bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rethinking Public Buildings’ Functions: The Case for Participatory Design Methodology
Authors: Kandusová V , Vácha T 
Published: June 2019

Abstract
Municipalities often struggle with reconstructions and refurbishing of buildings in public ownership. This is not only because of limited expert capacities that municipalities struggle with (municipal architect position or urban planner position is vacant, or non-existent etc.) or lack of finances. There is an increasing need and demand from municipalities for redefining buildings’ original purpose and finding new, sustainable and innovate functions. They have to decide not only how to reconstruct, but how to rethink its original purpose. The case study from a city of Slaný shows how participatory design can serve the goal of finding new functions of a public building and effectively contribute to the planning phase of reconstruction projects. Sustainable urban development should react to people’s needs, new technologies and environmental challenges. Reconstruction projects should reflect innovations in both technologies and approaches and respond to newly emerged functions. The methodology demonstrated in the case study can serve as a tool for assessing preferences of citizens, needs of the municipality and bridge the gap between politicians, experts and citizens by supporting efficient communication and evidence-based decision making. Moreover, this case shows how to ensure social sustainability and project effectiveness by involving multidisciplinary teams, in this case architects, urban planners, sociologists, communications experts and environmental and engineering psychologists.
An Examination of Flying Insects in Seven Hospitals in the United Kingdom and Carriage of Bacteria by True Flies (Diptera: Calliphoridae, Dolichopodidae, Fanniidae, Muscidae, Phoridae, Psychodidae, Sphaeroceridae)
Authors: Boiocchi Federica , Davies Matthew P , Hilton Anthony C 
Published: June 2019

AbstractInsects are efficient vectors of bacteria and in the hospital environment may have a role in spreading nosocomial infections. This study sampled the flying insect populations of seven hospitals in the United Kingdom and characterized the associated culturome of Diptera, including the antibiotic resistance profile of bacterial isolates. Flying insects were collected in seven U.K. hospitals between the period March 2010 to August 2011. The bacteria carried by Diptera were isolated using culture-based techniques, identified and characterized by antimicrobial susceptibility testing. A total of 19,937 individual insects were collected with Diptera being the most abundant (73.6% of the total), followed by Hemiptera (13.9%), Hymenoptera (4.7%), Lepidoptera (2.9%), and Coleoptera (2%). From Diptera, 82 bacterial strains were identified. The majority of bacteria belonged to the Enterobacteriaceae (42%), followed by Bacillus spp. (24%) and Staphylococcus spp. (19%). Less abundant were bacteria of the genus Clostridium (6%), Streptococcus (5%), and Micrococcus (2%). A total of 68 bacterial strains were characterized for their antibiotic resistance profile; 52.9% demonstrated a resistant phenotype to at least one class of antibiotic. Staphylococcus spp. represented the highest proportion of resistant strains (83.3%), followed by Bacillus spp. (60%) and Enterobacteriaceae (31.3%). Diptera were the predominant flying insects present in the U.K. hospital environments sampled and found to harbor a variety of opportunistic human pathogens with associated antimicrobial resistance profiles. Given the ability of flies to act as mechanical vectors of bacteria, they present a potential to contribute to persistence and spread of antimicrobial-resistant pathogenic bacteria in the hospital environment.
Stability of an RNA•DNA–DNA triple helix depends on base triplet composition and length of the RNA third strand
Authors: Kunkler Charlotte N , Hulewicz Jacob P , Hickman Sarah C , Wang Matthew C , McCown Phillip J , Brown Jessica A 
Published: June 2019

AbstractRecent studies suggest noncoding RNAs interact with genomic DNA, forming an RNA•DNA–DNA triple helix that regulates gene expression. However, base triplet composition of pyrimidine motif RNA•DNA–DNA triple helices is not well understood beyond the canonical U•A–T and C•G–C base triplets. Using native gel-shift assays, the relative stability of 16 different base triplets at a single position, Z•X–Y (where Z = C, U, A, G and X–Y = A–T, G–C, T–A, C–G), in an RNA•DNA–DNA triple helix was determined. The canonical U•A–T and C•G–C base triplets were the most stable, while three non-canonical base triplets completely disrupted triple-helix formation. We further show that our RNA•DNA–DNA triple helix can tolerate up to two consecutive non-canonical A•G–C base triplets. Additionally, the RNA third strand must be at least 19 nucleotides to form an RNA•DNA–DNA triple helix but increasing the length to 27 nucleotides does not increase stability. The relative stability of 16 different base triplets in DNA•DNA–DNA and RNA•RNA–RNA triple helices was distinctly different from those in RNA•DNA–DNA triple helices, showing that base triplet stability depends on strand composition being DNA and/or RNA. Multiple factors influence the stability of triple helices, emphasizing the importance of experimentally validating formation of computationally predicted triple helices.
An improved method for circular RNA purification using RNase R that efficiently removes linear RNAs containing G-quadruplexes or structured 3′ ends
Authors: Xiao Mei-Sheng , Wilusz Jeremy E 
Published: June 2019

