bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway
Authors: Lee Minji , Kim Jong Hyun , Yoon Ina , Lee Chulho , Fallahi Sichani Mohammad , Kang Jong Soon , Kang Jeonghyun , Guo Min , Lee Kang Young , Han Gyoonhee , Kim Sunghoon , Han Jung Min 
Published: May 2018

Significance
LRS, an enzyme involved in protein synthesis, and Sestrin2, a stress-induced metabolic protein, are suggested to function as leucine sensors for the mTORC1 pathway, a central regulator of cell metabolism, growth, proliferation, and survival. The Rag GTPase cycle regulates mTORC1; however, regulators of the Rag GTPase cycle and their coordination remain unknown. We show the dynamics of the RagD–RagB GTPase cycle during leucine signaling and describe contrasting yet complementary roles for LRS and Sestrin2 in the Rag GTPase–mTORC1 pathway, functioning as “ON” and “OFF” switches, respectively. Our results extend the current view of amino acid sensing by mTORC1 and will be invaluable for the development of novel approaches to combat mTORC1-related human diseases such as cancer.
Associated patterns of insecticide resistance in field populations of malaria vectors across Africa
Authors: Hancock Penelope A. , Wiebe Antoinette , Gleave Katherine A. , Bhatt Samir , Cameron Ewan , Trett Anna , Weetman David , Smith David L. , Hemingway Janet , Coleman Michael , Gething Peter W. , Moyes Catherine L. 
Published: May 2018

Significance
Malaria control programs rely on chemical insecticides to target mosquito vectors and are potentially threatened by the emergence of insecticide resistance in African vector populations. Insecticide resistance management initiatives require comprehensive quantification of resistance in field populations to the set of insecticides used in vector control. We analyzed patterns of variation and covariation in resistance to these insecticides, using statistical methods that handle the sparse spatiotemporal distribution of the available data. We found relationships across different insecticide types that are consistent across large parts of Africa, allowing prediction of resistance to be improved by incorporating observations across multiple insecticide types. We also found large-scale relationships between phenotypic resistance and patterns of genetic variation, demonstrating the potential utility of genetic markers.
Restoration of paper artworks with microemulsions confined in hydrogels for safe and efficient removal of adhesive tapes
Authors: Bonelli Nicole , Montis Costanza , Mirabile Antonio , Berti Debora , Baglioni Piero 
Published: May 2018

Significance
From Dead Sea Scrolls to Federico Fellini and Lucio Fontana drawings, pressure-sensitive tapes (PSTs) have been used as adhesive fasteners or as part of temporary conservation treatments that frequently became permanent. Their safe and efficient removal poses ethical and aesthetic questions: Adhesive tape residues damage the paper substrate and, due to discoloring, prejudice the artwork enjoyment and conservation. Selective removal without affecting the underlying support is challenging and often impossible. We tackled this issue from a physicochemical and a colloidal perspective, by designing a system where nanosized solvent droplets are confined within a hydrogel. This method has the potential to revolutionize the approaches used so far in the removal of PSTs and coatings from a plurality of materials.
VirB8 homolog TraE from plasmid pKM101 forms a hexameric ring structure and interacts with the VirB6 homolog TraD
Authors: Casu Bastien , Mary Charline , Sverzhinsky Aleksandr , Fouillen Aurélien , Nanci Antonio , Baron Christian 
Published: May 2018

Significance
The overproduction and purification of membrane proteins are intrinsically difficult, making their analysis challenging. We purified the TraE membrane protein from a bacterial conjugation system that is involved in plasmid transfer. Our results suggest that this protein forms hexamers with a central pore, and we also show that it binds to the TraD protein. The structure of TraE is completely different from that of the previously characterized periplasmic domain. This has intriguing implications for the role of TraE and of its interaction partner TraD in substrate translocation across the bacterial cell envelope. This work makes an important contribution to understanding of the mechanism of plasmid transfer, contributing to the design of approaches to inhibit the spread of antibiotic resistance genes.
Deletion of
LRRTM1 and LRRTM2
in adult mice impairs basal AMPA receptor transmission and LTP in hippocampal CA1 pyramidal neurons
Authors: Bhouri Mehdi , Morishita Wade , Temkin Paul , Goswami Debanjan , Kawabe Hiroshi , Brose Nils , Südhof Thomas C. , Craig Ann Marie , Siddiqui Tabrez J. , Malenka Robert 
Published: May 2018

