bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood bully: no difference in territorial response toward neighbors or strangers in marmots
Authors: Ferrandiz-Rovira Mariona , Zidat Timothée , Dupont Pierre , Berger Vérane , Rézouki Célia , Cohas Aurélie
Published: June 2020

Territorial animals are expected to adjust their response to intruders according to the perceived threat level. One of the factors that drives threat level is the identity of the intruder. The dear enemy phenomenon theory postulates that individuals should respond with lower intensity to neighbors, already possessing a territory, than to strangers that may fight to evict them. In social species, the hierarchical status of the intruder might also mediate this response. Such behavioral adjustments presuppose a capacity to discriminate between individuals posing different threat levels. Here, we tested the behavioral response of Alpine marmots to territorial intrusions in a wild population. We compared both dominant females’ and males’ responses to scents from neighbor and stranger dominant males (dear enemy phenomenon) and to dominant and subordinate stranger males (social status-specific response). In addition, we tested for any covariance between male scents and social status. We showed that female and male dominant marmots do not adjust the intensity of their behavioral responses to whether the intruder’s territory is bordering or not (neighbors or strangers) or to the intruder’s social status, even though dominant and subordinate males are thought to pose different threats and social status is encoded in scents. Thus, we did not find support for the dear enemy phenomenon and conclude instead that, in dominant Alpine marmots, no intruder should enter a foreign territory. Research taking a more holistic approach of the evolution and maintenance of territoriality is required to understand the flexibility of responses to intruders in group-living species.
Predicting microRNA–disease associations from lncRNA–microRNA interactions via Multiview Multitask Learning
Authors: Huang Yu-An , Chan Keith C C , You Zhu-Hong , Hu Pengwei , Wang Lei , Huang Zhi-An
Published: June 2020

Motivation

Identifying microRNAs that are associated with different diseases as biomarkers is a problem of great medical significance. Existing computational methods for uncovering such microRNA-diseases associations (MDAs) are mostly developed under the assumption that similar microRNAs tend to associate with similar diseases. Since such an assumption is not always valid, these methods may not always be applicable to all kinds of MDAs. Considering that the relationship between long noncoding RNA (lncRNA) and different diseases and the co-regulation relationships between the biological functions of lncRNA and microRNA have been established, we propose here a multiview multitask method to make use of the known lncRNA–microRNA interaction to predict MDAs on a large scale. The investigation is performed in the absence of complete information of microRNAs and any similarity measurement for it and to the best knowledge, the work represents the first ever attempt to discover MDAs based on lncRNA–microRNA interactions.

Results

In this paper, we propose to develop a deep learning model called MVMTMDA that can create a multiview representation of microRNAs. The model is trained based on an end-to-end multitasking approach to machine learning so that, based on it, missing data in the side information can be determined automatically. Experimental results show that the proposed model yields an average area under ROC curve of 0.8410+/−0.018, 0.8512+/−0.012 and 0.8521+/−0.008 when k is set to 2, 5 and 10, respectively. In addition, we also propose here a statistical approach to predicting lncRNA-disease associations based on these associations and the MDA discovered using MVMTMDA.

Availability

Python code and the datasets used in our studies are made available at https://github.com/yahuang1991polyu/MVMTMDA/.
CoMut: visualizing integrated molecular information with comutation plots
Authors: Crowdis Jett , He Meng Xiao , Reardon Brendan , Van Allen Eliezer M
Published: June 2020

Motivation

Large-scale sequencing studies have created a need to succinctly visualize genomic characteristics of patient cohorts linked to widely variable phenotypic information. This is often done by visualizing the co-occurrence of variants with comutation plots. Current tools lack the ability to create highly customizable and publication quality comutation plots from arbitrary user data.

Results

We developed CoMut, a stand-alone, object-oriented Python package that creates comutation plots from arbitrary input data, including categorical data, continuous data, bar graphs, side bar graphs and data that describes relationships between samples.

Availability and implementation

The CoMut package is open source and is available at https://github.com/vanallenlab/comut under the MIT License, along with documentation and examples. A no installation, easy-to-use implementation is available on Google Colab (see GitHub).
Accommodating trait overlap and individual variability in species diagnosis ofIschnosiphon(Marantaceae)
Authors: Buitrago Aristizábal María Alejandra , Oliveira Gouvêa De Figueiredo Fernando , André Thiago
Published: June 2020