AbstractThousands of eukaryotic protein-coding genes generate circular RNAs that have covalently linked ends and are resistant to degradation by exonucleases. To prove their circularity as well as biochemically enrich these transcripts, it has become standard in the field to use the 3′-5′ exonuclease RNase R. Here, we demonstrate that standard protocols involving RNase R can fail to digest &gt;20% of all highly expressed linear RNAs, but these shortcomings can largely be overcome. RNAs with highly structured 3′ ends, including snRNAs and histone mRNAs, are naturally resistant to RNase R, but can be efficiently degraded once a poly(A) tail has been added to their ends. In addition, RNase R stalls in the body of many polyadenylated mRNAs, especially at G-rich sequences that have been previously annotated as G-quadruplex (G4) structures. Upon replacing K+ (which stabilizes G4s) with Li+ in the reaction buffer, we find that RNase R is now able to proceed through these sequences and fully degrade the mRNAs in their entirety. In total, our results provide important improvements to the current methods used to isolate circular RNAs as well as a way to reveal RNA structures that may naturally inhibit degradation by cellular exonucleases.
“It’s Probably Going to Be the Hardest Film to Make”
Authors: Kolker Robert P. , Abrams Nathan 
Published: June 2019

Abstract
Stanley Kubrick wanted to film Arthur Schnitzler’s Traumnovelle since the early 1950s. His interest lay in Schnitzler’s fascination with sexuality and domesticity. The intersection of Schnitzler’s writings with those of Sigmund Freud was of particular interest. Kubrick’s favorite director, Max Ophüls, had adapted some of Schnitzler’s plays, and this also attracted the author to Kubrick. Even though he kept putting off the making of the film, its ideas percolated into those films he did make, from Fear and Desire through The Shining. During this long period of gestation, Kubrick entertained many ideas for writers and stars. At one point, he wanted to make it as a comedy. Only after the failure to get his Holocaust film or his science fiction film, A.I.: Artificial Intelligence, made did he finally turn to directing Eyes Wide Shut.
Precision medicine for acute pancreatitis: current status and future opportunities
Authors: Mukherjee Rajarshi , Nunes Quentin , Huang Wei , Sutton Robert 
Published: June 2019

Abstract
Acute pancreatitis is a common inflammatory condition affecting the pancreas, predominantly caused by gallstones, alcohol excess, and hypertriglyceridaemia, with severe disease carrying up to 50% mortality. Despite significant research and preclinical promise, no targeted drug treatments exist for the disease and precision medicine approaches are lacking significantly, when compared to other health conditions. Advances in omics applications will facilitate improved preclinical models and target identification as well as biomarker discovery for refined trial design, focusing on risk stratification, subject selection, and outcome determination. Randomised treatment of Acute Pancreatitis with Infliximab: Double-blind, placebo-controlled, multi-centre trial (RAPID-I) is a pioneering trial, currently under way in acute pancreatitis, which may serve as an innovative model for the implementation of precision medicine strategies for acute pancreatitis in the future.
IL-18 as a biomarker linking systemic juvenile idiopathic arthritis and macrophage activation syndrome
Authors: Yasin Shima , Fall Ndate , Brown Rachel A , Henderlight Maggie , Canna Scott W , Girard-Guyonvarc’h Charlotte , Gabay Cem , Grom Alexei A , Schulert Grant S 
Published: June 2019

