bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Temperatures and High Pressures on the Growth and Survivability of Methanogens and Stable Carbon Isotope Fractionation: Implications for Deep Subsurface Life on Mars
Authors: Sinha Navita , Nepal Sudip , Kral Timothy , Kumar Pradeep 
Published: March 2018

AbstractIn order to examine the potential survivability of life in the Martian deep subsurface, we have investigated the effects of temperature (45°C, 55°C, and 65°C) and pressure (1 atm, 400 atm, 800 atm, and 1200 atm) on the growth, carbon isotopic data, and morphology of chemolithoautotrophic anaerobic methanogenic archaea,Methanothermobacter wolfeii. The growth and survivability of this methanogen were determined by measuring the methane concentration in headspace gas samples after the cells were returned to their conventional growth conditions. Interestingly, this methanogen survived at all the temperatures and pressures tested.M. wolfeiidemonstrated the highest methane concentration following exposure to pressure of 800 atm and a temperature of 65°C. We found that the stable carbon isotopic fractionation of methane, δ13C(CH4), was slightly more enriched in12C at 1 atm and 55°C than the carbon isotopic data obtained in other temperature and pressure conditions. A comparison of the images of the cells before and after the exposure to different temperatures and pressures did not show any obvious alteration in the morphology ofM. wolfeii. The research reported here suggests that at least one methanogen,M. wolfeii, may be able to survive under hypothetical Martian subsurface conditions with respect to temperature and pressure.
Discrete Modeling Dynamical Systems That Determine the Role of Biodiversity in Different Regimes of Using Resources at Different Levels of Organization of Living Matter
Authors: Bespalov Yu.G. 
Published: March 2018

AbstractThe paper aims at mathematical modeling of dynamic systems that determine the role of biodiversity in different modes of resource usage at different levels of the organization of living matter. As a measure of biodiversity, the number of different strategies of the performance of a biological system is used, which differ in ways of usage of the resources by this system. This measure can be supplemented, and in some cases, replaced by the degree of evenness of the intensity of different ways of using resources. As a result of modeling with use of a new class of mathematical models called Discrete Models of Dynamical Systems, the appearance of matrices representing the sets of these strategies corresponding to combinations of values of the system’s parameters in columns, strategies observed for the regimes of maximum and limited usage of resources was analyzed. Using the case study related to a local fish population in a pond, it was shown that, in comparison with the regimes of limited use of resources, the regime of maximum usage distinguishes by a larger degree of evenness of the intensities of different ways of using resources by the system. Different size-age groups of the population play the role of resources. A similar result was obtained earlier for different regimes of the performance of the human cardiovascular system; in this case, the heart rate and blood pressure played the role of different ways of resources usage. The similarity of the results obtained for such different biological systems allows us to hope for the prospects of developing universal system approaches to the use of generalized biodiversity parameters for the diagnosis of the state of bioobjects, in particular, with the help of aerospace methods. The necessity of such methods is significantly increasing in the context of global climate change.
Spatiotemporal manipulation of ciliary glutamylation reveals its roles in intraciliary trafficking and Hedgehog signaling
Authors: Hong Shi-Rong , Wang Cuei-Ling , Huang Yao-Shen , Chang Yu-Chen , Chang Ya-Chu , Pusapati Ganesh V. , Lin Chun-Yu , Hsu Ning , Cheng Hsiao-Chi , Chiang Yueh-Chen , Huang Wei-En , Shaner Nathan C. , Rohatgi Rajat , Inoue Takanari , Lin Yu-Chun 
Published: March 2018

AbstractTubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells and are suggested to be involved in a wide range of cellular activities. However, the complexity and dynamic distribution of tubulin PTMs within cells have hindered the understanding of their physiological roles in specific subcellular compartments. Here we develop a method to rapidly deplete tubulin glutamlyation inside the primary cilia, a microtubule-based sensory organelle protruding on the cell surface, by targeting an engineered deglutamylase to the cilia in minutes. This rapid deglutamylation quickly leads to altered ciliary functions such as kinesin-2-mediated anterograde intraflagellar transport and Hedgehog signaling, along with no apparent crosstalk to other PTMs such as acetylation and detyrosination. Our study offers a feasible approach to spatiotemporally manipulate tubulin PTMs in living cells. Future expansion of the repertoire of actuators that regulate PTMs may facilitate a comprehensive understanding of how diverse tubulin PTMs encode ciliary as well as cellular functions.
High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of secondary mechanical hyperalgesia
Authors: Manresa José Biurrun , Andersen Ole Kæseler , Mouraux André , van den Broeke Emanuel N. 
Published: March 2018