Recognition and delimitation of taxonomic categories of biological organisms are still challenging and full of controversy. We used Ischnosiphon as a model to unravel the importance of morphometrics as individual-based variables to disentangle the morphological variability of plant species. Ischnosiphon spp. continue to be problematic for users, taxonomists and ecologists, due mainly to the huge morphological variability, the species criteria and circumscription proposed for many taxa and the many habitat and vegetative macro-morphological characters lacking in most currently available exsiccates. Twenty-three morphometric variables were sampled from 228 individuals, belonging to 22 Ischnosiphon spp. Principal components and discriminant multivariate analyses were used to describe and identify patterns of morphological variation in Ischnosiphon. Individual-landmark assessment analysed with multivariate methods captured morphometric intraspecific diversity and morphological variability in Ischnosiphon spp., along with the continuous variation of important morphological traits. By examining the morphology of Ischnosiphon spp. through individual-landmark assessment, we demonstrate that different morphological species concepts used today in the identification of the species are difficult to apply. We propose a replicable and analytical framework to accommodate individual variability in species diagnosis in morphologically diverse plant groups.
Immune Monitoring Using QuantiFERON®-CMV Assay in Congenital Cytomegalovirus Infection: Correlation With Clinical Presentation and CMV DNA Load
Authors: Capretti Maria Grazia , Marsico Concetta , Chiereghin Angela , Gabrielli Liliana , Aceti Arianna , Lazzarotto Tiziana
Published: June 2020

Background

Cytomegalovirus (CMV)-specific CD8 + T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown.

Methods

CMV-specific CD8 + T-cell responses were assessed in neonates with cCMV using QuantiFERON®-CMV assay, within day 14 of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON®-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels.

Results

Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON®-CMV result and 16/16 (100%) were asymptomatic, whereas 14/30 (47%) had a nonreactive or indeterminate QuantiFERON®-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON®-CMV result, and 17/17 (100%) were asymptomatic, whereas 12/29 (41%) had a nonreactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON®-CMV results correlated with lack of symptoms (P = .0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON®-CMV results as compared with subjects with nonreactive or indeterminate results (1.82 log IU/mL [1.82–2.89] vs 2.55 log IU/mL [1.82–4.42], P = .009). No correlation was found between QuantiFERON®-CMV results and gestational age at maternal infection nor with urine CMV DNA levels.

Conclusions

A detectable CMV-specific CD8 + T-cell response, evaluated using the QuantiFERON®-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.
Proton pump inhibitors do not increase the risk of dementia: a systematic review and meta-analysis of prospective studies
Authors: Desai Madhav , Nutalapati Venkat , Srinivasan Sachin , Fathallah Jihan , Dasari Chandra , Chandrasekhar Viveksandeep Thoguluva , Mohammad Bilal , Kohli Divyanshoo , Vaezi Michael , Katz Philip O , Sharma Prateek
Published: June 2020

Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer’s dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5–11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86–1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66–1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70–1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up.
Prognosis of segmentectomy and lobectomy for radiologically aggressive small-sized lung cancer
Authors: Kamigaichi Atsushi , Tsutani Yasuhiro , Mimae Takahiro , Miyata Yoshihiro , Ito Hiroyuki , Nakayama Haruhiko , Ikeda Norihiko , Okada Morihito
Published: June 2020

OBJECTIVES

The purpose of this study was to determine the radiological characteristics of aggressive small-sized lung cancer and to compare the outcomes between segmentectomy and lobectomy in patients with these lung cancers.

METHODS

A series of 1046 patients with clinical stage IA1–IA2 lung cancer who underwent lobectomy or segmentectomy at 3 institutions was retrospectively evaluated to identify radiologically aggressive small-sized (solid tumour size ≤ 2 cm) lung cancers. Prognosis of segmentectomy was compared with that of lobectomy in 522 patients with radiologically aggressive small-sized lung cancer using propensity score matching.

RESULTS

Multivariable analysis showed that increasing consolidation-to-tumour ratio on preoperative high-resolution computed tomography (CT) (P = 0.037) and maximum standardized uptake on 18 fluoro-2-deoxyglucose positron emission tomography/CT (P = 0.029) was independently associated with worse recurrence-free survival. Based on analysis of the receiver operating characteristic curve, radiologically aggressive lung cancer was defined as a radiologically solid (consolidation-to-tumour ratio ≥ 0.8) or highly metabolic (maximum standardized uptake ≥ 2.5) tumour. Among patients with radiologically aggressive lung cancer, no significant statistical differences in 5-year recurrence-free (81% vs 90%; P = 0.33) and overall (88% vs 93%; P = 0.76) survival comparing lobectomy (n = 392) to segmentectomy (n = 130) were observed. Among 115 propensity-matched pairs, 5-year recurrence-free survival and overall survival were similar between patients who underwent lobectomy and those who underwent segmentectomy (83.3% and 88.3% vs 90.9% and 94.5%, respectively).

