bluuebunny/crossref_metadata_2025 huggingface dataset:
Candidate gene modifiers of dystrophinopathy identified by the uniform application of genome-wide datasets to novel GWAS-identified loci
Authors: Flanigan Kevin M. , Waldrop Megan A. , Martin Paul T. , Alles Roxane , Dunn Diane M. , Alfano Lindsay N. , Simmons Tabatha R. , Moore-Clingenpeel Melissa , Burian John , Seok Sang-Cheol , Vieland Veronica J. , Weiss Robert B.
Published: November 2021

Although the major determinant of disease severity in patients with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether their dystrophin gene (DMD) mutation disrupts the mRNA reading frame or allows expression of a partially functional protein, other genes have been proposed or demonstrated to modify the severity of disease progression. In a companion paper to this one, we describe our novel approaches to genome-wide association study (GWAS) of loss of ambulation (LOA) in the largest genome-wide search to date for loci influencing disease severity in DMD patients. Candidate regulatory SNPs that modify disease progression were identified using an evidential statistical paradigm and here we present a uniform application of recent functional genomic datasets to explore the potential functional impact of the top six candidate regions with PPLD scores of ≥0.4. The results of this analysis of the largest DMD GWAS survey to date elucidate recurrent and potentially new pathways for intervention in the dystrophinopathies.
Long-term Pannexin 1 ablation promotes structural and functional modifications in hippocampal neurons through the regulation of actin cytoskeleton and Rho GTPases activity
Authors: Flores-Muñoz Carolina , García-Rojas Francisca , Perez Miguel A. , Santander Odra , Mery Elena , Lopez-Espíndola Daniela , Gonzalez-Jamett Arlek M. , Fuenzalida Marco , Martinez Agustín D. , Ardiles Álvaro O.
Published: November 2021

Enhanced activity and overexpression of Pannexin 1 (PANX1) channels contribute to neuronal pathologies, such as epilepsy and Alzheimer’s disease (AD). In the hippocampus, the PANX1 channels ablation alters glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, PANX1-knockout (KO) mice still preserve the ability to learn, suggesting that compensatory mechanisms work to stabilize neuronal activity. Here, we show that the absence of PANX1 in the adult brain promotes a series of structural and functional modifications in KO hippocampal synapses, preserving spontaneous activity. Adult CA1 neurons of KO mice exhibit enhanced excitability, complex dendritic branching, spine maturation, and multiple synaptic contacts compared to the WT condition. These modifications seem to rely on the actin-cytoskeleton dynamics as an increase in actin polymerization and an imbalance between Rac1 and RhoA GTPase activity is observed in the absence of PANX1. Our findings highlight a novel interaction between PANX1, actin, and small Rho GTPases that appear to be relevant for synapse maintenance as a long-term compensatory mechanism for PANX1 deficiency.
A trimeric NTD and RBD SARS-CoV-2 subunit vaccine induced protective immunity in CAG-hACE2 transgenic mice and rhesus macaques
Authors: Yu Jiaping , Yao Wenrong , Hu Yingsong , Wu Shuang , Li Jiao , Zhou Hongjun , Hong Kunxue , Chen Jianping , Liu Longding , Lan Ke , Zhu Feng-Cai , Liu Yong
Published: November 2021

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to significant public health, economic and social problems. Development of effective vaccines is still a priority to contain the virus and end the global pandemic. In this study, we reported that ReCOV, a recombinant trimeric NTD and RBD two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03 (an AS03-like squalene adjuvant), induced high levels of neutralizing antibodies against SARS-CoV-2 and the circulating variants in mice, rabbits and rhesus macaques. Notably, two-dose immunizations of ReCOV provided complete protection against challenge with SARS-CoV-2 in hACE2 transgenic mice and rhesus macaques, without observable antibody-dependent enhancement of infection. These results support further clinical development of ReCOV and the vaccine is currently being evaluated in a phase I clinical trial in New Zealand (NCT04818801).
The United States COVID-19 Forecast Hub dataset
Authors: Cramer Estee Y , Huang Yuxin , Wang Yijin , Ray Evan L , Cornell Matthew , Bracher Johannes , Brennen Andrea , Castero Rivadeneira Alvaro J , Gerding Aaron , House Katie , Jayawardena Dasuni , Kanji Abdul H , Khandelwal Ayush , Le Khoa , Niemi Jarad , Stark Ariane , Shah Apurv , Wattanchit Nutcha , Zorn Martha W , Reich Nicholas G
Published: November 2021

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident hospitalizations, incident cases, incident deaths, and cumulative deaths due to COVID-19 at national, state, and county levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages.
Whole Exome Sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes
Authors: Ganesh Suhas , Vemula Alekhya , Bhattacharjee Samsiddhi , Mathew Kezia , Ithal Dhruva , Navin Karthick , Nadella Ravi Kumar , Viswanath Biju , Sullivan Patrick F ,   The ADBS consortium, Jain Sanjeev , Purushottam Meera
Published: November 2021

Whole Exome Sequencing (WES) studies provide important insights into the genetic architecture of serious mental illness (SMI). Genes that are central to the shared biology of SMIs may be identified by WES in families with multiple affected individuals with diverse SMI (F-SMI). We performed WES in 220 individuals from 75 F-SMI families and 60 unrelated controls. Within pedigree prioritization employed criteria of rarity, functional consequence, and sharing by ≥3 affected members. Across the sample, gene and gene-set-wide case-control association analysis was performed with Sequence Kernel Association Test, accounting for kinship.

In 14/16 families with ≥3 affected individuals, we identified a total of 79 rare predicted deleterious variants in 79 unique genes shared by ≥3 members with SMI and absent in 60 unrelated controls. Twenty (25%) genes were implicated in monogenic neurodevelopmental syndromes in OMIM, a fraction that is a significant overrepresentation (Fisher’s Exact test OR = 2.47, p = 0.001). In gene-set wise SKAT, statistically significant association was noted for genes related to synaptic function (SKAT-p = 0.014). In this WES study in F-SMI, we identify private, rare, protein altering variants in genes previously implicated in Mendelian neuropsychiatric syndromes; suggesting pleiotropic influences in neurodevelopment between complex and Mendelian syndromes.
Risk of HCV infection associated with hospital-based invasive procedures: a systematic review and meta-analysis
Authors: Henriot Paul , Castry Mathieu , Luong Nguyen Liem Binh , Shimakawa Yusuke , Jean Kevin , Temime Laura
Published: November 2021

Background: Healthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions remains suboptimal. This study aims at better understanding and quantifying the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission.
Methods: We conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures performed in hospital settings. Based on expert opinion, invasive procedures were categorized into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed in meta-regressions.
Findings: A total of 71 studies were included in the analysis. The most frequently evaluated procedures were blood transfusion and surgery (60 and 37 studies, respectively). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95%CI: 1.14-1.88) for dental procedures to 3.84 (2.07-7.12) for wound care. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42-5.88) than for those without a specified date (2.26, 1.81-2.81). Finally, the country-level overall risk for all procedures was significantly associated with HCV prevalence, but not with the HAQ index. In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery.
Interpretation: Various invasive procedures were documented to be significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritization of infection control measures, especially in high HCV prevalence settings.
Funding: INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hepatites)
An integrative process-based model for biomass and yield estimation of hardneck garlic (Allium sativum)
Authors: Yun Kyungdahm , Shin Minji , Moon Kyung Hwan , Kim Soo-Hyung
Published: November 2021

We introduce an integrative process-driven crop model for garlic (Allium sativum). Building on our previous model that simulated key phenological, morphological, and physiological features of a garlic plant, the new garlic model provides comprehensive and integrative estimations of biomass accumulation and yield formation under diverse environmental conditions. This model also showcases an application of Cropbox to develop a comprehensive crop model. Cropbox is a crop modeling framework featuring declarative modeling language and unified simulation interface for building and improving crop models. Using Cropbox, we first evaluated the model performance against three datasets with an emphasis on biomass and yield measured under different environmental conditions and growing seasons. We then applied the model to simulate optimal planting dates under future climate conditions for assessing climate adaptation strategies between two contrasting locations in South Korea: the current growing region (Gosan) and an unfavorable cold winter region (Chuncheon, Gangwon-do). The model simulated the growth and development of a southern-type cultivar (Namdo, Jeju-do) reasonably well. Under RCP (Representative Concentration Pathway) scenarios, an overall delay in optimal planting date from a week to a month and a slight increase in potential yield were expected in Gosan. Expansion of growing region to northern area including Chuncheon was expected due to mild winter temperatures in the future and may allow Namdo cultivar production in more regions. The predicted optimal planting date in the new region was similar to the current growing region that favors early fall planting. Our new integrative garlic model provides mechanistic, process-driven crop responses to environmental cues and can be useful for assessing climate impacts and identifying crop specific climate adaptation strategies for the future.
Corticostriatal dynamics underlying components of binge-like eating in mice
Authors: Hildebrandt Britny A. , Fisher Hayley , LaPalombara Zoe , Young Michael E. , Ahmari Susanne E.
Published: November 2021

Binge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. Despite the substantial negative impact of BE on psychological and physiological health, its underlying neural mechanisms are largely unknown. Other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. Additionally, previous pre-clinical and clinical work has highlighted an imbalance between goal-directed and habitual responding in BE. The aim of the current study was to longitudinally examine in vivo neural activity within corticostriatal regions associated with habitual behavior– the infralimbic cortex (IL) and dorsolateral striatum (DLS)– in a robust pre-clinical model for BE. Female C57BL/6 mice (N=32) were randomized to receive: 1) intermittent (daily, 2-hour) binge-like access to palatable food (BE mice), or 2) continuous, non-intermittent (24-hour) access to palatable food (non-BE mice). In vivo calcium imaging was performed via fiber photometry at baseline and after chronic (4 weeks) engagement in the model for BE. Feeding behaviors (feeding bout onset/offset) during the recordings were captured using lickometers which generated TTL outputs for precise alignment of behavior to neural data. IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity at feeding onset and offset at the chronic timepoint when compared to baseline. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset at the chronic timepoint compared to non-BE mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention.

Significance Statement

Binge eating is a chronic and repetitive eating behavior that is associated with poor physiological and psychosocial outcomes. Despite the negative impact of binge eating, little is known about the neurobiological mechanisms contributing to the chronic course and persistence of the behavior. To investigate potential neural mechanisms underlying binge eating, we are using approaches developed to monitor neural activity in rodents. This study is the first to identify longitudinal changes in neural activity within regions of the prefrontal cortex and dorsal striatum during binge-like eating behavior in mice. Findings from this work could inform targeted biological treatments for binge eating.
Repeats Mimic Pathogen-Associated Patterns Across a Vast Evolutionary Landscape
Authors: Šulc Petr , Gioacchino Andrea Di , Solovyov Alexander , Marhon Sajid A. , Sun Siyu , Lindholm Håvard T , Chen Raymond , Hosseini Amir , Jiang Hua , Ly Bao-Han , Mehdipour Parinaz , Abdel-Wahab Omar , Vabret Nicolas , LaCava John , De Carvalho Daniel D. , Monasson Rémi , Cocco Simona , Greenbaum Benjamin D.
Published: November 2021

An emerging hallmark across human diseases – such as cancer, autoimmune and neurodegenerative disorders – is the aberrant transcription of typically silenced repetitive elements. Once active, a subset of repeats may be capable of “viral mimicry”: the display of pathogen-associated molecular patterns (PAMPs) that can, in principle, bind pattern recognition receptors (PRRs) of the innate immune system and trigger inflammation. Yet how to quantify the landscape of viral mimicry and how it is shaped by natural selection remains a critical gap in our understanding of both genome evolution and the immunological basis of disease. We propose a theoretical framework to quantify selective forces on virus-like features as the entropic cost a sequence pays to hold a non-self PAMP and show our approach can predict classes of viral-mimicry within the human genome and across eukaryotes. We quantify the breadth and conservation of viral mimicry across multiple species for the first time and integrate selective forces into predictive evolutionary models. We show HSATII and intact LINE-1 (L1) are under selection to maintain CpG motifs, and specific Alu families likewise maintain the proximal presence of inverted copies to form double-stranded RNA (dsRNA). We validate our approach by predicting high CpG L1 ligands of L1 proteins and the innate receptorZCCHC3, and dsRNA present both intracellularly and as MDA5 ligands. We conclude viral mimicry is a general evolutionary mechanism whereby genomes co-opt pathogen-associated features generated by prone repetitive sequences, likely offering an advantage as a quality control system against transcriptional dysregulation.
Zinc finger antiviral protein (ZAP) activity in mammalian and avian hosts in CpG and UpA-mediated restriction of RNA viruses and investigation of ZAP-mediated shaping of host transcriptome compositions
Authors: Odon Valerie , Fiddaman Steven R , Smith Adrian L. , Simmonds Peter
Published: November 2021

The ability of zinc finger antiviral protein (ZAP) to recognise and respond to RNA virus sequences with elevated frequencies of CpG dinucleotides has been proposed as a functional part of the vertebrate innate immune antiviral response. It has been further proposed that ZAP activity shapes compositions of cytoplasmic mRNA sequences to avoid self-recognition, particularly mRNAs for interferons (IFNs) and IFN-stimulated genes highly expressed when ZAP is upregulated during the antiviral state. We investigated the ZAP functional activity in different species of mammals and birds, and potential downstream effects of differences in CpG and UpA dinucleotide representations in host transcriptomes and in RNA viruses that infect them. Cell lines from different bird orders showed variability in restriction of influenza A virus and echovirus 7 replicons with elevated CpG frequencies and none restricted UpA-high mutants, in marked contrast to mammalian cell lines. Given this variability, we compared CpG and UpA representation in coding regions of ISGs and IFNs with the total cellular transcriptome to determine whether differences in ZAP activity shaped dinucleotide compositions of highly expressed genes during the antiviral state. While type 1 IFN genes typically showed often profound suppression of CpG and UpA frequencies, there was no over-suppression of CpGs or UpAs in ISGs in any species, irrespective of underlying ZAP activity. Similarly, mammalian and avian RNA virus genome sequences were compositionally equivalent as were IAV serotypes recovered from ducks, chickens and humans. Overall, we found no evidence for host variability in ZAP function impacting compositions of antiviral genes.
Cannabinoids accumulate in mouse breast milk and differentially regulate lipid composition and lipid signaling molecules involved in infant development
Authors: Johnson Clare T , Dias de Abreu Gabriel H , Mackie Ken , Lu Hui-Chen , Bradshaw Heather B
Published: November 2021

Maternal cannabis use during lactation may expose developing infants to cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD). CBs modulate lipid signaling molecules in the central nervous system in age- and cell-dependent ways, but their influence on the lipid composition of breastmilk has yet to be established. This study investigates the effects of THC, CBD, or their combination on milk lipids by analyzing the stomach contents of CD1 mouse pups that have been nursed by dams injected with CBs on postnatal days (PND) 1-10 collected 2 hours after the last injection on PND10. HPLC/MS/MS was used to identify and quantify over 80 endogenous lipid species and cannabinoids in pup stomach contents. We show that CBs differentially accumulate in milk, lead to widespread decreases in free fatty acids, decreases in N-acyl methionine species, increases N-linoleoyl species, as well as modulate levels of endogenous CBs (eCBs) AEA, 2-AG, and their structural congeners. Our data indicate the passage of CBs to pups through breast milk and that maternal CB exposure alters breast milk lipid compositions.
Ras protein abundance correlates with Ras isoform mutation patterns in cancer
Authors: Hood Fiona E. , Sahraoui Yasmina M. , Jenkins Rosalind E. , Prior Ian A.
Published: November 2021

Activating mutations of Ras genes are often observed in cancer. The protein products of the three Ras genes are almost identical. However, for reasons that remain unclear, KRAS is far more frequently mutated than the other Ras isoforms in cancer and RASopathies. We have quantified HRAS, NRAS, KRAS4A and KRAS4B protein abundance across a large panel of cell lines and healthy tissues. We observe consistent patterns of KRAS>NRAS>>HRAS protein expression in cells that correlate with the rank order of Ras mutation frequencies in cancer. Our data provide support for the model of a sweet-spot of Ras dosage mediating isoform-specific contributions to cancer and development. However, they challenge the notion that rare codons mechanistically underpin the predominance of KRAS mutant cancers. Finally, direct measurement of mutant versus wildtype KRAS protein abundance revealed a frequent imbalance that may suggest additional non-gene duplication mechanisms for optimizing oncogenic Ras dosage.
Diverse environmental perturbations reveal the evolution and context-dependency of genetic effects on gene expression levels
Authors: Lea Amanda J. , Peng Julie , Ayroles Julien F.
Published: November 2021

There is increasing appreciation that human complex traits are determined by poorly understood interactions between our genomes and daily environments. These “genotype x environment” (GxE) interactions remain difficult to map at the organismal level, but can be uncovered using molecular phenotypes. To do so at large-scale, we profiled transcriptomes across 12 cellular environments using 544 immortalized B cell lines from the 1000 Genomes Project. We mapped the genetic basis of gene expression across environments and revealed a context-dependent genetic architecture: the average heritability of gene expression levels increased in treatment relative to control conditions and, on average, each treatment revealed expression quantitative trait loci (eQTL) at 11% of genes. In total, 22% of all eQTL were context-dependent, and this group was enriched for trait- and disease-associated loci. Further, evolutionary analyses revealed that positive selection has shaped GxE loci involved in responding to immune challenges and hormones, but not man-made chemicals, suggesting there is reduced opportunity for selection to act on responses to molecules recently introduced into human environments. Together, our work highlights the importance of considering an exposure’s evolutionary history when studying and interpreting GxE interactions, and provides new insight into the evolutionary mechanisms that maintain GxE loci in human populations.
An End-to-End Deep Learning Speech Coding and Denoising Strategy for Cochlear Implants
Authors: Gajecki Tom , Nogueira Waldo
Published: November 2021

Cochlear implant (CI) users struggle to understand speech in noisy conditions. To address this problem, we propose a deep learning speech denoising sound coding strategy that estimates the CI electric stimulation patterns out of the raw audio data captured by the micro-phone, performing end-to-end CI processing. To estimate the relative denoising performance differences between various approaches, we compared this technique to a classic Wiener filter and to a convTasNet. Speech enhancement performance was assessed by means of signal-to-noise-ratio improvement and the short-time objective speech intelligibility measure. Additionally, 5 CI users were evaluated for speech intelligibility in noise to assess the potential benefits of each algorithm. Our results show that the proposed method is capable of replacing a CI sound coding strategy while preserving its general use for every listener and performing speech enhancement in noisy environments, without sacrificing algorithmic latency.
Conservation Genomics of Urban Populations of Streamside Salamander (Ambystoma barbouri)
Authors: Hubbs N. Wade , Hurt Carla R. , Niedzwiecki John , Leckie Brian , Withers David
Published: November 2021

In Tennessee, populations of the state endangered Streamside Salamander (Ambystoma barbouri) are in decline as their distribution lies mostly within rapidly developing areas in the Nashville Basin. Information regarding the partitioning of genetic variation among populations ofA. barbouri,and the taxonomic status of these populations relative to northern populations and their congener, the smallmouth salamander (A. texanum), have important implications for management and conservation of this species. Here we combined mitochondrial sequencing and genome-wide single nucleotide polymorphism (SNP) data generated using Genotyping-by-Sequencing (GBS) to investigate patterns of genetic variation within Tennessee populations ofA. barbouri, to assess their relationship to populations in Kentucky, and to examine their phylogenetic relationship to the closely relatedA. texanum. Results from phylogenetic reconstructions reveal a complex history of TennesseeA. barbouripopulations with regards to northern populations, unisexualA. barbouri,andA. texanum. Patterns of mitochondrial sequence variation suggest thatA. barbourimay have originated within Tennessee and expanded north multiple times into Kentucky, Ohio, Indiana and West Virginia. Phylogenetic reconstructions based on genome-wide SNP data contradict results based on mitochondrial DNA and correspond to geographic and taxonomic boundaries. Variation in allele frequencies at SNP genotypes, as identified by multivariate analyses and Bayesian assignment tests, identified three evolutionary significant units (ESUs) forA. barbouriwithin the state of Tennessee. Collectively, these results emphasize the need for prioritizing conservation needs of Tennessee populations ofA. barbourito ensure the long-term persistence of this species.
Neuromodulation enables temperature robustness and coupling between fast and slow oscillator circuits in Cancer borealis
Authors: Städele Carola , Stein Wolfgang
Published: November 2021

Acute temperature changes can disrupt neuronal activity and coordination with severe consequences for animal behavior and survival. Nonetheless, two rhythmic neuronal circuits in the crustacean stomatogastric ganglion (STG) and their coordination are maintained across a broad temperature range. However, it remains unclear how this temperature robustness is achieved. Here, we dissociate temperature effects on the rhythm generating circuits from those of upstream ganglia. We demonstrate that heat-activated factors extrinsic to the rhythm generators are essential to the slow gastric mill rhythm’s temperature robustness and contribute to the temperature response of the fast pyloric rhythm. The gastric mill rhythm crashed when only the STG circuits were heated. It could be restored when upstream ganglia were heated in addition, and the activity of the peptidergic modulatory projection neuron (MCN1) increased. Correspondingly, MCN1’s neuropeptide transmitter stabilized the rhythm and maintained it over a broad temperature range. Extrinsic neuromodulation is thus essential for the oscillatory circuits in the STG and enables neural circuits to maintain function in temperature-compromised conditions. In contrast, integer coupling between pyloric and gastric mill rhythms was independent of whether extrinsic inputs and STG pattern generators were temperature-matched or not, demonstrating that the temperature robustness of the coupling is enabled by properties intrinsic to the rhythm generators. However, at near-crash temperature, integer coupling was maintained only in some animals but was absent in others. This was true despite regular rhythmic activity in all animals, supporting that degenerate circuit properties result in idiosyncratic responses to environmental challenges.
SHIP164 is a Chorein Motif Containing Lipid Transport Protein that Controls Membrane Dynamics and Traffic at the Endosome-Golgi Interface
Authors: Hanna Michael G. , Suen Patreece , Wu Yumei , Reinisch Karin M. , De Camilli Pietro
Published: November 2021

Cellular membranes differ in protein and lipid composition as well as in the protein-lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to proteins. The recent structural and functional characterization of VPS13-family proteins has suggested a mechanism through which lipids can be transferred in bulk from one membrane to another at membrane contact sites, and thus independently of vesicular traffic. Here we show that SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with these proteins and is localized on a subpopulation of vesicle clusters in the early endocytic pathway whose membrane cargo includes the cation-independent mannose-6-phosphate receptor (MPR) and ATG9. Loss of SHIP164 disrupts retrograde traffic of these organelles to the Golgi complex. Our findings raise the possibility that bulk transfer of lipids to endocytic membranes may play a role in their traffic.
Rational control of structural off-state heterogeneity in a photoswitchable fluorescent protein provides switching contrast enhancement
Authors: Adam Virgile , Hadjidemetriou Kyprianos , Jensen Nickels , Shoeman Robert L. , Woodhouse Joyce , Aquila Andrew , Banneville Anne-Sophie , Barends Thomas R. M. , Bezchastnov Victor , Boutet Sébastien , Byrdin Martin , Cammarata Marco , Carbajo Sergio , Christou Nina Eleni , Coquelle Nicolas , De la Mora Eugenio , El Khatib Mariam , Chicano Tadeo Moreno , Doak R. Bruce , Fieschi Franck , Foucar Lutz , Glushonkov Oleksandr , Gorel Alexander , Grünbein Marie Luise , Hilpert Mario , Hunter Mark , Kloos Marco , Koglin Jason E. , Lane Thomas J. , Liang Mengning , Mantovanelli Angela , Nass Karol , Kovacs Gabriela Nass , Owada Shigeki , Roome Christopher M. , Schirò Giorgio , Seaberg Matthew , Stricker Miriam , Thépaut Michel , Tono Kensuke , Ueda Kiyoshi , Uriarte Lucas M. , You Daehyun , Zala Ninon , Domratcheva Tatiana , Jakobs Stefan , Sliwa Michel , Schlichting Ilme , Colletier Jacques-Philippe , Bourgeois Dominique , Weik Martin
Published: November 2021

Reversibly photoswitchable fluorescent proteins are essential markers for advanced biological imaging, and optimization of their photophysical properties underlies improved performance and novel applications. Here we establish a link between photoswitching contrast, a key parameter that largely dictates the achievable resolution in nanoscopy applications, and chromophore conformation in the non-fluorescent state of rsEGFP2, a widely employed label in REversible Saturable OpticaL Fluorescence Transitions (RESOLFT) microscopy. Upon illumination, the cis chromophore of rsEGFP2 isomerizes to two distinct off-state conformations, trans1 and trans2, located on either side of the V151 side chain. Reducing or enlarging the side chain at this position (V151A and V151L variants) leads to single off-state conformations that exhibit higher and lower switching contrast, respectively, compared to the rsEGFP2 parent. The combination of structural information obtained by serial femtosecond crystallography with high-level quantum chemical calculations and with spectroscopic and photophysical data determined in vitro suggests that the changes in switching contrast arise from blue- and red-shifts of the absorption bands associated to trans1 and trans2, respectively. Thus, due to elimination of trans2, the V151A variants of rsEGFP2 and its superfolding variant rsFolder2 display a more than two-fold higher switching contrast than their respective parent proteins, both in vitro and in E. coli cells. The application of the rsFolder2-V151A variant is demonstrated in RESOLFT nanoscopy. Our study rationalizes the connection between structural and photophysical chromophore properties and suggests a means to rationally improve fluorescent proteins for nanoscopy applications.
TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing
Authors: Demirdizen Engin , Al-Ali Ruslan , Narayanan Ashwin , Sun Xueyuan , Varga Julianna Patricia , Steffl Bianca , Brom Manuela , Krunic Damir , Schmidt Claudia , Schmidt Gabriele , Bestvater Felix , Taranda Julian , Turcan Şevin
Published: November 2021

Oligodendrogliomas are a subtype of isocitrate dehydrogenase (IDH) mutant gliomas defined by the co-deletion of chromosome arms 1p and 19q. Although the somatic genomic alterations of oligodendrogliomas have been well described, transcriptional changes unique to these tumors are not well studied. Here, we identify Tripartite Motif Containing 67 (TRIM67), an E3 ubiquitin ligase with essential roles during neuronal development, as an oncogene distinctly upregulated in oligodendrogliomas. We characterize the function of TRIM67 using high throughput assays, including RNA sequencing, total lysate-mass spectrometry (MS) and co-immunoprecipitation (IP)-MS using human neural progenitor cells and patient-derived glioma tumorspheres constitutively overexpressing TRIM67. Our high throughput data suggest that TRIM67 overexpression alters the abundance of cytoskeletal proteins, which were validated by functional assays, including immunofluorescence (IF) staining, co-IP and western blotting (WB). Additionally, IF staining results indicate that TRIM67 ectopic expression induces formation of membrane blebs in glioma cells, which could be reverted with the nonmuscle class II myosin inhibitor blebbistatin and selective ROCK inhibitor fasudil. GTP pulldown and WB assays further indicate that Rho GTPase/ROCK2 signaling is altered upon TRIM67 ectopic expression. Phenotypically, TRIM67 expression resulted in higher cell motility in wound healing experiments, reduced cell adherence in adhesion assays, accelerated tumor growth and reduced survival in mouse orthotopic implantation models of an oligodendroglioma-derived patient tumorsphere line. Taken together, our results demonstrate that upregulated TRIM67 induces blebbing-based rounded cell morphology through Rho GTPase/ROCK-mediated signaling thereby contributing to glioma pathogenesis.

Significance

We identify TRIM67 as a novel oncogene in oligodendroglioma that leads to increased cell motility, tumor growth, reduced adhesion, and survival in mice. Our results also show that constitutive TRIM67 expression transforms cell morphology from an adherent to a rounded appearance with membrane blebs. Mechanistic alteration of actin cytoskeleton and Rho GTPase signaling upon TRIM67 upregulation underlies the rounded cell structure and the membrane blebbing phenotype. TRIM67-induced blebbing is specifically regulated by RHOA-RAC1-ROCK2 signaling axis. TRIM67 overexpression also alters pathways associated with cell migration and wound healing in various glioma cell lines and human neural progenitor cells, suggesting a general oncogenic mechanism in gliomas. Overall, our study highlights TRIM67 as a novel player orchestrating cytoskeleton, Rho GTPase signaling and bleb-based cell movement, ultimately causing tumorigenic outcomes in oligodendrogliomas.
Evaluating anti-poverty policy efficiencies in China: meta-frontier analysis using the two-stage data envelopment analysis model
Authors: Yang Guotao , Wang Yue , Chang Huibin , Chen Qinghua
Published: November 2021

Purpose

This study examines the relative efficiencies of anti-poverty policies implemented in 28 Chinese provinces.

Design/methodology/approach

This study uses meta-frontier undesirable dynamic two-stage data envelopment analysis. The authors divide the poverty reduction process into two stages: agricultural production and poverty reduction. Public expenditure is the input for the second stage, and the population below the poverty line is the undesirable output. The authors compute the efficiencies (overall efficiency, efficiency of each stage and the efficiencies of individual inputs and outputs) using meta-frontier analysis for the 28 provinces.

Findings

The results show that: (1) a significant imbalance exists between the eastern and western regions in terms of input-output efficiencies; (2) the poverty reduction stage generally fared better than the agricultural production stage did. In particular, most provinces saw increases in poverty reduction efficiencies between 2013 and 2017; (3) the place-based poverty relief policies introduced in recent years are effective at reducing the poverty rate and reaching the government-set goals and (4) while disposable income has increased steadily over the past few years, income inequality has been exacerbated.

Research limitations/implications

The results show that: (1) a significant imbalance exists between the eastern and western regions in terms of input-output efficiencies; (2) the poverty reduction stage generally fared better than the agricultural production stage did. In particular, most provinces saw increases in poverty reduction efficiencies between 2013 and 2017; (3) the place-based poverty relief policies introduced in recent years are effective at reducing the poverty rate and reaching the government-set goals and (4) while disposable income has increased steadily over the past few years, income inequality has exacerbated.

Originality/value

A large amount of attention and public resources are devoted to fighting poverty and associated market failures in China. The extant literature focuses either on the agricultural production itself or the relationship between human capital and productivity levels. Making use of recent developments of the DEA method, the authors propose a new framework for evaluating the efficiencies of the poverty reduction process. Such a framework has the advantage of giving researchers and policymakers a more detailed diagnosis with regard to the components in the endeavor to eliminate poverty and providing useful information for policymakers to optimize public funds use. Methodologically, the framework is flexible enough to be employed for future research in similar appraisals, at different geographic and scale aggregation levels, for public projects including but not limited to poverty reduction.
A multi-objective grey wolf optimizer (GWO)-based multi-layer perceptrons (MLPs) trainer for optimal PMUs placement
Authors: Laouid Abdelkader Azzeddine , Mohrem Abdelkrim , Djalab Aicha
Published: November 2021

Purpose

This paper aims to find the minimum possible number of phasor measurement units (PMUs) to achieve maximum and complete observability of the power system and improve the redundancy of measurements, in normal cases (with and without zero injection bus [ZIB]), and then in conditions of a single PMU failure and outage of a single line.

Design/methodology/approach

An efficient approach operates adequately and provides the optimal solutions for the PMUs placement problem. The finest function of optimal PMUs placement (OPP) should be mathematically devised as a problem, and via that, the aim of the OPP problem is to identify the buses of the power system to place the PMU devices to ensure full observability of the system. In this paper, the grey wolf optimizer (GWO) is used for training multi-layer perceptrons (MLPs), which is known as Grey Wolf Optimizer (GWO) based Neural Network (“GW-NN”) to place the PMUs in power grids optimally.

Findings

Following extensive simulation tests with MATLAB/Simulink, the results obtained for the placement of PMUs provide system measurements with less or at most the same number of PMUs, but with a greater degree of observability than other approaches.

Practical implications

The efficiency of the suggested method is tested on the IEEE 14-bus, 24-bus, New England 39-bus and Algerian 114-bus systems.

Originality/value

This paper proposes a new method for placing PMUs in the power grids as a multi-objective to reduce the cost and improve the observability of these grids in normal and faulty cases.
Arab scholars’ acceptance of informal scholarly communication tools: applying the technology acceptance model 2 (TAM2)
Authors: Alwreikat Asma , Shehata Ahmed Maher Khafaga , Abu Zaid Mohammed Khair
Published: November 2021

Purpose

This paper aims to use the technology acceptance model 2 (TAM2) to investigate the perceived ease of use, perceived benefits, barriers to use and acceptance of Arab scholars of informal communication tools in research writing.

Design/methodology/approach

This study adopted a quantitative approach using a questionnaire distributed among Arab scholars in Jordan, Egypt and Oman. The questionnaire based on the TAM2 model aimed to measure the acceptance of the sample of informal scholarly communication tools.

Findings

The study’s findings confirmed that the sample is considering informal scholarly communication tools are useful for their research. Informal scholarly communication tools increase the papers’ visibility, leading to a higher number of citations, building scholars’ reputation, creating new collaboration opportunities and maintaining the established collaboration.

Research limitations/implications

The study’s findings can only be generalized on Arab scholars. The sample size could be one of the limitations, and the sample’s distribution was limited to three Arab universities in Jordan, Oman and Egypt. The authors recommend that future researchers use TAM2 model as a framework for studying the adoption of informal scholarly communication tools in different cultural contexts to achieve a better understanding of factors influencing the adoption of such tools.

Practical implications

A practical implication of this research is in drawing the attention of higher education institutions for the potentials of these scholarly communication tools in increasing the availability of publications of their scholars and increasing the citation of these publications, which would help in increasing the ranking of scholars, and the rank of these institutions which opens new opportunities of international research collaboration.

Social implications

The outcomes of this research have several implications for the successful adoption of the TAM2 model. This study brings new knowledge to the literature related to informal scholarly communication adoption by the application of TAM2 constructs to determine the adoption behavior; the findings offered evidence of the TAM2 success in predicting adoption of such tools.

Originality/value

To the best of the authors’ knowledge, adopting TAM2 in this research will add to knowledge by being one of the first studies to adopt TAM2 to measure acceptance of informal scholarly communication tools.
An Islamic vision and approach for entrepreneurship: developing through a multi-stage comparative analysis of systems, ideologies and code of ethics
Authors: Javaid Omar
Published: November 2021

Purpose

The purpose of this paper is to highlight the Islamic character of entrepreneurial activity along with its systemic, ideological and ethical particularities in contrast to the tech-based entrepreneurial model of Silicon Valley.

Design/methodology/approach

Hollingsworth’s framework of institutional analysis is used to analyze and compare the institutional design of tech-based entrepreneurship originated in Silicon Valley with the Islamic alternative.

Findings

An ideal Muslim entrepreneur will have a service-oriented-collectivist mindset, as opposed to an individualistic-self-centric mindset, where solving problems for all stakeholders is a priority instead of profit maximization at the expense of other stakeholders. A Muslim entrepreneur while ensuring the financial sustainability of the firm would avoid complexity on a systemic level, thus would adopt a personalized-family-like atmosphere. A Muslim entrepreneur will also constructively engage local stakeholders and will not possess a disintegrating tendency toward the local social structures.

Practical implications

The paper can help Muslim entrepreneurs to critically evaluate their entrepreneurial activities and firm design in contrast to the contemporary tech-based model.

Originality/value

A number of papers already have discussed the features of an Islamic model of entrepreneurship, however, none has done so while sequentially comparing the Islamic alternative with the contemporary model using Hollingsworth’s framework of institutional analysis. In this paper, the resulting model of Islamic entrepreneurship can be clearly evaluated and contrasted, feature by feature, with its tech-based counterpart.
Financial inclusion and legal system quality: are they correlated?
Authors: Ozili Peterson K.
Published: November 2021

Purpose

This study investigates the correlation between financial inclusion and legal system quality.

Design/methodology/approach

Pearson correlation analysis was used to assess the correlation between financial inclusion and legal system quality.

Findings

The author finds evidence for a positive correlation between financial inclusion and legal system quality. The findings suggest that improvements in legal system quality go hand in hand with improvements in the level of financial inclusion. More specifically, higher supply of ATM per 100,000 adults is correlated with stronger insolvency resolution framework among G7, European and non-European countries. Also, the number of bank branch per 100,000 adults is positively correlated with strong rule of law and legal rights in non-European countries. Also, the number of ATMs per 100,000 adults is positively correlated with strength of insolvency resolution framework and negatively correlated with the time it takes to resolve insolvency before, during and after the global financial crisis.

Originality/value

No study has explicitly analyzed the correlation between financial inclusion and legal system quality. This present study contributes to the literature by filling this research gap.
Getting acquainted with social networks and apps: talking about TikTok
Authors: Anderson Katie Elson
Published: November 2021

Purpose

This paper aims to provide information and promote discussion around the social media platform TikTok.

Design/methodology/approach

Research, literature review.

Findings

Libraries and library and information professionals should be aware of the potential of TikTok for engagement and information sharing.

Originality/value

Adds to the research on the social media platform TikTok.
Incorporating customer profitability analysis into quality management systems
Authors: Sedevich-Fons Leonardo
Published: November 2021

Purpose

The specific purpose of this article is to describe customer profitability analysis and evaluate its compatibility with quality management systems. Besides, its more general objective consists in shedding further light on the links between management accounting and quality management, which is still an emerging topic.

Design/methodology/approach

The first part of the document presents a theoretical description of the disciplines and tools that are relevant to the study. Afterward, an explanation of the way in which customer profitability analysis is operationalized in practice is provided. Subsequently, a framework for the incorporation of customer profitability analysis into a quality management system is introduced. The final section includes some recommendations for future research.

Findings

Through the analysis of the benefits of the incorporation of customer profitability analysis into an ISO 9000 model, the study provides further support to the premise that the joint consideration of management accounting techniques and quality management tools is beneficial to organizations.

Originality/value

The article combines two disciplines closely related in practice but seldom concurrently addressed in the literature.