bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immuno-Detection by sequencing (ID-seq) enables large-scale high-dimensional phenotyping in cells
Authors: van Buggenum Jessie A.G. , Gerlach Jan P. , Tanis Sabine E.J. , Hogeweg Mark , Middelwijk Jesse , van der Steen Ruud , Albers Cornelis A. , Mulder Klaas W. 
Published: July 2017

AbstractCell-based small molecule screening is an effective strategy leading to new medicines. Scientists in the pharmaceutical industry as well as in academia have made tremendous progress in developing both large-scale and smaller-scale screening assays. However, an accessible and universal technology for measuring large numbers of molecular and cellular phenotypes in many samples in parallel is not available. Here, we present the Immuno-Detection by sequencing (ID-seq) technology that combines antibody-based protein detection and DNA-sequencing via DNA-tagged antibodies. We used ID-seq to simultaneously measure 84 (phospho-)proteins in hundreds of samples and screen the effects of ~300 kinase inhibitor probes on primary human epidermal stem cells to characterise the role of 225 kinases. Our work highlighted a previously unrecognized downregulation of mTOR signaling during differentiation and uncovered 13 kinases regulating epidermal renewal through distinct mechanisms.
Methods for the Refolding of Disulfide-Rich Proteins
Authors: Haggarty-Weir Christopher N , Galloway Roma , Godfrey William 
Published: July 2017

AbstractEschericia coliremains the workhorse producing recombinant proteins given its ease of handling, access and genetic manipulation using standard laboratory techniques. However, disulfide-rich proteins can be difficult to produce inE. coli, in large part due to the reducing environment of the bacterial cytoplasm. Refolding from insoluble inclusion bodies can be a viable strategy for generating substantial quantities of disulfide-rich protein. For the best chance of successfully refolding a protein, it is vital to carry out a variety of small-scale test refolds under a swathe of conditions including altering the concentration of urea, salts, reduced and oxidized glutathione, temperature, length of refold time and protein dilution factor. Once a protein has undergone refolding it is vital to determine that the final product is natively folded given the chance of soluble misfolded protein. For determination of correct folding, a variety of techniques can be employed, and ideally, numerous should be used together. For proteins that possess enzymatic function the gold standard to assess correct folding is an activity assay. Non-enzymatic proteins can be assessed using a combination of circular dichroism and nuclear magnetic resonance spectroscopy. These techniques should be utilized alongside mass spectrometry, Western blotting and SDS-PAGE.
Single-cell replication profiling reveals stochastic regulation of the mammalian replication-timing program
Authors: Dileep Vishnu , Gilbert David M. 
Published: July 2017

AbstractIn mammalian cells, distinct replication domains (RDs), corresponding to structural units of chromosomes called topologically-associating domains (TADs), replicate at different times during S-phase1–4. Further, early/late replication of RDs corresponds to active/inactive chromatin interaction compartments5,6. Although replication origins are selected stochastically, such that each cell is using a different cohort of origins to replicate their genomes7–12, replication-timing is regulated independently and upstream of origin selection13and evidence suggests that replication timing is conserved in consecutive cell cycles14. Hence, quantifying the extent of cell-to-cell variation in replication timing is central to studies of chromosome structure and function. Here we devise a strategy to measure variation in single-cell replication timing using DNA copy number. We find that borders between replicated and un-replicated DNA are highly conserved between cells, demarcating active and inactive compartments of the nucleus. Nonetheless, measurable variation was evident. Surprisingly, we detected a similar degree of variation in replication timing from cell-to-cell, between homologues within cells, and between all domains genome-wide regardless of their replication timing. These results demonstrate that stochastic variation in replication timing is independent of elements that dictate timing or extrinsic environmental variation.
Enabling healthy food choices in the workplace: the canteen operators’ perspective
Authors: Price Sarah , Bray Jeffery , Brown Lorraine 
Published: June 2017

Purpose
Employees eat regularly in workplace foodservice settings, thus the food served can significantly impact their overall diet. Workplace foodservice providers are facing several challenges, including changing consumer demands, partial blame for high levels of obesity and the delivery of accessible information that can encourage healthier food choices. The purpose of this paper is to explore the industry perspective on consumer information needs and to assess the challenges faced by foodservice providers in terms of responding to these in a workplace setting.

Design/methodology/approach
A qualitative approach was adopted, involving ten in-depth semi-structured interviews with contract catering managers in the UK and Germany.

Findings
Canteen operators have a sound understanding of what is important to their customers. However, the amount of dish information currently provided is limited, and the reasons for this are discussed. The menu remains the traditional medium of communication of information on dishes, but there is openness to technical platforms, which not only reduce information overload but also increase customer engagement.

