bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing disease risks to British forests: an exploration of costs and benefits of nursery best practices
Authors: Valatin Gregory , Price Colin , Green Sarah
Published: February 2022

Trade-disseminated Phytophthora species are implicated in a recent upsurge of Phytophthora diseases in the UK and the establishment and spread of these pathogens in the wider UK environment via diseased propagation material. The costs and benefits of introducing best practices in the nursery sector and for society at large were explored in relation to avoiding potential impacts of introductions of new pathogens in the wider woodland environment. The analysis formed part of a wider project on the drivers of introduction and spread of Phytophthora species and opportunities for mitigation by plant nurseries. The effect in reducing the risk of introductions of new pathogens is not easily quantified, but the shorter the interval between avoided outbreaks, the greater the benefit of introducing best practices. The maximum interval between avoided outbreaks for the benefits to exceed the costs from a nursery perspective can be estimated. The results indicate that the benefits of introducing nursery best practices are unlikely to outweigh the costs from a nursery perspective where Phytophthora alone is considered. The analysis is extended by also considering benefits in reducing risks of Xylella. Scenario analysis based upon modelling harvested wood and carbon impacts is then used to investigate potential costs that would be expected to be borne by society in the event of the introduction and spread of a new Phytophthora species affecting either oak or Sitka spruce stands in Britain. The results indicate the magnitude of the externality involved, with the cost of an outbreak affecting oak estimated at around £500 million and one affecting Sitka spruce at £11 300 million. While approaches taken in the paper are exploratory, there seems a strong case for some social incentives or control in the nursery sector, to reduce the probability of new diseases infecting British forests.
GABAA α subunit control of hyperactive behavior in developing zebrafish
Authors: Barnaby Wayne , Dorman Barclay Hanna E , Nagarkar Akanksha , Perkins Matthew , Teicher Gregory , Trapani Josef G , Downes Gerald B
Published: February 2022

GABAA receptors mediate rapid responses to the neurotransmitter gamma-aminobutyric acid and are robust regulators of the brain and spinal cord neural networks that control locomotor behaviors, such as walking and swimming. In developing zebrafish, gross pharmacological blockade of these receptors causes hyperactive swimming, which is also a feature of many zebrafish epilepsy models. Although GABAA receptors are important to control locomotor behavior, the large number of subunits and homeostatic compensatory mechanisms have challenged efforts to determine subunit-selective roles. To address this issue, we mutated each of the 8 zebrafish GABAA α subunit genes individually and in pairs using a CRISPR-Cas9 somatic inactivation approach and, then, we examined the swimming behavior of the mutants at 2 developmental stages, 48 and 96 h postfertilization. We found that disrupting the expression of specific pairs of subunits resulted in different abnormalities in swimming behavior at 48 h postfertilization. Mutation of α4 and α5 selectively resulted in longer duration swimming episodes, mutations in α3 and α4 selectively caused excess, large-amplitude body flexions (C-bends), and mutation of α3 and α5 resulted in increases in both of these measures of hyperactivity. At 96 h postfertilization, hyperactive phenotypes were nearly absent, suggesting that homeostatic compensation was able to overcome the disruption of even multiple subunits. Taken together, our results identify subunit-selective roles for GABAA α3, α4, and α5 in regulating locomotion. Given that these subunits exhibit spatially restricted expression patterns, these results provide a foundation to identify neurons and GABAergic networks that control discrete aspects of locomotor behavior.
Estimating SNP heritability in presence of population substructure in biobank-scale datasets
Authors: Lin Zhaotong , Seal Souvik , Basu Saonli
Published: February 2022

Single nucleotide polymorphism heritability of a trait is measured as the proportion of total variance explained by the additive effects of genome-wide single nucleotide polymorphisms. Linear mixed models are routinely used to estimate single nucleotide polymorphism heritability for many complex traits, which requires estimation of a genetic relationship matrix among individuals. Heritability is usually estimated by the restricted maximum likelihood or method of moments approaches such as Haseman–Elston regression. The common practice of accounting for such population substructure is to adjust for the top few principal components of the genetic relationship matrix as covariates in the linear mixed model. This can get computationally very intensive on large biobank-scale datasets. Here, we propose a method of moments approach for estimating single nucleotide polymorphism heritability in presence of population substructure. Our proposed method is computationally scalable on biobank datasets and gives an asymptotically unbiased estimate of heritability in presence of discrete substructures. It introduces the adjustments for population stratification in a second-order estimating equation. It allows these substructures to vary in their single nucleotide polymorphism allele frequencies and in their trait distributions (means and variances) while the heritability is assumed to be the same across these substructures. Through extensive simulation studies and the application on 7 quantitative traits in the UK Biobank cohort, we demonstrate that our proposed method performs well in the presence of population substructure and much more computationally efficient than existing approaches.
Wavefield reconstruction and wave equation inversion for seismic surface waves
Authors: Shaiban A , de Ridder S A L , Curtis A
Published: February 2022

