bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoid receptor 2 evolutionary gene loss makes parrots more susceptible to neuroinflammation
Authors: Divín Daniel , Goméz Samblas Mercedes , Kuttiyarthu Veetil Nithya , Voukali Eleni , Świderská Zuzana , Krajzingrová Tereza , Těšický Martin , Beneš Vladimír , Elleder Daniel , Bartoš Oldřich , Vinkler Michal
Published: December 2022

In vertebrates, cannabinoids modulate neuroimmune interactions through two cannabinoid receptors (CNRs) conservatively expressed in the brain (CNR1, syn. CB1) and in the periphery (CNR2, syn. CB2). Our comparative genomic analysis indicates several evolutionary losses in the
CNR2
gene that is involved in immune regulation. Notably, we show that the
CNR2
gene pseudogenized in all parrots (Psittaciformes). This
CNR2
gene loss occurred because of chromosomal rearrangements. Our positive selection analysis suggests the absence of any specific molecular adaptations in parrot
CNR1
that would compensate for the
CNR2
loss in the modulation of the neuroimmune interactions. Using transcriptomic data from the brains of birds with experimentally induced sterile inflammation we highlight possible functional effects of such a
CNR2
gene loss. We compare the expression patterns of CNR and neuroinflammatory markers in
CNR2
-deficient parrots (represented by the budgerigar,
Melopsittacus undulatus
and five other parrot species) with
CNR2
-intact passerines (represented by the zebra finch,
Taeniopygia guttata
). Unlike in passerines, stimulation with lipopolysaccharide resulted in neuroinflammation in the parrots linked with a significant upregulation of expression in proinflammatory cytokines (including interleukin 1 beta (
IL1B
) and 6 (
IL6
)) in the brain. Our results indicate the functional importance of the
CNR2
gene loss for increased sensitivity to brain inflammation.
Genomic correlates for migratory direction in a free-ranging cervid
Authors: Bonar Maegwin , Anderson Spencer J. , Anderson Charles R. , Wittemyer George , Northrup Joseph M. , Shafer Aaron B. A.
Published: December 2022

Animal migrations are some of the most ubiquitous and one of the most threatened ecological processes globally. A wide range of migratory behaviours occur in nature, and this behaviour is not uniform among and within species, where even individuals in the same population can exhibit differences. While the environment largely drives migratory behaviour, it is necessary to understand the genetic mechanisms influencing migration to elucidate the potential of migratory species to cope with novel conditions and adapt to environmental change. In this study, we identified genes associated with a migratory trait by undertaking pooled genome-wide scans on a natural population of migrating mule deer. We identified genomic regions associated with variation in migratory direction, including FITM1, a gene linked to the formation of lipids, and DPPA3, a gene linked to epigenetic modifications of the maternal line. Such a genetic basis for a migratory trait contributes to the adaptive potential of the species and might affect the flexibility of individuals to change their behaviour in the face of changes in their environment.
Isolation and Characterization of Porcine Endocardial Endothelial Cells
Authors: Brown Kathleen N. , Phan Hong Kim T. , Jui Elysa L. , Kang Marci K. , Connell Jennifer P. , Keswani Sundeep G. , Grande-Allen K. Jane
Published: December 2022

The heart contains six different types of endothelial cells, each with a unique function. We sought to characterize the endocardial endothelial cells (EECs), which line the chambers of the heart. EECs are relatively understudied, yet their dysregulation can lead to various cardiac pathologies. Due to the lack of commercial availability of this cell line, we developed a protocol for isolating EECs from porcine hearts and detailed our methodology for establishing populations of EECs through cell sorting. Additionally, we compared the EEC phenotype and fundamental behaviors to a well-studied endothelial cell line, human umbilical vein endothelial cells (HUVECs). The EECs were slightly smaller than HUVECs, and they stained positively for classic endothelial phenotypic markers such as CD31, von Willebrand Factor, and vascular endothelial (VE) cadherin. The EECs proliferated more quickly than HUVECs, yet migrated more slowly to cover a scratch wound assay. Finally, the EECs maintained their robust endothelial phenotype (expression of CD31) through more than a dozen passages. In contrast, the HUVECs showed significantly reduced CD31 expression in later passages. These important phenotypic differences between EECs and HUVECs highlight the need for researchers to utilize the most relevant cell lines when studying or modeling a disease of interest.

