bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigational strategies underlying temporal phototaxis inDrosophilalarvae
Authors: Zhu Maxwell L. , Herrera Kristian J. , Vogt Katrin , Bahl Armin 
Published: January 2020

AbstractNavigating across light gradients is essential for survival for many animals. However, we still have a poor understanding of the algorithms that underlie such behaviors. Here we develop a novel phototaxis assay forDrosophilalarvae in which light intensity is always spatially uniform but updates depending on the location of the animal in the arena. Even though larvae can only rely on temporal cues in this closed-loop setup, we find that they are capable of finding preferred areas of low light intensity. Further detailed analysis of their behavior reveals that larvae turn more frequently and that heading angle changes increase when they experience brightness increments over extended periods of time. We suggest that temporal integration of brightness change during runs is an important – and so far largely unexplored – element of phototaxis.Summary statementUsing a novel closed-loop behavioral assay, we show thatDrosophilalarvae can navigate light gradients exclusively using temporal cues. Analyzing and modeling their behavior in detail, we propose that larvae achieve this by integrating brightness change during runs.
Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling
Authors: Johnson Jeffrey R. , Crosby David C. , Hultquist Judd F. , Li Donna , Marlett John , Swann Justine , Hüttenhain Ruth , Verschueren Erik , Johnson Tasha L. , Newton Billy W. , Shales Michael , Beltrao Pedro , Frankel Alan D. , Marson Alexander , Fregoso Oliver I. , Young John A. T. , Krogan Nevan J. 
Published: January 2020

SUMMARYViruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We used quantitative proteomics to measure changes in two PTM types – phosphorylation and ubiquitination – in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis revealed a requirement for Aurora kinase A activity in HIV-1 infection and furthermore revealed that AMP-activated kinase activity is modulated during infection via HIV-1 Vif-mediated degradation of B56-containing protein phosphatase 2A (PP2A). Finally, we demonstrated that the Cullin4A-DDB1-DCAF1 E3 ubiquitin ligase ubiquitinates histone H1 somatic isoforms and that HIV-1 Vpr inhibits this process, leading to defects in DNA repair. Thus, global PTM profiling of infected cells serves as an effective tool for uncovering specific mechanisms of host pathway modulation.
Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau
Authors: Ait-Bouziad Nadine , Chiki Anass , Limorenko Galina , Xiao Shifeng , Eliezer David , Lashuel Hilal A. 
Published: January 2020

ABSTRACTThe microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer’s disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau normal functions and its pathogenic properties in Tauopathies. Very little is known about how phosphorylation of tyrosine residues influences the structure, aggregation, and microtubule- and lipid-binding properties of Tau. In this work, we aimed to address this knowledge gap and determine the relative contribution of phosphorylation of one or several of the five tyrosine residues in Tau (Y18, Y29, Y197, Y310 and Y394) to the regulation of its biophysical, aggregation and functional properties. Towards this goal, we used a combination of site-specific mutagenesis andin vitrophosphorylation by c-Abl kinase to generate Tau species phosphorylated at all tyrosine residues, all tyrosine residues except Y310 or Y394 (pTau-Y310F, pTau-Y394F) and Tau phosphorylated only at Y310 or Y394 (4F\pY310 or 4F\pY394). Our results show that phosphorylation at all five tyrosine residues, multiple N-terminal tyrosine residues (Y18, Y29 and Y197) or site-specific phosphorylation at residue Y310, itself located in the microtubule-binding and aggregation-prone domain of Tau, was sufficient to abolish Tau aggregation and inhibit its microtubule- and lipid-binding properties. NMR studies demonstrated that these effects were mediated by a local decrease in β−sheet propensity of the PHF6 domain. Our findings underscore the unique role of Y310 phosphorylation in the regulation of Tau aggregation, microtubule and lipid interactions and highlight the importance of conducting further studies to elucidate its role in the regulation of Tau normal functions and its pathogenic properties.
Revisiting and expanding the meta-analysis of variation: The log coefficient of variation ratio, lnCVR
Authors: Senior Alistair M. , Viechtbauer Wolfgang , Nakagawa Shinichi 
Published: January 2020

