case organisation through publicly available corporate information.Design/methodology/approachVideo, document/text and interview material are used to investigate the perception and status quo of IT at the case organisation. Data were analysed in two coding stages to derive at the categories/themes that have the most explanatory power regarding the phenomenon under study.FindingsThe study contributes the organisational habitus of handling uncertainty and disruption, which governs the IT and IR initiative and development in the case organisation. Furthermore, it illustrates an empirical example of how an organisation has grown its IT approach over time and has introduced IR as a result of that, as a reflection on the IT approach.Originality/valueThis paper investigates a global organisation, the first provider of an integrated report in their geographical region, and its IT and reporting approach. The findings reflect on the organisational habitus of handling uncertainty and disruption, which leads to IT and ultimately IR. The case organisation constitutes a “natural integrated thinker” in their agile asset-light approach to their business and their integration of stakeholders beyond the organisation. They are the regional vanguard of sustainability and integration, as a result of which they have become one of the few global players of their region.
Defining and developing a scale to measure strategic thinking
Authors: Dhir Sanjay , Dhir Swati , Samanta Payel 
Published: June 2018

PurposeThis study aims to derive a sound definition of strategic thinking by horizontal analysis of past research and discussions with professionals.Design/methodology/approachThe research design includes three broad stages: item generation, scale development and assessment of scale’s psychometric properties.FindingsThe eclectic composition cuts across vocations, religions, sex and age strengthen the flexibility of application of the scale. The resulting scale shows strong psychometric properties and is expected to be useful for academics, practitioners and organizations alike.Research limitations/implicationsThe information on strategic thinking was self-reported through strategic thinking questionnaire (STQ) and is consequently at risk to be influenced by self-bias.Practical implicationsUsing the scale of strategic thinking will empower strategic thinkers to draw a more extensive scope of strategies at all levels. This will additionally bring about higher-quality procedures, increased performance and greater competitive advantage.Social implicationsThe study represents to be an imperative predecessor to strategic decision-making and may give a key to better comprehend authoritative change marvels and at last survival.Originality/valueAs the sample for our STQ has been collected from all across the country cross-sectioning different culture, gender and position of responsibility, the scale has significant robustness and implicative potential.
Dr Amit Goffer, co-founder at UPnRIDE, serial inventor and entrepreneur
Authors: Pransky Joanne 
Published: June 2018

Purpose
The following article is a “Q&A interview” conducted by Joanne Pransky of Industrial Robot Journal as a method to impart the combined technological, business and personal experience of a prominent industry engineer-turned successful innovator and entrepreneur regarding the development of his inventions and the challenges he faced. This paper aims to discuss these issues.

Design/methodology/approach
The interviewee is Dr Amit Goffer, Chief Technology Officer and President at UPnRIDE Robotics Ltd., a startup that makes a wheeled robotic device for almost anyone who is unable to physically stand or walk. He served as Chief Executive Officer (until 2012) and President and Chief Technical Officer of ReWalk Robotics, a company he founded in 2001 (previously called Argo Medical Technologies Ltd). Prior to Argo/ReWalk, Dr Goffer served as the Founder at Odin Medical Technologies Ltd. (later acquired by Medtronic), President and Chief Executive Officer. As an accomplished inventor and serial entrepreneur of medical devices, Goffer describes how his education in school and in running his companies combined with his life experiences led to his breakthroughs.

Findings
Dr Amit Goffer completed BSc from Technion-Israel Institute of Technology, MSc from Tel-Aviv University, Israel, and PhD from Drexel University, Philadelphia, USA, all in electrical and computer engineering. After working for Elscint, a medical imaging company, Goffer started Odin Medical to provide real-time magnetic resonance imaging images for brain surgery. After a tragic accident confined him to a wheelchair, Goffer created ReWalk, a robotic exoskeleton that enables people with lower limb disabilities to stand, walk, ascend/descend stairs and more. He recently founded his latest company, UPnRIDE.

Originality/value
Dr Amit Goffer is highly regarded as a pioneer of the emerging exoskeleton industry. His invention and development of the ReWalk Robotics wearable exoskeleton has enabled so far hundreds of wheelchair users to walk again, and another estimated 500,000 could benefit from it. Despite Goffer not being able to use the ReWalk himself, as he is a quadriplegic, his greatest passion is to improve the disabled’s self-esteem and quality of life. ReWalk was the first commercially available exoskeleton in the USA. It was named “best invention” by Popular Science and Time magazines. ReWalk Robotics went public in 2014. In 2015, the US Veteran’s Administration announced they would provide ReWalks for all eligible veterans with spinal cord injuries. Goffer recently devised UPnRIDE as a new product, allowing millions of wheelchair users worldwide, including himself, full mobility in the standing position in almost any urban environment.