Practical implications
Technological solutions are discussed as a way to overcome barriers to information provision providing workplace caterers with a clear approach to effectively communicate enhanced dish information.

Social implications
The provision of enhanced dish information has been found to influence consumers’ to make more healthful selections. This is an important public health issue given the growing rates of obesity and diabetes type 2.

Originality/value
This study makes an original contribution by exploring the industry perspective on consumer needs for information and on how this information can be provided.
Does more energy consumption support economic growth in net energy-importing countries?
Authors: Esen Ömer , Bayrak Metin 
Published: June 2017

PurposeThis study aims to examine the effects of energy consumption on economic growth by means of a panel data analysis of 75 net energy-importing countries for the period 1990 to 2012.Design/methodology/approachFor the purpose of the analysis, the countries are classified into two groups, and each group is then classified into subgroups. The first group is formed based on the energy import dependence of the countries and is classified into two subgroups according to whether their dependence is greater than or less than 50 per cent. The second group is formed based on the income level of the countries and is classified into four subgroups, specifically, low-income economies, lower-middle-income economies, upper-middle-income economies and high-income economies.FindingsThe findings obtained for both panel data and for each country indicate that there is a positive and statistically significant relationship between energy consumption and economic growth over the long term such that energy consumption contributes more to economic growth as the import dependence of the country decreases. Moreover, the effect of energy consumption on economic growth decreases as the income level of the country increases. This indicates that the efficient use of energy is as important as energy consumption, which is regarded as an important indicator of economic development.Originality/valueThe authors expect that these findings will make a valuable contribution to the results of future studies, as they analyze the relationships among the variables by including the energy intensities of the countries.
Building police legitimacy in a high demand environment: the case of Yukon, Canada
Authors: Taylor Griffiths Curt , Clark Peter 
Published: June 2017

Purpose
Police legitimacy has emerged as a core concept in the study of twenty-first century policing. The purpose of this paper is to contribute new knowledge by examining the dynamics surrounding policing legitimacy in a high demand environment in Northern Canada.

Design/methodology/approach
A case study approach was used to explore the historical and contemporary factors that contributed to the challenges surrounding the police-First Nations relations, how these challenges affected public confidence in, and trust of, the police, and how the communities, police, and government took action to address these issues.

Findings
The findings reveal that it is possible for the police, First Nations, and government in high demand environments to implement reforms and to create the foundation for police-community collaboration. The development of relationships based on trust and a continuing dialogue is important components in building police legitimacy.

Research limitations/implications
The study was conducted in one northern jurisdiction. The findings may apply to other jurisdictions where the police are involved in policing indigenous peoples.

Practical implications
The case study provides insight into the processes required to fundamentally alter the police-First Nations relations, to improve police service delivery in high demand environments, and to ensure that reforms are sustained.

Originality/value
Police legitimacy has been examined primarily in urban environments where police services have considerable capacities and there re-extensive networks of support from various agencies and organizations. The dynamics of policing in northern communities are appreciably different and present challenges as well as opportunities for improving police legitimacy.
The FgSRP1 SR‐protein gene is important for plant infection and pre‐mRNA processing in Fusarium graminearum
Authors: Zhang Yimei , Gao Xuli , Sun Manli , Liu Huiquan , Xu Jin‐Rong 
Published: June 2017

SummaryThe versatile functions of SR (serine/arginine‐rich) proteins in pre‐mRNA splicing and processing are modulated by reversible phosphorylation. Previous studies showed that FgPrp4, the only protein kinase among spliceosome components, is important for intron splicing and the FgSrp1 SR protein is phosphorylated at five conserved sites in Fusarium graminearum. In this study, we showed that the Fgsrp1 deletion mutant rarely produced conidia and caused only limited symptoms on wheat heads and corn silks. Deletion of FgSRP1 also reduced ascospore ejection and deoxynivalenol (DON) production. Interestingly, FgSRP1 had two transcript isoforms due to alternative splicing and both of them were required for its normal functions in growth and DON biosynthesis. FgSrp1 localized to the nucleus and interacted with FgPrp4 in vivo. Deletion of all four conserved phosphorylation sites but not individual ones affected the FgSRP1 function, suggesting their overlapping functions. RNA‐seq analysis showed that the expression of over thousands of genes and splicing efficiency in over 140 introns were affected. Taken together, FgSRP1 is important for conidiation, and pathogenesis and alternative splicing is important for its normal functions. The FgSrp1 SR protein is likely important for pre‐mRNA processing or splicing of various genes in different developmental and infection processes.
Identification and occurrence of the hydroxamate siderophores aerobactin, putrebactin, avaroferrin and ochrobactin C as virulence factors from entomopathogenic bacteria
Authors: Hirschmann Merle , Grundmann Florian , Bode Helge B. 
Published: June 2017