Impact statement

Many researchers model cardiovascular disease via tissue engineering to determine disease etiology on the cellular and molecular level. However, researchers usually rely on commercially-available cell lines, which can result in utilizing cells that are not specific to the region of the heart being modeled and could lead to incorrect conclusions. By providing a detailed protocol for isolating and purifying endocardial endothelial cells, we are enabling other researchers to access this cell line and model cardiovascular disease states more accurately.
Cost-effective hybrid long-short read assembly delineates alternative GC-richStreptomyceschassis for natural product discovery
Authors: Heng Elena , Tan Lee Ling , Tay Dillon W. P. , Lim Yee Hwee , Yang Lay-Kien , Seow Deborah C.S. , Leong Chung Yan , Ng Veronica , Ng Siew Bee , Kanagasundaram Yoganathan , Wong Fong Tian , Koduru Lokanand
Published: December 2022

With the advent of rapid automatedin silicoidentification of biosynthetic gene clusters (BGCs), genomics presents vast opportunities to accelerate natural product (NP) discovery. However, prolific NP producers,Streptomyces, are exceptionally GC-rich (>80%) and highly repetitive within BGCs. These pose challenges in sequencing and high-quality genome assembly which are currently circumventedviaintensive sequencing. Here, we outline a more cost-effective workflow using multiplex Illumina and Oxford Nanopore sequencing with hybrid long-short read assembly algorithms to generate high quality genomes. Our protocol involves subjecting long read-derived assemblies to up to 4 rounds of polishing with short reads to yield accurate BGC predictions. We successfully sequenced and assembled 8 GC-richStreptomycesgenomes whose lengths range from 7.1 to 12.1 Mb at an average N50 of 5.9 Mb. Taxonomic analysis revealed previous misrepresentation among these strains and allowed us to propose a potentially new species,Streptomyces sydneybrenneri. Further comprehensive characterization of their biosynthetic, pan-genomic and antibiotic resistance features especially for molecules derived from type I polyketide synthase (PKS) BGCs reflected their potential as NP chassis. Thus, the genome assemblies and insights presented here are envisioned to serve as gateway for the scientific community to expand their avenues in NP discovery.

Graphic abstract

Schematic of hybrid long- and short read assembly workflow for genome sequencing of GC-richStreptomyces. Boxes shaded blue and grey correspond to experimental andin silicoworkflows, respectively.

Highlights

A cost-effective genome sequencing approach for GC-richStreptomycesis presented

Hybrid assembly improves BGC annotation and identification

A new species,Streptomyces sydneybrenneri, identified by taxonomic analysis

Genomes of 8Streptomycesspecies are reported and analysed in this study
Embodied Latch Mechanism of the Mandible to Power at an Ultrahigh Speed in the Trap-jaw AntsOdontomachus kuroiwae
Authors: Aonuma Hitoshi , Naniwa Keisuke , Sugimoto Yasuhiro , Ohkawara Kyohsuke , Kagaya Katsushi
Published: December 2022

Rapid movements of limbs and appendages, faster than those produced by simple muscle contraction alone, are generated through mechanical networks consisting of springs and latches. The latch plays a central role in these spring-loaded mechanisms, but the structural details of the latch are not always known. The mandibles of the trapjaw antOdontomachus kuroiwaecloses the mandible extremely quickly to capture prey or to perform mandible-powered defensive jumps to avoid potential threats. The jump is mediated by a mechanical spring and latch system embodied in the mandible. An ant can strike the tip of the mandible onto the surface of an obstacle (prey, predator, or ground) in order to bounce its body away from potential threats. The angular velocity of the closing mandible was 2.3×104rad/s. Latching of the joint is a key mechanism to aid the storage of energy required to power the ballistic movements of the mandibles. We have identified the fine structure of two latch systems on the mandible forming a ‘balljoint’ using an X-ray micro-computational tomography system (X-ray micro-CT) and X-ray live imaging with a synchrotron. Here we describe the surface of the inner section of the socket and a projection on the lip of the ball. The X-ray live imaging and movements of the 3D model show that the ball with a detent ridge slipped into a socket and over the socket ridge before snapping back at the groove edge. Our results give insight into the complex spring-latch systems that underpin ultra-fast movements in biological systems.
Bi-directional Mendelian randomization and multi-phenotype GWAS show causality and shared pathophysiology between depression and type 2 diabetes
Authors: Maina Jared G , Balkhiyarova Zhanna , Nouwen Arie , Pupko Igor , Ulrich Anna , Boissel Mathilde , Bonnefond Amélie , Froguel Philippe , Khamis Amna , Prokopenko Inga , Kaakinen Marika
Published: December 2022

OBJECTIVE

Depression is a common co-morbidity of type 2 diabetes. However, the causality and underlying mechanisms remain unclear.

RESEARCH DESIGN AND METHODS

We applied bi-directional Mendelian randomization (MR) to assess causality between type 2 diabetes and self-reported depression. Using the UK biobank, we performed 1) GWAS, separately, and 2) multi-phenotype GWAS (MP-GWAS) of type 2 diabetes (cases=19,344, controls=463,641) and depression, using two depression definitions–clinically diagnosed major depressive disorder (MDD, cases=5,262, controls=86,275) and self-reported depressive symptoms (PHQ-9, n=153,079). The FinnGen study was used for replication for MDD (n=23,424) and type 2 diabetes (n=32,469). Based on the results, we analyzed expression quantitative trait loci (eQTL) data from public databases to identify target genes in relevant tissues.