CONCLUSIONS

Difference in survival was not identified with segmentectomy and lobectomy in patients with radiologically aggressive small-sized lung cancer with high risk of recurrence.
An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group
Authors: Kunadian Vijay , Chieffo Alaide , Camici Paolo G , Berry Colin , Escaned Javier , Maas Angela H E M , Prescott Eva , Karam Nicole , Appelman Yolande , Fraccaro Chiara , Louise Buchanan Gill , Manzo-Silberman Stephane , Al-Lamee Rasha , Regar Evelyn , Lansky Alexandra , Abbott J Dawn , Badimon Lina , Duncker Dirk J , Mehran Roxana , Capodanno Davide , Baumbach Andreas
Published: June 2020

This consensus document, a summary of the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), appraises the importance of ischaemia with non-obstructive coronary arteries (INOCA). Angina pectoris affects approximately 112 million people globally. Up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease, more common in women than in men, and a large proportion have INOCA as a cause of their symptoms. INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. INOCA can result from heterogeneous mechanism including coronary vasospasm and microvascular dysfunction and is not a benign condition. Compared to asymptomatic individuals, INOCA is associated with increased incidence of cardiovascular events, repeated hospital admissions, as well as impaired quality of life and associated increased health care costs. This consensus document provides a definition of INOCA and guidance to the community on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.
Digital rock physics in four dimensions: simulating cementation and its effect on seismic velocity
Authors: Singh J , Cilli P A , Hosa A , Main I G
Published: June 2020

Porosity exerts a strong control on the mechanical and hydraulic properties of rocks, but can often only be imaged indirectly from the surface using geophysical measurements, such as seismic velocity. Understanding and quantifying the relationship between seismic velocity and porosity is therefore a fundamental goal of many rock physics models. Simulating the geological processes that control porosity to generate digital rocks, and numerically modelling wave propagation to estimate their elastic properties, allows for flexible and rapid calibration of velocity–porosity trends. Here, the initial deposition of two digital carbonate sediments are simulated: grainstone (near spherical grains) and coquina (anisotropic shell fragments). The gradual precipitation of cement is then simulated, resulting in a suite of 3-D volumes of varying porosity with otherwise constant and known mineral and grain phases. These models are then used as input to a 3-D acoustic staggered-grid finite difference simulation of wavefield propagation, from which we estimate bulk seismic velocity and calculate the estimated bulk modulus. The resulting bulk modulus varies systematically with respect to porosity within the physical limits imposed by the Hashin–Shtrikman bounds. The samples exhibit anisotropy in the measured velocity consistent with structural anisotropy due to the settling of elongate grains under gravity. We use the resulting bulk velocity–porosity trends to test competing rock physics models, including one that accounts for varying effective pore-aspect ratio with porosity. The results validate the hypothesis that there is a power-law relationship between effective pore aspect ratio and porosity. This relationship is consistent with similar results obtained from a suite of natural carbonate grainstones examined in the laboratory. The results show the optimal rock physics model to be relatively insensitive to the degree of anisotropy in the fabric of the starting material, and may now be used with more confidence to link observed changes in effective pore aspect ratio to changes in porosity due to a range of geological processes, for example fracturing, dissolution and compaction, where other process-based models are available.
Squirt-flow seismic dispersion models: a comparison
Authors: Sun Yongyang , Carcione José M , Gurevich Boris
Published: June 2020

The anelastic properties of porous rocks depend on the pore characteristics, specifically, the pore aspect ratio and the pore fraction (related to the soft porosity). At high frequencies, there is no fluid pressure communication throughout the pore space and the rock becomes stiffer than at low frequencies, where the pore pressure is fully equilibrated. This causes a significant difference between the moduli at low and high frequencies, which is known as seismic dispersion and is commonly explained by the squirt-flow mechanism. In this paper, we consider and contrast three squirt-flow dispersion models: the modified Mavko–Jizba model, valid for a porous medium with arbitrary shapes of the pores and cracks, and two other models, based on idealized geometries of spheres and ellipsoids: the EIAS (equivalent inclusion-average stress) and CPEM (cracks and pores effective medium) models. We first perform analytical comparisons and then compute several numerical examples to demonstrate similarities and differences between the models. The analytical comparison shows that when the stiff pores are spherical and the crack density is small, the theoretical predictions of the three models are very close to each other. However, when the stiff pores are spheroids with an aspect ratio smaller than 1 (say, between 0.2 and 1), the predictions of inclusion based models are not valid at frequencies of ultrasonic measurements on rock samples. In contrast, the predictions of the modified Mavko–Jizba model are valid at ultrasonic frequencies of about 106 Hz, which is a typical frequency of laboratory measurements on core samples. We also introduce Zener-based bulk and shear dispersion indices, which are proportional to the difference between the high- and low-frequency stiffness moduli, and are a measure of the degree of anelasticity, closely related to the quality factors by view of the Kramers–Kronig relations. The results show that the three models yield similar moduli dispersion with very small differences when the crack density is relatively high. The indices versus crack density can be viewed as a template to obtain the crack properties from low- and high-frequency velocity measurements.
Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression
Authors: Murugesan Gavuthami , Correia Viviana G , Palma Angelina S , Chai Wengang , Li Chunxia , Feizi Ten , Martin Eva , Laux Brigitte , Franz Alexandra , Fuchs Klaus , Weigle Bernd , Crocker Paul R
Published: June 2020

Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors, which plays an important role in osteoclast development and function. It is also expressed by tumor-associated macrophages and by some tumors, where it is thought to contribute to the immunosuppressive microenvironment. It was shown previously that engagement of macrophage-expressed Siglec-15 with tumor cells expressing its ligand, sialyl Tn (sTn), triggered production of TGF-β. In the present study, we have further investigated the interaction between Siglec-15 and sTn on tumor cells and its functional consequences. Based on binding assays with lung and breast cancer cell lines and glycan-modified cells, we failed to see evidence for recognition of sTn by Siglec-15. However, using a microarray of diverse, structurally defined glycans, we show that Siglec-15 binds with higher avidity to sialylated glycans other than sTn or related antigen sequences. In addition, we were unable to demonstrate enhanced TGF-β secretion following co-culture of Siglec-15-expressing monocytic cell lines with tumor cells expressing sTn or following Siglec-15 cross-linking with monoclonal antibodies. However, we did observe activation of the SYK/MAPK signaling pathway following antibody cross-linking of Siglec-15 that may modulate the functional activity of macrophages.
Host glycan utilization within the Bacteroidetes Sus-like paradigm
Authors: Brown Haley A , Koropatkin Nicole M
Published: June 2020

The Bacteroidetes are numerically abundant Gram-negative organisms of the distal human gut with a greatly expanded capacity to degrade complex glycans. A subset of these are adept at scavenging host glycans within this environment, including mucin O-linked glycans, N-linked glycoproteins and highly sulfated glycosaminoglycans (GAGs) such as heparin (Hep) and chondroitin sulfate (CS). Several recent biochemical studies have revealed the specific polysaccharide utilization loci (PULs) within the model symbiont Bacteroides thetaiotaomicron for the deconstruction of these host glycans. Here we discuss the Sus-like paradigm that defines glycan uptake by the Bacteroidetes and the salient details of the PULs that target heparin/heparan sulfate (HS) and chondroitin sulfate/dermatan sulfate (DS)/hyaluronic acid (HA), respectively, in B. thetaiotaomicron. The ability of the Bacteroidetes to target highly sulfated host glycans is key to their success in the gut environment but can lead to inflammation in susceptible hosts. Therefore, our continued understanding of the molecular strategies employed by these bacteria to scavenge carbohydrate nutrition is likely to lead to novel ways to alter their metabolism to promote host health.
Effect of TQM educational interventions on the management policy standard of health promoting hospitals
Authors: Hamidi Yadollah , Moghadam Seyedeh Melika Kharghani , Hazavehei Seyed Mohammad Mahdi , Karimi-Shahanjarini Akram , Seif Rabiei Mohammad Ali , Farhadian Maryam , Alimohammadi Shohreh
Published: June 2020

The purpose of this study was to manage total quality management (TQM) to increase the standard of management policy and contribute to achieve the standards for health promotion hospitals (HPHs). This was a quasi-experimental intervention study. A total of 35 managers participated in this study were selected in the census. Based on the TQM components, educational items were provided as lectures, posters and pamphlets. The TQM questionnaire and HPHs checklist used to collect data in three different periods: before the interventions, immediately after the interventions and 3 months after the interventions (follow-up). The data analysis was done by means of SPSS software (version 23). The results showed that the average difference of the components of the qualitative groups (p < 0.001), education (p = 0.004), evaluation and feedback (p < 0.001), customer-orientation (p < 0.001), suggestion system (p = 0.024), leadership commitment (p < 0.001) was significant over the three periods. Excluding the employment status before the educational intervention (p = 0.002), there was no significant relationship between the demographic characteristics and mean score of TQM (p > 0.05). Based on the findings of this study, the educational interventions had a positive effect on quality management and management policy. Therefore, educational interventions should be accompanied by changes in the culture and management policies of the hospital to meet HPH standards.
Correction of amyotrophic lateral sclerosis related phenotypes in induced pluripotent stem cell-derived motor neurons carrying a hexanucleotide expansion mutation in C9orf72 by CRISPR/Cas9 genome editing using homology-directed repair
Authors: Ababneh Nidaa A , Scaber Jakub , Flynn Rowan , Douglas Andrew , Barbagallo Paola , Candalija Ana , Turner Martin R , Sims David , Dafinca Ruxandra , Cowley Sally A , Talbot Kevin
Published: June 2020

