bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Ca2+-regulated deAMPylation switch in human and bacterial FIC proteins
Authors: Veyron Simon , Oliva Giulia , Rolando Monica , Buchrieser Carmen , Peyroche Gérald , Cherfils Jacqueline 
Published: May 2018

AbstractFIC proteins regulate molecular processes from bacteria to humans by catalyzing post-translational modifications (PTM), the most frequent being the addition of AMP using ATP as a cofactor, a reaction coined AMPylation. In a large group of AMPylating FIC proteins, which includes single-domain bacterial FIC proteins and animal FICD/HYPE, AMPylation is intrinsically repressed by a structurally conserved glutamate. Curiously, FICD departs from previously characterized bacterial FIC proteins in that it acts bifunctionally to AMPylate and deAMPylate its target, the endoplasmic reticulum BiP/GRP78 chaperone. BiP is a key component of the unfolded protein response (UPR), and is AMPylated under normal conditions where its activity is low, while its activation correlates with its deAMPylation. Currently, a direct signal regulating AMPylation efficiency in bacterial and animal FIC proteins has not been identified. Here, we addressed this question for a FIC protein from the bacterial pathogen Enterococcus faecalis (EfFIC) and for human FICD. We discover that EfFIC catalyzes both AMPylation and deAMPylation within the same active site, suggesting that the conserved glutamate is the signature of AMPylation/deAMPylation bifunctionality. Crystal structures and PTM assays identify a multi-position metal switch implemented by the glutamate, whereby EfFIC uses Mg2+ and Ca2+ to control AMPylation and deAMPylation differentially without conformational change. Remarkably, we find that variations in Ca2+ levels also tune deAMPylation of BiP by human FICD. Together, our results identify metals as diffusible signals that can regulate bifunctional FIC proteins directly, and they suggest that FICD has features of an enzymatic sensor of Ca2+ depletion, a hallmark of the UPR.
Win-concurrent sensory cues can promote riskier choice
Authors: Cherkasova Mariya V. , Clark Luke , Barton Jason J.S. , Schulzer Michael , Shafiee Mahsa , Kingstone Alan , Stoessl A. Jon , Winstanley Catharine A. 
Published: May 2018

ABSTRACTReward-related stimuli can potently influence behaviour; for example, exposure to drug-paired cues can trigger drug use and relapse in people with addictions. Psychological mechanisms that generate such outcomes likely include cue-induced cravings and attentional biases. Recent animal data suggest another candidate mechanism: reward-paired cues can enhance risky decision making, yet whether this translates to humans is unknown. Here, we examined whether sensory reward-paired cues alter decision making under uncertainty and risk, as measured respectively by the Iowa Gambling Task and a two-choice lottery task. In the cued version of both tasks, gain feedback was augmented with reward-concurrent audiovisual stimuli. Healthy human volunteers (53 males, 78 females) performed each task once, one with and the other without cues (cued IGT/uncued VGT: n = 63; uncued IGT/cued VGT: n = 68), with concurrent eye-tracking. Reward-paired cues did not affect choice on the Iowa Gambling Task. On the two-choice lottery task, the cued group displayed riskier choice and reduced sensitivity to probability information. The cued condition was associated with reduced eye fixations on probability information shown on the screen and greater pupil dilation related to decision and reward anticipation. This pupil effect was unrelated to the risk-promoting effects of cues: the degree of pupil dilation for risky versus risk-averse choices did not differ as a function of cues. Taken together, our data show that sensory reward cues can promote riskier decisions and have additional and distinct effects on arousal.SIGNIFICANCE STATEMENT:Animal data suggest that reward-paired cues can promote maladaptive reward-seeking by biasing cost-benefit decision making. Whether this finding translates to humans is unknown. We examined the effects of salient reward-paired audio-visual cues on decision making under risk and uncertainty in human volunteers. Cues had risk-promoting effects on a risky choice task and independently increased task-related arousal as measured by pupil dilation. By demonstrating risk-promoting effects of cues in human participants, our data identify a mechanism whereby cue reactivity could translate into maladaptive behavioural outcomes in people with addictions.
GRIMM: GRaph IMputation and Matching for HLA Genotypes
Authors: Maiers Martin , Halagan Michael , Gragert Loren , Bashyal Pradeep , Schneider Joel , Lutsker Polina , Louzoun Yoram 
Published: May 2018

