bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virulence factors regulation by the quorum-sensing and Rsm systems in the marine strain Pseudomonas aeruginosa ID4365, a natural mutant in lasR
Authors: Cocotl-Yañez Miguel , Soto-Aceves Martín Paolo , González-Valdez Abigail , Servín-González Luis , Soberón-Chávez Gloria 
Published: June 2020

ABSTRACT
Pseudomonas aeruginosa is an opportunistic human pathogen that is able to produce several virulence factors such as pyocyanin, rhamnolipids and elastase. In the clinical reference strain PAO1, synthesis of these virulence factors is regulated transcriptionally by quorum sensing (QS) and post-transcriptionally by the Rsm system. Herein, we investigated the role of these systems in the control of the pyocyanin, rhamnolipids and elastase production in the marine strain ID4365. We found that this strain carries a nonsense mutation in lasR that makes it a natural mutant in the Las QS system. However, its QS response is still functional with the Rhl system activating virulence factors synthesis. We found that the Rsm system affects virulence factors production, since overexpression of RsmA reduces pyocyanin production whereas RsmY overexpression increases its synthesis. Unexpectedly, and in contrast to the type strain PAO1, inactivation of rsmA increases pyocyanin but reduces elastase and rhamnolipids production by a reduction of RhlR levels. Thus, QS and Rsm systems are involved in regulating virulence factors production, but this regulation is different to the PAO1 strain even though their genomes are highly conserved. It is likely that these differences are related to the different ecological niches in which these strains lived.
Geometric controls on megathrust earthquakes
Authors: Plescia Steven M , Hayes Gavin P 
Published: June 2020

SUMMARYThe role of subduction zone geometry in the nucleation and propagation of great-sized earthquake ruptures is an important topic for earthquake hazard, since knowing how big an earthquake can be on a given fault is fundamentally important. Past studies have shown subducting bathymetric features (e.g. ridges, fracture zones, seamount chains) may arrest a propagating rupture. Other studies have correlated the occurrence of great-sized earthquakes with flat megathrusts and homogenous stresses over large distances. It remains unclear, however, how subduction zone geometry and the potential for great-sized earthquakes (M 8+) are quantifiably linked—or indeed whether they can be. Here, we examine the potential role of subduction zone geometry in limiting earthquake rupture by mapping the planarity of seismogenic zones in the Slab2 subduction zone geometry database. We build from the observation that historical great-sized earthquakes have preferentially occurred where the surrounding megathrust is broadly planar, and we use this relationship to search for geometrically similar features elsewhere in subduction zones worldwide. Assuming geometry exerts a primary control on earthquake propagation and termination, we estimate the potential size distribution of large (M 7+) earthquakes and the maximum earthquake magnitude along global subduction faults based on geometrical features alone. Our results suggest that most subduction zones are capable of hosting great-sized earthquakes over much of their area. Many bathymetric features previously identified as barriers are indistinguishable from the surrounding megathrust from the perspective of slab curvature, meaning that they either do not play an important role in arresting earthquake rupture or that their influence on slab geometry at depth is not resolvable at the spatial scale of our subduction zone geometry models.
Management of COVID-19 Pandemic in Spanish Inflammatory Bowel Disease Units: Results From a National Survey
Authors: Martin Arranz Eduardo , Suarez Ferrer Cristina , García Ramírez Laura , Rueda García Jose Luis , Sánchez-Azofra María , Poza Cordón Joaquín , Noci Jesus , Zabana Yamile , Barreiro-de Acosta Manuel , Martín-Arranz María Dolores 
Published: June 2020

Abstract

Background
The outbreak of COVID-19 has rapidly evolved into a pandemic that has represented a challenge to health systems worldwide. Inflammatory bowel disease (IBD) units have been forced to change their practices to address the disease and to ensure the quality of care.

Methods
We conducted a national survey among IBD gastroenterologist members of the Spanish Working Group on Crohn’s Disease and Colitis regarding changes of practice, IBD treatments, and diagnosis and treatment of COVID-19.