Surface waves are a particular type of seismic wave that propagate around the surface of the Earth, but which oscillate over depth ranges beneath the surface that depend on their frequency of oscillation. This causes them to travel with a speed that depends on their frequency, a property called dispersion. Estimating surface wave dispersion is of interest for many geophysical applications using both active and passive seismic sources, not least because the speed–frequency relationship can be used to infer the subsurface velocity structure at depth beneath the surface. We present an inversion scheme that exploits spatial and temporal relationships in the scalar Helmholtz (wave) equation to estimate dispersion relations of the elastic surface wave data in both active and passive surveys, while also reconstructing the wavefield continuously in space (i.e. between the receivers at which the wavefield was recorded). We verify the retrieved dispersive phase velocity by comparing the results to dispersion analysis in the frequency-slowness domain, and to the local calculation of dispersion using modal analysis. Synthetic elastic examples demonstrate the method under a variety of recording scenarios. The results show that despite the scalar approximation made to represent these intrinsically elastic waves, the proposed method reconstructs both the wavefield and the phase dispersion structure even in the case of strong aliasing and irregular sampling.
Ground motion simulations in Quito (Ecuador) due to major earthquakes from the subduction zone
Authors: Courboulex Francoise , Castro-Cruz David Alejandro , Laurendeau Aurore , Bonilla Luis Fabian , Alvarado Alexandra , Bertrand Etienne
Published: February 2022

In 1906, an earthquake with a magnitude estimated between Mw 8.4 and 8.8 occurred in the subduction zone along the coast of Ecuador and Colombia. This earthquake caused extensive damage on the coast but had a rather small impact on the capital city of Quito, situated 180 km away. At that time, the city of Quito extended over a small area with a few thousand inhabitants, while today it stretches over 40 km and has a population of over 3 million, with most of the city built without paraseismic regulations. The aim of this study is to obtain new insights on the impact that large earthquakes from the subduction zone would have on the city today. This question is crucial since we know that the city of Quito is prone to site effects and that the southern part of the city amplifies seismic waves at low frequencies, around 0.3–0.4 Hz. In April 2016, an Mw 7.8 earthquake occurred on the subduction interface in the Pedernales area. This event was the first large earthquake in the city of Quito to be well recorded by 13 stations of the permanent accelerometric network (RENAC). In this study, we take advantage of this data set (main shock and large aftershock recordings) to (1) test an empirical Green's function blind simulation approach where the input stress drop is taken from a global catalogue of source time functions, (2) compare the synthetic accelerograms and ground motion values we obtain for an Mw 7.8 earthquake with the actual recordings of the Pedernales earthquake and then (3) simulate larger earthquakes of Mw 8.2 and 8.5 from the subduction zone. For Mw 7.8 simulations, our approach allows a good reproduction of the ground motions in the whole frequency bands and properly takes into account site effects. For Mw 8.2 and 8.5 simulations, we obtain for the stations in the southern part of the basin, larger values at low frequencies than the predicted motion given by ground motion models. These values, although high, should be supported by new or recent buildings if they are constructed respecting the building code that applies in Quito. Therefore, for this type of strong but distant earthquake, the seismic standards appear to be well suited and it is imperative to ensure that they are well considered in the design of the new buildings to be constructed, especially in the southern part of the expanding city.
Seasonal temperature regulates network connectivity of salmon louse
Authors: Huserbråten M B O , Johnsen I A
Published: February 2022

Chronically high infestation of salmon louse (Lepeophtheirus salmonis) questions the sustainability of the Norwegian Atlantic salmon (Salmo salar) aquaculture industry. The confinement of millions of hosts, within hundreds of farms with overlapping larval dispersal kernels create the structure for extremely persistent parasite meta-populations. However, the processes regulating the temporal variation in cross-contamination of pelagic salmon louse stages among farms (i.e. connectivity), a vital process driving louse population dynamics, are not well described. Here, we employ a data driven biophysical dispersal model that reproduces three-and-a-half years of production histories of 132 salmon farms in western Norway and quantifies the connectivity of infective pelagic lice stages among the farms with the ocean currents. We show that although the complex geography of western Norwegian fjords governs the long-term topology of the connectivity network, there was a strong seasonal component to network fragmentation. The main de-structuring agent was the delayed infectivity of the pelagic lice stages at cooler temperatures increasing dispersal distances, enhanced by occasional large scale wind forcing events. Coordinated fallowing strategies and de-lousing treatments only played a marginal role in network fragmentation, suggesting that novel lice restraining strategies that consider the environmentally sensitive transport distances must be developed to successfully break up the connectivity network.
Does early extubation after cardiac surgery lead to a reduction in intensive care unit length of stay?
Authors: Taylor Marcus , Apparau Denish , Mosca Roberto , Nwaejike Nnamdi
Published: February 2022