AbstractMotivation: For over 10 years allele-level HLA matching for bone marrow registries has been performed in a probabilistic context. HLA typing technologies provide ambiguous results in that they could not distinguish among all known HLA allele sequences, therefore registries have implemented matching algorithms that provide lists of donor and cord blood units ordered in terms of the likelihood of allele-level matching at specific HLA loci. With the growth of registry sizes, current match algorithm implementations are unable to provide match results in real time.Results: We present here novel computationally-efficient open source implementation of an HLA imputation and match algorithm using a graph database platform. Using graph traversal, our algorithm runtime grows slowly with registry size. This implementation generates results that agree with consensus output on a publicly-available match algorithm crossvalidation dataset.Availability: The Python, Perl and Neo4jJcode is available at https://git.com/nmdp-bioinformatics/grimmSupplementary information: Supplementary data are available at Bioinformatics online.
Magnaporthe oryzaeCK2 is involved in rice blast pathogenesis and accumulates in nuclei, nucleoli, at septal and appressoria pores and forms a large ring structure in appressoria
Authors: Zhang Lianhu , Zhang Dongmei , Chen Yunyun , Ye Wenyu , Lin Qingyun , Lu Guodong , Ebbole Daniel J. , Olsson Stefan , Wang Zonghua 
Published: May 2018

ABSTRACTMagnaporthe oryzae(Mo) is a model pathogen causing rice blast resulting in yield and economic losses world-wide. CK2 is a constitutively active, serine/threonine kinase in eukaryotes, having a wide array of known substrates and involved in many cellular processes. We investigated the localization and role of MoCK2 during growth and infection. BLAST search for MoCK2 components and targeted deletion of subunits was combined with protein-GFP fusions to investigate localization. We found one CKa and two CKb subunits of the CK2 holoenzyme. Deletion of the catalytic subunit CKa was not possible and might indicate that such deletions are lethal. The CKb subunits could be deleted but they were both necessary for normal growth and pathogenicity. Localization studies showed that the CK2 holoenzyme needed to be intact for normal localization at septal pores and at appressorium penetration pores. Nuclear localization of CKa was however not dependent on the intact CK2 holoenzyme. In appressoria, CK2 formed a large ring perpendicular to the penetration pore and the ring formation was dependent on the presence of all CK2 subunits. The effects on growth and pathogenicity of deletion of the b subunits combined with the localization indicate that CK2 can have important regulatory functions not only in the nucleus/nucleolus but also at fungal specific structures as septa and appressorial pores.
Serotonin and neuropeptides are both released by the HSN command neuron to initiateC. elegansegg laying
Authors: Brewer Jacob , Collins Kevin M. , Koelle Michael R. 
Published: May 2018

1AbstractNeurons typically release both a small molecule neurotransmitter and one or more neuropeptides, but how these two types of signal from the same neuron might act together remains largely obscure. For example, serotonergic neurons in mammalian brain express the neuropeptide Substance P, but it is unclear how serotonin signaling might be modulated by a coreleased neuropeptide. We studied this issue inC. elegans, in which all serotonergic neurons express the neuropeptide NLP-3. The serotonergic Hermaphrodite Specific Neurons (HSNs) are command motor neurons within the egg-laying circuit that have previously been shown to release serotonin to initiate egg-laying behavior. We found that egg-laying defects in animals lacking serotonin were far milder than in animals lacking HSNs, suggesting that HSNs must release other signal(s) in addition to serotonin to stimulate egg laying. While null mutants fornlp-3had only mild egg-laying defects, animals lacking both serotonin and NLP-3 had severe defects, like those of animals lacking HSNs. Optogenetic activation of HSNs induced egg laying in wild-type animals, or in mutant animals lacking either serotonin or NLP-3, but failed to induce egg laying in animals lacking both. We recorded calcium activity in the egg-laying muscles of animals lacking either serotonin, NLP-3, or both. The single mutants, and to a greater extent the double mutant, showed muscle activity that was uncoordinated and unable to expel eggs, such that the vm2 muscles cells that are direct postsynaptic targets of the HSN failed to contract simultaneously with other egg-laying muscle cells. Our results show that the HSN neurons use serotonin and the neuropeptide NLP-3 as partially redundant cotransmitters that together stimulate and coordinate activity of the target cells onto which they are released.
Achilles tendon structure in distance runners does not change following a competitive season
Authors: Hullfish Todd J. , Hagan Kenton L. , Casey Ellen , Baxter Josh R. 
Published: May 2018