SummaryEffective iron acquisition and fine‐tuned intracellular iron storage systems are the main prerequisites for a successful host invasion by a pathogen. Bacteria have developed several different strategies to sequester this essential element from their environment, one relies on the secretion of low molecular weight compounds with high affinity for ferric iron, the so‐called siderophores. Here, we report hydroxamate siderophore structures produced by entomopathogenic bacteria of the species Xenorhabdus and Photorhabdus, which are known for their potential to produce bioactive natural products, required for their role as nematode symbiont and insect pathogen. Four siderophores could be identified, namely aerobactin, putrebactin, avaroferrin and ochrobactin C, which was found previously only in marine bacteria. While the putrebactin and avaroferrin producing biosynthesis gene cluster (BGC) is more widespread and most likely was present in a common ancestor of these bacteria, the aerobactin and ochrobactin producing BGC was probably taken up by a few strains individually. For aerobactin a role in virulence towards Galleria mellonella larvae is shown.
The Piwi‐piRNA pathway: road to immortality
Authors: Sturm Ádám , Perczel András , Ivics Zoltán , Vellai Tibor 
Published: June 2017

SummaryDespite its medical, social, and economic significance, understanding what primarily causes aging, that is, the mechanisms of the aging process, remains a fundamental and fascinating problem in biology. Accumulating evidence indicates that a small RNA‐based gene regulatory machinery, the Piwi‐piRNA pathway, represents a shared feature of nonaging (potentially immortal) biological systems, including the germline, somatic cancer stem cells, and certain ‘lower’ eukaryotic organisms like the planarian flatworm and freshwater hydra. The pathway primarily functions to repress the activity of mobile genetic elements, also called transposable elements (TEs) or ‘jumping genes’, which are capable of moving from one genomic locus to another, thereby causing insertional mutations. TEs become increasingly active and multiply in the genomes of somatic cells as the organism ages. These characteristics of TEs highlight their decisive mutagenic role in the progressive disintegration of genetic information, a molecular hallmark associated with aging. Hence, TE‐mediated genomic instability may substantially contribute to the aging process.
Management of pancreaticojejunal strictures after pancreaticoduodenectomy: clinical experience and review of literature
Authors: Ghazanfar Mudassar A. , Soonawalla Zahir , Silva Michael A. , Reddy Srikanth 
Published: June 2017

BackgroundSymptomatic pancreaticojejunal anastomotic stricture (PJS) is a rare complication following pancreaticoduodenectomy. The incidence, presentation and management of this condition are infrequently reported in the literature. Revision surgery is thought to be an effective treatment. Recent literature shows some success from endoscopic management.MethodsThe patients treated for symptomatic PJS from January 2005 to June 2014 were identified. Their clinical presentation and management was retrospectively reviewed. Patients were followed up in clinic or by telephonic interviews to assess their symptoms.ResultsThree patients (two females and one male) had symptomatic PJS out of 314 who underwent pancreaticoduodenectomy (0.9%). Main presentating symptom was intermittent abdominal pain. The diagnosis was confirmed by computed tomography scan and/or magnetic resonance cholangiopancreatography. One patient underwent a failed endoscopic retrograde cholangiopancreatography attempt to dilate the stricture. A redo‐pancreaticojejunostomy was performed in all patients. At a mean follow‐up of 8 months, two patients had complete resolution of symptoms and one patient had partial benefit. Five out of seven case series in literature support surgical management.ConclusionSymptomatic PJS can be successfully treated with redo‐pancreaticojejunostomy, with good medium‐term outcomes. Although endoscopic intervention has been described, review of the literature shows that success rates are low and the long‐term results are unknown.
Distinction and the Ethics of Violence: On the Legal Construction of Liminal Subjects and Spaces
Authors: Perugini Nicola , Gordon Neve 
Published: July 2017

AbstractThis paper interrogates the relationship among visibility, distinction, international humanitarian law and ethics in contemporary theatres of violence. After introducing the notions of “civilianization of armed conflict” and “battlespaces”, we briefly discuss the evisceration of one of international humanitarian law's axiomatic figures: the civilian. We show how liberal militaries have created an apparatus of distinction that expands that which is perceptible by subjecting big data to algorithmic analysis, combining the traditional humanist lens with a post‐humanist one. The apparatus functions before, during, and after the fray not only as an operational technology that directs the fighting or as a discursive mechanism responsible for producing the legal and ethical interpretation of hostilities, but also as a force that produces liminal subjects. Focusing on two legal figures—“enemies killed in action” and “human shields”—we show how the apparatus helps justify killing civilians and targeting civilian spaces during war.
D‐512, a novel dopamine D2/3 receptor agonist, demonstrates greater anti‐Parkinsonian efficacy than ropinirole in Parkinsonian rats
Authors: Lindenbach David , Das Banibrata , Conti Melissa M , Meadows Samantha M , Dutta Aloke K , Bishop Christopher 
Published: July 2017