Results
We received 54 answers from Spanish hospitals. One hundred percent of the IBD units rescheduled onsite visits to telematic consultation, and elective endoscopic and surgical procedures were delayed. Protective measures were also taken in the infusion units (100% of health centers) and hospital pharmacies, with 40.7% sending subcutaneous medications to patients. No switching between intravenous and subcutaneous anti-tumor necrosis factor drugs were made. We also found that 96.1% of IBD units advised their patients to maintain treatment if they were asymptomatic for COVID-19. For patients with COVID-19 symptoms, 92.6% of IBD units referred them to primary care or the emergency department. In addition, 7.5% of IBD units made a COVID-19 diagnosis through polymerase chain reaction and/or chest x-ray.
Modifications in IBD treatment and treatment recommended for COVID-19 are also discussed.

Conclusions
We report a representative national survey of changes made in the structure, diagnosis of COVID-19, and modifications in IBD treatments within IBD units.
Phenotypic Variation in Mitochondria-Related Performance Traits Across New Zealand Snail Populations
Authors: Greimann Emma S , Ward Samuel F , Woodell James D , Hennessey Samantha , Kline Michael R , Moreno Jorge A , Peters Madeline , Cruise Jennifer L , Montooth Kristi L , Neiman Maurine , Sharbrough Joel 
Published: June 2020

SynopsisMitochondrial function is critical for energy homeostasis and should shape how genetic variation in metabolism is transmitted through levels of biological organization to generate stability in organismal performance. Mitochondrial function is encoded by genes in two distinct and separately inherited genomes—the mitochondrial genome and the nuclear genome—and selection is expected to maintain functional mito-nuclear interactions. The documented high levels of polymorphism in genes involved in these mito-nuclear interactions and wide variation for mitochondrial function demands an explanation for how and why variability in such a fundamental trait is maintained. Potamopyrgus antipodarum is a New Zealand freshwater snail with coexisting sexual and asexual individuals and, accordingly, contrasting systems of separate vs. co-inheritance of nuclear and mitochondrial genomes. As such, this snail provides a powerful means to dissect the evolutionary and functional consequences of mito-nuclear variation. The lakes inhabited by P. antipodarum span wide environmental gradients, with substantial across-lake genetic structure and mito-nuclear discordance. This situation allows us to use comparisons across reproductive modes and lakes to partition variation in cellular respiration across genetic and environmental axes. Here, we integrated cellular, physiological, and behavioral approaches to quantify variation in mitochondrial function across a diverse set of wild P. antipodarum lineages. We found extensive across-lake variation in organismal oxygen consumption and behavioral response to heat stress and differences across sexes in mitochondrial membrane potential but few global effects of reproductive mode. Taken together, our data set the stage for applying this important model system for sexual reproduction and polyploidy to dissecting the complex relationships between mito-nuclear variation, performance, plasticity, and fitness in natural populations.
Translational Development Strategies for TAK-063, a Phosphodiesterase 10A Inhibitor
Authors: Macek Thomas A , Suzuki Kazunori , Asin Karen , Kimura Haruhide 
Published: June 2020

Abstract

Background
TAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of the striatum. PDE10A hydrolyzes both cyclic adenosine monophosphate and cyclic guanosine monophosphate and modulates dopamine signaling downstream of receptor activation in both direct and indirect pathways of the striatum. TAK-063 exhibited antipsychotic-like effects in animal models; however, the translatability of these models to the clinical manifestations of schizophrenia and the meaningfulness for new targets such as PDE10A has not been established.

Methods
The TAK-063 phase 1 program included a comprehensive translational development strategy with the main objective of determining whether the antipsychotic-like pharmacodynamic effects seen in nonclinical models would translate to human subjects. To evaluate this objective, we conducted a single-rising dose study (84 healthy subjects), a positron emission tomography (PET) study (12 healthy subjects), a functional magnetic resonance imaging blood oxygen level-dependent (BOLD) study (27 healthy subjects), and a multiple-rising dose study that included people with schizophrenia (30 healthy Japanese subjects and 47 subjects with stable schizophrenia). In addition, assessments of cognition and electroencephalography (27 healthy subjects and 47 subjects with stable schizophrenia) were included.