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether early extubation (EE) after cardiac surgery leads to a reduction in intensive care unit (ICU) length of stay (LOS)? A total of 564 papers were found using the reported search, of which 4 were randomized trials and hence represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. EE was defined as extubation in theatre (n = 2), within 6 h of surgery (n = 1) and within 8 h of surgery (n = 1). EE was associated with significantly reduced ICU LOS in all studies. Despite the Society of Thoracic Surgeons using extubation <6 h after surgery as a measure of quality, this study has demonstrated that no standardized definition for EE currently exists. The body of evidence identified in this work has demonstrated that for appropriately selected patients (avoiding patients with multiple comorbidities, advanced age and undergoing complex non-elective surgery) early tracheal extubation is associated with a reduction in ICU LOS without an increase in the rate of postoperative complications.
Body mass index rebound and pubertal timing in girls with and without a family history of breast cancer: the LEGACY girls study
Authors: Houghton Lauren C , Wei Ying , Wang Tianying , Goldberg Mandy , Paniagua-Avila Alejandra , Sweeden Rachel L , Bradbury Angela , Daly Mary , Schwartz Lisa A , Keegan Theresa , John Esther M , Knight Julia A , Andrulis Irene L , Buys Saundra S , Frost Caren J , O’Toole Karen , White Melissa L , Chung Wendy K , Terry Mary Beth
Published: February 2022

Background

Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty.

Methods

In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models.

Results

The median age at BMI rebound was 5.3 years (interquartile range: 3.6–6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83–0.97) and menarche (HR = 0.86; 95% CI = 0.79–0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development.

Conclusions

Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk.
Patients’ knowledge, attitudes and concerns regarding the disposal of expired/unused medication
Authors: Jankie Satish , Barsatee Naveeta , Dookhan Vicky , Sookdeo Kadita , Hernandez Sasha , Villarroel Stuart Arlene
Published: February 2022

Objectives

Unused/expired medicines that are improperly disposed of can enter soil and water supply and have negative implications for public health. This study aimed to assess patients’ knowledge and understanding of medication disposal practices and their willingness to participate in a medication takeback programme.

Methods

A self-administered questionnaire comprising of 26 questions based on demographics, knowledge, beliefs, practices and concerns was utilized in this study. The study was conducted over 12 weeks at outpatient pharmacy sites located in the four Regional Health Authorities in Trinidad. Statistical Package for the Social Sciences (SPSS) version 24 was used for statistical analysis.

Key findings

A total of 547 persons completed the questionnaire. Knowledge of the dangers of improper medication disposal was highest in those aged 18–25 years (P = 0.007) and having secondary/tertiary level education (P = 0.002). Disposal of unused/expired medication via household thrash (86.1%) was the most commonly encountered practice. Only 14.1% (n = 77) of respondents asked the pharmacist for advice on best disposal practice, although 47.3% (n = 259) thought that the pharmacist should be the main source of advice for information on medication disposal practices. There was a willingness to participate in a medicine takeback programme from 82% (n = 449) of the respondents, and the majority (67.5%) (n = 303) would prefer it if medication takeback programmes were implemented at private community pharmacies.

Conclusions

Patients in Trinidad utilized household garbage as their main disposal method. There is a need to implement a medication takeback programme and educate the public on proper medication disposal.
A Quantized Analogue of the Markov–Krein Correspondence
Authors: Goel Gopal K , Yao Andrew
Published: February 2022

We study a family of measures originating from the signatures of the irreducible components of representations of the unitary group, as the size of the group goes to infinity. Given a random signature $\lambda $ of length $N$ with counting measure $\textbf {m}$, we obtain a random signature $\mu $ of length $N-1$ through projection onto a unitary group of lower dimension. The signature $\mu $ interlaces with the signature $\lambda $, and we record the data of $\mu ,\lambda $ in a random rectangular Young diagram $w$. We show that under a certain set of conditions on $\lambda $, both $\textbf {m}$ and $w$ converge as $N\to \infty $. We provide an explicit moment-generating function relationship between the limiting objects. We further show that the moment-generating function relationship induces a bijection between bounded measures and certain continual Young diagrams, which can be viewed as a quantized analogue of the Markov–Krein correspondence.
Lift of the Trivial Representation to a Nonlinear Double Cover
Authors: Tsai Wan-Yu
Published: February 2022

Let $\widetilde G$ be the nonlinear double cover of the real points of a connected, simply connected, semisimple complex group. In [16], we introduce a set of genuine small representations of $\widetilde G$ with infinitesimal character $\lambda $, denoted $\prod _\lambda ^s (\widetilde G)$. In this paper, we show that $\prod _{\rho /2} ^s (\widetilde G)$ is precisely the set of genuine irreducible representations arising from the Kazhdan–Patterson lifting of the trivial representation, when $\widetilde G$ is simply laced and split.
On Geometry of the Unit Ball of Paley–Wiener Space Over Two Symmetric Intervals
Authors: Ulanovskii Alexander , Zlotnikov Ilya
Published: February 2022