RESULTS

MR demonstrated a significant causal effect of depression on type 2 diabetes (OR=1.18[1.06-1.32], p=0.0024), but not in the reverse direction. GWAS of type 2 diabetes and depressive symptoms did not identify any shared loci between them, whereas MP-GWAS identified seven shared loci mapped toTCF7L2, CDKAL1, IGF2BP2, SPRY2, CCND2-AS1, IRS1, CDKN2B-AS1. MDD did not yield genome-wide significant loci in either GWAS or MP-GWAS. We found that most MP-GWASlocihad an eQTL, including SNPs implicating the cell cycle geneCCND2in pancreatic islets and brain, and key insulin signaling geneIRS1in adipose tissue, suggesting a multi-tissue and pleiotropic underlying mechanism.

CONCLUSION

Our study reveals the complexity in the depression-diabetes relationship and our results have important implications for a more efficient prevention of type 2 diabetes from early adulthood when depressive symptoms usually occur.
Glycoprotein Acetyls and Depression: testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses
Authors: Crick Daisy C P , Sanderson Eleanor , Jones Hannah , Goulding Neil , Borges Maria Carolina , Clayton Gemma , Carter Alice R , Halligan Sarah , Lawlor Deborah A , Khandaker Golam M , Fraser Abigail
Published: December 2022

Background

Inflammation is implicated in depression, but the issue of causality remains unclear.

Objectives

To investigate potential causality and direction of effect between inflammation and depression.

Methods

Using data from the ALSPAC birth cohort (n=4021), we used multivariable regression to investigate bidirectional longitudinal associations of GlycA and depression symptoms score and diagnosis, assessed at ages 18y and 24y.

We used two-sample Mendelian randomization (MR) to investigate potential causality and directionality. Genetic variants for GlycA were obtained from UK Biobank (UKBB) (N=115,078); for depression from the Psychiatric Genomics Consortium and UKBB (N=500,199); and for depressive symptoms (N=161,460) from the Social Science Genetic Association Consortium. In addition to the Inverse Variance Weighted (IVW) method, we used sensitivity analyses to strengthen causal inference. We conducted multivariable MR adjusting for body mass index (BMI) due to known genetic correlation between inflammation, depression and BMI.

Results

After adjusting for potential confounders we found no association between GlycA and depression symptoms score orvice versa. We observed an association between GlycA and depression diagnosis (OR=1.18, 95% CI: 1.03-1.36).

MR suggested no causal effect of GlycA on depression, but there was evidence of a causal effect of depression on GlycA (mean difference in GlycA = 0.09; 95% CI: 0.03-0.16), which was maintained in some, but not all, sensitivity analyses.

Conclusion

We found no consistent evidence for an effect of the inflammatory marker GlycA on depression. There was some evidence that depression may increase GlycA, but this may be confounded/mediated by BMI.
Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision
Authors: Vromman Marieke , Anckaert Jasper , Bortoluzzi Stefania , Buratin Alessia , Chen Chia-Ying , Chu Qinjie , Chuang Trees-Juen , Dehghannasiri Roozbeh , Dieterich Christoph , Dong Xin , Flicek Paul , Gaffo Enrico , Gu Wanjun , He Chunjiang , Hoffmann Steve , Izuogu Osagie , Jackson Michael S. , Jakobi Tobias , Lai Eric C. , Nuytens Justine , Salzman Julia , Santibanez-Koref Mauro , Stadler Peter , Thas Olivier , Eynde Eveline Vanden , Verniers Kimberly , Wen Guoxia , Westholm Jakub , Yang Li , Ye Chu-Yu , Yigit Nurten , Yuan Guo-Hua , Zhang Jinyang , Zhao Fangqing , Vandesompele Jo , Volders Pieter-Jan
Published: December 2022

The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed by computational detection tools. During the last decade, a plethora of such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools were used and detected over 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were empirically validated using three orthogonal methods. Generally, tool-specific precision values are high and similar (median of 98.8%, 96.3%, and 95.5% for qPCR, RNase R, and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant tool differentiators. Furthermore, we demonstrate the complementarity of tools through the increase in detection sensitivity by considering the union of highly-precise tool combinations while keeping the number of false discoveries low. Finally, based on the benchmarking results, recommendations are put forward for circRNA detection and validation.
Distinguishing Happiness and Meaning in Life from Depressive Symptoms: a GWAS-by-subtraction study in the UK Biobank
Authors: de Vries Lianne P. , Demange Perline A. , Baselmans Bart M.L. , Vinkers Christiaan H. , Pelt Dirk H.M. , Bartels Meike
Published: December 2022

Background

Hedonic (e.g., happiness) and eudaimonic (e.g., meaning in life) well-being are negatively related to depressive symptoms. Genetic variants play a role in this association, reflected in substantial genetic correlations. We investigated the (genetic) overlap and differences between well-being and depressive symptoms.

Methods

We used results of Genome-Wide Association studies (GWAS) and applied GWAS-by-subtraction in the UK Biobank sample. Analyses were pre-registered.