The G4C2 hexanucleotide repeat expansion (HRE) in C9orf72 is the commonest cause of familial amyotrophic lateral sclerosis (ALS). A number of different methods have been used to generate isogenic control lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and non-homologous end-joining by deleting the repeat region, with the risk of creating indels and genomic instability. In this study, we demonstrate complete correction of an induced pluripotent stem cell (iPSC) line derived from a C9orf72-HRE positive ALS/frontotemporal dementia patient using CRISPR/Cas9 genome editing and homology-directed repair (HDR), resulting in replacement of the excised region with a donor template carrying the wild-type repeat size to maintain the genetic architecture of the locus. The isogenic correction of the C9orf72 HRE restored normal gene expression and methylation at the C9orf72 locus, reduced intron retention in the edited lines and abolished pathological phenotypes associated with the C9orf72 HRE expansion in iPSC-derived motor neurons (iPSMNs). RNA sequencing of the mutant line identified 2220 differentially expressed genes compared with its isogenic control. Enrichment analysis demonstrated an over-representation of ALS relevant pathways, including calcium ion dependent exocytosis, synaptic transport and the Kyoto Encyclopedia of Genes and Genomes ALS pathway, as well as new targets of potential relevance to ALS pathophysiology. Complete correction of the C9orf72 HRE in iPSMNs by CRISPR/Cas9-mediated HDR provides an ideal model to study the earliest effects of the hexanucleotide expansion on cellular homeostasis and the key pathways implicated in ALS pathophysiology.
A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance
Authors: Stroup Bridget M , Marom Ronit , Li Xiaohui , Hsu Chih-Wei , Chang Cheng-Yen , Truong Luan D , Dawson Brian , Grafe Ingo , Chen Yuqing , Jiang Ming-Ming , Lanza Denise , Green Jennie Rose , Sun Qin , Barrish J P , Ani Safa , Christiansen Audrey E , Seavitt John R , Dickinson Mary E , Kheradmand Farrah , Heaney Jason D , Lee Brendan , Burrage Lindsay C
Published: June 2020

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed. Hence, we generated two mouse models with global Slc7a7 deficiency (Slc7a7em1Lbu/em1Lbu; Slc7a7Lbu/Lbu and Slc7a7em1(IMPC)Bay/em1(IMPC)Bay; Slc7a7Bay/Bay) using CRISPR/Cas9 technology by introducing a deletion of exons 3 and 4. Perinatal lethality was observed in Slc7a7Lbu/Lbu and Slc7a7Bay/Bay mice on the C57BL/6 and C57BL/6NJ inbred genetic backgrounds, respectively. We noted improved survival of Slc7a7Lbu/Lbu mice on the 129 Sv/Ev × C57BL/6 F2 background, but postnatal growth failure occurred. Consistent with human LPI, these Slc7a7Lbu/Lbu mice exhibited reduced plasma and increased urinary concentrations of the cationic amino acids. Histopathological assessment revealed loss of brush border and lipid vacuolation in the renal cortex of Slc7a7Lbu/Lbu mice, which combined with aminoaciduria suggests proximal tubular dysfunction. Micro-computed tomography of L4 vertebrae and skeletal radiographs showed delayed skeletal development and suggested decreased mineralization in Slc7a7Lbu/Lbu mice, respectively. In addition to delayed skeletal development and delayed development in the kidneys, the lungs and liver were observed based on histopathological assessment. Overall, our Slc7a7Lbu/Lbu mouse model on the F2 mixed background recapitulates multiple human LPI phenotypes and may be useful for future studies of LPI pathology.
Biallelic variants in the RNA exosome gene EXOSC5 are associated with developmental delays, short stature, cerebellar hypoplasia and motor weakness
Authors: Slavotinek Anne , Misceo Doriana , Htun Stephanie , Mathisen Linda , Frengen Eirik , Foreman Michelle , Hurtig Jennifer E , Enyenihi Liz , Sterrett Maria C , Leung Sara W , Schneidman-Duhovny Dina , Estrada-Veras Juvianee , Duncan Jacque L , Haaxma Charlotte A , Kamsteeg Erik-Jan , Xia Vivian , Beleford Daniah , Si Yue , Douglas Ganka , Treidene Hans Einar , van Hoof Ambro , Fasken Milo B , Corbett Anita H
Published: June 2020

The RNA exosome is an essential ribonuclease complex required for processing and/or degradation of both coding and non-coding RNAs. We identified five patients with biallelic variants in EXOSC5, which encodes a structural subunit of the RNA exosome. The clinical features of these patients include failure to thrive, short stature, feeding difficulties, developmental delays that affect motor skills, hypotonia and esotropia. Brain MRI revealed cerebellar hypoplasia and ventriculomegaly. While we ascertained five patients, three patients with distinct variants of EXOSC5 were studied in detail. The first patient had a deletion involving exons 5–6 of EXOSC5 and a missense variant, p.Thr114Ile, that were inherited in trans, the second patient was homozygous for p.Leu206His and the third patient had paternal isodisomy for chromosome 19 and was homozygous for p.Met148Thr. The additional two patients ascertained are siblings who had an early frameshift mutation in EXOSC5 and the p.Thr114Ile missense variant that were inherited in trans. We employed three complementary approaches to explore the requirement for EXOSC5 in brain development and assess consequences of pathogenic EXOSC5 variants. Loss of function for exosc5 in zebrafish results in shortened and curved tails/bodies, reduced eye/head size and edema. We modeled pathogenic EXOSC5 variants in both budding yeast and mammalian cells. Some of these variants cause defects in RNA exosome function as well as altered interactions with other RNA exosome subunits. These findings expand the number of genes encoding RNA exosome subunits linked to human disease while also suggesting that disease mechanism varies depending on the specific pathogenic variant.
Epigenetic Potential in Native and Introduced Populations of House Sparrows (Passer domesticus)
Authors: Hanson Haley E , Koussayer Bilal , Kilvitis Holly J , Schrey Aaron W , Maddox J Dylan , Martin Lynn B
Published: June 2020