AbstractMeta-analyses are frequently used to quantify the difference in the average values of two groups (e.g., control and experimental treatment groups), but examine the difference in the variability (variance) of two groups. For such comparisons, the two relatively new effect size statistics, namely the log-transformed ‘variability ratio’ (the ratio of two standard deviations; lnVR) and the log-transformed ‘CV ratio’ (the ratio of two coefficients of variation; lnCVR) are useful. In practice, lnCVR may be of most use because a treatment may affect the mean and the variance simultaneously. We review current, and propose new, estimators for lnCVR and lnVR. We also present methods for use when the two groups are dependent (e.g., for cross-over and pre-test-post-test designs). A simulation study evaluated the performance of these estimators and we make recommendations about which estimators one should use to minimise bias. We also present two worked examples that illustrate the importance of accounting for the dependence of the two groups. We found that the degree to which dependence is accounted for in the sampling variance estimates can impact heterogeneity parameters such asτ2(i.e., the between-study variance) andI2(i.e., the proportion of the total variability due to between-study variance), and even the overall effect, and in turn qualitative interpretations. Meta-analytic comparison of the variability between two groups enables us to ask completely new questions and to gain fresh insights from existing datasets. We encourage researchers to take advantage of these convenient new effect size measures for the meta-analysis of variation.
Regulation of HDAC2-PDX1 by RNF125 defines pancreatic cancer development
Authors: Hasnis Erez , Kim Hyungsoo , Verma Sachin , Feng Yongmei , Almog Ronit , Matsliah Sivan , Vavinskaya Vera , Apelbaum Ron , Ben-Ishay Offir , Tuveson David , Sears Rosalie , Ronai Ze’ev A. 
Published: January 2020

AbstractThere is an urgent need to define mechanisms underlying pancreatic adenocarcinoma (PDA) development. Our studies of ubiquitin ligases that may underlie PDA development led us to identify and characterize RNF125. We show that RNF125 exhibits nuclear expression in acinar cells, with reduced and largely cytosolic expression in ductal cells, PanIN and PDA specimens. We find that RNF125 interacts with histone deacetylase 2 (HDAC2) and promotes its non-canonical K63-linked ubiquitination. Inhibition of HDAC2 activity by RNF125 resulted in elevated expression of the pancreatic and duodenal homeobox 1 (PDX1). Correspondingly, inhibition of RNF125 expression enhanced organoid growth in culture and orthotopic tumor development. Conversely, restoration of PDX1 levels in human or mouse PDA cells and organoids depleted of RNF125, inhibited cell proliferation and growth, while expression of HDAC2 enhanced it. Notably, higher expression of RNF125 and PDX1 coincided with differentiated tumor phenotypes, and better outcome in PDA patients. In demonstrating the importance of RNF125 control of PDX1 expression via HDAC2 ubiquitination in PDA development, our findings highlight markers (RNF125, PDX1) and targets (HDAC2) for monitoring and possible treatment of PDA.
Identifying strategies to target the metabolic flexibility of tumours
Authors: Méndez-Lucas Andrés , Lin Wei , Driscoll Paul C. , Legrave Nathalie , Vilaseca Laura Novellasdemunt , Xie Chencheng , Charles Mark , Wilson Zena , Jones Neil P. , Rayport Stephen , Rodríguez-Justo Manuel , Li Vivian , MacRae James I. , Hay Nissim , Chen Xin , Yuneva Mariia 
Published: January 2020

SummaryPlasticity of cancer metabolism can be a major obstacle for efficient targeting of tumour-specific metabolic vulnerabilities. Here, we identify and quantify the compensatory mechanisms following the inhibition of major pathways of central carbon metabolism in c-MYC-induced liver tumours. We find that glutaminase isoform Gls2, expressed in normal liver, compensates for the deletion of Gls1 isoform expressed in tumours. Inhibiting both glutaminases significantly delays tumourigenesis but does not completely block glutamine catabolism through the Krebs cycle. We reveal that glutamine catabolism is then driven by amidotransferases. Consistently, the synergistic effect of glutaminase and amidotransferase inhibitors on proliferation of mouse and human tumour cells is observedin vitroandin vivo. Furthermore, when Gls1 is deleted the Krebs cycle activity and tumour formation can also be significantly affected if glycolysis is co-inhibited (Gls1KO/Hk2KO). Finally, the inhibition of either serine (Psat1KO) or fatty acid (FasnKO) biosynthesis can be compensated by uptake of circulating nutrients. Thus, removing these nutrients from the diet produces synergistic effects on suppression of tumourigenesis. These results highlight the high flexibility of tumour metabolism and demonstrate how targeting compensatory mechanisms can improve a therapeutic outcome.
Optimization of electroslag melting towards to titanium morphology improvement in combined Kroll process
Authors: Platacis Ernests , Kaldre Imants , Blumbergs Ervins , Goldsteins Linards , Gailitis Karlis 
Published: January 2020

Purpose
The paper aims to optimize calcium difluoride electrical melting process towards creating titanium production with improved morphology by combining titanium reduction and electroslag melting processes. The study aims to explore optimal electrical heating power in the slag supplied via tungsten electrode and formation of a stable skull layer on water-cooled walls of a cylindrical stainless steel reactor, which is crucial for electroslag melting.

Design/methodology/approach
The multi-physical numerical modelling approach using commercial software COMSOL Multiphysics is presented in the paper by coupling electrical, heat transfer and fluid flow problems. The slag material phase change and corresponding changes of physical properties such as electrical conductivity and viscosity are modelled by step function, sharply changing value of parameter near the phase change temperature. A parametric study of applied electrical power has been carried out to find optimal conditions for the skull-layer formation.

Findings
The paper provides an estimation of necessary electrical power to avoid overheating or solidification of the top layer of slag, which is unacceptable for the combined Kroll process. The study also revealed important poloidal buoyancy flow with characteristic velocity of few cm/s of in the reactor, which governs the heat transfer process and formation of the skull layer.

Research limitations/implications
The presented simplification in numerical model offers high calculation speed but lacks fully developed phase change model, e.g. excluding latent heat. Also, heat transfer through radiation is neglected in the model.

Originality/value
The paper presents an original way to overcome the complexity of modelling slag electrical melting/solidification phenomena using temperature-dependent properties with step functions.
Diversity in tourism: a perspective article
Authors: Higgins Desbiolles Freya 
Published: January 2020

Purpose
This paper aims to consider growing calls for diversity and inclusion in tourism scholarship, practices and operations. It briefly overviews evolution in the thinking on diversity in tourism and considers issues arising for the future.

Design/methodology/approach
Drawing on theories of intersectionality and decolonial thinking, this paper offers a review of the evolution of thinking on diversity in tourism.

Findings
Diversity is essential to the future of tourism to build more just, equitable and sustainable futures.

Research limitations/implications
The tourism academy and the tourism industry must engage in all forms of diversity to respond to a rapidly changing world. Engagement with diversity also allows for innovative and creative thinking that will be essential for a just and sustainable future.

Originality/value
This paper addresses an under-studied development in tourism: transitions to diversity. It reviews concepts emerging in tourism scholarship, including intersectionality and decolonial thinking. These are essential tools for understanding diversity in tourism and developing just and sustainable futures.
SdsA1, a secreted sulfatase, contributes to the in vivo virulence of Pseudomonas aeruginosa in mice
Authors: Kida Yutaka , Yamamoto Takeshi , Kuwano Koichi 
Published: January 2020

AbstractMucin is a glycoprotein that is the primary component of the mucus overlaying the epithelial tissues. Because mucin functions as a first line of the innate immune system, Pseudomonas aeruginosa appears to require interaction with mucin to establish infection in the host. However, the interactions between P. aeruginosa and mucin have been poorly understood. In this study, using in vivo expression technology (IVET), we attempted to identify mucin‐inducible promoters that are likely to be involved in the establishment of P. aeruginosa infection. The IVET analysis revealed that the genes encoding glycosidases, sulfatases, and peptidases that are thought to be required for the utilization of mucin as a nutrient are present in 13 genes downstream of the identified promoters. Our results indicated that, among them, sdsA1 encoding a secreted sulfatase plays a central role in the degradation of mucin. It was then demonstrated that disruption of sdsA1 leads to a decreased release of sulfate from mucin and sulfated sugars. Furthermore, the sdsA1 mutant showed a reduction in the ability of mucin gel penetration and an attenuation of virulence in leukopenic mice compared with the wild‐type strain. Collectively, these results suggest that SdsA1 plays an important role as a virulence factor of P. aeruginosa.
Microfacies Analysis and Paleoecology of the Oligocene Succession in a Central Tethyan Carbonate Platform, Zagros Basin, SW Iran
Authors: HABIBI Tahereh 
Published: January 2020

