bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Clustering and Nomenclature for Beta Turns Derived from High-Resolution Protein Structures
Authors: Shapovalov Maxim , Vucetic Slobodan , Dunbrack Roland L. 
Published: August 2018

AbstractProtein loops connect regular secondary structures and contain 4-residue beta turns which represent 63% of the residues in loops. The commonly used classification of beta turns (Type I, I’, II, II’, VIa1, VIa2, VIb, and VIII) was developed in the 1970s and 1980s from analysis of a small number of proteins of average resolution, and represents only two thirds of beta turns observed in proteins (with a generic class Type IV representing the rest). We present a new clustering of beta turn conformations from a set of 13,030 turns from 1078 ultra-high resolution protein structures (≤1.2 Å). Our clustering is derived from applying the DBSCAN andk-medoids algorithms to this data set with a metric commonly used in directional statistics applied to the set of dihedral angles from the second and third residues of each turn. We define 18 turn types compared to the 8 classical turn types in common use. We propose a new 2-letter nomenclature for all 18 beta-turn types using Ramachandran region names for the two central residues (e.g., ‘A’ and ‘D’ for alpha regions on the left side of the Ramachandran map and ‘a’ and ‘d’ for equivalent regions on the right-hand side; classical Type I turns are ‘AD’ turns and Type I’ turns are ‘ad’). We identify 11 new types of beta turn, 5 of which are sub-types of classical beta turn types. Up-to-date statistics, probability densities of conformations, and sequence profiles of beta turns in loops were collected and analyzed. A library of turn types,BetaTurnLib18, and cross-platform software,BetaTurnTool18, which identifies turns in an input protein structure, are freely available and redistributable fromdunbrack.fccc.edu/betaturnandgithub.com/sh-maxim/BetaTurn18. Given the ubiquitous nature of beta turns, this comprehensive study updates understanding of beta turns and should also provide useful tools for protein structure determination, refinement, and prediction programs.
The capsule ofCryptococcus neoformansmodulates phagosomal pH through its acid-base properties
Authors: De Leon-Rodriguez Carlos M. , Fu Man Shun , Corbali M. Osman , Cordero Radames J.B. , Casadevall Arturo 
Published: August 2018

AbstractPhagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that include interference with phagosome maturation. The human pathogenic fungusCryptococcus neoformansresides in acidic phagosome after macrophage ingestion that actually provides a favorable environment for replication since the fungus replicates faster at acidic pH. We hypothesized that the glucuronic acid residues in the capsular polysaccharide had the capacity to affect phagosome acidity through their acid-base properties. A ratiometric fluorescence comparison of imaged phagosomes containingC. neoformansto those containing beads showed that the latter were significantly more acidic. Similarly, phagosomes containing non-encapsulatedC. neoformanscells were more acidic than those containing encapsulated cells. Acid-base titrations of isolatedC. neoformanspolysaccharide revealed that it behaves as a weak acid with maximal buffering capacity around pH 4-5. We interpret these results as indicating that the glucuronic acid residues in theC. neoformanscapsular polysaccharide can buffer phagosomal acidification. Interference with phagosomal acidification represents a new function for the cryptococcal capsule in virulence and suggests the importance of considering the acid-base properties of microbial capsules in the host-microbe interaction for other microbes with charged residues in their capsules.ImportanceCryptococcus neoformansis the causative agent of cryptococcosis, a devastating fungal disease that affects thousands of individuals worldwide. This fungus has the capacity to survive inside phagocytic cells, which contributes to persistence of infection and dissemination. One of the major mechanisms of host phagocytes is to acidify the phagosomal compartment after ingestion of microbes. This study shows that the capsule ofC. neoformanscan interfere with full phagosomal acidification by serving as a buffer.
“Visual” Cortices of Congenitally Blind Adults Respond to Executive Demands Authors
Authors: Loiotile Rita E. , Bedny Marina 
Published: August 2018

AbstractHow functionally flexible is human cortex? In congenitally blind individuals, “visual” cortices are active during auditory and tactile tasks. The cognitive role of these responses and the underlying mechanisms remain uncertain. A dominant view is that, in blindness, “visual” cortices process information from low-level auditory and somatosensory systems. An alternative hypothesis is that higher-cognitive fronto-parietal systems take over “visual” cortices. We report that, in congenitally blind individuals, right-lateralized “visual” cortex responds to executiveload in a go/no-go task. These right-lateralized occipital cortices of blind, but not sighted, individuals mirrored the executive-function pattern observed in fronto-parietal systems. In blindness, the same “visual” cortex area, at rest, also increases its synchronization with prefrontal executive control regions and decreases its synchronization with auditory and sensorimotor cortices. These results support the hypothesis of top-down fronto-parietal takeover of “visual” cortices, and suggest that human cortex is highly flexible at birth.
Development of novel lipidic particles for siRNA delivery that are highly effective after 12 months storage
Authors: Clarke Daniel , Idris Adi , McMillan Nigel AJ 
Published: August 2018