AbstractAchilles tendon structure differs between trained distance runners and healthy controls, but the progression of tendon remodeling over the course of a competitive season is poorly understood. Therefore, the purpose of this study was to quantify Achilles tendon structure at the beginning and completion of a cross country season. We hypothesized that athletes who did not develop tendinopathy would not present with changes in tendon structure. Ultrasound assessments of the right Achilles tendon mid-substance were performed to quantify tendon organization, thickness, and echogenicity. Subjective structural measures and reported outcomes were also collected to determine if tendinopathy was present in any of the subjects. None of the subjects developed symptomatic tendinopathy over the course of the competitive season, but one runner did show signs of mild neovascularization. Tendon organization and echogenicity did not change over the course of the season. Tendon thickness increased by 7% (P < 0.001) but the effect size was small (d = 0.36). Runners who do not develop symptomatic tendinopathy have habituated tendon structure that may serve as a protective mechanism against the rigors of distance running. Monitoring tendon structure may serve as a means of detecting signs of structural indicators of tendinopathy prior to the presentation of symptoms.
Transcription drives DNA replication initiation and termination in human cells
Authors: Chen Yu-Hung , Keegan Sarah , Kahli Malik , Tonzi Peter , Fenyö David , Huang Tony T. , Smith Duncan J. 
Published: May 2018

ABSTRACTThe locations of active DNA replication origins in the human genome, and the determinants of origin activation, remain controversial. Additionally, neither the predominant sites of replication termination nor the impact of transcription on replication-fork mobility have been defined. We demonstrate that replication initiation occurs preferentially in the immediate vicinity of the transcription start site of genes occupied by high levels of RNA polymerase II, ensuring co-directional replication of the most highly transcribed genes. Further, we demonstrate that dormant replication origin firing represents the global activation of pre-existing origins. We also show that DNA replication naturally terminates at the polyadenylation site of transcribed genes. During replication stress, termination is redistributed to gene bodies, generating a global reorientation of replication relative to transcription. Our analysis provides a unified model for the coupling of transcription with replication initiation and termination in human cells.
Cell type specific profiling of alternative translation identifies novel protein isoforms in the mouse brain
Authors: Sapkota Darshan , Lake Allison M. , Yang Wei , Yang Chengran , Wesseling Hendrik , Guise Amanda , Uncu Ceren , Dalal Jasbir S. , Kraft Andrew , Lee Jin-Moo , Sands Mark S. , Steen Judith A. , Dougherty Joseph D. 
Published: May 2018