Synopsis

Epigenetic potential, defined as the capacity for epigenetically-mediated phenotypic plasticity, may play an important role during range expansions. During range expansions, populations may encounter relatively novel challenges while experiencing lower genetic diversity. Phenotypic plasticity via epigenetic potential might be selectively advantageous at the time of initial introduction or during spread into new areas, enabling introduced organisms to cope rapidly with novel challenges. Here, we asked whether one form of epigenetic potential (i.e., the abundance of CpG sites) in three microbial surveillance genes: Toll-like receptors (TLRs) 1B (TLR1B), 2A (TLR2A), and 4 (TLR4) varied between native and introduced house sparrows (Passer domesticus). Using an opportunistic approach based on samples collected from sparrow populations around the world, we found that introduced birds had more CpG sites in TLR2A and TLR4, but not TLR1B, than native ones. Introduced birds also lost more CpG sites in TLR1B, gained more CpG sites in TLR2A, and lost fewer CpG sites in TLR4 compared to native birds. These results were not driven by differences in genetic diversity or population genetic structure, and many CpG sites fell within predicted transcription factor binding sites (TFBS), with losses and gains of CpG sites altering predicted TFBS. Although we lacked statistical power to conduct the most rigorous possible analyses, these results suggest that epigenetic potential may play a role in house sparrow range expansions, but additional work will be critical to elucidating how epigenetic potential affects gene expression and hence phenotypic plasticity at the individual, population, and species levels.
Straddling the line: high potential impact on vulnerable marine ecosystems by bottom-set longline fishing in unregulated areas beyond national jurisdiction
Authors: Brewin Paul E , Farrugia Thomas J , Jenkins Chris , Brickle Paul
Published: June 2020

Impacts of Patagonian toothfish bottom-set longline fishing on vulnerable marine ecosystems (VMEs) are examined in a licenced fishery and adjacent areas beyond national jurisdiction (ABNJ) lacking fishery management. VME taxa distributions were predicted using MaxEnt and compared to fishing footprints of ABNJ and licenced fleets. The ABNJ fishery footprint was almost twice as large as in licenced waters. Whilst the footprint of low fishing effort (0.0–3.4 h km−2) was similar between areas, footprints of medium (3.4–10.2 h km−2) and high (10.2–45.3 h km−2) fishing effort were 4 and 13 times greater, respectively, in ABNJ. Percent overlap of licenced fishing distribution on VME indicator taxa groups was low (6.45–9.82%) compared to the considerably higher (32.62–61.99%) percentage fishing overlap on VME indicator distribution in ABNJ. Our results show that, despite the main area of VME indicator taxa being found within jurisdictional waters, there are important VME habitats on the adjacent high-seas that are potentially highly impacted by unregulated fishing. This raises concerns regarding the potential for ABNJ fisheries to undermine domestic VME management where VMEs straddle managed areas and areas that are inconsistently managed or unmanaged. Management of VMEs would benefit from strengthening regional high-seas fishing governance and monitoring procedures.
A Note on Real Operator Monotone Functions
Authors: Gaál Marcell , Pálfia Miklós
Published: June 2020

In this paper, we initiate the study of real operator monotonicity for functions of tuples of operators, which are multivariate structured maps with a functional calculus called free functions that preserve the order between real parts (or Hermitian parts) of bounded linear Hilbert space operators. We completely characterize such functions on open convex free domains in terms of ordinary operator monotone free functions on self-adjoint domains. Further assuming the more stringent free holomorphicity, we prove that all such functions are affine linear with completely positive nonconstant part. This problem has been proposed by David Blecher at the biannual OTOA conference held in Bangalore in December 2016.
Stereotyped B-cell response that counteracts antigenic variation of influenza viruses
Authors: Tonouchi Keisuke , Adachi Yu , Moriyama Saya , Sano Kaori , Tabata Koshiro , Ide Keigo , Takeyama Haruko , Suzuki Tadaki , Takahashi Yoshimasa
Published: June 2020

Influenza A subtypes are categorized into group 1 and group 2 based on the hemagglutinin (HA) sequence. Owing to the phylogenetic distance of HAs in different groups, antibodies that bind multiple HA subtypes across different groups are extremely rare. In this study, we demonstrated that an immunization with acid-treated HA antigen elicits germinal center (GC) B cells that bind multiple HA subtypes in both group 1 and group 2. The cross-group GC B cells utilized mostly one VH gene (1S56) and exhibited a sign of clonal evolution within GCs. The 1S56-lineage IgGs derived from GC B cells were able to bind to HA protein on the infected cell surface but not to the native form of HA protein, suggesting the cryptic nature of the 1S56 epitope and its exposure in infected cells. Finally, the 1S56-lineage IgGs provided protection against lethal infection in an Fc-dependent manner, independent of the virus-neutralizing activity. Thus, we identified 1S56-lineage antibodies as a unique stereotype for achieving cross-group influenza specificity. The antigens exposing the 1S56 epitope may be good candidates for broadly protective immunogens.
Birth weight affects body protein retention but not nitrogen efficiency in the later life of pigs
Authors: van der Peet-Schwering Carola M C , Verschuren Lisanne M G , Hedemann Mette S , Binnendijk Gisabeth P , Jansman Alfons J M
Published: June 2020

Exploring factors that might affect nitrogen (N) efficiency in pigs could support the development of precision feeding concepts. Therefore, an experiment was conducted to determine the effects of birth weight (BiW) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in male pigs of 14 wk of age. BiW of the low BiW (LBW) and high BiW (HBW) pigs was 1.11 ± 0.14 and 1.79 ± 0.12 kg, respectively. Twenty LBW and 20 HBW pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design and fed restrictedly 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention in g/d was higher in the HBW than in the LBW pigs (P < 0.001). The N retention in g/(kg BW0.75·d) and N efficiency (= 100% × N retention / N intake), however, were not affected by BiW of the pigs. Moreover, fecal digestibility of N and urinary concentration of N and urea were not affected by BiW of the pigs. The concentration of insulin (P = 0.08) and insulin-like growth factor-1 (IGF-1;P = 0.05) in blood plasma was higher in HBW pigs, whereas the concentration of α-amino N tended to be lower in HBW pigs (P = 0.06). The LBW and HBW pigs could not be discriminated based on the plasma and urinary metabolites retrieved by nontargeted metabolomics. Restricting dietary protein supply decreased N retention (P < 0.001), N efficiency (P = 0.07), fecal N digestibility (P < 0.001), urinary concentration of N and urea (P < 0.001), and concentration of urea (P < 0.001), IGF-1 (P < 0.001), and α-amino N (P < 0.001) in blood plasma. The plasma and urinary metabolites differing between dietary protein regime were mostly amino acids (AA) or their derivatives, metabolites of the tricarboxylic acid cycle, and glucuronidated compounds, almost all being higher in the pigs fed the A regime. This study shows that BiW affects absolute N retention but does not affect N efficiency in growing pigs. Therefore, in precision feeding concepts, BiW of pigs should be considered as a factor determining protein deposition capacity but less as a trait determining N efficiency.
Scientific Impact and Clinical Influence: Identifying Landmark Studies in Burns
Authors: Ring Justine , Castanov Valera , McLaren Christie , Hajjar Alexander E J , Jeschke Marc G
Published: June 2020

Although many reviews describe significant advances in burn care, no studies have yet examined why these papers had such profound impact. Our objective was to identify the most highly cited, as well as the most clinically influential studies in burns, and describe their characteristics, to inform future research in the field. Web of Science was searched using keywords related to burns to identify the 100 most-cited burns papers. Study design, year and journal of publication, and subject of the paper were recorded. A mixed-methods approach was used to identify papers in burn research leading to change in clinical practice. Characteristics of these papers were compared with identify any factors predictive of future citations or clinical influence. The 100 highly cited papers were cited between 159 and 907 times. There was no correlation between total citations and journal impact factor, year of publication, or subject area. Level of evidence did not predict future citations or influence, but may be influenced by evolving research standards. Of 23 clinically influential studies, 6 were not among 100 most-cited. Using papers only from the 100 most-cited list was not sufficient to identify leading researchers in burns. Citation analysis is a beneficial, however not alone sufficient to identify landmark papers, particularly for multidisciplinary fields such as burns.
The Psychic Chaitanya: Global Occult and Vaishnavism in Fin de Siècle Bengal
Authors: Bhatia Varuni
Published: June 2020

This article explores the intersections between Spiritualism, Mesmerism, and Bengali Vaishnavism in fin de siècle Bengal through the experiments in spirit communication conducted by the Ghosh family of Amrita Bazar Patrika Press fame. As a result of these engagements, the Amrita Bazar Patrika group proposed a novel understanding of Krishna Chaitanya/Gauranga (1486–1533) as a psychic who was able to channelize God through his unique powers of mediumship. It contributes to a nascent but growing body of scholarship around the relationship between religious modernity in colonial India and transnational occult networks. The article is written in three parts: part one discusses transnational occult networks crisscrossing Calcutta in the mid-to-late nineteenth century, with a focus on Theosophy and Spiritualism. It explores the initial goodwill between Madame Blavatsky and Sishir Kumar Ghosh, which dissipated later. The second part focuses on the Ghosh family séance, with the aim of parsing out how traditional and popular Bengali ‘ghosts’ were incorporated into a spectrum of occult knowledge about ‘higher’ spirits. This section also brings to light the caste and gender relationships exposed during séances held in the Ghosh family circle. Part three singles out the image of the ‘psychic Chaitanya’ from the pages of the Hindu Spiritual Magazine to bring into focus interactions between Yoga and occult in the context of the development of modern Bengali Vaishnavism.
Generating synthetic cosmological data with GalSampler
Authors: Hearin Andrew , Korytov Danila , Kovacs Eve , Benson Andrew , Aung Han , Bradshaw Christopher , Campbell Duncan ,   (The LSST Dark Energy Science Collaboration)
Published: June 2020

As part of the effort to meet the needs of the Large Synoptic Survey Telescope Dark Energy Science Collaboration (LSST DESC) for accurate, realistically complex mock galaxy catalogues, we have developed galsampler, an open-source python package that assists in generating large volumes of synthetic cosmological data. The key idea behind galsampler is to recast hydrodynamical simulations and semi-analytic models as physically motivated galaxy libraries. galsampler populates a new, larger volume halo catalogue with galaxies drawn from the baseline library; by using weighted sampling guided by empirical modelling techniques, galsampler inherits statistical accuracy from the empirical model and physically motivated complexity from the baseline library. We have recently used galsampler to produce the cosmoDC2 extragalactic catalogue made for the LSST DESC Data Challenge 2. Using cosmoDC2 as a guiding example, we outline how galsampler can continue to support ongoing and near-future galaxy surveys such as the Dark Energy Survey, the Dark Energy Spectroscopic Instrument, WFIRST, and Euclid.
JINGLE – IV. Dust, H i gas, and metal scaling laws in the local Universe
Authors: De Looze I , Lamperti I , Saintonge A , Relaño M , Smith M W L , Clark C J R , Wilson C D , Decleir M , Jones A P , Kennicutt R C , Accurso G , Brinks E , Bureau M , Cigan P , Clements D L , De Vis P , Fanciullo L , Gao Y , Gear W K , Ho L C , Hwang H S , Michałowski M J , Lee J C , Li C , Lin L , Liu T , Lomaeva M , Pan H-A , Sargent M , Williams T , Xiao T , Zhu M
Published: June 2020

Scaling laws of dust, H i gas, and metal mass with stellar mass, specific star formation rate, and metallicity are crucial to our understanding of the build-up of galaxies through their enrichment with metals and dust. In this work, we analyse how the dust and metal content varies with specific gas mass (MH i/M⋆) across a diverse sample of 423 nearby galaxies. The observed trends are interpreted with a set of Dust and Element evolUtion modelS (DEUS) – including stellar dust production, grain growth, and dust destruction – within a Bayesian framework to enable a rigorous search of the multidimensional parameter space. We find that these scaling laws for galaxies with −1.0 ≲ log MH i/M⋆ ≲ 0 can be reproduced using closed-box models with high fractions (37–89 ${{\ \rm per\ cent}}$) of supernova dust surviving a reverse shock, relatively low grain growth efficiencies (ϵ = 30–40), and long dust lifetimes (1–2 Gyr). The models have present-day dust masses with similar contributions from stellar sources (50–80 ${{\ \rm per\ cent}}$) and grain growth (20–50 ${{\ \rm per\ cent}}$). Over the entire lifetime of these galaxies, the contribution from stardust (>90 ${{\ \rm per\ cent}}$) outweighs the fraction of dust grown in the interstellar medium (<10 ${{\ \rm per\ cent}}$). Our results provide an alternative for the chemical evolution models that require extremely low supernova dust production efficiencies and short grain growth time-scales to reproduce local scaling laws, and could help solving the conundrum on whether or not grains can grow efficiently in the interstellar medium.
An [O iii] search for extended emission around AGN with H i mapping: a distant cloud ionized by Mkn 1
Authors: Knese Erin Darnell , Keel William C , Knese Greg , Bennert Vardha N , Moiseev Alexei , Grokhovskaya Aleksandra , Dodonov Sergei N
Published: June 2020

Motivated by the discovery of large ionized clouds around AGN, and particularly the large fraction of those that are consistent with photoionized gaseous tidal debris, we searched for [O iii] emission around Seyfert galaxies previously mapped in H i, many with extended gas features. Of 26 Seyfert galaxies, we find one spatially extended emission feature, a discrete cloud projected ≈12 kpc SW from the centre of Mkn 1 and spanning a transverse extent of 8 kpc. Optical spectroscopy (Kast/Lick and SCORPIO/BTA) of this cloud confirms its association with the Mkn 1–NGC 451 galaxy pair, closely matching the kinematics of nearby H i structures, and reveals emission-line ratios requiring photoionization by the AGN at roughly the direct observed luminosity of the nucleus. For the entire sample, the full opening angle of the ionization cones (bicones) must be <20° if the AGNs are continuously bright for scales longer than the light-traveltimes to the H i structures. Since typical AGN ionization cones are observed to be much broader than this, our low detection fraction may add to evidence for the ubiquity of strong variations in AGN luminosity on scales 104–105 yr.