ABSTRACTHigh frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin (secondary hyperalgesia). Moreover, it has been shown that brief high intensity CO2 laser stimuli, activating both Aδ- and C-fiber nociceptors, are perceived as more intense when delivered in the area of secondary hyperalgesia. To investigate the contribution of A-fiber nociceptors to secondary hyperalgesia the present study assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating Aδ-fiber nociceptors, are increased in the area of secondary hyperalgesia. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. HFS induced a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive inputs conveyed by AMH-II nociceptors. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that AMH-II nociceptors do not contribute to HFS-induced secondary hyperalgesia.
Immunostimulatory guide RNAs mediate potent antiviral response
Authors: Cai Yujia , Knudsen Alice , Windross Samuel Joseph , Thomsen Martin K , Paludan Søren R 
Published: March 2018

AbstractGenome-editing with CRISPR has emerged as a technology with broad therapeutic potential. However, it is unclear whether CRISPR will elicit innate immune responses, which could impact both positively and negatively on the desired therapeutic effects. Here, we have examined the immune-stimulatory properties of different variants of guide RNAs (gRNAs) – in vitro transcribed gRNA (IVT-gRNA) and synthetic gRNAs with or without chemical modifications, full-length or duplexed. We find that only IVT-gRNA evokes strong expression of cytokines in a panel of cell lines while all the synthetic RNAs do not. We further find that sensing of IVT-gRNA proceeds mainly through the RIG-I/MAVS RNA sensing axis. One potential use of CRISPR is for antiviral therapy. The antiviral actions of the gRNA tested up until now have been relying purely on the gene editing function of the CRISPR machinery, which weakens its feasibility due to the difficulty to target all infected cells. When IVT-gRNA was combined with unmodified Cas9 mRNA, which also induces cytokine expression, strong immune response was obtained while maintaining nuclease activity of CRISPR. Remarkably, such combination inhibited herpes simplex virus type-1 (HSV-1) replication even though the nuclease activity was modest, and provided ‘bystander protection’ to the cells that were not transfected with CRIPSR molecules. The antiviral activity of IVT-gRNA was also observed in vivo in HSV-1-infected Cas9+ mice, thus demonstrating the therapeutic potential. Our study further extends the applications of CRISPR by exploiting the immunostimulatory function of gRNAs.
ERASE: a novel surface reconditioning strategy for single-molecule experiments
Authors: Bo Broadwater D W , Altman Roger B , Blanchard Scott C , Kim Harold D 
Published: March 2018

AbstractWhile surface-based single-molecule experiments have revolutionized our understanding of biology and biomolecules, the workflow in preparing for such experiments, especially surface cleaning and functionalization remains labor-intensive and time-consuming. Even worse, meticulously assembled flow channels can be used only once for most experiments. A reusable surface would thus dramatically increase productivity and efficiency of single-molecule experiments. In this paper, we report a novel surface reconditioning strategy termed ERASE (Epitaxial Removal Aided by Strand Exchange) that allows a single flow cell to be used for vast repetition of single-molecule experiments. In this method, biomolecules immobilized to the surface through a nucleic acid duplex are liberated when a competing DNA strand disrupts the duplex via toehold-mediated strand displacement. We demonstrate the wide-range applicability of this method with various common surface preparation techniques, fluorescent dyes, and biomolecules including the bacterial ribosome. Beyond time and cost savings, we also show ERASE can assort molecules based on a nucleic acid barcode sequence, thus allowing experiments on different molecules in parallel. Our method increases the utility of prepared surfaces and is a significant improvement to the current single-use paradigm.
Reversible inhibition of specific transcription factor-DNA interactions using CRISPR
Authors: Shariati Ali , Dominguez Antonia , Wernig Marius , Qi Lei S. , Skotheim Jan M. 
Published: March 2018

AbstractThe control of gene expression by transcription factor binding sites frequently determines phenotype. However, it has been difficult to assay the function of single transcription factor binding sites within larger transcription networks. Here, we developed such a method by using deactivated Cas9 to disrupt binding to specific sites on the genome. Since CRISPR guide RNAs are longer than transcription factor binding sites, flanking sequence can be used to target specific sites. Targeting deactivated Cas9 to a specific Oct4 binding site in the Nanog promoter blocked Oct4 binding, reduced Nanog expression, and slowed division. Multiple guide RNAs allows simultaneous inhibition of multiple binding sites and conditionally-destabilized dCas9 allows rapid reversibility. The method is a novel high-throughput approach to systematically interrogate cis-regulatory function within complex regulatory networks.
DIA-NN: Deep neural networks substantially improve the identification performance of Data-independent acquisition (DIA) in proteomics
Authors: Demichev Vadim , Messner Christoph B. , Lilley Kathryn S. , Ralser Markus 
Published: March 2018