AbstractTranslation canonically begins at a single AUG and terminates at the stop codon, generating one protein species per transcript. However, some transcripts may use alternative initiation sites or sustain translation past their stop codon, generating multiple protein isoforms. Through other mechanisms such as alternative splicing, both neurons and glia exhibit remarkable transcriptional diversity, and these other forms of post-transcriptional regulation are impacted by neural activity and disease. Here, using ribosome footprinting, we demonstrate that alternative translation is likewise abundant in the central nervous system and modulated by stimulation and disease. First, in neuron/glia mixed cultures we identify hundreds of transcripts with alternative initiation sites and confirm the protein isoforms corresponding to a subset of these sites by mass spectrometry. Many of them modulate their alternative initiation in response to KCl stimulation, indicating activity-dependent regulation of this phenomenon. Next, we detect several transcripts undergoing stop codon readthrough thus generating novel C-terminally-extended protein isoforms in vitro. Further, by coupling Translating Ribosome Affinity Purification to ribosome footprinting to enable cell-type specific analysis in vivo, we find that several of both neuronal and astrocytic transcripts undergo readthrough in the mouse brain. Functional analyses of one of these transcripts, Aqp4, reveals readthrough confers perivascular localization, indicating readthrough can be a conserved mechanism to modulate protein function. Finally, we show that AQP4 readthrough is disrupted in multiple gliotic disease models. Our study demonstrates the extensive and regulated use of alternative translational events in the brain and indicates that some of these events alter key protein properties.
Bone Morphology is Regulated Modularly by Global and Regional Genetic Programs
Authors: Eyal Shai , Kult Shiri , Rubin Sarah , Krief Sharon , Pineault Kyriel M. , Wellik Deneen M. , Zelzer Elazar 
Published: May 2018

ABSTRACTDuring skeletogenesis, a variety of protrusions of different shapes and sizes develop on the surfaces of long bones. These superstructures provide stable anchoring sites for ligaments and tendons during the assembly of the musculoskeletal system. Despite their importance, the mechanism by which superstructures are patterned and ultimately give rise to the unique morphology of each long bone is far from understood. In this work, we provide further evidence that long bones form modularly fromSox9+cells, which contribute to their substructure, and fromSox9+/Scx+progenitors that give rise to superstructures. Moreover, we identify components of the genetic program that controls the patterning ofSox9+/Scx+progenitors and show that this program includes both global and regional regulatory modules.Using light sheet fluorescence microscopy combined with genetic lineage labeling, we mapped the broad contribution of theSox9+/Scx+progenitors to the formation of bone superstructures. Additionally, by combining literature-based evidence and comparative transcriptomic analysis of differentSox9+/Scx+progenitor populations, we identified genes potentially involved in patterning of bone superstructures. We present evidence indicating thatGli3is a global regulator of superstructure patterning, whereasPbx1, Pbx2, Hoxa11andHoxd11act as proximal and distal regulators, respectively. Moreover, by demonstrating a dose-dependent pattern regulation inGli3andPbx1compound mutations, we show that the global and regional regulatory modules work coordinately. Collectively, our results provide strong evidence for genetic regulation of superstructure patterning that further supports the notion that long bone development is a modular process.
Understanding the effects of WeChat on perceived social capital and psychological well-being among Chinese international college students in Germany
Authors: Pang Hua 
Published: May 2018

Purpose
The purpose of this paper is to explore how the intensity use of WeChat is associated with perceived social capital and psychological well-being factors among Chinese international students in Germany.

Design/methodology/approach
Based on an online survey data collected from 212 Chinese international college students in Germany, correlation analysis and structural equation modeling were sequentially implemented to deal with the research questions.

Findings
The correlation analysis results indicate that the intensity of WeChat use is positively correlated with bridging, bonding, and maintained social capital. Additionally, a path model demonstrates that bonding social capital is positively related to life satisfaction and negatively related to the sense of loneliness. Furthermore, both bonding and maintained social capital mediate the relationship between WeChat use and these two well-being outcomes.

Research limitations/implications
Theoretically, the research is an initial study contributing to the existing social media literature on evaluating the effects of WeChat use on social capital and well-being. Practically, these obtained results can be beneficial to the understanding the dynamics of how social media may potentially impact students’ social connectedness and life quality.

Originality/value
Although WeChat has become the most prevalent social networking site in Mainland China, the social and psychological implications of the emerging technology are not completely understood. The paper offers evidence that WeChat has functioned as an efficient platform for sojourners to develop diverse types of social capital and promote well-being in an intercultural setting.
The unpaid social cost of carbon
Authors: Linnenluecke Martina , Smith Tom , Whaley Robert E. 
Published: May 2018