Let $PW_S^1$ be the space of integrable functions on ${\mathbb {R}}$ whose Fourier transform vanishes outside $S$, where $S = [-\sigma ,-\rho ]\cup [\rho ,\sigma ]$, $0<\rho <\sigma $. In the case $\rho>\sigma /2$, we present a complete description of the set of extreme and the set of exposed points of the unit ball of $PW_S^1$ . The structure of these sets becomes more complicated when $\rho <\sigma /2$.
The Basic de Rham Complex of a Singular Foliation
Authors: Miyamoto David
Published: February 2022

A singular foliation $\mathcal {F}$ gives a partition of a manifold $M$ into leaves whose dimension may vary. Associated to a singular foliation are two complexes, that of the diffeological differential forms on the leaf space $M / \mathcal {F}$ and that of the basic differential forms on $M$. We prove the pullback by the quotient map provides an isomorphism of these complexes in the following cases: when $\mathcal {F}$ is a regular foliation, when points in the leaves of the same dimension assemble into an embedded (more generally, diffeological) submanifold of $M$, and, as a special case of the latter, when $\mathcal {F}$ is induced by a linearizable Lie groupoid or is a singular Riemannian foliation.
Influence of tedizolid on the cytokine response to the endotoxin challenge in healthy volunteers: a cross-over trial
Authors: Jorda Anselm , Wulkersdorfer Beatrix , Schörgenhofer Christian , Matzneller Peter , Al Jalali Valentin , Bauer Martin , Wölf-Duchek Michael , Lackner Edith , Dorn Christoph , Jilma Bernd , Zeitlinger Markus
Published: February 2022

Background

Preclinical data suggested anti-inflammatory properties of tedizolid.

Objectives

To investigate the influence of tedizolid on the cytokine response to the human endotoxin challenge and the effect of endotoxaemia on the pharmacokinetics and protein binding of tedizolid.

Methods

In this cross-over trial, 14 male healthy volunteers underwent two treatment periods: (A) 200 mg of tedizolid phosphate once daily for 6 days (3 days orally and 3 days intravenously), followed by an intravenous bolus of 2 ng/kg body weight of LPS on the last treatment day; and (B) intravenous bolus of LPS (2 ng/kg body weight) without concomitant tedizolid treatment. Participants underwent first period A or B, separated by at least 6 weeks. Plasma was sampled to assess cytokines and the pharmacokinetics of tedizolid.

Results

Following the endotoxin challenge, the peak plasma concentration (median [IQR]; 280 [155–502] versus 287 [132–541]  pg/mL; P = 0.875) and AUC0–24 (979 [676–1319] versus 1000 [647–1632]  pg·h/mL; P = 0.638) of interleukin-6 remained unchanged with and without concomitant tedizolid treatment. The peak concentration and AUC0–24 of TNF-α remained also unchanged with and without tedizolid (47 [31–61] versus 54 [27–69]  pg/mL; P = 0.73 and 197 [163–268] versus 234 [146–280]  pg·h/mL; P = 0.875, respectively). The total maximum concentration (mean ± SD; 2.94 ± 0.69 versus 2.96 ± 0.62 mg/L), total AUC0–24 (22.3 ± 3.8 versus 21.1 ± 3.6 mg·h/L) and protein binding (21.4% ± 1.7% versus 21.6% ± 1.9%) of tedizolid were similar with and without the endotoxin challenge.

Conclusions

Tedizolid did not attenuate the LPS-induced cytokine response in healthy volunteers. Furthermore, endotoxaemia did not influence the plasma pharmacokinetics of tedizolid.
Clinical Utility and Analytical Aspects of Direct Measurements of Free Hormones Using Mass Spectrometry-Based Methods
Authors: Kushnir Mark M , Nelson Heather A , Doyle Kelly
Published: February 2022

Background

The free hormone (FH) hypothesis states that hormone action and the corresponding biological effects are mediated by the unbound (free) fraction of hormone in circulation. The in vivo relationship between protein-bound and FH is complex and dynamic. In most individuals, measurement of total hormone (TH) is usually adequate to reflect the hormone status; however, certain physiological conditions and/or medications can affect protein binding and alter FH concentration. In these cases, measurement of FH will provide a better measure of the bioactive hormone status than measurement of the TH. Measurement of FH presents many challenges, as the concentrations are very low and there are number of pitfalls, which may affect the measured concentrations.

Content

In this review, we discuss techniques used in the separation and direct quantitation of FH concentrations in biological samples using mass spectrometry for analysis. We also highlight clinical situations in which FH analysis is warranted and when mass spectrometry should be the preferred methodology over immunoassays.