Results

Subtracting GWAS summary statistics of depressive symptoms from those of happiness and meaning in life, we obtained GWASs of respectively ‘pure’ happiness (neffective= 216,497) and ‘pure’ meaning” (neffective=102,300). For both, we identified one genome-wide significant SNP (rs1078141 and rs79520962, respectively). After the subtraction, SNP heritability reduced from 6.3% to 3.3% for pure happiness and from 6.2% to 4.2% for pure meaning. The genetic correlation between the well-being measures reduced from .78 to .65, indicating that only a part of the genetic overlap between happiness and meaning in life is due to overlap with depressive symptoms. Pure happiness and pure meaning became genetically unrelated to traits strongly associated with depressive symptoms, including tiredness, loneliness, and psychiatric disorders. For several other traits, including ADHD, income, educational attainment, smoking, and drinking alcohol, the genetic correlations of well-being versus pure well-being changed substantially.

Conclusions

GWAS-by-subtraction allowed us to investigate the genetic variance of well-being unrelated to depressive symptoms. Genetic correlations with different traits led to new insights about this unique part of well-being. The findings can have implications for interventions to increase well-being and/or decrease depressive symptoms.
Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous ECM
Authors: Martins-Costa Catarina , Pham Vincent , Sidhaye Jaydeep , Novatchkova Maria , Peer Angela , Möseneder Paul , Corsini Nina S. , Knoblich Jürgen A.
Published: December 2022

Establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and the developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) is crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous ECM supplementation. While neuroepithelial development is recapitulated in cerebral organoids, the effects of different ECM sources in tissue morphogenesis remain unexplored. Here, we show that exposure to exogenous ECM at early neuroepithelial stages causes rapid tissue polarization and complete rearrangement of neuroepithelial architecture within 3 days. In unexposed cultures, endogenous ECM production by NPCs results in gradual polarity acquisition over an extended time. After the onset of neurogenesis, tissue architecture and neuronal differentiation are largely independent of the initial ECM source. These results advance the knowledge on neuroepithelial biology in vitro, with a focus on mechanisms of exogenously- and endogenously-guided morphogenesis. They demonstrate the self-sustainability of neuroepithelial cultures by endogenous processes, prompting an urgent reassessment of indiscriminate use of exogenous ECM in these model systems.
Phase separation-mediated actin bundling by the postsynaptic density condensates
Authors: Chen Xudong , Jia Bowen , Zhu Shihan , Zhang Mingjie
Published: December 2022

The volume and the electric strength of an excitatory synapse is near linearly correlated with the area of its postsynaptic density (PSD). Extensive research in the past have revealed that the PSD assembly directly communicates with actin cytoskeleton in the spine to coordinate activity-induced spine volume enlargement as well as long-term stable spine structure maintenance. However, the molecular mechanism underlying the communication between the PSD assembly and spine actin cytoskeleton is poorly understood. In this study, we discover thatin vitroreconstituted PSD condensates can promote actin polymerization and filamentous actin bundling without help of any actin regulatory proteins. The Homer scaffold within the PSD condensates and a positively charged actin binding surface of the Homer EVH1 domain are essential for the PSD condensate-induced actin bundle formationin vitroand for spine growth in neurons. Homer-induced actin bundling can only occur when Homer forms condensates with other PSD scaffold proteins such as Shank and SAPAP. The PSD-induced actin bundle formation is sensitively regulated by CaMKII or by the product of the immediate early geneHomer1a. Thus, the communication between PSD and spine cytoskeleton may be modulated by targeting the phase separation of the PSD condensates.
8-HQA Adjusts the Number and Diversity of Bacteria in the Gut Microbiome ofSpodoptera littoralis
Authors: Mazumdar Tilottama , Hänniger Sabine , Shukla Shantanu P. , Murali Aishwarya , Bartram Stefan , Heckel David G. , Boland Wilhelm
Published: December 2022

Quinolinic carboxylic acids are known for their metal ion chelating properties in insects, plants and bacteria. The larval stages of the lepidopteran pest,Spodoptera littoralis, produce 8-hydroxyquinoline-2-carboxylic acid (8-HQA) in high concentrations from tryptophan in the diet. At the same time, the larval midgut is known to harbor a bacterial population. The motivation behind the work was to investigate whether 8-HQA is controlling the bacterial community in the gut by regulating the concentration of metal ions. Knocking out the gene for kynurenine 3-monooxygenase (KMO) in the insect using CRISPR/Cas9 eliminated production of 8-HQA and significantly increased bacterial numbers and diversity in the larval midgut. Adding 8-HQA to the diet of knockout larvae caused a dose-dependent reduction of bacterial numbers with minimal effects on diversity.Enterococcus mundtiidominates the community in all treatments, probably due to its highly efficient iron uptake system and production of the colicin, mundticin. Thus host factors and bacterial properties interact to determine patterns of diversity and abundance in the insect midgut.
The E2 SUMO-conjugating enzyme UBE2I coordinates the oocyte and zygotic transcriptional programs
Authors: Briley Shawn M. , Ahmed Avery A. , Jiang Peixin , Hartig Sean M. , Schindler Karen , Pangas Stephanie A.
Published: December 2022