Significance
Brain function requires high-fidelity transmission of information between individual brain cells at synapses, physical contacts that contain a specialized machinery for passing and receiving signals. Synaptic cell adhesion proteins form physical bridges between neurons and are critical for fine-tuning synaptic properties. Because of their roles in synaptic transmission, mutations in these proteins contribute to a wide range of neuropsychiatric diseases. Here, we study the role of two synaptic cell adhesion proteins, LRRTM1 and LRRTM2, in signaling at excitatory synapses utilizing a conditional knockout mouse line. Genetically deleting these proteins in mature neurons dramatically impairs basal synaptic transmission and disrupts long-term potentiation, a prominent form of synaptic plasticity that is critical for learning and memory.
Short-chain dehydrogenase/reductase governs steroidal specialized metabolites structural diversity and toxicity in the genus
Solanum
Authors: Sonawane Prashant D. , Heinig Uwe , Panda Sayantan , Gilboa Netta Segal , Yona Meital , Kumar S. Pradeep , Alkan Noam , Unger Tamar , Bocobza Samuel , Pliner Margarita , Malitsky Sergey , Tkachev Maria , Meir Sagit , Rogachev Ilana , Aharoni Asaph 
Published: May 2018

Significance
Plants synthesize a vast repertoire of steroidal specialized metabolites. These include the well-known class of antinutritional steroidal glycoalkaloids (SGAs), which act as defensive chemicals in the Solanaceae, and the pharmacologically important and widespread steroidal saponins. Here, we uncover an elusive enzymatic step that acts on unsaturated steroidal metabolites. We find that GLYCOALKALOID METABOLISM25 (GAME25) acts at a key branch point in the biosynthesis pathways of steroidal specialized metabolites. The activity of GAME25 not only affects the enormous diversity of SGAs and steroidal saponins, which are produced in hundreds of plant species, but also modulates the molecules’ toxic effects. This work helps explain the extensive structural diversity in specialized metabolism through a relatively simple chemical modification in a single metabolite backbone.
cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis
Authors: Yoon Young-Sil , Tsai Wen-Wei , Van de Velde Sam , Chen Zhijiang , Lee Kuo-Fen , Morgan Donald A. , Rahmouni Kamal , Matsumura Shigenobu , Wiater Ezra , Song Youngsup , Montminy Marc 
Published: May 2018

Significance
Physiologic systems often maintain homeostasis through negative-feedback loops. Unlike most regulatory targets for the sympathetic nervous system, interscapular brown adipose tissue (BAT) lacks parasympathetic inputs that might otherwise counterbalance the stimulatory effects of catecholamines. We found that the cAMP response element-binding protein (CREB) coactivator cAMP-regulated transcriptional coactivator 3 (CRTC3) reduces BAT function by down-regulating sympathetic nerve activity and vascularization. Mice with a knockout of CRTC3 in BAT have reduced adiposity and are more cold tolerant. CRTC3 inhibits BAT activity by disrupting the expression of neurotrophins and proangiogenic factors that otherwise promote sympathetic innervation and vascularization of BAT. These studies highlight an important feedback mechanism that maintains energy homeostasis via its effects in brown fat.
The Moral Obligation of Nutrition and Hydration in the Tradition and Magisterium of the Catholic Church
Authors: Giovanelli Giorgio 
Published: May 2018

The recent publication of the fifth edition of the Ethical and Religious Directives for Catholic Health Care Services on November 17, 2009, by mandate of the United States bishops, witnessed the eruption of a controversy in the U.S. with regard to nutrition and hydration for the seriously ill and dying. 1 Among the major philosophical and moral thinkers in the field, there are some on the one hand who—out of respect for the wishes of the patient as expressed in normal situations—see no need for nutrition and hydration if such are the patient's wishes, even though they may have been expressed before the patient became ill. On the other hand, there are those who—out of respect for human dignity and with the understanding that any act of euthanasia is morally unacceptable—do not see how the interruption of life support can be acceptable unless it comes to be a burden and no longer a benefit under end-of-life conditions. In light of all this, the present article aims to provide reflections on the nature of assisted nutrition and hydration (ANH) and the obligation to use it in cases where clinical evidence requires it, with a particular focus on the ongoing bioethical debate in the U.S.
Educating Openness: Umberto Eco’s Poetics of Openness as a Pedagogical Value
Authors: Campbell Cary 
Published: May 2018

AbstractThe poetics of openness, as formulated by Umberto Eco in his pre-semiotic work The Open Work (1962), has already been useful and applicable to cultural studies and textual analysis. I propose that this poetics of openness be applied to critical educational practices as well. In this article, I argue that a poetics of openness when coupled with active ‘on the ground’ “critical public pedagogics” can provide a flexible framework for approaching the education of interpretation. Through this framework, a text or sign system is understood as ‘closed’ if it elicits univocal meanings: expecting a predetermined response from a generic/average reader. A text is ‘open’ when it fosters a plurality of interpretative possibilities that actively engage the “existential credentials” of the interpreter. Aesthetic openness is part of adopting a semiotic perspective toward educational processes. A theory of model reader pedagogically helps protect against the kind of radical constructivism this interpretative approach can seem to foster. Openness is not presented as a system or methodology of education, but as a pedagogical value: encouraging both educators and students to bring a perspective of critical openness to all the sign systems and discourses they engage with.
Presence of Counterfeit Marlboro Gold Packs in Licensed Retail Stores in New York City: Evidence From Test Purchases
Authors: Kurti Marin , He Yi , Silver Diana , Giorgio Margaret , von Lampe Klaus , Macinko James , Ye Hua , Tan Fidelis , Mei Victoria 
Published: May 2018

Abstract

Background
There are no independent studies measuring the availability of premium brand counterfeit cigarettes in New York City from licensed retailers.