Equilibrium dialysis, ultrafiltration, or size-exclusion separation coupled with liquid chromatography–tandem mass spectrometry provides a sensitive and specific method to measure FH concentrations. These direct methods are useful in iatrogenic or physiological states that alter hormone binding or metabolism.
Considerations and best practices in animal science 16S ribosomal RNA gene sequencing microbiome studies
Authors: Weinroth Margaret D , Belk Aeriel D , Dean Chris , Noyes Noelle , Dittoe Dana K , Rothrock Michael J , Ricke Steven C , Myer Phillip R , Henniger Madison T , Ramírez Gustavo A , Oakley Brian B , Summers Katie Lynn , Miles Asha M , Ault-Seay Taylor B , Yu Zhongtang , Metcalf Jessica L , Wells James E
Published: February 2022

Microbiome studies in animal science using 16S rRNA gene sequencing have become increasingly common in recent years as sequencing costs continue to fall and bioinformatic tools become more powerful and user-friendly. The combination of molecular biology, microbiology, microbial ecology, computer science, and bioinformatics—in addition to the traditional considerations when conducting an animal science study—makes microbiome studies sometimes intimidating due to the intersection of different fields. The objective of this review is to serve as a jumping-off point for those animal scientists less familiar with 16S rRNA gene sequencing and analyses and to bring up common issues and concerns that arise when planning an animal microbiome study from design through analysis. This review includes an overview of 16S rRNA gene sequencing, its advantages, and its limitations; experimental design considerations such as study design, sample size, sample pooling, and sample locations; wet lab considerations such as field handing, microbial cell lysis, low biomass samples, library preparation, and sequencing controls; and computational considerations such as identification of contamination, accounting for uneven sequencing depth, constructing diversity metrics, assigning taxonomy, differential abundance testing, and, finally, data availability. In addition to general considerations, we highlight some special considerations by species and sample type.
A Population-Based Study of Treatment and Survival in Older Glioma Patients
Authors: Reiner Anne S , Lobaugh Stephanie M , Gonen Selin , Diamond Eli L , Panageas Katherine S
Published: February 2022

Background

Population-based analyses of patterns of care and survival of older patients diagnosed with grade II-III oligodendroglioma (OLI) or astrocytoma (AST) can aid clinicians in their understanding and care of these patients.

Methods

We identified patients diagnosed between 2006 and 2015 with primary glioma diagnoses (OLI or AST) who were older than 65 years using the latest release of the Surveillance, Epidemiology, and End Results-Medicare–linked database. Medicare claims were used to identify cancer treatments (surgery, chemotherapy, and radiation therapy) from 2006 to 2016. Kaplan-Meier methodology was used to describe overall survival (OS). Cox proportional hazards regression was used to associate variables of interest, including treatments in a time-dependent manner, with OS. Hazard ratios (HRs) and 95% confidence intervals (CIs) from multivariable, cause-specific competing risk models identified associations with treatments. All statistical tests were 2-sided.

Results

We identified 1291 patients comprising 158 with OLI, 1043 with AST, and 90 with mixed histologies. Median OS was 6.5 (95% CI = 6.1 to 7.3) months for the overall cohort, 22.6 (95% CI = 13.9 to 33.1) months for OLI, and 5.8 (95% CI = 5.3 to 6.4) months for AST. Patients who received surgery and patients who received both chemotherapy and radiation therapy in combination experienced better OS (HR = 0.87, 95% CI = 0.79 to 0.96, and HR = 0.58, 95% CI = 0.35 to 0.96, respectively). Over the time frame studied, there was a 4.0% increase per year in prescription of chemotherapy (P = .03) and a 2.0% improvement in OS for each calendar year (P = .003).

Conclusions

We provide population-based evidence that patients older than 65 years with grade II-III glioma have experienced increased chemotherapy use as well as improvement in survival over time.
The application of natural compounds in uveal melanoma drug discovery
Authors: Niu Yihe , Wang Ke , Zhu Xue , Zhang Stanley , Cherepanoff Svetlana , Conway R Max , Madigan Michele C , Lim Li-Anne , Zhu Ling , Murray Michael , Zhou Fanfan
Published: February 2022

Objectives

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. UM has a poor overall prognosis and ~50% of patients progress to metastatic disease that has a median survival of 5.2 months. There are currently no proven pharmacological treatments for primary or metastatic UM. Research efforts continue to seek new agents. Many natural compounds have shown promising anti-UM activity in in-vitro and/or in-vivo studies. This review summarises the current findings for natural compounds that may be potentially useful in treating UM.

Key findings

Literature suggests that natural compounds, such as pristimerin, picropodophyllin, oridonin, zeaxanthin, withaferin and FR-900359, may be promising candidate compounds to treat UM. Most of these compounds have demonstrated satisfactory efficacy in inhibiting in-vitro UM cell growth.