In mammals, meiotically competent oocytes develop cyclically during ovarian folliculogenesis. During folliculogenesis, prophase I arrested oocytes are transcriptionally active, producing and storing transcripts required for their growth and for early stages of embryogenesis prior to the maternal to zygotic transition. Defective oocyte development during folliculogenesis leads to meiotic defects, aneuploidy, follicular atresia, or non-viable embryos. Here we generated a novel oocyte-specific knockout of the SUMO E2 ligase,Ube2i, usingZp3-creto test its function during folliculogenesis.

Ube2i Zp3-cre+ female mice are sterile with oocytes that arrest in meiosis I with defective spindles and chromosome alignment. Fully grown mutant oocytes abnormally maintain transcription but downregulate maternal effect genes and prematurely activate the zygotic transcriptional program. Thus, this work uncovers UBE2i as a novel orchestrator of chromatin and transcriptional regulation in mouse oocytes.

Teaser

Oocyte-specific deletion ofUbe2icauses loss of transcriptional repression and premature activation of the zygotic genome.
Itch receptor MRGPRX4 interacts with the receptor activity-modifying proteins (RAMPs)
Authors: Kotliar Ilana B. , Ceraudo Emilie , Kemelmakher-Liben Kevin , Oren Deena A. , Lorenzen Emily , Dodig-Crnković Tea , Horioka-Duplix Mizuho , Huber Thomas , Schwenk Jochen M. , Sakmar Thomas P.
Published: December 2022

Cholestatic itch is a severe and debilitating symptom in liver diseases with limited treatment options. The class A G protein-coupled receptor (GPCR) Mas-related GPCR subtype X4 (MRGPRX4) has been identified as a receptor for bile acids, which are potential cholestatic pruritogens. An increasing number of GPCRs have been shown to interact with receptor activity-modifying proteins (RAMPs), which can modulate different aspects of GPCR biology. Using a combination of multiplexed immunoassay and proximity ligation assay we show that MRGPRX4 interacts with RAMPs. The interaction of MRGPRX4 with RAMP2, but not RAMP1 or 3, causes attenuation of basal and agonist-dependent signaling, which correlates with a decrease of MRGPRX4 cell surface expression as measured using a quantitative NanoBRET pulse-chase assay. Finally, we use AlphaFold Multimer to predict the structure of the MRGPRX4-RAMP2 complex. The discovery that RAMP2 regulates MRGPRX4 may have direct implications for future drug development for cholestatic itch.
Role of interneuron subtypes in controlling trial-by-trial output variability in the neocortex
Authors: Guo Lihao , Kumar Arvind
Published: December 2022

Trial-by-trial variability is a ubiquitous property of neuronal activity in vivo and affects the stimulus response. Computational models have revealed how local network structure and feedforward inputs control the trial-by-trial variability. However, the role of input statistics and different interneuron subtypes in shaping the trial-by-trial variability was less understood. Here we investigated the dynamics of stimulus response in a model of cortical microcircuit with one excitatory and three inhibitory interneuron populations (PV, SST, VIP). We show that the variance ratio of inputs to different neuron populations and input covariances are the main determinants of output trial-by-trial variability. The effect of input covariances is contingent on the input variance ratios. In general, the network shows smaller output trial-by-trial variability in a PV-dominated regime than in an SST-dominated regime. Our work reveals mechanisms by which output trial-by-trial variability can be controlled in a context, state, and task-dependent manner.
Pulse-chase experiments reveal dynamics of RNA binding protein Exuperantia inDrosophila melanogaster eggchambers
Authors: Vieira Diana V. , Carlota Rita R. , de-Carvalho Jorge , Telley Ivo A.
Published: December 2022

In cells, mRNA can be associated with various proteins, forming ribonucleoprotein complexes (RNPs) which take part in spatiotemporal control of translation. In theDrosophila melanogasterdeveloping egg chamber, a set of RNPs is transported from the nurse cells to the oocyte and targeted selectively to specific cellular locations. This mRNA sorting process leads to the final oocyte polarization pre-defining the body axes of the future embryo. However, how mRNA is encoded for selection and directed transport is mechanistically not well understood. A master mRNA involved in body axes formation isbicoid, which localizes anterolaterally and is essential for head and thorax definition of the embryo. A protein that was identified essential forbicoidanterior localization is Exuperantia (Exu). Here, we use a live imaging–based pulse-chase approach, which reveals selective transport dynamics of Exu from nurse cells to the oocyte during mid to late-stage oogenesis.
Unsupervised reference-free inference reveals unrecognized regulated transcriptomic complexity in human single cells
Authors: Dehghannasiri Roozbeh , Henderson George , Bierman Rob , Baharav Tavor , Chaung Kaitlin , Wang Peter , Salzman Julia
Published: December 2022