AbstractObjectivesSystemic juvenile idiopathic arthritis (sJIA) is a childhood arthritis with features of autoinflammation and high risk of macrophage activation syndrome (MAS). IL-18 has been shown to have key roles in sJIA and MAS. We aimed to examine IL-18 levels in sJIA in relation to disease activity and history of MAS and other disease biomarkers namely S100 proteins and CXCL9.MethodsTotal IL-18, CXCL9 and S100 proteins levels were determined in 40 sJIA patients, and IL-18 levels were compared between patients with regards to disease activity, history of MAS, and other biomarkers.ResultsTotal IL-18 levels were significantly higher in patients with active sJIA (median 16 499 pg/ml; interquartile range (IQR) 4816–61 839), and remained persistently elevated even in the majority of patients with inactive disease (1164 pg/ml; IQR 587–3444). Patients with history of MAS had significantly higher IL-18 levels (13 380 pg/ml; IQR 4212–62 628) as compared with those without MAS history (956.5 pg/ml; IQR 276.3–4262.5). Total IL-18 performed well with area under the curve of 0.8145 and 0.84 in predicting disease activity and history of MAS, respectively. We observed moderate correlation between IL-18 and CXCL9 (R = 0.56), S100A8/A9 (R = 0.47) and S100A12 (R = 0.46). The correlation was stronger for ferritin (R = 0.74) and overall for those with active disease.ConclusionTotal IL-18 levels were elevated in the majority of sJIA patients regardless of clinical features, but were higher in patients with active disease and history of MAS. Change in IL-18 may reflect increased disease activity or development of MAS.
SOAPTyping: an open-source and cross-platform tool for Sanger sequence-based typing for HLA class I and II alleles
Authors: Zhang Yong , Chen Yongsheng , Xu Huixin , Fang Junbin , Zhao Zijian , Hu Weipeng , Yang Xiaoqin , Ye Jia , Cheng Yun , Wang Jiayin , Wang Jian , Yang Huanming , Yan Jing , Fang Lin 
Published: June 2019

ABSTRACTSummaryThe human leukocyte antigen (HLA) gene family plays a key role in the immune response and thus is crucial in many biomedical and clinical settings. Utilizing Sanger sequencing - the gold standard technology for HLA typing – enables accurate identification of HLA alleles with high-resolution. However, there exists a current hurdle that only commercial software such as UType, SBT-Assign and SBTEngine, instead of any open source tools could be applied to perform HLA typing based on Sanger sequencing. To fill the gap, we developed a stand-alone, open-source and cross-platform software, known as SOAPTyping, for Sanger-based typing in HLA class I and II alleles.Availability and implementationSOAPTyping is implemented in C++ language and Qt framework, which is supported on Windows, Mac and Linux. Source code and detailed documentation are accessible via the project GitHub page: https://github.com/BGI-flexlab/SOAPTyping.Contactfangl@genomics.cnSupplementary informationSupplementary data are available at Bioinformatics online.
A framework for annotation of antigen specificities in high-throughput T-cell repertoire sequencing studies
Authors: Pogorelyy Mikhail V , Shugay Mikhail 
Published: June 2019

AbstractRecently developed molecular methods allow large-scale profiling of T-cell receptor (TCR) sequences that encode for antigen specificity and immunological memory of these cells. However, it is well known, that the even unperturbed TCR repertoire structure is extremely complex due to the high diversity of TCR rearrangements and multiple biases imprinted by VDJ rearrangement process. The latter gives rise to the phenomenon of “public” TCR clonotypes that can be shared across multiple individuals and non-trivial structure of the TCR similarity network. Here we outline a framework for TCR sequencing data analysis that can control for these biases in order to infer TCRs that are involved in response to antigens of interest. Using an example dataset of donors with known HLA haplotype and CMV status we demonstrate that by applying HLA restriction rules and matching against a database of TCRs with known antigen specificity it is possible to robustly detect motifs of an epitope-specific responses in individual repertoires. We also highlight potential shortcomings of TCR clustering methods and demonstrate that highly expanded TCRs should be individually assessed to get the full picture of antigen-specific response.
Biofilm formation displays intrinsic offensive and defensive features of Bacillus cereus
Authors: Joaquin Caro-Astorga , Elrike Frenzel , Richard Perkins James , de Vicente Antonio , Ranea Juan A.G. , Kuipers Oscar P. , Diego Romero 
Published: June 2019

AbstractBackgroundBiofilm formation is a strategy of many bacterial species to adapt to a variety of stresses and has become a part of infections, contaminations or beneficial interactions. We previously observed that B. cereus ATCC 14579 (CECT148), formed a thick biomass of cells firmly adhered to abiotic surfaces.ResultsIn this study, we combined two techniques, RNAseq and iTRAQ mass spectrometry, to demonstrate the profound physiological changes that permit Bacillus cereus to switch from a floating to a sessile lifestyle, to undergo further maturation of the biofilm, and to differentiate into offensive or defensive populations. The rearrangement of nucleotides, sugars, amino acids and energy metabolism lead to changes promoting reinforcement of the cell wall, activation of ROS detoxification strategies or secondary metabolite production, all oriented to defend biofilm cells from external aggressions. However, floating cells maintain a fermentative metabolic status along with a higher aggressiveness against hosts, evidenced by the production of toxins and other virulent factors.ConclusionsWe show that biofilm-associated cells seem to direct the energy to the individual and global defense against external aggressions and competitors. By contrary, floating cells are more aggressive against hosts. The maintenance of the two distinct subpopulations is an effective strategy to face changeable environmental conditions found in the life cycle of B. cereus.
Cutaneous Wounds in Mice Lacking Tumor Necrosis Factor-stimulated Gene-6 Exhibit Delayed Closure and an Abnormal Inflammatory Response
Authors: Shakya Sajina , Mack Judith A. , Alipour Minou , Maytin Edward V. 
Published: June 2019