The evidence regarding the anti-UM effects of natural compounds is mainly limited to in-vitro studies; to date, only a small number of these agents have been evaluated in vivo. The molecular mechanisms underpinning the anti-UM properties of these compounds remain largely undefined. Further studies are required to evaluate the in-vivo anticancer activity, appropriate dosage regimen and safety of natural compounds that could be developed for use in UM.
Out of Print: Excising and Preserving the Daniel Tradition in Early Printed Greek Bibles
Authors: Grillo Jennie
Published: February 2022

The life in print of the Greek version of Daniel is a case study in the ways in which editors and printers mediate notional texts into particular material objects shaped by their own contingencies. From antiquity onwards all MSS of the Greek Bible naturally include the ‘Additions’ which distinguish the longer Greek texts from the shorter Hebrew and Aramaic tradition, and this continues into the age of print: the Greek pluses are integral in the first two complete printed Greek Bibles, the Complutensian Polyglot published in 1522 and the Aldine edition of 1518–19. This all changes with Johannes Lonicerus’ 1526/4 Septuagint: Lonicerus excises the ‘additional’ material in the Greek texts of the book of Daniel to create a totally synthetic Greek version, a Greek Bible laid over the template of the Hebrew and trimmed to fit it, yielding a Greek text that had never previously existed in Greek. This practice continues right into the modern scholarly study of the Septuagint, only ending with Tischendorf’s 1850 Septuagint. Yet alongside this pattern of excision is a balancing pattern of persistence, as the motif of the Three Hebrews singing and praying in the fire proves surprisingly difficult to eradicate.
Starch synthase II plays a crucial role in starch biosynthesis and the formation of multienzyme complexes in cassava storage roots
Authors: He Shutao , Hao Xiaomeng , Wang Shanshan , Zhou Wenzhi , Ma Qiuxiang , Lu Xinlu , Chen Luonan , Zhang Peng
Published: February 2022

Starch is a glucose polymer synthesized by green plants for energy storage and is crucial for plant growth and reproduction. The biosynthesis of starch polysaccharides is mediated by members of the large starch synthase (SS) protein superfamily. Here, we showed that in cassava storage roots, soluble starch synthase II (MeSSII) plays an important role in starch biosynthesis and the formation of protein complexes with other starch biosynthetic enzymes by directly interacting with MeSSI, MeSBEII, and MeISAII. MeSSII-RNAi cassava lines showed increased amylose content and reduced biosynthesis of the intermediate chain of amylopectin (B1 type) in their storage roots, leading to altered starch physicochemical properties. Furthermore, gel permeation chromatography analysis of starch biosynthetic enzymes between wild type and MeSSII-RNAi lines confirmed the key role of MeSSII in the organization of heteromeric starch synthetic protein complexes. The lack of MeSSII in cassava also reduced the capacity of MeSSI, MeSBEII, MeISAI, and MeISAII to bind to starch granules. These findings shed light on the key components of the starch biosynthesis machinery in root crops.
Simulating time-varying strong lenses
Authors: Vernardos G
Published: February 2022

We present a self-consistent and versatile forward modelling software package that can produce time series and pixel-level simulations of time-varying strongly lensed systems. The time dimension, which needs to take into account different physical mechanisms for variability such as microlensing, has been missing from existing approaches and it is of direct relevance to time delay, and consequently H0, measurements and caustic crossing event predictions. Such experiments are becoming more streamlined, especially with the advent of time domain surveys, and understanding their systematic and statistical uncertainties in a model-aware and physics-driven way can help improve their accuracy and precision. Here, we demonstrate the software’s capabilities by exploring the effect of measuring time delays from lensed quasars and supernovae in many wavelengths and under different microlensing and intrinsic variability assumptions. In this initial application, we find that the cadence of the observations and combining information from different wavelengths plays an important role in the correct recovery of the time delays. The mock lenses in time software package is available at https://github.com/gvernard/molet.
Spectral study of the diffuse synchrotron source in the galaxy cluster Abell 523
Authors: Vacca Valentina , Shimwell Timothy , Perley Richard A , Govoni Federica , Murgia Matteo , Feretti Luigina , Giovannini Gabriele , Loi Francesca , Carretti Ettore , Cova Filippo , Gastaldello Fabio , Girardi Marisa , Enßlin Torsten , Akamatsu Hiroki , Bonafede Annalisa , Bonnassieux Etienne , Boschin Walter , Botteon Andrea , Brunetti Gianfranco , Brüggen Marcus , Finoguenov Alexis , Hoang Duy , Iacobelli Marco , Orrú Emanuela , Paladino Rosita , Röttgering Huub , van Weeren Reinout , Vitello Fabio , Wittor Denis
Published: February 2022

The galaxy cluster Abell 523 (A523) hosts an extended diffuse synchrotron source historically classified as a radio halo. Its radio power at 1.4 GHz makes it one of the most significant outliers in the scaling relations between observables derived from multiwavelength observations of galaxy clusters: it has a morphology that is different and offset from the thermal gas, and it has polarized emission at 1.4 GHz typically difficult to observe for this class of sources. A magnetic field fluctuating on large spatial scales (∼1 Mpc) can explain these peculiarities but the formation mechanism for this source is not yet completely clear. To investigate its formation mechanism, we present new observations obtained with the LOw Frequency ARray at 120–168 MHz and the Jansky Very Large Array at 1–2 GHz, which allow us to study the spectral index distribution of this source. According to our data the source is observed to be more extended at 144 MHz than previously inferred at 1.4 GHz, with a total size of about 1.8 Mpc and a flux density $S_{\rm 144\, MHz}=(1.52\pm 0.31)$ Jy. The spectral index distribution of the source is patchy with an average spectral index α ∼ 1.2 between 144 MHz and 1.410 GHz, while an integrated spectral index $\alpha \, \sim \, 2.1$ has been obtained between 1.410 and 1.782 GHz. A previously unseen patch of steep spectrum emission is clearly detected at 144 MHz in the south of the cluster. Overall, our findings suggest that we are observing an overlapping of different structures, powered by the turbulence associated with the primary and a possible secondary merger.
Anti-ganglionic nicotinic acetylcholine receptor α3 subunit antibody as a potential biomarker associated with lupus enteritis
Authors: Aso Kuniyuki , Kono Michihito , Abe Nobuya , Fujieda Yuichiro , Kato Masaru , Atsumi Tatsuya
Published: February 2022