Results
PDE10A engagement by TAK-063 was verified with a novel PET radiotracer for use in primates and humans. TAK-063 showed favorable pharmacokinetic and safety profiles in humans, and TAK-063 reduced ketamine-induced changes in electroencephalography and BOLD signaling in animal models and healthy human subjects. In addition, analogous effects on cognition were observed in animal models and human subjects.

Conclusions
Overall, the phase 1 results showed some consistent evidence of antipsychotic activity. This translational strategy may be valuable for the future development of novel therapeutic approaches, even when relevant nonclinical models are not available.
Use of Population-Based Surveys for Estimating the Population Size of Persons Who Inject Drugs in the United States
Authors: Bradley Heather , Rosenthal Elizabeth M , Barranco Meredith A , Udo Tomoko , Sullivan Patrick S , Rosenberg Eli S 
Published: June 2020

Abstract

Background
In the United States, injection is an increasingly common route of administration for opioids and other substances. Estimates of the number of persons who inject drugs (PWID) are needed for monitoring risk-specific infectious disease rates and health services coverage.

Methods
We reviewed design and instruments for 4 national household surveys, 2012–2016, for their ability to produce unbiased injection drug use (IDU) prevalence estimates. We explored potential analytic adjustments for reducing biases through use of external data on (1) arrest, (2) narcotic overdose mortality, and (3) biomarker-based sensitivity of self-reported illicit drug use.

Results
Estimated national past 12 months IDU prevalence ranged from 0.24% to 0.59% across surveys. All surveys excluded unstably housed and incarcerated persons, and estimates were based on &lt;60 respondents reporting IDU behavior in 3 surveys. No surveys asked participants about nonmedical injection of prescription drugs. Analytic adjustments did not appreciably change IDU prevalence estimates due to suboptimal specificity of data points.

Conclusions
PWID population size estimates in the United States are based on small numbers and are likely biased by undercoverage of key populations and self-report. Novel methods as discussed in this article may improve our understanding of PWID population size and their health needs.
Contestation before Compliance: History, Politics, and Power in International Humanitarian Law
Authors: Kinsella Helen M , Mantilla Giovanni 
Published: June 2020

AbstractDespite the common reference to international humanitarian law (IHL) in the discourse and practice of international politics, international relations (IR) scholarship has yet to consistently engage in an analysis of IHL that extends beyond the relatively narrow specifications of its regulative and strategic effects. In this theory note, we argue that this prevailing focus leaves the discipline with an impoverished understanding of IHL and its operation in international politics. We propose that the study of IHL should be expanded through a deeper engagement with the law's historical development, the politics informing its codification and interpretation, and its multiple potential effects beyond compliance. This accomplishes three things. First, it corrects for IR's predominantly ahistorical approach to evaluating both IHL and compliance, revealing the complicated, contested, and productive construction of some of IHL's core legal concepts and rules. Second, our approach illuminates how IR's privileging of civilian targeting requires analytical connection to other rules such as proportionality and military necessity, none of which can be individually assessed and each of which remain open to debate. Third, we provide new resources for analyzing and understanding IHL and its contribution to “world making and world ordering.”
Multivariate Logistic-Assisted Estimators of Totals from Clustered Survey Samples
Authors: Kennel Timothy L , Valliant Richard 
Published: June 2020