Background and PurposeSymptoms of Parkinson's disease are commonly managed using selective dopamine D2/3 receptor agonists, including ropinirole. While D2/3 agonists are useful in early‐stage Parkinson's disease, they tend to lose efficacy in later disease stages and do not appear to modify disease progression. We have recently developed a novel ‘multifunctional’ compound, D‐512: a high‐affinity D2/3 receptor agonist with antioxidant and other neuroprotective properties that may limit Parkinson's disease progression. This study sought to compare the anti‐Parkinsonian properties of the clinically used compound, ropinirole, with those of the novel compound, D‐512.Experimental ApproachA rat model of Parkinson's disease was created by unilaterally infusing 6‐hydroxydopamine, a dopamine neurotoxin, into the medial forebrain bundle. D‐512 was compared with ropinirole for ability to stimulate spontaneous motor activity and reverse Parkinsonian akinesia. These beneficial effects were compared against each drug's liability to provoke dyskinesia, a common motor side effect.Key ResultsBoth compounds increased spontaneous movement, but D‐512 showed a longer duration of action. Only D‐512 was able to significantly reverse forelimb akinesia. Drug‐induced dyskinesia was similar for equivalent doses.Conclusions and ImplicationsCompared with ropinirole, D‐512 showed greater peak‐dose efficacy and a longer duration of action, despite a similar side‐effect profile. Our results add to earlier data showing that D‐512 is superior to available D2/3 agonists and could merit clinical investigation.
Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies
Authors: O'Tuathaigh Colm M P , Moran Paula M , Zhen Xuechu C , Waddington John L 
Published: July 2017

The presence and severity of cognitive symptoms, including working memory, executive dysfunction and attentional impairment, contributes materially to functional impairment in schizophrenia. Cognitive symptoms have proved to be resistant to both first‐ and second‐generation antipsychotic drugs. Efforts to develop a consensus set of cognitive domains that are both disrupted in schizophrenia and are amenable to cross‐species validation (e.g. the National Institute of Mental Health Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia and Research Domain Criteria initiatives) are an important step towards standardization of outcome measures that can be used in preclinical testing of new drugs. While causative genetic mutations have not been identified, new technologies have identified novel genes as well as hitherto candidate genes previously implicated in the pathophysiology of schizophrenia and/or mechanisms of antipsychotic efficacy. This review comprises a selective summary of these developments, particularly phenotypic data arising from preclinical genetic models for cognitive dysfunction in schizophrenia, with the aim of indicating potential new directions for pro‐cognitive therapeutics.Linked ArticlesThis article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc
Synthesis and evaluation of novel thiazole‐based derivatives as selective inhibitors of DNA‐binding domain of the androgen receptor
Authors: Xu Ruixue , Tian Ye , Huang Shenzhen , Yu Jiang , Deng Yufang , Zhan Miao , Zhang Tao , Wang Fangying , Zhao Lifeng , Chen Yuanwei 
Published: July 2017

A series of thiazole‐based inhibitors selectively targeting DNA‐binding domain of the androgen receptor (AR) were synthesized and evaluated, and the SAR data were summarized. We identified a novel compound SKLB‐C2807 that effectively inhibited the human prostate cancer cell line LNCaP/AR with the IC50 value of 0.38 μm without significant antiproliferative effects on other cell lines PC‐3 (AR‐negative), SW620, MCF‐7 (ER‐positive), and L‐O2 (non‐cancerous). This compound also considerably decreased the expression of prostate‐specific antigen. Its binding mode to the AR‐DBD was studied. These efforts lay the foundation for developing the next generation of anti‐androgens.
Politics of innovation and development: The role of industry associations in integrating political, bureaucratic, industrial and health systems in India and South Africa
Authors: Papaioannou Theo , Watkins Andrew , Kale Dinar , Mugwagwa Julius 
Published: June 2017

AbstractIntegrating political, bureaucratic, industrial and healthcare systems has been a major challenge for politics of innovation and development policy in low‐ and middle‐income countries. This challenge has so far been understood in terms of separate industrial and health‐related innovation policies without paying adequate attention to the institutional roles of biopharmaceutical and other umbrella associations. This article seeks to examine such roles in the developmental contexts of South Africa and India. The argument put forward is that, in both countries, biopharmaceutical and umbrella associations have evolved from lobbying organizations to institutional partners who influence the politics of innovation and development—and therefore the degree of integration and fragmentation—of political, bureaucratic, industrial innovation and health systems.