Methods
We forensically analyzed the cigarette packaging of Marlboro Gold (n = 1021) purchased from licensed tobacco retailers in New York City, using ultraviolet irradiation and light microscopy to determine whether they were counterfeit.

Results
We find that while only 0.5% (n = 5) of our sample exhibits at least one characteristic synonymous with counterfeit packaging, none of our packs can be conclusively classified as counterfeit.

Conclusions
We do not find any counterfeit Marlboro Gold packs purchased at full price from licensed cigarette retailers throughout New York City. Future research using test purchases should include other venues (eg, street and online) and specifically ask for discounts to ascertain the overall presence of counterfeit cigarettes.

Implications
This is the first study to independently measure the availability of counterfeit cigarette packs purchased at full price from licensed retailers in New York City. We find that none of the Marlboro Gold packs purchased from licensed cigarette retailers are counterfeit.
Performance of TEM-PCR vs Culture for Bacterial Identification in Pediatric Musculoskeletal Infections
Authors: Wood James B , Sesler Cheryl , Stalons Donald , Grigorenko Elena , Schoenecker Jonathan G , Creech C Buddy , Thomsen Isaac P 
Published: May 2018

Abstract
Improved diagnostics are needed for children with musculoskeletal infections (MSKIs). We assessed the performance of target-enriched multiplex polymerase chain reaction (TEM-PCR) in children with MSKI. TEM-PCR was concordant with culture in pathogen identification and antibiotic susceptibility testing, while increasing the overall yield of pathogen detection. This technology has the potential to inform judicious antimicrobial use early in the disease course.
Retromastoid Approach for Posterior Fossa Skull Base Rosai–Dorfman Disease—A Rare Pathology: 3-Dimensional Operative Video
Authors: Nanda Anil , Savardekar Amey R , Patra Devi Prasad , Dossani Rimal Hanif , Georgescu Maria-Magdalena 
Published: May 2018

Abstract
Rosai–Dorfman disease, originally described by Juan Rosai and Ronald F. Dorfman, is a rare benign histiocytic proliferative disorder, classically presenting with massive lymphadenopathy and a self-limiting clinical course.
1
Isolated intracranial skull base involvement is extremely rare and often resembles meningiomas, schwannomas, or other benign skull base lesions.
2
The disease is difficult to diagnose radiographically, and tissue diagnosis with open skull base approaches has significant perioperative risks.
2,3
We present the case of a 48-yr-old Caucasian male presenting with progressively worsening headaches, giddiness, hearing difficulty, and diplopia. Magnetic resonance imaging of the brain revealed T1-weighted isointense, T2-weighted hypointense, and contrast-enhancing dural-based lesion in the left cerebellopontine angle. The patient underwent maximally safe resection of the lesion through the retromastoid approach with careful preservation of the lower cranial nerve complex. The intraoperative findings of a variegated and lobulated mass adherent to the skull base, the surgical strategy of safe resection, and eventual good outcome in this patient are depicted in this 3-dimensional video presentation. The majority of patients with skull base Rosai–Dorfman disease reported in literature have had stable or regression of disease (78%) after initial conservative surgical treatment and hence aggressive surgical resection is of unproven efficacy.
3

The patient has consented to depiction of his surgical video and intraoperative images in this video manuscript.
Microsurgical Resection of a Solitary Spinal Epidural Cavernous Angioma: 3-Dimensional Operative Video
Authors: Ceccato Guilherme H W , Henning Lucélio , Prado Julyana L , Rassi Marcio S , Borba Luis A B 
Published: May 2018

Abstract
Solitary spinal epidural cavernous angiomas are rare vascular malformations. Surgical excision is the treatment of choice, as these lesions tend to grow or bleed at some point. In this 3-dimensional, narrated video, we present the case of a 61-year-old male who presented with progressive pain in the right paravertebral region secondary to an epidural cavernous angioma located at the T6/T7 level. Under intraoperative neurophysiological monitoring, a laminectomy between T5 and T7 was performed. A reddish, well delimited, and highly vascularized epidural mass was identified and dissected from the adjacent dura and nerve root, and an en bloc total resection was achieved. The patient was discharged neurologically intact on postoperative day 4, presenting a remarkable improvement of his pain at 2-month follow-up. Total excision of these lesions is possible in most of cases, remaining the standard treatment, with minimum complications.
All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All data related to patient identification were removed from this surgical video and manuscript, with no need of a written informed consent.
‘Less Stale, Only Slightly Less Male, but Overwhelmingly Less Pale’: the 2015 New Conservative Brexiters in the House of Commons
Authors: Alexandre-Collier Agnès 
Published: May 2018

AbstractThis article will study the new face of Conservative Euroscepticism in the House of Commons, with a special focus on the 2015 intake of MPs who were supposedly ‘less stale, male and pale’ and their attitudes to the British referendum on the EU. In this respect, this article will also take a specific interest in new Conservative Black and Asian Minority Ethnic (BAME) MPs who turned out to be more active on the ‘leave’ side of the referendum campaign, thus serving as a showcase for the party's strategy of ‘decontaminating’ the Brexit brand and its hyperglobalist geopolitical perspective.
A Study of Non-Urgent Demand to Identify Opportunities for Demand Reduction
Authors: Walley Paul , Jennison-Phillips Anna 
Published: May 2018

Abstract
Police forces often struggle to meet all demands placed upon them because of budgetary and other resource constraints. UK police forces are now embarking on a series of initiatives to find ways of managing demand so that there is a closer match between the resource requirements and those available. This article presents an in-depth analysis of a sample of demand and response to non-urgent incidents from one UK police region, so that there is a better understanding of how demand can be either reduced or more efficiently met. The concept of ‘failure demand’ is introduced as a means of identifying ways to reduce resource consumption.
From skeletal development to the creation of pluripotent stem cell-derived bone-forming progenitors
Authors: Tam Wai Long , Luyten Frank P. , Roberts Scott J. 
Published: May 2018

Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors. Despite promising preclinical data, limited translation towards the clinic has been observed to date. There may be several reasons for this including the lack of robust cell populations with favourable proliferative and differentiation capacities. However, perhaps the most pertinent reason is the failure to produce an implant that can replicate the developmental programme that is observed during skeletal repair. Pluripotent stem cells (PSCs) can potentially offer a solution for bone tissue engineering by providing unlimited cell sources at various stages of differentiation. In this review, we summarize key embryonic signalling pathways in bone formation coupled with PSC differentiation strategies for the derivation of bone-forming progenitors.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Assessment of stem cell differentiation based on genome-wide expression profiles
Authors: Godoy Patricio , Schmidt-Heck Wolfgang , Hellwig Birte , Nell Patrick , Feuerborn David , Rahnenführer Jörg , Kattler Kathrin , Walter Jörn , Blüthgen Nils , Hengstler Jan G. 
Published: May 2018

In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived ‘mature’ cells and primary target cells or tissue. It consists of a principal component analysis to represent global expression changes and to identify possible problems of the dataset that require special attention, such as: batch effects; clustering techniques to identify gene groups with similar features; over-representation analysis to characterize biological motifs and transcriptional control factors of the identified gene clusters; and metagenes as well as gene regulatory networks for quantitative cell-type assessment and identification of influential transcription factors. Possibilities and limitations of the analysis pipeline are illustrated using the example of human embryonic stem cell and human induced pluripotent cells to generate ‘hepatocyte-like cells'. The pipeline quantifies the degree of incomplete differentiation as well as remaining stemness and identifies unwanted features, such as colon- and fibroblast-associated gene clusters that are absent in real hepatocytes but typically induced by currently available differentiation protocols. Finally, transcription factors responsible for incomplete and unwanted differentiation are identified. The proposed method is widely applicable and allows an unbiased and quantitative assessment of stem cell-derived cells.
This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Cell-based liver therapies: past, present and future
Authors: Iansante Valeria , Chandrashekran Anil , Dhawan Anil 
Published: May 2018

Liver transplantation represents the standard treatment for people with an end-stage liver disease and some liver-based metabolic disorders; however, shortage of liver donor tissues limits its availability. Furthermore, whole liver replacement eliminates the possibility of using native liver as a possible target for future gene therapy in case of liver-based metabolic defects. Cell therapy has emerged as a potential alternative, as cells can provide the hepatic functions and engraft in the liver parenchyma. Various options have been proposed, including human or other species hepatocytes, hepatocyte-like cells derived from stem cells or more futuristic alternatives, such as combination therapies with different cell types, organoids and cell–biomaterial combinations. In this review, we aim to give an overview of the cell therapies developed so far, highlighting preclinical and/or clinical achievements as well as the limitations that need to be overcome to make them fully effective and safe for clinical applications.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.