Abstract
Estimators based on linear models are the standard in finite population estimation. However, many items collected in surveys are better described by nonlinear models; these include variables that have binary, binomial, or multinomial distributions. We extend previous work on generalized difference, model-calibrated, and pseudo-empirical likelihood estimators to two-stage cluster sampling and derive their theoretical properties with particular emphasis on multinomial data. We present asymptotic theory for both the point estimators of totals and their variance estimators. The alternatives are tested via simulation using artificial and real populations. The two real populations are one of educational institutions and degrees awarded and one of owned and rented housing units.
Effects of Cell-Derived Microparticles on Immune Cells and Potential Implications in Clinical Medicine
Authors: Noulsri Egarit 
Published: June 2020

AbstractIn the past few years, interest has increased in cell-derived microparticles (MPs), which are defined by their size of from 0.1 to 1 μm, and can be derived from various cell types, including endothelial cells, leukocytes, red blood cells (RBCs), and platelets. These MPs carry negatively charged phosphatidylserine (PS) on their surfaces and proteins packaged from numerous cellular components. MPs that have been shed by the body can play important roles in the pathophysiology of diseases and can affect various biological systems. Among these systems, the immune components have been shown to be modulated by MPs. Therefore, understanding the roles of MPs in the immune system is crucial to developing alternative therapeutic treatments for diseases. This review describes the effects of MPs on various immune cells and provides plausible potential applications of the immune-modulating properties of MPs in clinical medicine.
The glories of immigration: How soccer wins shape opinion on immigration
Authors: Lago Ignacio , Lago-Peñas Carlos 
Published: June 2020

AbstractWhile there is a great deal of anecdotal evidence on the impact of soccer wins on attitudes toward immigrants and immigration, there is relatively little hard empirical evidence. It is expected that soccer stimulates more positive attitudes towards immigrants when it highlights immigration benefits rather than costs and increases exposure to famous members of an out-group. Individual-level data from the eight rounds of the European Social Survey (2002–16) in Spain and aggregate data from the Spanish professional soccer league, La Liga, were used to test the hypothesis that the more foreign players in the team of the club winning the corresponding season of Spain’s La Liga, the more favourable the views of immigrants in the club’s region in that year. The empirical evidence from linear and ordinal regression using different measures of opinions on immigration shows that soccer can affect attitudes toward immigrants and immigration.
Uniqueness and Modesty: How Permissivists Can Live on the Edge
Authors: Bradley Darren 
Published: June 2020

Abstract
There is a divide in epistemology between those who think that, for any hypothesis and set of total evidence, there is a unique rational credence in that hypothesis (Uniqueness), and those who think that there can be many rational credences (Permissivism). Schultheis (2018) offers a novel and potentially devastating objection to Permissivism, on the grounds that Permissivism permits dominated credences. I will argue that Permissivists can plausibly block Schultheis argument. The issue turns on getting clear about whether we should be certain whether our credences are rational.
Study of the effects of magnetic braking on the lithium abundances of the Sun and solar-type stars
Authors: Caballero Navarro R , García Hernández A , Ayala A , Suárez J C 
Published: June 2020

ABSTRACT
The study of lithium (Li) surface abundance in the Sun and young stellar globular clusters which are seemingly anomalous in present-day scenarios, as well as the influence of rotation and magnetic braking (MB) on its depletion during pre-main sequence (PMS) and main sequence (MS). In this work, the effects of rotational mixing and of the rotational hydrostatic effects on Li abundances are studied by simulating several grids of PMS and MS rotating and non-rotating models. Those effects are combined with the additional impact of the MB (with magnetic field intensities ranging between 3.0 and 5.0 G). The data obtained from simulations are confronted by comparing different stellar parameters. The results show that the surface Li abundance for the Sun-like models at the end of the PMS and throughout the MS decreases when rotational effects are included, that is the Li depletion rate for rotating models is higher than for non-rotating ones. This effect is attenuated when the MB produced by a magnetic field is present. This physical phenomena impacts also the star effective temperature (Teff) and its location in the HR diagram. The impact of MB in Li depletion is sensitive to the magnetic field intensity: the higher it is, the lower the Li destruction. A direct link between the magnetic fields and the convective zone (CZ) size is observed: stronger magnetic fields produce shallower CZ’s. This result suggests that MB effect must be taken into consideration during PMS if we aim to reproduce Li abundances in young clusters.
EDGES signal in the presence of magnetic fields
Authors: Natwariya Pravin Kumar , Bhatt Jitesh R 
Published: June 2020