AbstractData-independent acquisition (DIA-MS) strategies, like SWATH-MS, have been developed to increase consistency, quantification precision and proteomic depth in label-free proteomic experiments. They aim to overcome stochasticity in the selection of precursor ions by utilising (mass-) windowed acquisition that is followed by computational reconstruction of the chromatograms. While DIA methods increasingly outperform typical data-dependent methods in identification consistency and precision specifically on large sample series, possibilities remain for further improvements. At present, only a fraction of the information recorded in the complex DIA spectra is extracted by the software analysis pipelines. Here we present a software tool (DIA-NN) that introduces artificial neural nets and a new quantification strategy to enhance signal processing in DIA-data. DIA-NN greatly improves identification of precursor ions and, as a consequence, protein quantification accuracy. The performance of DIA-NN demonstrates that deep learning provides opportunities to boost the analysis of data-independent acquisition workflows in proteomics.
Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis dependence
Authors: Feng Zhou , Kaeli Zimmermann , Fei Xin , Scheele Dirk , Dau Wolfgang , Banger Markus , Weber Bernd , Hurlemann René , Kendrick Keith M , Becker Benjamin 
Published: March 2018

ABSTRACTThe transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral to dorsal striatal control of behavior, however this shift has not been directly examined in humans. Against this background the present resting state fMRI study employed a two-step approach to (1) precisely map striatal alterations using a novel, data-driven network classification strategy combining Intrinsic Connectivity Contrast (ICC) with Multivoxel Pattern Analysis (MVPA) and, (2) to determine whether a ventral to dorsal striatal shift in connectivity with reward and and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral ACC) and executive / regulatory functions (dorsomedial PFC). Specifically, in the cannabis dependent subjects connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.
Inhibitory Units: An Organizing Nidus for Feature-Selective Sub-Networks in Area V1
Authors: Palagina Ganna , Meyer Jochen F. , Smirnakis Stelios M. 
Published: March 2018

SUMMARYSensory stimuli are encoded by the joint firing of neuronal groups composed of pyramidal cells and interneurons, rather than single isolated neurons (Uhlhaas et al, 2009, Buzsaki, 2010). However, the principles by which these groups are organized to encode information remain poorly understood. A leading hypothesis is that similarly tuned pyramidal cells that preferentially connect to each other may form multi-cellular encoding units yoked to a similar purpose. The existence of such groups would be reflected on the profile of spontaneous events observed in neocortical networks. We used 2-photon calcium imaging to study spontaneous population-burst events in layer 2/3 of mouse area V1 during postnatal maturation (postnatal day 8–52). Throughout the period examined both size and duration of spontaneously occurring population-bursts formed scale-free distributions obeying a power law. The same was true for the degree of “functional connectivity,” a measure of pairwise synchrony across cells. These observations are consistent with a hierarchical small-world-net architecture, characterized by groups of cells with high local connectivity (“small worlds”, cliques) connected to each other via a restricted number of “hub” cells” (Bonifazi et al., 2009, Sporns, 2011, Luce & Perry, 1949). To identify candidate “small world” groups we searched for cells whose calcium events had a consistent temporal relationship to events recorded from local inhibitory interneurons. This was guided by the intuition that groups of neurons whose synchronous firing represents a “temporally coherent computational unit” (or feature) ought to be inhibited together. This strategy allowed us to identify clusters of pyramidal neurons whose firing is temporally “linked” to one or more local interneurons. These “small-world” clusters did not remain static, during postnatal development: both cluster size and overlap with other clusters decreased over time as pyramidal neurons became progressively more selective, “linking” to fewer neighboring interneurons. Notably, pyramidal neurons in a cluster show higher tuning function similarity than expected with each other and with their “linked” interneurons. Our findings suggest that spontaneous population events in the visual cortex are shaped by “small-world” networks of pyramidal neurons that share functional properties and work in concert with one or more local interneurons. We argue that such groups represent a fundamental neocortical unit of computation at the population level.
A genetic perspective on the relationship between eudaimonic –and hedonic well-being
Authors: Baselmans B.M.L. , Bartels M. 
Published: March 2018