AbstractTwo stratigraphic sections (Arjooieh and Firoozabad) of the Mymand anticline, located in the Interior Fars sub‐basin of the Zagros Mountains, were measured and sampled, in order to document sedimentological characteristics, microfacies types and paleo‐seagrasses indicators of the Oligocene succession (Asmari Fm.). Planktonic and benthic foraminifera and coralline red algae are the principal fossils from these strata. Foraminifera are represented by the following families: Soritidae, Peneroplidae, Austrotrillinidae, Alveolinidae, Planorbulinidae, Discorbidae, Lepidocyclinidae, Amphisteginidae, Rotaliidae, Nummulitidae and Globigerinidae. Nine microfacies types were recognized, namely planktonic foraminifera‐peloidal packstone (MF1), bioclast nummulitid/Nerorotalia/Amphistegina packstone‐grainstone‐rudstone‐floatstone (MF2), Neorotalia‐echinoid coralline red algae packstone‐grainstone (MF3), coral boundstone (MF4), coral/coralline red algae rudstone‐floatstone‐packstone‐grainstone (MF5), diverse imperforate foraminifera bioclast packstone‐grainstone (MF6), peloid wackestone‐packstone‐grainstone (MF7), fenestrated mudstone and microbial mats (MF8) and anhydrite (MF9). MF1 indicates an outer ramp, MFs 2‐4 represent a mid‐ramp and MFs 5–9 are interpreted as inner ramp environment. Paleo‐seagrass indicators consisting of foraminifera, hooked and tabular forms of coralline red algae and corals. They were identified in MFs 5 and 6, reflecting the presence of vegetated environments within the mid/inner ramp setting. The Mymand anticline was dominated by the outer ramp environment at the start of the Rupelian. Mid to inner ramp environments prevailed during the Rupelian. The Chattian corresponds to the spread of the inner ramp setting over the Mymand anticline.
Measuring bone density in axial spondyloarthropathy: Time to turn things on their side?
Authors: Fitzgerald Gillian , Anachebe Tochukwu , McCarroll Kevin , O'Shea Finbar 
Published: January 2020

AbstractAimOsteoporosis in axial spondyloarthropathy (axSpA) is difficult to accurately diagnose due to osteoproliferation of the spine interfering with conventional (anteroposterior, AP) dual‐energy X‐ray absorptiometry (DXA). This study compares AP and lateral projections of DXA when assessing bone mineral density (BMD) of the spine and investigates the impact of osteoproliferation on AP DXA.MethodIn this cross‐sectional study, structured standardized assessments collected demographic, clinical, laboratory and radiographic data. DXA assessed BMD of the spine using PA and lateral projections. Hip BMD was assessed in the usual manner. World Health Organization (WHO) criteria assessed prevalence of low BMD. Incorporating lateral DXA in the bone health assessment of axSpA was investigated. SPSS was used for statistical analysis.ResultsA total of 100 patients had paired AP and lateral DXA studies: 78% were male, mean (SD) age 52 (12) years. BMD of the spine measured by AP projection was significantly higher than BMD measured by lateral projection (mean difference 0.34 g/cm2, 95% CI 0.30‐0.37). More patients had low BMD with lateral compared to AP projection (47% vs 16%, P = .01). At the hip, 34% of patients had low BMD. Disease duration, body mass index and radiographic severity independently predicted a difference between AP and lateral measurements of the spine.ConclusionLateral DXA of the spine is unaffected by osteoproliferation of the spine in axSpA and detects significantly more cases of low BMD than conventional AP DXA. Lateral DXA should be included in BMD assessment of patients with axSpA.
Influence of crown‐to‐implant ratio and different prosthetic designs on the clinical conditions of short implants in posterior regions: A 4‐year retrospective clinical and radiographic study
Authors: Tang Yiman , Yu Huajie , Wang Juan , Gao Ming , Qiu Lixin 
Published: January 2020