Myriad mechanisms diversify the sequence content of eukaryotic transcripts at both the DNA and RNA levels, leading to profound functional consequences. Examples of this diversity include RNA splicing and V(D)J recombination. Currently, these mechanisms are detected using fragmented bioinformatic tools that require predefining a form of transcript diversification and rely on alignment to an incomplete reference genome, filtering out unaligned sequences, potentially crucial for novel discoveries. Here, we present SPLASH+, significantly advancing biological discovery possible with SPLASH, our recently introduced efficient, reference-free statistical approach. Integrating a micro-assembly and biological interpretation framework, SPLASH+ enables new discoveries including broad and novel examples of transcript diversification in single cellsde novo, without the need for cell type metadata, which is impossible with current algorithms. Applied to 10,326 primary human single cells across 19 tissues profiled with SmartSeq2, SPLASH+ discovers a set of splicing and histone regulators with highly conserved intronic regions that are themselves subject to complex splicing regulation. Additionally, it reveals unreported transcript diversity in the heat shock proteinHSP90AA1, as well as diversification in centromeric RNA expression, V(D)J recombination, RNA editing, and repeat expansion, all missed by existing methods. SPLASH+ is highly efficient, enabling the discovery of an unprecedented breadth of RNA regulation and diversification in single cells through a new automated paradigm of unbiased transcriptomic analysis.
Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: a systematic review
Authors: Kampaite Agniete , Gustafsson Rebecka , York Elizabeth N. , Foley Peter , MacDougall Niall J. J. , Bastin Mark E. , Chandran Siddharthan , Waldman Adam D. , Meijboom Rozanna
Published: December 2022

Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review.

Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies.

The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri.

Qualitative analysis suggests neuropathological effects, possibly due to axonal and/or myelin damage, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive. This highlights the need for studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue as functional and microstructural studies more consistently show correlations. Further studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrate underlying these symptoms in pwRRMS.
Transforming libraries into learning collaborative hubs: the current state of physical spaces and the perceptions of Greek librarians concerning implementation of the “Learning Commons” model
Authors: Garoufali Angeliki , Garoufallou Emmanouel
Published: December 2022

Purpose

With the technological innovation dominating higher education, the university libraries, as physical spaces, continue to play a crucial role in connecting students with knowledge. The emergence of the “Learning Commons” serves as a catalyst in the design of library spaces, renewing libraries’ roles and missions and making them popular to Millennials for new reasons. This study aims to record Greek librarians' views on the current situation in Greek academic libraries regarding physical space design, services provided and the existence of the “Learning Commons” model characteristics.

Design/methodology/approach

This study was conducted through an online survey structured questionnaire (closed-ended, five-point Likert scale, multiple-choice and statements questions). This study population comprised librarians working in 37 academic institutions and colleges. The collected data were subjected to descriptive statistical analysis. The research questions were answered using variables creation and the tests, t-test, ANOVA and Kruskal–Wallis. The groups of questions were tested for their reliability using the Cronbach's alpha coefficient.

Findings

In total, 186 librarians responded to this study. The responses revealed that participants were willing and ready to accept and support a different approach to academic library physical spaces use, according to the shared learning spaces model. However, this requires changes in the organization's vision, further growth and evolution. Although recently most Greek academic libraries have made significant progress in developing their services to function as information and digital hubs, they do not function as learning collaborative hubs, since the “Learning Commons” model is not reflected in their buildings.

Originality/value

The creation of new academic libraries according to the “common” model is a rapidly evolving issue that affects Greek libraries. This paper highlights the characteristics of libraries that should be adopted in the modern era, the new roles of academic librarians and the importance of an appropriate design of the physical space to achieve optimal learning outcomes. At the same time, this paper is one of the few that illustrates librarians', and not users', perceptions of these changes. This paper is a good research example, and the methodology for measuring this type of context could be used by other future research approaches in other countries.
Towards the design and optimisation of future compact aero-engines: intake/fancowl trade-off investigation
Authors: Tejero Fernando , MacManus David , Matesanz García Jesús , Swarthout Avery , Sheaf Christopher
Published: December 2022

Purpose

Relative to in-service aero-engines, the bypass ratio of future civil architectures may increase further. If traditional design rules are applied to these new configurations and the housing components are scaled, then it is expected that the overall weight, nacelle drag and the effects of aircraft integration will increase. For this reason, the next generation of civil turbofan engines may use compact nacelles to maximise the benefits from the new engine cycles. The purpose of this paper is to present a multi-level design and optimisation process for future civil aero-engines.

Design/methodology/approach

An initial set of multi-point, multi-objective optimisations for axisymmetric configurations are carried out to identify the trade-off between intake and fancowl bulk parameters of highlight radius and nacelle length on nacelle drag. Having identified the likely optimal part of the design space, a set of computationally expensive optimisations for three-dimensional non-axisymmetric configurations is performed. The process includes cruise- and windmilling-type operating conditions to ensure aerodynamic robustness of the downselected configurations.