ABSTRACTWe investigated how loss of tumor necrosis factor-stimulated gene-6 (TSG-6) affects wound closure and skin inflammation. TSG-6 has several known biological functions including enzymatic transfer of heavy chain proteins (HC) from inter-α-trypsin inhibitor to hyaluronan (HA) to form HC-HA complexes. TSG-6 and HC-HA are constitutively expressed in normal skin and increase post-wounding, but are completely absent in TSG-6 null mice. Wound closure rates are significantly delayed in TSG-6 null mice relative to wildtype mice. Neutrophil recruitment is delayed in early wounds (12 h and Day 1), whereas late wounds (Day 7) show elevated neutrophil accumulation.In addition, the granulation phase is delayed, with persistent blood vessels and reduced dermal collagen at 10 days. The pro-inflammatory cytokine TNFα is elevated >3 fold in unwounded TSG-6 null skin, and increases further after wounding (from 12 h to 7 days) before returning to baseline by day 10. Other cytokines examined such as IL-6, IL-10, and MCP-1 showed no consistent differences. Importantly, reintroduction of TSG-6 into TSG-6 null wounds rescues both the delay in wound closure and the aberrant neutrophil phenotype. In summary, our study indicates that TSG-6 plays an important role in regulating wound closure and inflammation during cutaneous wound repair.
The genomic impact of European colonization of the Americas
Authors: Ongaro Linda , Scliar Marilia O. , Flores Rodrigo , Raveane Alessandro , Marnetto Davide , Sarno Stefania , Gnecchi-Ruscone Guido A. , Alarcon-Riquelme Marta , Patin Etienne , Wangkumhang Pongsakorn , Hellenthal Garrett , Gonzalez-Santos Miguel , King Roy J. , Kouvatsi Anastasia , Balanovsky Oleg , Balanovska Elena , Atramentova Lubov , Turdikulova Shahlo , Mastana Sarabjit , Marjanovic Damir , Kovacevic Lejla , Leskovac Andreja , Lima-Costa Maria F. , Pereira Alexandre C. , Barreto Mauricio L. , Horta Bernardo L. , Mabunda Nédio , May Celia A. , Moreno-Estrada Andres , Achilli Alessandro , Olivieri Anna , Semino Ornella , Tambets Kristiina , Kivisild Toomas , Luiselli Donata , Torroni Antonio , Capelli Cristian , Tarazona-Santos Eduardo , Metspalu Mait , Pagani Luca , Montinaro Francesco 
Published: June 2019

AbstractThe human genetic diversity of the Americas has been shaped by several events of gene flow that have continued since the Colonial Era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored.Here we compiled a genome-wide dataset of ∼12,000 individuals from twelve American countries and ∼6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected i) the genetic structure, ii) the admixture profile, iii) the demographic history and iv) sex-biased gene-flow dynamics, of the Americas.We revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East and to specific regions of Africa.
SKELETAL MyBP-C ISOFORMS TUNE THE MOLECULAR CONTRACTILITY OF DIVERGENT SKELETAL MUSCLE SYSTEMS
Authors: Li Amy , Nelson Shane , Rahmanseresht Sheema , Braet Filip , Cornachione Anabelle S. , Previs Samantha Beck , O’Leary Thomas S. , McNamara James W. , Rassier Dilson E. , Sadayappan Sakthivel , Previs Michael J. , Warshaw David M. 
Published: June 2019