PurposeThis paper aims to examine the complex issue of the social cost of carbon. The authors review the existing literature and the strengths and deficiencies of existing approaches. They introduce a simple methodology that estimates the amount of “legal looting” in the fossil fuel industry as an alternative approach to calculate an unpaid social cost of carbon. The “looting amount” can be defined as society’s failure to charge fossil fuel firms for the damage that their activities cause represents an implied subsidy.Design/methodology/approachThe methodology used in this paper combines decisions in the form of policymakers setting carbon taxes and rational investors investing in carbon emission markets.FindingsThe authors show that the unpaid social cost of carbon in the fossil fuel industry was US$12.7tn over 1995-2013, but may be as high as US$115.5tn.Originality/valueOver the same period, the sum of industry profits, emission trading scheme carbon permit and carbon tax revenue totalled US$7tn, indicating the industry would not be viable if it was made to pay for damages to society.
Developing and validating lean manufacturing constructs: an SEM approach
Authors: Nawanir Gusman , Lim Kong Teong , Othman Siti Norezam , Adeleke A.Q. 
Published: May 2018

PurposeThe purpose of this paper is to provide valid and reliable constructs for lean manufacturing (LM) for assessing its implementation level in order to target areas of improvement.Design/methodology/approachBased on an extensive review on LM literature and content validity assessment from practitioners and academicians, nine LM constructs were identified. Measurement items for each construct were developed to become a complete questionnaire. The questionnaire booklets were distributed to large and discrete manufacturing companies in Indonesia. Out of 1,000 survey questionnaires sent, 236 usable responses were returned giving response rate of 23.60 percent. Subsequently, an empirical assessment on the constructs was done by using structural equation modeling approach.FindingsThe study identified the valid and reliable LM constructs, consisting of nine LM constructs and 64 measurement items. The study found that all the constructs are complementary and mutually supportive with each other. Indeed, it suggests the holistic implementation of all the LM practices.Research limitations/implicationsOwing the time and resource constraint, this study only involved large and discrete process manufacturing industries in Indonesia. Hence, the generalization of the result is slightly limited. More studies in several different contexts are required.Practical implicationsThis study provided a valuable tool for researchers for gaining deeper understanding regarding the LM and its implementation. For practitioners, it is useful to evaluate the degree of LM employment in their companies, to target area of improvement, as well as to take possible actions in attempting to enhance the organizational performance. More importantly, practitioners should adopt all the LM practices in a holistic manner.Originality/valueThis study is the first attempt to develop LM constructs for evaluating the LM implementation in Indonesia.
Logistics outsourcing: a structured literature review
Authors: Akbari Mohammadreza 
Published: May 2018

PurposeThe purpose of this paper is to provide a structured literature review (SLR) and systematic insight into logistics outsourcing research, in order to identify gaps in knowledge, and provide future research direction in the logistics outsourcing discipline.Design/methodology/approachThis paper identifies and synthesises information from academic journals and examines research designs and methods, data analysis techniques, geographic locations, industry engagements, year of publication, publishers, university and author affiliations. A collection of online databases from 1991 to 2016 were explored, using the keywords “third-party”, “logistics” and “outsourcing” in their title and/or abstract, to deliver an inclusive listing of journal articles in this discipline area. Based on this approach, a total of 263 articles were found and data were derived from a succession of variables.FindingsThere has been a significant increase and concentration by researchers over the past 25 years focussing on logistics outsourcing. A need to implement best practice has been universally identified, owing to increasing global supply chain complexity. This analysis shows that only seven literature reviews were published in the logistics outsourcing discipline. Additionally, this study revealed that 42 per cent of the work in this field was found to be survey based and this trend in research indicates the development of the structural equation modelling and multi-criterion decision-making methods. Investigations between 2010–2012 and 2015–2016 accounted for 151 of the total 263 articles published. Finally, reverse logistics is an area that requires special attention.Research limitations/implicationsThis paper is limited to a review of academic articles obtainable from online databases, containing the words “logistics” and “outsourcing” in the title and/or abstract. Additionally, only papers from high quality, peer-reviewed journals were evaluated. Other academic sources such as books and conference papers were not included in this study.Originality/valueThis review will provide an increased understanding of the existing state of current research, trends and future research directions in the logistics outsourcing discipline.