Findings

Relative to a conventional aero-engine nacelle, the developed process yielded a compact aero-engine configuration with mid-cruise drag reduction of approximately 1.6% of the nominal standard net thrust.

Originality/value

The multi-point, multi-objective optimisation is carried out with a mixture of regression and classification functions to ensure aerodynamic robustness of the downselected configurations. The developed computational approach enables the optimisation of future civil aero-engine nacelles that target a reduction of the overall fuel consumption.
The use of a flipped classroom and experiential learning in an undergraduate management course
Authors: Lantu Donald Crestofel , Labdhagati Haifa , Bangun Yuni Ros , Sumarli Felicia Dwirahma
Published: December 2022

Purpose

This paper reflects on a semester-long psychology and organizational behaviour course in an Indonesian business school. The course applied a flipped classroom (FC) approach combined with an experiential learning (EL) project that empowered students to work closely with local communities.

Design/methodology/approach

This study compares students' final scores from an FC and EL class with students from other classes who used the traditional lecture method. Focus group interviews were conducted to gain insight into the students' experience.

Findings

The study results show that FC-EL students achieved higher final scores than traditional-learning students. The majority of students also reported having positive views regarding the approach, with a minority opposing the learning method. The students' projects were successfully implemented, empowered local communities and fostered reflexivity in the students.

Research limitations/implications

The school has yet to implement FC and EL as course delivery methods in other courses. Therefore, the positive outcomes achieved in this study were obtained from only a single course.

Originality/value

The course combined flipped classroom and experiential learning methods.
Implementing Article 12 of the United Nations Convention on the Rights of the Child in health care: a scoping review
Authors: Davies Clare , Waters Donna , Fraser Jennifer Anne
Published: December 2022

Purpose

The purpose of this paper is to present the results of a scoping review on the implementation of Article12 in health care. The scoping review will provide a summary and overview of the key concepts and published literature on this topic internationally. Article 12 of the United Nations Convention on the Rights of the Child (1989) states that children have a right to express their views, to have them heard and for their views to be given due weight in all matters that affect them. Despite increased calls for Article 12 to be given attention in health care, there is little evidence to suggest this has been well implemented and embedded in Australian health-care delivery. The scoping review was undertaken to provide a summary and overview of the key concepts and published literature on this topic internationally.

Design/methodology/approach

A five-step methodological framework described by Arksey and O’Malley (2005) was used to undertake the scoping review. Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used as a guideline for undertaking the study selection.

Findings

Children are still not routinely involved in health-care decision-making, are frequently left out of service planning and evaluation and the perception that they lack the capability to make rational decisions persists.

Originality/value

While there has been a focus on research that investigates children’s participation in health-care decision-making in recent years, there is little that directs attention specifically to the implementation of Article 12, particularly in Australian health care. Recommendations are made for further research in these areas.
Top management’s green transformational leadership and competitive advantage: the mediating role of green organizational learning capability
Authors: Özgül Burcu , Zehir Cemal
Published: December 2022

Purpose

This study aims to develop an original green organizational learning capability (GOLC) framework to examine the effects of green transformational leadership (GTL) on competitive advantage (CA) through GOLC by making use of the natural resource-based view (NRBV).

Design/methodology/approach

The current research proposes GOLC as a novel construct that simultaneously integrates green absorptive capability (GAC) and green transformative capability (GTC). Furthermore, this study presents a theoretical model that investigates GOLC as an intermediate mechanism in the relationship between GTL and CA based on the NRBV. The partial least squares method is used to test the data collected from 265 firms included in the list of Turkey’s Top 500 Industrial Enterprises in 2019 and having ISO 14001 certificate.

Findings

Top management’s GTL positively affects the firm’s GOLC. Moreover, GOLC positively affects the firm’s CA. This study further shows that GTL has a significant indirect effect on CA through GOLC.

Practical implications

This study demonstrates how firm managers can be persuasive in adopting GOLC with a critical role in developing and promoting green products and services to improve the firm’s environmental sustainability and CA by exhibiting GTL.

Originality/value

This research applies the NRBV theory to propose a novel concept, GOLC and develops an integral conceptual model to discover its managerial impacts, antecedent and consequence. No prior literature has examined the impact of top management’s GTL on GOLC and CA.
Nearby large islands diminish biodiversity of the focal island by a negative target effect
Authors: Wang Duorun , Zhao Yuhao , Tang Shupei , Liu Xiangxu , Li Wande , Han Peng , Zeng Di , Yang Yangheshan , Wei Guangpeng , Kang Yi , Si Xingfeng
Published: December 2022

The Equilibrium Theory of Island Biogeography postulates that larger and closer islands support higher biodiversity through the dynamic balance of colonization and extinction processes. The negative diversity–isolation (i.e. the distance to the mainland) relationship is derived based on the assumption that the mainland is the only source pool for island biotas. However, nearby islands could also act as species sources for focal islands via a source effect. In this study, we move a further step and hypothesize that nearby islands may reduce bird colonizers of the focal island and diminish its biodiversity, resulting in a negative target effect.

To test our hypothesis, we assessed the effects of island area and isolation (metrics considering both the mainland and nearby islands) on taxonomic (i.e. species richness), functional and phylogenetic diversity of terrestrial breeding birds on 42 islands in the largest archipelago of China, the Zhoushan Archipelago. Furthermore, we compared the predictive power of the distance to the large island under a set of relative area thresholds and the relative area of nearby islands on species richness under a set of distance thresholds to explore the role of nearby islands as a source and/or target island.

We found that island area had a positive effect on species richness, phylogenetic diversity and functional diversity, while the distance to the mainland had a negative effect only on species richness. Species richness on the focal island increased with increasing distance to the nearest larger island, indicating the negative target effect. Furthermore, the negative target effect depended on the area of nearby islands relative to the area of the focal island.

Our finding of the negative target effect suggests islands located between the mainland and the focal island can be not only sources or stepping stones, but also colonization targets. This result demonstrates the importance of considering multiple geographical attributes of islands in island biogeographic studies, especially the characteristics related to source and/or target effects.
Temporal dynamics of soil bacterial network regulate soil resistomes
Authors: Xiang Qian , Zhu Dong , Qiao Min , Yang Xiao‐Ru , Li Gang , Chen Qing‐Lin , Zhu Yong‐Guan
Published: December 2022

Soil bacteria are diverse and form complicated ecological networks through various microbial interactions, which play important roles in soil multi‐functionality. However, the seasonal effects on the bacterial network, especially the relationship between bacterial network topological features and soil resistomes remains underexplored, which impedes our ability to unveil the mechanisms of the temporal‐dynamics of antibiotic resistance genes (ARGs). Here, a field investigation was conducted across four seasons at the watershed scale. We observed significant seasonal variation in bacterial networks, with lower complexity and stability in autumn, and a wider bacterial community niche in summer. Similar to bacterial communities, the co‐occurrence networks among ARGs also shift with seasonal change, particularly with respect to the topological features of the node degree, which on average was higher in summer than in the other seasons. Furthermore, the nodes with higher betweenness, stress, degree, and closeness centrality in the bacterial network showed strong relationships with the 10 major classes of ARGs. These findings highlighted the changes in the topological properties of bacterial networks that could further alter antibiotic resistance in soil. Together, our results reveal the temporal dynamics of bacterial ecological networks at the watershed scale, and provide new insights into antibiotic resistance management under environmental changes.
Species distribution modelling of the endangered Mahogany Glider (Petaurus gracilis) reveals key areas for targeted survey and conservation
Authors: Chang Yiyin , Bertola Lorenzo V. , Hoskin Conrad J.
Published: December 2022

The Mahogany Glider (Petaurus gracilis) is one of the most endangered marsupials in Australia. Its known distribution is an approximately 120 km strip of fragmented coastal woodland in north‐east Queensland, from north of Townsville to the Tully area. Records are clustered in a number of well‐surveyed areas, with significant areas of lowland habitat unsurveyed. Around 30% of historic records fall in areas that were subsequently cleared for farmland, and ongoing clearing and fragmentation of lowland sclerophyll forest continues within the potential distribution. Resolving the distribution is an urgent requirement to guide conservation but Mahogany Gliders are difficult to detect in the field. Species distribution modelling offers a technique for estimating the fine‐scale distribution and for targeting further field survey and conservation efforts. We used known occurrence records (N = 481) to predict the distribution of Mahogany Gliders across the Wet Tropics bioregion. We used climatic, topographic and other environmental predictors to generate distribution models using Maxent and Random Forest algorithms, each with two bias correction methods. The predictions revealed that many unknown populations may exist within the currently defined distribution and in important areas beyond this (e.g. Hinchinbrook Island). There was reasonable congruence between models, and we include syntheses of the models to present the most likely current distribution. The most important predictor variables across the models were precipitation seasonality (high seasonality), elevation (generally <100 m), soil type (hydrosols) and vegetation type (including Eucalyptus and Melaleuca woodlands). Our results identify core habitat and reveal key areas that require targeted field surveys. Importantly, the predicted suitable habitat is highly fragmented and ongoing conservation efforts need to improve habitat connectivity and limit further fragmentation.
Community Funds of Knowledge and Identity: A Mesogenetic Approach to Education
Authors: Esteban‐Guitart Moises , Iglesias Edgar , Serra Josep Maria , Subero David
Published: December 2022

This theoretical article explores the concept of community funds of knowledge and identity to complement the two related notions of funds of knowledge (focused on the knowledge and skills of families) and funds of identity (students' practices and lived experiences). Bycommunity funds of knowledge and identity, we mean the historically accumulated and culturally developed bodies of knowledge, skills, and personal/social identifications embedded in particular geographical spaces, social institutions, or any educational resource available in any community.