ABSTRACTLiposomes are versatile and well-proven as a means to deliver nucleic acids into cells. Most of the formulation procedures used are labour intensive and result in unstable end products. We have previously reported on the development of a simple, yet efficient, hydration-of-freeze-dried-matrix (HFDM) method to entrap siRNA within lipid particles. Here we show that the particles are stable up to 12 months after storage room temperature (RT), 4°C or - 20°C. While RT storage results in changes in particle size and polydispersity, gene silencing of all particles was similar to freshly prepared particles following storage for 3, 6, 9 or 12 months at all temperatures. This is the first report of such long-term stability in siRNA-loaded liposomes.
Pleotropic effects of mutations in the effector domain of influenza A virus NS1 protein
Authors: Pereira Carina F. , Wise Helen M. , Kurian Dominic , Pinto Rute M. , Amorim Maria J. , Gill Andrew C. , Digard Paul 
Published: August 2018

AbstractObjectiveThe multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested the effects of NS1 effector domain mutations known to affect homo-dimerisation or interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear export of viral mRNAs.ResultsThe NS1 dimerisation mutant W187R retained the functions of binding cellular NXF1 as well as stabilising NXF1 interaction with viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1 interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but no longer supported mRNA nuclear export. Analysis of WT and mutant NS1 interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A. Whilst these data suggest the possibility of functional links between NS1’s effects on intracellular signalling and its role in viral mRNA nuclear export, they also indicate potential pleiotropic effects of the NS1 mutations; in the case of E96A/E97A possibly via disrupted protein folding leading to chaperone recruitment.
The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster
Authors: Kido Takashi , Miyagawa Shigeru , Goto Takasumi , Tamai Katsuto , Ueno Takayoshi , Toda Koichi , Kuratani Toru , Sawa Yoshiki 
Published: August 2018

AbstractObjectivesWe hypothesized that systemic administration of high-mobility group box 1 fragment attenuates the progression of myocardial fibrosis and cardiac dysfunction in a hamster model of dilated cardiomyopathy by recruiting bone marrow mesenchymal stem cells thus causing enhancement of a self-regeneration system.MethodsTwenty-week-old J2N-k hamsters, which are δ-sarcoglycan-deficient, were treated with systemic injection of high-mobility group box 1 fragment (HMGB1, n=15) or phosphate buffered saline (control, n=11). Echocardiography for left ventricular function, cardiac histology, and molecular biology were analyzed. The life-prolonging effect was assessed separately using the HMGB1 and control groups, in addition to a monthly HMGB1 group which received monthly systemic injections of high-mobility group box 1 fragment, 3 times (HMGB1, n=11, control, n=9, monthly HMGB1, n=9).ResultsThe HMGB1 group showed improved left ventricular ejection fraction, reduced myocardial fibrosis, and increased capillary density. The number of platelet-derived growth factor receptor-alpha and CD106 positive mesenchymal stem cells detected in the myocardium was significantly increased, and intra-myocardial expression of tumor necrosis factor α stimulating gene 6, hepatic growth factor, and vascular endothelial growth factor were significantly upregulated after high-mobility group box 1 fragment administration. Improved survival was observed in the monthly HMGB1 group compared with the control group.ConclusionsSystemic high-mobility group box 1 fragment administration attenuates the progression of left ventricular remodeling in a hamster model of dilated cardiomyopathy by enhanced homing of bone marrow mesenchymal stem cells into damaged myocardium, suggesting that high-mobility group box 1 fragment could be a new treatment for dilated cardiomyopathy.
Role of the high-affinity leukotriene B4receptor signaling in fibrosis after unilateral ureteral obstruction in mice
Authors: Kamata Mariko , Amano Hideki , Ito Yoshiya , Fujita Tomoe , Hosono Kanako , Kamata Kouju , Takeuchi Yasuo , Yokomizo Takehiko , Shimizu Takao , Majima Masataka 
Published: August 2018

AbstractLeukotriene B4(LTB4) is a lipid mediator that acts as a potent chemoattractant for inflammatory leukocytes. Kidney fibrosis is caused by migrating inflammatory cells and kidney-resident cells. Here, we examined the role of the high-affinity LTB4receptor BLT1 during development of kidney fibrosis in wild-type (WT) mice and BLT1 knockout (BLT1-/-) mice with unilateral ureteral obstruction (UUO). We found elevated expression of 5-lipoxygenase (5-LOX), which generates LTB4, in the renal tubules of WT and BLT1-/-UUO mice. Accumulation of immunoreactive type I collagen in UUO kidneys of WT mice increased over time; however, the increase was less prominent in BLT1-/-mice. Accumulation of S100A4-positive fibroblasts also increased temporally in WT UUO kidneys, but was again less pronounced in those of BLT1-/-mice. The same was true of mRNA encoding transforming growth factor-β (TGF)-β and fibroblast growth factor (FGF)-2. Finally, accumulation of F4/80-positive macrophages, which secrete TGF-β, also increased temporally in WT UUO and BLT1-/-kidneys, but to a lesser extent in the latter. Following LTB4stimulationin vitro, macrophages showed increased expression of mRNA encoding TGF-β/FGF-2 and Col1a1, whereas L929 fibroblasts showed increased expression of mRNA encoding α smooth muscle actin (SMA). Bone marrow (BM) transplantation studies revealed that the area positive for type I collagen was significantly smaller in BLT1-/--BM→WT UUO kidneys than in WT-BM→WT kidneys. Thus, LTB4-BLT1 signaling plays a critical role in fibrosis in UUO kidneys by increasing accumulation of macrophages and fibroblasts. Therefore, blocking BLT1 may prevent renal fibrosis.
Cracking the problem of neural representations of abstract words: grounding word meanings in language itself
Authors: Hultén Annika , van Vliet Marijn , Lammi Lotta , Kivisaari Sasa , Lindh-Knuutila Tiina , Faisal Ali , Salmelin Riitta 
Published: August 2018

AbstractIn order to describe how humans represent meaning in the brain, one must be able to account for not just concrete words but, critically, also abstract words which lack a physical referent. Hebbian formalism and optimization are basic principles of brain function, and they provide an appealing approach for modeling word meanings based on word co-occurrences. Here, we built a model of the semantic space based on word statistics in a large text corpus, which was able to decode items from brain signals. In the model, word abstractness emerged from the statistical regularities of the language environment. This salient property of the model co-varied, at 280–420 ms after word presentation, with activity in the left-hemisphere frontal, anterior temporal and superior parietal cortex that have been linked with processing of abstract words. In light of these results, we propose that the neural encoding of word meanings is importantly grounded in language through statistical regularities.
Sucrose intensity coding and decision-making in rat gustatory cortices
Authors: Fonseca Esmeralda , Lafuente Victor de , Simon Sidney A. , Gutierrez Ranier 
Published: August 2018

AbstractSucrose’s sweet intensity is one attribute contributing to the overconsumption of high-energy palatable foods. However, it is not known how sucrose intensity is encoded and used to make perceptual decisions by neurons in taste-sensitive cortices. We trained rats in a sucrose intensity discrimination task and found that sucrose evoked a widespread response in neurons recorded in posterior-Insula (pIC), anterior-Insula (aIC), and Orbitofrontal cortex (OFC). Remarkably, only a few Intensity-selective neurons conveyed the most information about sucrose’s intensity, indicating that for sweetness the gustatory system used a compact and distributed code. Sucrose intensity was encoded in both firing-rates and spike-timing. The pIC, aIC, and OFC neurons tracked movement direction, with OFC neurons yielding the most robust response. aIC and OFC neurons encoded the subject’s choices, whereas all three regions tracked reward omission. Overall, these multimodal areas provide a neural representation of perceived sucrose intensity, and of task-related information underlying perceptual decision-making.
Emerging financial risks from climate changes on building assets in the UK
Authors: Alzahrani Abdullah , Boussabaine Halim , Almarri Khalid 
Published: August 2018

Purpose
The different scenarios of climate change, such as floods, temperature change and storms, are considered the main drivers influencing the building sector. Understanding how and when these climatic risks will emerge, specifically financial risks, is pivotal in dealing with these risks and applying the adaptation and mitigation strategies so as to minimise the effects and damages. Thus, the purpose of this paper is to discover the financial risks emerging from climate change impact on the building sector and determine the timescale of occurrence for such risks.

Design/methodology/approach
The research methodology formulated in this study is founded on a systematic literature review and statistical analysis. Built on this, the potential financial risks emerging from climate change scenarios (CCS) were identified and designed as a questionnaire to collect data from UK expert professionals. Statistical methods were used to rank and compare the outcomes of the survey.

Findings
The research observed that around 40 per cent of the participants in this study indicated that one-third of the total identified financial risks (23 factors) would emerge within 5-10 years. The most important factors are increased insurance excess and additional expense in insuring buildings in flood risk zones, whilst the least important financial risks are inability to repay debts and un-insurability because of climate change.

Research limitations/implications
This study is limited to the UK, and regional implications are not covered. However, it is a starting point.

Originality/value
The main contribution of this research project is establishing and developing clusters of the potential risks emerging from CCS, which can assist professionals in the building sector in the management and development of strategies to cope with these emerging risks.
Is job satisfaction of high-level managers and self-employed more pro-cyclical than normal employees?
Authors: Sánchez-Sánchez Nuria , Namkee Ahn 
Published: August 2018

PurposeThe recent economic crisis in Spain is felt most severely in the labour market. The purpose of this paper is to examine job satisfaction among the occupied workers according to their job types throughout the ongoing economic cycle comparing the period of boom and that of bust.Design/methodology/approachSurprisingly, the average job satisfaction has stayed virtually constant between the two periods, which suggests the existence of compensating forces operating among the occupied population. The authors find first the compositional change of working population, such as a decreasing proportion of temporary contract workers had only small effects, unable to explain the puzzle. The authors also find that macroeconomic conditions affect workers’ job satisfaction differently by the type of workers or jobs. In fact, high-level managerial workers and self-employed employers have suffered a significantly large reduction in their job satisfaction during the crisis while some other types of workers such as ordinary employees have enjoyed increased job satisfaction. In order to explore the causes of these differences, the authors examine the satisfaction in different job domains.FindingsThe results suggest that in the case of self-employed, decrease in job satisfaction with respect to wages job stability superior evaluation is significant and the promotion prospect is not relevant for self-employed, while for managerial workers, the only significant decrease is due to superior evaluation.Research limitations/implicationsThe Spanish data with a reasonable sample size which include information on job satisfaction are the Spanish Survey of Life Quality at Work. Unfortunately, the survey is not longitudinal, therefore unable to examine the factors affecting transitions in satisfaction level or to control for fixed individual effects, and the data only cover until 2010. Further investigation including more recent data and data from other countries would be helpful to better understand the consequences of economic crisis on job satisfaction.Originality/valueThis paper contributes in two ways. First, the authors show what has been happening to the job-related well-being during the recession in Spain by the type of workers: high-level managers, managers, self-employed and employees. Job satisfaction can be determined by pressures to work harder and longer hours, reduced wages, lower promotion possibility and higher layoff probability, and all of them could have been changed by the economic crisis. Consequently, the second contribution is to analyse different dimensions of job satisfaction as satisfaction with wages, flexibility, stability, stress and promotion to determine the causes of the changes in average level of job satisfaction.
Public provision of employment support services to youth jobseekers
Authors: Petreski Marjan 
Published: August 2018

PurposeThe purpose of this paper is to investigate if public provision of employment support services to youth leads to reduced informality and increased wages in transition economies.Design/methodology/approachThe author uses the school-to-work transition data sets of the International Labor Organization for seven transition economies of Southeast Europe and the Commonwealth of Independent States. The author focuses on two econometric issues: the selectivity into informal employment and the endogeneity of the public employment support service provision with respect to informal employment and wages. The authors achieves identification by employing internal regressors which are uncorrelated with the product of heteroskedastic errors, a-la Lewbel (2012), as the author could not prove the external validity of the commonly used external instruments in similar contexts.FindingsResults suggest that the public provision of employment support services matters for relegating informal employment, but not for wages, in general. Placement in education or training programs is most powerful in reducing informal employment among the four different employment support services, while only advice for job search works positively for wages probably through enabling better match.Social implicationsIncreasing budget allocations, varying the array of public employment support measures, enhanced targeting, and advancement of the profiling system may significantly contribute to strengthening the public employment support service effect on youth employment in transition economies.Originality/valueThe paper brings a couple of novelties to the current literature. First, it is among the early papers dealing with the issue of informality, public employment support service and labor market prospects of youth in general in a rigorous manner. Second, it fills an important gap for transition economies which were less researched due to the long-lasting transition process as well due to data scarcity. Third, it utilizes the recently collected School-to-Work Transition Surveys (SWTS). Finally, and likely most importantly, it thoroughly addresses the issues of selectivity bias and endogeneity of PESS by utilizing a recent approach of Lewbel (2012) whereby internally generated variables are used as instruments. Hence, the paper accounts for the endogeneity stemming from unobservables in a novel manner, contrary to the common approaches in the literature based either on propensity score matching addressing selectivity on observables only, or relying on commonly used instruments in the labor market literature – mainly regional employment variables – whose external validity is easily disputed.