ABSTRACTSkeletal muscle myosin-binding protein C (MyBP-C) is a myosin thick filament-associated protein; localized through its C terminus to distinct regions (C-zones) of the sarcomere. MyBP-C modulates muscle contractility, presumably through its N terminus extending from the thick filament and interacting with either the myosin head region and/or the actin thin filament. Two isoforms of MyBP-C (fast- and slow-type) are expressed in a muscle-type specific manner. Are the expression, localization, and Ca2+-dependent modulatory capacities of these isoforms different in fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles derived from Sprague-Dawley rats? By mass spectrometry, four MyBP-C isoforms (one fast-type MyBP-C and three N-terminally spliced slow-type MyBP-C) were expressed in EDL but only the three slow-type MyBP-C isoforms in SOL. Using EDL and SOL native thick filaments in which the MyBP-C stoichiometry and localization are preserved, native thin filament sliding over these thick filaments showed that only in the C-zone, MyBP-C Ca2+-sensitizes the thin filament and slows thin filament velocity. These modulatory properties depended on MyBP-C’s N-terminus, as N-terminal proteolysis attenuated MyBP-C’s functional capacities. To determine each MyBP-C isoform’s contribution to thin filament Ca2+-sensitization and slowing in the C-zone, we used a combination ofin vitromotility assays using expressed recombinant N-terminal fragments andin silicomechanistic modeling. Our results suggest that each skeletal MyBP-C isoform’s N terminus is functionally distinct and has modulatory capacities that depend on the muscle-type in which they are expressed, providing the potential for molecular tuning of skeletal muscle performance through differential MyBP-C expression.SIGNIFICANCEMyosin-binding protein C (MyBP-C) is a critical component of the skeletal muscle sarcomere, muscle’s smallest contractile unit. MyBP-C’s importance is evident by genetic mutations leading to human myopathies, such as distal arthrogryposis (i.e. club foot). However, the molecular basis of MyBP-C’s functional impact on skeletal muscle contractility is far from certain. Complicating matters further is the expression of fast- and slow-type MyBP-C isoforms that depend on whether the muscle is fast- or slow-twitch. Using multi-scale proteomic, biophysical and mathematical modeling approaches, we define the expression, localization, and modulatory capacities of these distinct skeletal MyBP-C isoforms in rat skeletal muscles. Each MyBP-C isoform appears to modulate muscle contractility differentially; providing the capacity to fine-tune muscle’s mechanical performance as physiological demands arise.
Discovery of small molecule antagonists of the USP5 zinc finger ubiquitin-binding domain
Authors: Mann Mandeep K. , Franzoni Ivan , de Freitas Renato Ferreira , Tempel Wolfram , Houliston Scott , Arrowsmith Cheryl H. , Harding Rachel J. , Schapira Matthieu 
Published: June 2019

AbstractUSP5 disassembles unanchored polyubiquitin chains to recycle free mono-ubiquitin, and is one of twelve ubiquitin-specific proteases featuring a zinc finger ubiquitin-binding domain (ZnF-UBD). This distinct structural module has been associated with substrate positioning or allosteric modulation of catalytic activity, but its cellular function remains unclear. We screened a chemical library focused on the ZnF-UBD of USP5, crystallized hits in complex with the protein, and generated a preliminary structure-activity relationship which enables the development of more potent and selective compounds. This work serves as a framework for the discovery of a chemical probe to delineate the function of USP5 ZnF-UBD in proteasomal degradation and other ubiquitin signalling pathways in health and disease.
Degradation of Polycomb Repressive Complex 2 with an EED-targeted Bivalent Chemical Degrader
Authors: Potjewyd Frances , Turner Anne-Marie W. , Beri Joshua , Rectenwald Justin M. , Norris-Drouin Jacqueline L. , Cholensky Stephanie H. , Margolis David M. , Pearce Kenneth H. , Herring Laura E. , James Lindsey I. 
Published: June 2019

SUMMARYProtein degradation via the use of bivalent chemical degraders provides an alternative strategy to block protein function and assess the biological roles of putative drug targets. This approach capitalizes on the advantages of small molecule inhibitors while moving beyond the restrictions of traditional pharmacology. Herein we report a first-in-class chemical degrader (UNC6852) that targets Polycomb Repressive Complex 2 (PRC2). UNC6852 contains an EED226 derived ligand and a ligand for VHL which bind to the WD40 aromatic cage of EED and CRL2VHL, respectively, to induce proteasomal degradation of PRC2 components, EED, EZH2, and SUZ12. Degradation of PRC2 with UNC6852 blocks the histone methyltransferase activity of EZH2, decreasing H3K27me3 levels in HeLa cells and diffuse large B-cell lymphoma (DLBCL) cells containing an EZH2Y641N gain-of-function mutation. UNC6852 degrades both wild type EZH2 and EZH2Y641N, and additionally displays anti-proliferative effects in this cancer model system.Abstract Figure