ABSTRACT
We study the 21-cm differential brightness temperature in the presence of primordial helical magnetic fields for redshift z = 10–30. We argue that the α-effect that sets in at earlier time can be helpful in lowering the gas temperature to 3.2 K at z = 17. This effect can arise in the early Universe due to some parity-violating high-energy processes. Using the EDGES (Experiment to Detect the Global Epoch of Reionization Signature) results, we find the upper and lower limits on the primordial magnetic field to be 6 × 10−3 and 5 × 10−4 nG, respectively. We also discuss the effect of Ly α background on the bounds. Our results do not require any new physics in terms of dark matter.
Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila
Authors: Zhe Qu , Yiu Wing Chung , Yip Ho Yin , Nong Wenyan , Yu Clare W C , Lee Ivy H T , Wong Annette Y P , Wong Nicola W Y , Cheung Fiona K M , Chan Ting Fung , Lau Kwok Fai , Zhong Silin , Chu Ka Hou , Tobe Stephen S , Ferrier David E K , Bendena William G , Hui Jerome H L 
Published: June 2020

Abstract
A striking feature of micro-RNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a micro-RNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this micro-RNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of micro-RNA cluster members were also constructed. Expression of individual micro-RNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient micro-RNAs together (miR-5/4/286/3/309) or more recently evolved clustered micro-RNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed downregulation of leg-patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of micro-RNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct micro-RNAs. Considered together, the micro-RNA targets and the evolutionary ages of each micro-RNA in the cluster demonstrate the importance of micro-RNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing micro-RNAs.
Key words: micro-RNA, cluster, evolution.
Efficacy and safety of PT20, an iron-based phosphate binder, for the treatment of hyperphosphataemia: a randomized, double-blind, placebo-controlled, dose-ranging, Phase IIb study in patients with haemodialysis-dependent chronic kidney disease
Authors: Sampson Mark , Faria Nuno , Powell Jonathan J ,   the PEACH study investigators
Published: June 2020

Abstract

Background
Hyperphosphataemia is a common complication of chronic kidney disease (CKD). PT20 (ferric iron oxide adipate) is an investigational molecule engineered to offer enhanced phosphate-binding properties relative to other phosphate binders.

Methods
In this double-blind, parallel-group, placebo-controlled, dose-ranging study (ClinicalTrials.gov identifier NCT02151643), the efficacy and safety of 28 days of oral PT20 treatment were evaluated in patients with dialysis-dependent CKD. Participants were randomly assigned in an 8:8:8:13:13 ratio to receive PT20 (400, 800, 1600 or 3200 mg) or placebo three times daily.

Results
Among 153 participants, 129 completed treatment [7 discontinued because of adverse events (AEs), 2 because of hyperphosphataemia and 15 for other reasons]. PT20 treatment for 28 days resulted in a statistically significant and dose-dependent reduction in serum phosphate concentration. There were no statistically significant effects of PT20 treatment on changes in haemoglobin or ferritin concentrations or transferrin saturation between Days 1 and 29. The incidence of treatment-emergent AEs was broadly similar across the PT20 and placebo groups (42–59% versus 44%). The most common PT20 treatment-related AEs were gastrointestinal, primarily diarrhoea (13–18%) and discoloured faeces (3–23%). No serious AEs were considered to be related to study treatment. There were no clinically significant changes in laboratory results reflecting acid/base status or increases in ferritin that could indicate the absorption of components of PT20.

Conclusions
In this first study investigating the efficacy and safety of PT20 in patients with hyperphosphataemia and dialysis-dependent CKD, PT20 significantly lowered serum phosphate concentrations and was generally well tolerated.