AbstractWhether hedonism or eudaimonism are two distinguishable forms of well-being is a topic of ongoing debate. To shed light on the relation between the two, large-scale available molecular genetic data were leveraged to gain more insight into the genetic architecture of the overlap between hedonic and eudaimonic well-being. Hence, we conducted the first genome-wide association studies (GWAS) of eudaimonic well-being (N = ∼108K) and linked it to a GWAS of hedonic well-being (N = ∼ 222K). We identified the first two genome-wide significant independent loci for eudaimonic well-being and 6 independent loci for hedonic well-being. Joint analyses revealed a moderate phenotypic correlation (r = 0.53), but a high genetic correlation (rg = 0.78) between eudaimonic and hedonic well-being. For both traits we identified enrichment in the frontal cortex -and cingulate cortex as well as the cerebellum to be top ranked. Bi-directional Mendelian Randomization analyses using two-sample MR indicated some evidence for a causal relationship from hedonic well-being to eudaimonic well-being whereas no evidence was found for the reverse. Additionally, genetic correlations patterns with a range of positive and negative related phenotypes were largely similar for hedonic –and eudaimonic well-being. Our results reveal a large genetic overlap between hedonism and eudaimonism.
Cochaperones enable Hsp70 to fold proteins like a Maxwell’s demon
Authors: Xu Huafeng 
Published: March 2018

AbstractThe heat shock protein 70 (Hsp70) chaperones, vital to the proper folding of proteins inside cells, consume ATP and require cochaperones in assisting protein folding. It is unclear whether Hsp70 can utilize the free energy from ATP hydrolysis to fold a protein into a native state that is thermodynamically unstable in the chaperone-free equilibrium. Here we present a model of Hsp70-mediated protein folding, which predicts that Hsp70, as a result of differential stimulation of ATP hydrolysis by its Hsp40 cochaperone, dissociates faster from a substrate in fold-competent conformations than from one in misfolding-prone conformations, thus elevating the native concentration above and suppressing the misfolded concentration below their respective equilibrium values. Previous models would not make or imply these predictions, which are experimentally testable. Our model quantitatively reproduces experimental refolding kinetics, predicts how modulations of the Hsp70/Hsp40 chaperone system affect protein folding, and suggests new approaches to regulating cellular protein quality.
An immune genetic algorithm for simple assembly line balancing problem of type 1
Authors: Zhang Han-ye 
Published: March 2018

Purpose
The purpose of this study is to develop an immune genetic algorithm (IGA) to solve the simple assembly line balancing problem of type 1 (SALBP-1). The objective is to minimize the number of workstations and workstation load for a given cycle time of the assembly line.

Design/methodology/approach
This paper develops a new solution method for SALBP-1, and a user-defined function named ψ(·) is proposed to convert all the individuals to satisfy the precedence relationships during the operation of IGA.

Findings
Computational experiments suggest that the proposed method is efficient.

Originality/value
An IGA is proposed to solve the SALBP-1 for the first time.
Corporate risk-taking and performance in Malaysia: the effect of board composition, political connections and sustainability practices
Authors: Chong Lee-Lee , Ong Hway-Boon , Tan Siow-Hooi 
Published: March 2018

PurposeThis paper aims to examine how board composition, political connections and sustainability practices affect risk-taking and performance of firms.Design/methodology/approachThis paper used secondary data and regression technique to analyse the relationship. A sample consisting of 290 firm-year observations was applied in the analysis.FindingsThe findings show that a larger board size contributes to greater financial risk; however, this risk can be reduced with more independent directors in the boardroom. An optimal board size with appropriate number of independent directors is desired, as a large board size can be harmful to firm performance. Politically connected firms also generate lower risk-taking and performance, and the double-edged sword effect of political connections needs to be considered. In terms of sustainability practices, firms have to engage in sustainable development to maximise the firms’ value, not ignoring the vital role of women in strategising business performance. However, the effect of sustainability practices on firms’ risk-taking is still not noticeable.Research limitations/implicationsEven though the sample size is not large because of the limited availability of data, the findings, to a certain extent, could be generalised to emerging markets, as most emerging markets do have similar financial and economic developments.Practical implicationsThe findings from this paper can be used to support the implementation of sustainability practices, especially in those countries where sustainability initiatives are yet to be widely accepted.Originality/valueThis is one of the first few studies that examined the effect of non-financial information on risk-taking and performance of firms. This study concludes the positive effect of sustainability practices on firm performance.