Objectives

We aimed to identify the clinical significance of anti-ganglionic nicotinic acetylcholine receptor α3 subunit (gAChRα3) antibodies (Abs) in patients with systemic lupus erythematosus (SLE).

Methods

This retrospective study comprised adult patients with SLE who visited our hospital from 2006 through 2019. Anti-gAChRα3 Abs were measured in the sera of patients with SLE using a luciferase immunoprecipitation system assay. The clinical features of the patients with or without anti-gAChRα3 Abs were compared. We evaluated whether the Abs predict a specific manifestation and affect its development or relapse rate.

Results

Among 144 patients, anti-gAChRα3 Abs were detected in 29 patients. Lupus enteritis (LE) was more frequently seen in anti-gAChRα3 Ab-positive patients than negative patients. The levels of anti-gAChRα3 Abs were significantly higher in patients with LE than those with other lupus manifestations. Logistic regression analysis revealed the anti-gAChRα3 Abs were independent predictors for LE (odds ratio 6.2, 95% confidence interval 1.9–20.3, p = .002). Kaplan–Meier analysis showed the rate of LE development or relapse from the time of sera collection was higher in anti-gAChRα3 Ab-positive patients than in negative patients (p < .001).

Conclusion

Anti-gAChRα3 Abs could be a predictive biomarker for the development or relapse of LE.
Rheumatoid arthritis caused by non-tuberculous mycobacteria infection
Authors: Takaoka Hirokazu , Shimomura Taizo , Suzushima Hitoshi
Published: February 2022

A 72-year-old Japanese woman had right digital flexor tenosynovitis with a non-tuberculous mycobacteria (NTM) infection, which was identified as Mycobacterium marinum in culture. She had been treated at another hospital with clarithromycin, rifampicin, and ethambutol for the non-tuberculous tenosynovitis. However, the swelling of her right hand worsened, and 5 months later, her left hand swelled and she exhibited symmetrical arthritis. Blood tests detected elevated serum C-reactive protein and rheumatoid factor positivity. Although rheumatoid arthritis (RA) was suspected and corticosteroid treatment was started, she came to our hospital because of the insufficient treatment effect. Musculoskeletal ultrasonography showed intra-articular and peritendinous power Doppler signal-positive symmetrical synovitis. A contrast-enhanced magnetic resonance imaging (MRI) evaluation of the left hand without NTM tenosynovitis revealed findings of inflammatory synovitis accompanied by bone marrow oedema. We diagnosed RA and started treatment with weekly low-dose methotrexate pulses and 2 weeks of tocilizumab administration; her symptoms then disappeared within 2 months. This is a rare case of RA manifested with NTM-associated arthritis.
Flexible TALEs for an expanded use in gene activation, virulence and scaffold engineering
Authors: Becker Sebastian , Mücke Stefanie , Grau Jan , Boch Jens
Published: February 2022

Transcription activator-like effectors (TALEs) are bacterial proteins with a programmable DNA-binding domain, which turned them into exceptional tools for biotechnology. TALEs contain a central array of consecutive 34 amino acid long repeats to bind DNA in a simple one-repeat-to-one-nucleotide manner. However, a few naturally occurring aberrant repeat variants break this strict binding mechanism, allowing for the recognition of an additional sequence with a −1 nucleotide frameshift. The limits and implications of this extended TALE binding mode are largely unexplored. Here, we analyse the complete diversity of natural and artificially engineered aberrant repeats for their impact on the DNA binding of TALEs. Surprisingly, TALEs with several aberrant repeats can loop out multiple repeats simultaneously without losing DNA-binding capacity. We also characterized members of the only natural TALE class harbouring two aberrant repeats and confirmed that their target is the major virulence factor OsSWEET13 from rice. In an aberrant TALE repeat, the position and nature of the amino acid sequence strongly influence its function. We explored the tolerance of TALE repeats towards alterations further and demonstrate that inserts as large as GFP can be tolerated without disrupting DNA binding. This illustrates the extraordinary DNA-binding capacity of TALEs and opens new uses in biotechnology.
A look on food intake and satiety: from humans to rodent models
Authors: Costa Daniela G , Almeida Cláudia , Cavadas Cláudia , Carmo-Silva Sara
Published: February 2022