AbstractBackgroundShort implants (intra‐bony length ≤ 8 mm) are generally considered as an alternative to bone augmentation in challenging situations; however, clinical evidence from large‐scale studies with long follow‐up regarding the application of short implants remains deficient.PurposeThe present study aimed to assess the mid‐term clinical outcomes of short implants supporting fixed prostheses in the posterior region, and to investigate the effects of the crown‐to‐implant ratio (C/I), and other patient‐, implant‐, prosthesis‐relevant factors on the clinical conditions around short implants.Materials and methods180 Thommen short implants in 130 partially edentulous patients were enrolled in the study after 3 to 7 (mean 4.2) years of follow‐up. Potential risk factors (patient sex and age, implant diameter and location, splinted vs single‐tooth restorations, retention mode, anatomical and clinical C/I ratios) were evaluated according to the following outcomes: Implant survival, marginal bone loss (MBL), and mechanical and biological complications.ResultsIn total, four implants in four patients failed as a result of peri‐implantitis. The cumulative survival rate was 97.8% for implant‐based analysis. The peri‐implant MBL around 180 short implants was 0.90 ± 0.78 mm. The mean clinical C/I ratio was 1.16 ± 0.36. Correlation analysis revealed that the influence of the clinical C/I ratio and patient age were significant for MBL (P < .05), whereas other potential risk factors showed no significant association with the outcome. Among 180 short implants, 24 cases (13.3%) had biological complications and 32 cases (17.8%) had mechanical complications, respectively. Peri‐implant MBL and complication rates around splinted and non‐splinted implants were not statistically different.ConclusionWithin the limitations of this study, short implants supporting fixed prostheses in the posterior region achieved predictable clinical outcomes over a 3 to 7 year period. Within the range of 0.47 to 3.01, the higher the C/I ratio, the less the peri‐implant MBL.
The effect of inhaled corticosteroids in the outcomes of community‐acquired pneumonia: ICCAP study (TURKCAP Database)
Authors: Baha Ayse , Kokturk Nurdan , Bahcecioglu Sakine Nazik , Yapar Dilek , Aksakal Nur , Gündüz Canan , Tasbakan Sezai , Sayiner Abdullah , Coskun Aysin Sakar , Durmaz Feride , Cilli Aykut , Celenk Burcu , Kılınc Oguz , Salman Seda , Hazar Armagan , Tokgoz Fatma 
Published: January 2020

AbstractObjectiveWe aimed to investigate the effect of inhaled corticosteroids (ICS) in the outcomes of community‐acquired pneumonia (CAP), as well as to determine if ICS usage is exist among the risk factors for mortality in those patients.Materials and MethodsIn this retrospective cross‐sectional multicentre study, 1069 hospitalised CAP patients were investigated using CAP Database of Turkish Thoracic Society (TURKCAP Database). The patients were divided into two groups, depending on their ICS use. The data were analysed by appropriate statistical methods.Results172 (75.8%) of the 227 patients who were on ICS had COPD and 37 (16.3%) had asthma. There were fewer patients with fever among ICS‐users compared to non‐ICS users (P = 0.013), and less muscle pain (P = 0.015) and fewer GIS symptoms (P = 0.022). No statistically significant difference was found between ICS use/ type of ICS and the duration of hospitalisation (P = 0.286). The multivariate regression analysis showed that patients using ICS had lower body temperature and, less crackles/bronchial sound. In the multivariate logistic regression model lung cancer (OR: 6.75), glucose (OR: 1.01) and CURB‐65 (OR: 1.72) were significantly associated with mortality in the CAP patients. ICS usage were not found to be associated with mortality.ConclusionThe use of ICS by the patients with CAP admitted to the hospital is not independently related with any radiological pattern, hospitalisation duration and mortality. ICS usage may diminish fever response and may suppress the findings of crackles and/or bronchial sounds. This needs further confirmation.