Satiety is a complex state, influenced by numerous factors that go beyond food ingestion. Satiety influences food habits and behavior, thus affecting human health. This review provides an overview of physiological mechanisms involved in satiety and of methodologies to assess food intake and satiety in both animal models and humans. The following topics are highlighted: differences between satiety and satiation; how the central nervous system regulates food intake and satiety; the impact of different macronutrients on satiety; and how the manipulation of food composition might influence overall satiety. Bringing together knowledge on this myriad of satiety mechanisms and how we can study them is useful to better understand and control obesity and other eating disorders.
Metasomatic Modification of the Mesoarchaean Ulamertoq Ultramafic Body, Southern West Greenland
Authors: Nishio Ikuya , Morishita Tomoaki , Itano Keita , Guotana Juan Miguel , Tamura Akihiro , Szilas Kristoffer , Harigane Yumiko , Tani Kenichiro , Pearson D Graham
Published: February 2022

Numerous ultramafic rocks occur as lens-shaped bodies in the Archaean continental crust exposed in southern West Greenland. As some of the oldest exposed ultramafic bodies, determining their origin, as mantle segments or magmatic cumulates, is an important yet controversial issue. The origin of these Archaean ultramafic rocks remains unclear, in-part because these rocks have undergone metasomatic modification since their formation, yet the effects of this metasomatism have so far not been assessed in detail, despite being crucial for understanding their geochemical evolution. Here, we examined the petrology, mineral and whole-rock chemistry of the largest ultramafic body located within the Mesoarchaean Akia terrane, known as the Ulamertoq ultramafic body, to elucidate the poly-metamorphic and metasomatic events that overprinted the protolith. Pronounced lithologic zoning from hydrous mineral-rich layers to orthopyroxene-rich ultramafic rocks at the boundaries between ultramafic rocks and the granitoid country rocks was formed locally by metasomatic reactions related to the granitoids. The main body of ultramafic rocks, far from the contacts, can be classified into four types based on mineral assemblage and chemistry. The fine-grained orthopyroxene aggregates and large poikilitic orthopyroxenes have low Cr2O3 and CaO contents, suggesting a secondary origin. Trace element compositions of orthopyroxene and/or amphibole in the main ultramafic rocks indicate that at least three types of metasomatic agents were required to form these minerals and the associated whole-rock chemical variations within the ultramafic body. Variations represent differences in the proportions of metasomatic orthopyroxene and/or amphibole and phlogopite added to a dunitic protolith. The main body of Ulamertoq ultramafics experienced metasomatism under granulite-facies. Retrograde cooling occurred, to 650°C–850°C and <1.8 GPa prior to local metasomatism via country-rock reaction. The presence of titanian clinohumite and its associated mineral assemblage in the least-metasomatised dunites suggest the possibility that the main ultramafic rocks went through a hydration/dehydration process at ~800°C–900°C and <2 GPa prior to metasomatic modification. This study demonstrates that it is important to consider the effects of multi-stage metasomatism and metamorphism in order to elucidate the origin of the Archaean ultramafic rocks in Greenland and elsewhere.
INVESTIGATION OF SHORT-TERM CHEMICAL CHANGE IN STABLE RUTHENIUM ADDED TO RAINWATER THROUGH X-RAY ABSORPTION FINE STRUCTURE ANALYSIS
Authors: Unno Yusuke , Takeda Akira , Takaku Yuichi
Published: February 2022

Radioactive ruthenium may be accidentally released from spent nuclear fuel reprocessing plants to the surrounding environment. To obtain basic information regarding the effect of radioactive ruthenium on the environment, we investigated changes in the source form of stable ruthenium added to rainwater through X-ray absorption fine structure analysis. Ruthenium tetroxide (RuO4), ruthenium dioxide (RuO2), ruthenium nitrosyl nitrate (Ru(NO)(NO3)3) and ruthenium chloride (RuCl3) were employed as test sources. The Ru K-edge X-ray absorption near edge structure spectra acquired immediately after addition to ultrapure water differed among various sources. With RuO4 addition, a black deposit was observed 1 d after addition, and the spectrum was similar to that of RuO2. For RuO2, Ru(NO)(NO3)3 and RuCl3, no variances were observed between the spectra acquired immediately after addition and 1 d after addition. These results indicate that the chemical forms of RuO2, Ru(NO)(NO3)3 and RuCl3 did not change within a 1-d span in rainwater.
Childhood Trauma May Increase Risk of Psychosis and Mood Disorder in Genetically High-risk Children and Adolescents by Enhancing the Accumulation of Risk Indicators
Authors: Berthelot Nicolas , Garon-Bissonnette Julia , Jomphe Valérie , Doucet-Beaupré Hélène , Bureau Alexandre , Maziade Michel
Published: February 2022

Background

Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk.

Methods

We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring.

Results

Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58).

Conclusion

Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders.