bluuebunny/crossref_metadata_2025 huggingface dataset:
Bite force performance from wild derived mice has undetectable heritability despite having heritable morphological components
Authors: Ginot Samuel , Hallgrímsson Benedikt , Agret Sylvie , Claude Julien
Published: December 2021

Fitness-related traits tend to have low heritabilities. Conversely, morphology tends to be highly heritable. Yet, many fitness-related performance traits such as running speed or bite force depend critically on morphology. Craniofacial morphology correlates with bite performance in several groups including rodents. However, within species, this relationship is less clear, and the genetics of performance, morphology and function are rarely analyzed in combination. Here, we use a half-sib design in outbred wild-derived Mus musculus to study the morphology-bite force relationship and determine whether there is additive genetic (co-)variance for these traits. Results suggest that bite force has undetectable additive genetic variance and heritability in this sample, while morphological traits related mechanically to bite force exhibit varying levels of heritability. The most heritable traits include the length of the mandible which relates to bite force. Despite its correlation with morphology, realized bite force was not heritable, which suggests it is less responsive to selection in comparison to its morphological determinants. We explain this paradox with a non-additive, many-to-one mapping hypothesis of heritable change in complex traits. We furthermore propose that performance traits could evolve if pleiotropic relationships among the determining traits are modified.
Contour, a semi-automated segmentation and quantitation tool for cryo-soft-X-ray tomography
Authors: Nahas Kamal L , Fernandes João Ferreira , Crump Colin , Graham Stephen , Harkiolaki Maria
Published: December 2021

Cryo-soft-X-ray tomography is being increasingly used in biological research to study the morphology of cellular compartments and how they change in response to different stimuli, such as viral infections. Segmentation of these compartments is limited by time-consuming manual tools or machine learning algorithms that require extensive time and effort to train. Here we describeContour, a new, easy-to-use, highly automated segmentation tool that enables accelerated segmentation of tomograms to delineate distinct cellular compartments. UsingContour, cellular structures can be segmented based on their projection intensity and geometrical width by applying a threshold range to the image and excluding noise smaller in width than the cellular compartments of interest. This method is less laborious and less prone to errors from human judgement than current tools that require features to be manually traced, and does not require training datasets as would machine-learning driven segmentation. We show that high-contrast compartments such as mitochondria, lipid droplets, and features at the cell surface can be easily segmented with this technique in the context of investigating herpes simplex virus 1 infection.Contourcan extract geometric measurements from 3D segmented volumes, providing a new method to quantitate cryo-soft-X-ray tomography data.Contourcan be freely downloaded atgithub.com/kamallouisnahas/Contour.

Impact Statement

More research groups are using cryo-soft-X-ray tomography as a correlative imaging tool to study the ultrastructure of cells and tissues but very few tomograms are segmented with existing segmentation programs. Segmentation is usually a prerequisite for measuring the geometry of features in tomograms but the time- and labour-intensive nature of current segmentation techniques means that such measurements are rarely across a large number of tomograms, as is required for robust statistical analysis.Contourhas been designed to facilitate the automation of segmentation and, as a result, reduce manual effort and increase the number of tomograms that can be segmented. Because it requires minimal manual intervention,Contouris not as prone to human error as programs that require the users to trace the edges of cellular features. Geometry measurements of the segmented volumes can be calculated using this program, providing a new platform to quantitate cryoSXT data.Contouralso supports quantitation of volumes imported from other segmentation programs. The generation of a large sample of segmented volumes withContourthat can be used as a representative training dataset for machine learning applications is a long-term aspiration of this technique.
Physical association of functionally antagonistic enzymes: KDM5A interacts with MLLs to regulate gene expression in a promoter specific manner facilitating EMT and pluripotency
Authors: Kirtana R , Manna Soumen , Patra Samir Kumar
Published: December 2021

Differential expression of genes involved in physiological processes are a collaborative outcome of interactions among signalling molecules, downstream effectors and epigenetic modifiers, which together dictate the regulation of genes in response to specific stimuli. MLLs and KDM5A are functionally antagonistic proteins as one acts as writer and the other as eraser of the active chromatin mark, i.e., H3K4me3. KDM5A promotes EMT by occupying promoters of both epithelial and mesenchymal markers. Through this work, it is illustrated that when bound to E-cadherin promoter, KDM5A acts as a classical repressor by demethylating H3K4me3, but on mesenchymal marker promoters, it acts as a transcriptional activator by inhibiting the activity of HDACs and increasing H3K18ac. Further it is demonstrated that KDM5A occupancy enhances either MLL1 or MLL2 by physically interacting with them and that signalling pathways regulate the enzymatic activity of KDM5A probably by phosphorylation. When not active, KDM5A signals for MLL occupancy, a mechanism that can be called epigenetic signalling.
Tumor protein D54 binds intracellular nanovesicles via an amphipathic lipid packing sensor (ALPS) motif
Authors: Reynaud Antoine , Magdeleine Maud , Patel Amanda , Gay Anne Sophie , Debayle Delphine , Abelanet Sophie , Antonny Bruno
Published: December 2021

Tumor Protein D54 (TPD54) is an abundant cytosolic protein that belongs to the TPD52 family, a family of four proteins (TPD52, 53, 54 and 55) that are overexpressed in several cancer cells. Even though the functions of these proteins remain elusive, recent investigations indicate that TPD54 binds to very small cytosolic vesicles with a diameter of ca. 30 nm, half the size of classical transport vesicles (e.g. COPI and COPII). Here, we investigated the mechanism of intracellular nanovesicle capture by TPD54. Bioinformatical analysis suggests that TPD54 contains a small coiled-coil followed by several amphipathic helices, which could fold upon binding to lipid membranes. One of these helices has the physicochemical features of an Amphipathic Lipid Packing Sensor (ALPS) motif, which, in other proteins, enables membrane binding in a curvature-dependent manner. Limited proteolysis, CD spectroscopy, tryptophan fluorescence and cysteine mutagenesis coupled to covalent binding of a membrane sensitive probe show that binding of TPD54 to small liposomes is accompanied by large structural changes in the amphipathic helix region. TPD54 binding to artificial liposomes is very sensitive to liposome size and to lipid unsaturation but is poorly dependent on lipid charge. Cellular investigations confirmed the key role of the ALPS motif in vesicle targeting. Surprisingly, the vesicles selected by TPD54 poorly overlap with those captured by the golgin GMAP-210, a long vesicle tether at the Golgi apparatus, which displays a dimeric coiled-coil architecture and an N-terminal ALPS motif. We propose that TPD54 recognizes nanovesicles through a combination of ALPS-dependent and -independent mechanisms.
Magnetic particle imaging of magnetotactic bacteria as living contrast agents is improved by altering magnetosome structures
Authors: Makela Ashley V. , Schott Melissa A. , Madsen Cody , Greeson Emily , Contag Christopher H.
Published: December 2021

Iron nanoparticles used as imaging contrast agents can help differentiate between normal and diseased tissue, or track cell movement and localize pathologies. Magnetic particle imaging (MPI) is an imaging modality that uses the magnetic properties of iron nanoparticles to provide specific, quantitative and sensitive imaging data. MPI signals depend on the size, structure and composition of the nanoparticles; MPI-tailored nanoparticles have been developed by modifying these properties. Magnetotactic bacteria produce magnetosomes which mimic synthetic nanoparticles, and thus comprise a living contrast agent in which nanoparticle formation can be modified by mutating genes. Specifically, genes that encode proteins critical to magnetosome formation and regulation, such as mamJ which helps with filament turnover. Deletion of mamJ in Magnetospirillum gryphiswaldense, MSR-1 led to clustered magnetosomes instead of the typical linear chains. Here we examined the effects of this magnetosome structure and revealed improved MPI signal and resolution from clustered magnetosomes compared to linear chains. Bioluminescent MSR-1 with the mamJ deletion were injected intravenously into tumor-bearing and healthy mice and imaged using both in vivo bioluminescence imaging (BLI) and MPI. BLI revealed the location and viability of bacteria which was used to validate localization of MPI signals. BLI identified the viability of MSR-1 for 24 hours and MPI detected iron in the liver and in multiple tumors. Development of living contrast agents offers new opportunities for imaging and therapy by using multimodality imaging to track the location and viability of the therapy and the resulting biological effects.
Death-associated protein kinase 3 (DAPK3) contributes to intestinal epithelial wound healing and the resolution of experimental colitis in mice
Authors: Chen Huey-Miin , Carlson David A. , Haystead Timothy A.J. , MacDonald Justin A.
Published: December 2021

Various signaling molecules affecting epithelial restitution and wound healing are dysregulated in ulcerative colitis. Recent evidence demonstrates the necessity of Hippo-YAP/TAZ signaling, interceded by cytoskeletal remodeling, for intestinal regeneration. Death-associated protein kinase 3 (DAPK3) is a regulator of actin cytoskeleton reorganization that controls proliferation and apoptosis. Pharmacological inhibition of DAPK3 in Caco-2 human intestinal epithelial cells (IECs) with the HS38 compound augmented cell proliferation and enhanced wound closure. This phenotype corresponded with the increased colocalization of Yes-associated protein (YAP) with F-actin, which is indicative of YAP activation. The administration of HS38 impeded the resolution of intestinal injury and attenuated epithelial-specific proliferation after acute colitis induced by dextran-sodium-sulphate (DSS) in mice. During recovery from DSS-induced colitis, IEC proliferation was repressed, and mice exhibited increased disease severity when HS38 was applied to inhibit DAPK3. Moreover, HS38 treatment increased YAP nuclear localization in IECs, an indicator of signal activation. In summary, this study established DAPK3 as a key factor in intestinal epithelial regeneration and colitis progression by way of YAP signaling. Nevertheless, the role that DAPK3 play in different cell types will need further investigation to decipher the full consequence of DAPK3 inhibition on epithelial homeostasis.
Converting antimicrobial into targeting peptides reveals key features governing protein import into mitochondria and chloroplasts
Authors: Caspari Oliver D , Garrido Clotilde , Law Chris O , Choquet Yves , Wollman Francis-André , Lafontaine Ingrid
Published: December 2021

We asked what peptide features govern targeting to the mitochondria versus the chloroplast using antimicrobial peptides as a starting point. This approach was inspired by the endosymbiotic hypothesis that organelle-targeting peptides derive from antimicrobial amphipathic peptides delivered by the host cell, to which organelle progenitors became resistant. To explore the molecular changes required to convert antimicrobial into targeting peptides, we expressed a set of 13 antimicrobial peptides inChlamydomonas reinhardtii. Peptides were systematically modified to test distinctive features of mitochondrial and chloroplast targeting peptides, and we assessed their targeting potential by following the intracellular localization and maturation of a Venus fluorescent reporter used as cargo protein. Mitochondrial targeting can be achieved by some unmodified antimicrobial peptide sequences. Targeting to both organelles is improved by replacing Lysines with Arginines. Chloroplast targeting is enabled by the presence of flanking unstructured sequences, additional constraints consistent with chloroplast endosymbiosis having occurred in a cell that already contained mitochondria. If indeed targeting peptides evolved from antimicrobial peptides, required modifications imply a temporal evolutionary scenario with an early exchange of cationic residues, and a late acquisition of chloroplast specific motifs.
Host-Adapted Strains of Spodoptera frugiperda Hold and Share a Core Microbial Community Across the Western Hemisphere
Authors: Oliveira Nathalia C. , Rodrigues Pedro A.P. , Cônsoli Fernando L.
Published: December 2021

The fall armyworm Spodoptera frugiperda is an important polyphagous agricultural pest in the Western Hemisphere and currently invasive to countries of the Eastern Hemisphere. This species has two host-adapted strains named “rice” and “corn” strains. Our goal was to identify the occurrence of core members in the gut bacterial community of Fall armyworm larvae from distinct geographical distribution and/or host strain. We used next-generation sequencing to identify the microbial communities of S. frugiperda from corn fields in Brazil, Colombia, Mexico, Panama, Paraguay, and Peru, and rice fields from Panama. The larval gut microbiota of S. frugiperda larvae did not differ between the host strains neither was it affected by the geographical distribution of the populations investigated. Our findings provide additional support for Enterococcus and Pseudomonas as core members of the bacterial community associated with the larval gut of S. frugiperda, regardless of the site of collection or strain, suggesting that these bacteria may maintain true symbiotic relationships with the fall armyworm. Further investigations are required for a deeper understanding of the nature of this relationship.
Subfamily-specific differential contribution of individual monomers and the tether sequence to mouse L1 promoter activity
Authors: Kong Lingqi , Saha Karabi , Hu Yuchi , Tschetter Jada N. , Habben Chase E. , Whitmore Leanne S. , Yao Changfeng , Ge Xijin , Ye Ping , Newkirk Simon J. , An Wenfeng
Published: December 2021

Background

The internal promoter in L1 5’UTR is critical for autonomous L1 transcription and initiating retrotransposition. Unlike the human genome, which features one contemporarily active subfamily, four subfamilies (A_I, Gf_I and Tf_I/II) have been amplifying in the mouse genome in the last one million years. Moreover, mouse L1 5’UTRs are organized into tandem repeats called monomers, which are separated from ORF1 by a tether domain. In this study, we aim to compare promoter activities across young mouse L1 subfamilies and investigate the contribution of individual monomers and the tether sequence.

Results

We observed an inverse relationship between subfamily age and the average number of monomers among evolutionarily young mouse L1 subfamilies. The youngest subgroup (A_I and Tf_I/II) on average carry 3-4 monomers in the 5’UTR. Using a single-vector dual-luciferase reporter assay, we compared promoter activities across six L1 subfamilies (A_I/II, Gf_I and Tf_I/II/III) and established their antisense promoter activities in a mouse embryonic fibroblast cell line. Using consensus promoter sequences for three subfamilies (A_I, Gf_I and Tf_I), we dissected the differential roles of individual monomers and the tether domain in L1 promoter activity. We validated that, across multiple subfamilies, the second monomer consistently enhances the overall promoter activity. For individual promoter components, monomer 2 is consistently more active than the corresponding monomer 1 and/or the tether for each subfamily. Importantly, we revealed intricate interactions between monomer 2, monomer 1 and tether domains in a subfamily-specific manner. Furthermore, using three-monomer 5’UTRs, we established a complex nonlinear relationship between the length of the outmost monomer and the overall promoter activity.

Conclusions

The laboratory mouse is an important mammalian model system for human diseases as well as L1 biology. Our study extends previous findings and represents an important step toward a better understanding of the molecular mechanism controlling mouse L1 transcription as well as L1’s impact on development and disease.
Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection pre-T cells
Authors: Ratiu Jeremy J , Barclay William , Wang Qun , Mehta Naren , Harnois Melissa J , DiPalma Devon , Wellford Sebastian , Roy Sumedha , Contreras Alejandra V , Wiest David , Zhuang Yuan
Published: December 2021

Production of a diverse peripheral T cell compartment requires massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment at the DN2 stage and following successful rearrangement and selection for functional TCRβ chains in DN3 thymocytes, which promotes development of DN4 cells to the DP stage. Signals driving expansion of DN2 thymocytes are well studied, however, factors regulating the proliferation and survival of DN4 cells remain poorly understood. Here, we uncover an unexpected link between the transcription factor Zfp335 and control of cGAS/STING-dependent cell death in post-β-selection DN4 thymocytes. Zfp335 controls survival by sustaining expression of Ankle2, which suppresses cGAS/STING-dependent cell death. Together, this study identifies Zfp335 as a key transcription factor controlling the survival of proliferating post-β-selection thymocytes and demonstrates a key role for the cGAS/STING pathway driving apoptosis of developing T cells.
Ecophysiological genomics identifies a pleiotropic locus mediating drought tolerance in sorghum
Authors: Maina Fanna , Harou Abdou , Hamidou Falalou , Morris Geoffrey P.
Published: December 2021

Drought is a key constraint on plant productivity and threat to food security. Sorghum (Sorghum bicolorL. Moench), a global staple food and forage crop, is among the most drought-adapted cereal crops, but its adaptation is not yet well understood. This study aims to better understand the genetic basis of preflowering drought in sorghum and identify loci underlying variation in water use and yield components under drought. A panel of 219 diverse sorghum from West Africa was phenotyped for yield components and water use in an outdoor large-tube lysimeter system under well-watered (WW) versus a preflowering drought water-stressed (WS) treatment. The experimental system was validated based on characteristic drought response in international drought tolerance check genotypes and genome-wide association studies (GWAS) that mapped the major height locus atQHT7.1andDw3. GWAS further identified marker trait associations (MTAs) for drought-related traits (plant height, flowering time, forage biomass, grain weight, water use) that each explained 7–70% of phenotypic variance. Most MTAs for drought-related traits correspond to loci not previously reported, but some MTA for forage biomass and grain weight under WS co-localized with staygreen post-flowering drought tolerance loci (Stg3aandStg4). A globally common allele at S7_50055849 is associated with several yield components under drought, suggesting that it tags a major pleiotropic variant controlling assimilate partitioning to grain versus vegetative biomass. The GWAS findings revealed oligogenic variants for drought tolerance in sorghum landraces which could be used as trait predictive markers for improved drought adaptation.
Plug and play: Is “directed endosymbiosis” of chloroplasts possible?
Authors: Shapiro Karin Olszewski
Published: December 2021

The origin of mammalian mitochondria and plant chloroplasts is thought to be endosymbiosis. Millennia ago, a bacterium related to typhus-causing bacteria may have been consumed by a proto-eukaryote and over time evolved into an organelle inside eukaryotic cells, known as a mitochondrion. The plant chloroplast is believed to have evolved in a similar fashion from cyanobacteria. This project attempted to use “directed endosymbiosis” (my term) to investigate if chloroplasts can be taken up by a land animal and continue to function. It has been shown previously that mouse fibroblasts could incorporate isolated chloroplasts when co-cultured. Photosynthetic bacteria containing chloroplasts have been successfully injected into zebrafish embryos, mammalian cells, and ischemic rodent hearts. The photosynthetic alga Chlamydomonas reinhardtii (C. reinhardtii) has also been injected into zebrafish embryos. However, to the best of my knowledge, injection of isolated chloroplasts into a land animal embryo has not been attempted before.

In four pilot experiments, solutions of chloroplasts in PBS were microinjected into Drosophila melanogaster (D. melanogaster) embryos to determine if the embryos would tolerate the foreign protein. Interestingly, results indicated that a portion of the D. melanogaster embryos appeared to tolerate the injections and survive to adulthood. To determine if chloroplasts had indeed been transferred, larvae were placed under fluorescent microscopy. Chlorophyll (serving as the reporter) was found to be present in several larvae and to decline in amount over time. To investigate if the chloroplasts still functioned, a radiotracer food intake assay was performed. It was hypothesized that if the chloroplasts were generating ATP (and possibly glucose), the larvae might need less food. Results indicated a decrease in intake, however this might have occurred for other reasons.
Single cell profiling of Hofbauer cells and fetal brain microglia reveals shared programs and functions
Authors: Ceasrine Alexis M , Batorsky Rebecca , Shook Lydia L. , Kislal Sezen , Bordt Evan A. , Devlin Benjamin A. , Perlis Roy H. , Slonim Donna K. , Bilbo Staci D. , Edlow Andrea G.
Published: December 2021

Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many of which are mediated by in utero microglial programming. Microglia remain inaccessible at birth and throughout development, thus identification of noninvasive biomarkers that can reflect fetal brain microglial programming may permit screening and intervention during critical developmental windows. Here we used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells). Single-cell RNA sequencing of murine fetal brain and placental macrophages demonstrated shared transcriptional programs. Comparison with human datasets demonstrated that placental resident macrophage signatures are highly conserved between mice and humans. Single-cell RNA-seq identified sex differences in fetal microglial and Hofbauer cell programs, and robust differences between placenta-associated maternal macrophage/monocyte (PAMM) populations in the context of a male versus a female fetus. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, potentially facilitating the early identification of offspring most vulnerable to neurodevelopmental disorders.
A genome-wide CRISPR screen identifies the glycosylation enzyme DPM1 as a modifier of DPAGT1 deficiency and ER stress
Authors: Dalton Hans M. , Viswanatha Raghuvir , Brathwaite Ricky , Zuno Jae Sophia , Mohr Stephanie E. , Perrimon Norbert , Chow Clement Y.
Published: December 2021

Partial loss-of-function mutations in glycosylation pathways underlie a set of rare diseases called Congenital Disorders of Glycosylation (CDGs). In particular, DPAGT1-CDG is caused by mutations in the gene encoding the first step in N-glycosylation, DPAGT1, and this disorder currently lacks effective therapies. To identify potential therapeutic targets for DPAGT1-CDG, we performed CRISPR knockout screens in Drosophila cells for genes associated with better survival and glycoprotein levels under DPAGT1 inhibition. We identified hundreds of candidate genes that may be of therapeutic benefit. Intriguingly, inhibition of the mannosyltransferase Dpm1, or its downstream glycosylation pathways, could rescue two in vivo models of DPAGT1 inhibition and ER stress, even though impairment of these pathways alone usually cause CDGs. While both in vivo models ostensibly cause ER stress (through DPAGT1 inhibition or a misfolded protein), we found a novel difference in fructose metabolism that may indicate glycolysis as a modulator of DPAGT1-CDG. Our results provide new therapeutic targets for DPAGT1-CDG, include the unique finding of Dpm1-related pathways rescuing DPAGT1 inhibition, and reveal a novel interaction between fructose metabolism and ER stress.
Microglia Mediate Early Corticostriatal Synapse Loss and Cognitive Dysfunction in Huntington’s Disease Through Complement-Dependent Mechanisms
Authors: Wilton D.K. , Mastro K. , Heller M.D. , Gergits F.W. , Willing C R. , Frouin A. , Daggett A. , Gu X. , Kim A.Y. , Faull R. , Jayadev S. , Yednock T , Yang X.W. , Stevens B.
Published: December 2021

Huntington’s disease (HD) is a devastating monogenic neurodegenerative disease characterized by early, selective pathology in the basal ganglia despite the ubiquitous expression of mutant huntingtin. The molecular mechanisms underlying this region-specific neuronal degeneration and how these relate to the development of early cognitive phenotypes are poorly understood. Here, we show that there is selective loss of synaptic connections between the cortex and striatum in postmortem tissue from HD patients that is associated with the increased activation and localization of complement proteins, innate immune molecules, to markers of these synaptic elements. We also find that levels of these secreted innate immune molecules are elevated in the CSF of premanifest HD patients and correlate with established measures of disease burden.

In preclinical genetic models of HD we show that complement proteins mediate the selective elimination of corticostriatal synapses at an early stage in disease pathogenesis marking them for removal by microglia, the brain’s resident macrophage population. This process requires mutant huntingtin to be expressed in both cortical and striatal neurons and inhibition of this complement-dependent elimination mechanism through administration of a therapeutically relevant C1q function blocking antibody or genetic ablation of a complement receptor on microglia, prevented synapse loss, increased excitatory input to the striatum and rescued the early development of visual discrimination learning and cognitive flexibility deficits in these models. Together, our findings implicate microglia and the complement cascade in the selective, early degeneration of corticostriatal synapses and the development of cognitive deficits in presymptomatic HD, and also provide new preclinical data to support complement as a therapeutic target for early intervention.
Glutamine deficiency in solid tumors confers resistance to ribosomal RNA synthesis inhibitors
Authors: Pan Melvin , Zorbas Christiane , Sugaya Maki , Ishiguro Kensuke , Kato Miki , Nishida Miyuki , Zhang Hai-Feng , Candeias Marco M , Okamoto Akimitsu , Ishikawa Takamasa , Soga Tomoyoshi , Aburatani Hiroyuki , Sakai Juro , Matsumura Yoshihiro , Suzuki Tsutomu , Proud Christopher G. , Lafontaine Denis L. J. , Osawa Tsuyoshi
Published: December 2021

Ribosome biogenesis involves the processing of precursor ribosomal RNAs (pre-rRNAs) and sequential assembly with ribosomal proteins. Here we report that nutrient deprivation severely impairs pre-rRNA processing and leads to the accumulation of unprocessed rRNAs. Upon nutrient restoration, the accumulated pre-rRNAs are processed into mature rRNAs that are utilized for ribosome biogenesis. Failure to accumulate pre-rRNAs under nutrient deprivation leads to perturbed ribosome assembly during nutrient restoration and subsequent apoptosis via uL5/uL18-mediated activation of p53. Restoration of glutamine alone activates p53 by triggering uL5/uL18 translation. Induction of uL5/uL18 protein synthesis by glutamine was dependent on the translation factor eukaryotic elongation factor 2 (eEF2), which was in turn dependent on Raf/MEK/ERK signalling. Depriving cells of glutamine prevents the activation of p53 by rRNA synthesis inhibitors. Our data reveals a mechanism that cancer cells can exploit to suppress p53-mediated apoptosis during fluctuations in environmental nutrient availability.
Protection and waning of natural and hybrid COVID-19 immunity
Authors: Goldberg Yair , Mandel Micha , Bar-On Yinon M. , Bodenheimer Omri , Freedman Laurence , Ash Nachman , Alroy-Preis Sharon , Huppert Amit , Milo Ron
Published: December 2021

BACKGROUND

Infection with SARS-CoV-2 provides substantial natural immunity against reinfection. Recent studies have shown strong waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown.

METHODS

Data on confirmed SARS-CoV-2 infections were extracted from the Israeli Ministry of Health database for the period August to September 2021 regarding all persons previously infected or vaccinated. We compared infection rates as a function of time since the last immunity-conferring event using Poisson regression, adjusting for possible confounding factors.

RESULTS

Confirmed infection rates increased according to time elapsed since the last immunity-conferring event in all cohorts. For unvaccinated previously infected individuals they increased from 10.5 per 100,000 risk-days for those previously infected 4-6 months ago to 30.2 for those previously infected over a year ago. For individuals receiving a single dose following prior infection they increased from 3.7 per 100,000 person days among those vaccinated in the past two months to 11.6 for those vaccinated over 6 months ago. For vaccinated previously uninfected individuals the rate per 100,000 person days increased from 21.1 for persons vaccinated within the first two months to 88.9 for those vaccinated more than 6 months ago.

CONCLUSIONS

Protection from reinfection decreases with time since previous infection, but is, nevertheless, higher than that conferred by vaccination with two doses at a similar time since the last immunity-conferring event. A single vaccine dose after infection helps to restore protection.
Asymptomatic carriers of the p.A53T SNCA mutation: data from the PPMI study
Authors: Simitsi Athina Maria , Koros Christos , Stamelou Maria , Beratis Ion , Efthymiopoulou Efthymia , Papadimitriou Dimitra , Bougea Anastasia , Picillo Marina , Stanitsa Evangelia , Papagiannakis Nikolaos , Antonelou Roubina , Pachi Ioanna , Papageorgiou Sokratis G. , Barone Paolo , Stefanis Leonidas
Published: December 2021

Introduction

There has been great interest in the prodromal phase of Parkinson’s disease (PD), especially in subjects who are asymptomatic carriers of genetic mutations leading to PD because of the high risk to convert to PD. The objective of the present study was to assess non motor characteristics of asymptomatic p.A53T mutation carriers (A53T-AC) compared with healthy controls (HC).

Methods

We compared 12 A53T-AC with 36 matched HC enrolled into in the Parkinson’s Progression Markers Initiative (PPMI) study. Baseline data extracted from the PPMI database, contained demographics and non-motor symptoms (e.g. the Montreal Cognitive Assessment (MOCA) for cognition, the University of Pennsylvania Smell Identification Test (UPSIT) for olfaction, MDS-UPDRS I etc.)

Results

The mean UPSIT score was lower in A53T-AC vs HC (p =0.000). MoCA test showed a trend towards lower scores in A53T AC. We found a significant positive correlation between UPSIT score and MOCA in A53T-AC (rs = 0,68, p=0,021) but not in HC. Total scores for MDS-UPDRS I did not differ between the groups but the subscore of anxiety was more prevalent in A53T-AC.

Conclusion

The more affected olfaction in A53T-AC may indicate that olfactory function is affected quite early in A53T carriers. The strong positive correlation between UPSIT and MOCA in the A53T-AC group may indicate that cognitive dysfunction and olfactory impairment progress alongside, prior to nigrostriatal degeneration. Anxiety was also more prevalent in A53T-AC and may represent an additional prodromal feature in this group of subjects.
Can 10x cheaper, lower-efficiency particulate air filters and box fans complement High-Efficiency Particulate Air (HEPA) purifiers to help control the COVID-19 pandemic?
Authors: Srikrishna Devabhaktuni
Published: December 2021

Public health departments such as CDC and California Department of Public Health (CA-DPH) advise HEPA-purifiers to limit transmission of SARS-CoV-2 indoor spaces. CA-DPH recommends air exchanges per hour (ACH) of 4-6 air for rooms with marginal ventilation and 6-12 in classrooms often necessitating multiple HEPA-purifiers per room, unaffordable in under-resourced community settings. Pressure to seek cheap, rapid air filtration resulted in proliferation of lower-cost, Do-It-Yourself (DIY) air purifiers whose performance is not well characterized compared to HEPA-purifiers. Primary metrics are clean air delivery rate (CADR), noise generated (dBA), and affordability ($$). CADR measurement often requires hard-to-replicate laboratory experiments with generated aerosols. We use simplified, low-cost measurement tools of ambient aerosols enabling scalable evaluation of aerosol filtration efficiencies (0.3 to 10 microns), estimated CADR, and noise generation to compare 3 HEPA-purifiers and 9 DIY purifier designs. DIY purifiers consist of one or two box fans coupled to single MERV 13-16 filters (1”-5” thick) or quad filters in a cube. Accounting for reduced filtration efficiency of MERV 13-16 filters (versus HEPA) at the most penetrating particle size of 0.3 microns, estimated CADR of DIY purifiers using 2” (67%), 4” (66%), and 5” (85%) filters at lowest fan speed was 293 cfm ($35), 322 cfm ($58), and 405 cfm ($120) comparable to best-in-class, low-noise generating HEPA-purifier running at maximum speed with at 282 cfm ($549). Quad filter designs, popularly known Corsi-Rosenthal boxes, achieved gains in estimated CADR below 80% over single filter designs, less than the 100% gain by adding a second DIY purifier. Replacing one of the four filters with a second fan resulted in gains of 125%-150% in estimated CADR. Tested DIY alternatives using lower-efficiency, single filters compare favorably to tested HEPA-purifiers in estimated CADR, noise generated at five to ten times lower cost, enabling cheap, rapid aerosol removal indoors.
Cortical Face-Selective Responses Emerge Early in Human Infancy
Authors: Kosakowski Heather L. , Cohen Michael A. , Herrera Lyneé , Nichoson Isabel , Kanwisher Nancy , Saxe Rebecca
Published: December 2021

In human adults, multiple cortical regions respond robustly to faces, including the occipital face area (OFA) and fusiform face area (FFA), implicated in face perception, and the superior temporal sulcus (STS) and medial prefrontal cortex (MPFC), implicated in higher level social functions. When in development does face selectivity arise in each of these regions? Here, we combined two awake infant functional magnetic resonance neuroimaging (fMRI) datasets to create a sample size twice the size of previous reports (n=65 infants, 2.6-9.6 months). Infants watched movies of faces, bodies, objects, and scenes while fMRI data were collected. Despite variable amounts of data from each infant, individual subject whole-brain activations maps revealed a significant response to faces compared to non-face visual categories in the approximate location of OFA, FFA, STS, and MPFC. To determine the strength and nature of face selectivity in these regions, we used cross-validated functional region of interest (fROI) analyses. Across this larger sample size, face responses in OFA, FFA, STS, and MPFC were significantly greater than responses to bodies, objects, and scenes. Even the youngest infants (2-5 months) showed significantly face-selective responses in FFA, STS, and MPFC, but not OFA. These results demonstrate that face selectivity is present in multiple cortical regions within months of birth, providing powerful constraints on theories of cortical development.

Significance Statement

Social cognition often begins with face perception. In adults, several cortical regions respond robustly to faces, yet little is known about when and how these regions first arise in development. To test whether face selectivity changes in the first year of life, we combined two datasets, doubling the sample size relative to previous reports. In the approximate location of the fusiform face area (FFA), superior temporal sulcus (STS), and medial prefrontal cortex (MPFC) but not occipital face area (OFA), face selectivity was present in the youngest group. These findings demonstrate that face-selective responses are present across multiple lobes of the brain very early in life.
Assessing measurement invariance of the CETSCALE in Guangxi, China
Authors: Tang Hsiang-Lin , Liu Xuelin , Fu Qi
Published: December 2021

Purpose

This study sets about assessing measurement invariance of the widely used CETSCALE in the context of an economically disadvantageous inland city in China. The 10-item CETSCALE (Shimp and Sharma 1987) was administered to a college-level student sample (male = 55 and female = 198) in Nanning City, Guangxi Zhuang Autonomous Region. AMOS v. 20 was used to conduct confirmatory factor analysis and assess measurement invariance across gender.

Design/methodology/approach

This study is designed to assess measurement invariance of the 10-item CETSCALE with student sample in Nanning, the capital city of Guangxi, China.

Findings

The results support full metric invariance and factor variance invariance and partial scalar invariance and measurement residual invariance for the refined 5-item CETSCALE. It is found that college students in an economically underdeveloped multi-ethnic inland city like Nanning were less consumer ethnocentric than those in the affluent coastal cities.

Originality/value

This is the first study to assess measurement invariance of the CETSCALE with student sample from an economically underdeveloped multi-ethnic inland city in China.
An analysis of a third-party food delivery app during the COVID-19 pandemic
Authors: Chen McCain Shiang-Lih , Lolli Jeffrey , Liu Emma , Lin Li-Chun
Published: December 2021

Purpose

The study aims to analyze guest comments on the Uber Eats food delivery app (FDA) in the USA during the April–June 2020 COVID-19 pandemic lockdown period. Three aspects influencing customer satisfaction with the FDA were evaluated in this study: (1) performance on the app, (2) product quality and (3) service quality.

Design/methodology/approach

One thousand customer comments posted on the Uber Eats Google Play app from April 1 to June 30, 2020 were analyzed in this study. The text mining technique was applied to discover the hidden, but meaningful patterns from the unstructured text. Content analysis was applied to systematically analyze the text into organized categories and themes.

Findings

Among the three dimensions evaluated in this study, the most important dimension regarding customers' perceptions toward the FDA was the service quality dimension (40.02%), followed by the FDA's performance dimension (39.43%) and the product quality dimension (20.54%) was least important. Additionally, customers' perceptions towards the three dimensions were all unfavorable and there were more negative comments than the positive comments: FDAs (P/N = 0.728), product quality (P/N = 0.60) and service quality (P/N = 0.865).

Originality/value

Previous studies investigating FDAs assessed solely the performance of the app. However, customers' experience of a food delivery service is comprised of multiple components including the app, the restaurant and the delivery driver. To fill the void, this study evaluated a third-party app performance, product quality and service quality to capture the totality of customers' food delivery service experience.
The role of the industry's cultural-cognitive elements on actors' intention to adopt BIM: an empirical study in Peru
Authors: Murguia Danny , Demian Peter , Soetanto Robby
Published: December 2021

Purpose

The current understanding of building information modelling (BIM) adoption often neglects the industry context in which BIM is deployed. This is particularly problematic when policymakers are planning to enact top-down policies to promote BIM adoption in public-funded construction. Therefore, the aim of this study is to establish the industry-level factors that constraint or enable actors' intention to adopt BIM.

Design/methodology/approach

Using institutional theory with an emphasis on the cultural-cognitive elements, the authors aim to complement the understanding of BIM adoption by incorporating institutional elements into the unified theory of acceptance and use of technology (UTAUT). The cultural-cognitive elements were extracted from focus groups and interviews with architecture, construction and engineering (AEC) professionals in Peru. A modified UTAUT was empirically tested using confirmatory factor analysis (CFA) and structural equation modelling (SEM) with a dataset from 171 questionnaire responses.

Findings

The industry characteristics, standardisation, affordability and technology/methodology definition of BIM were found to be the cultural-cognitive elements having direct effects on individual reactions to BIM. These findings suggest that BIM adoption policies should focus on designing incentives schemes, training/educating professionals on BIM collaborative processes and developing/adapting applicable standards. However, a BIM adoption mandate would require policymakers to create collaborative procurement environments in tandem with information management and process standards.

Practical implications

Findings can be used by policymakers to significantly promote BIM adoption in contexts without a government mandate for public sector construction.

Originality/value

The study of institutional elements on BIM adoption is still limited. This study provides empirical evidence on how the cultural-cognitive elements of the industry context are associated with actors' intention to adopt BIM. Therefore, this study bridges industry and individual levels of analysis. Furthermore, this study enables policymakers to initiate actions that significantly encourage BIM adoption.
Global carbon emission spatial pattern in 2030 under INDCs: using a gridding approach based on population and urbanization
Authors: Tao Le , Su Yun , Fang Xiuqi
Published: December 2021

Purpose

The intended nationally determined contributions (INDCs) is a major outcome of the Paris Agreement on international cooperation to reduce emissions, and is likely to be the future scenario for carbon emissions. This paper aims to obtain the fine spatial pattern of carbon emissions in 2030, identify hot spots and analyze changes of carbon emissions with a spatial grid method.

Design/methodology/approach

Based on the integrated quantified INDCs of each economy in 2030, the authors predict the population density pattern in 2030 by using the statistics of current population density, natural growth rates and differences in population growth resulting from urbanization within countries. Then the authors regard population density as a comprehensive socioeconomic indicator for the top-bottom allocation of the INDC data to a 0.1° × 0.1° grid. Then, the grid spatial pattern of carbon emissions in 2030 is compared with that in 2016.

Findings

Under the unconditional and conditional scenarios, the global carbon emission grid values in 2030 will be within [0, 59,200.911] ktCO2 and [0, 51,800.942] ktCO2, respectively; eastern China, northern India, Western Europe and North America will continue to be the major emitters; grid carbon emissions will increase in most parts of the world compared to 2016, especially in densely populated areas.

Originality/value

While many studies have explored the overall global carbon emissions or warming under the INDC scenario, attention to spatial details is also required to help us make better emissions attributions and policy decisions from the perspective of the grid unit rather than the administrative unit.
A comprehensive analysis of the 21st century's research trends in English Mobile Learning: a bibliographic review of the literature
Authors: Khodabandelou Rouhollah , Fathi Masood , Amerian Mohammad , Fakhraie Mohammad Reza
Published: December 2021

Purpose

This study examines the importance of English Mobile Learning research as a foundation for lifelong and sustainable education from different points of view, including those of technology innovation experts, psychologists and educators. It aims to explore the current status and relevant research trends through the application of bibliometric mapping and bibliometric analysis.

Design/methodology/approach

For this study, all Web of Science records (in total 5,343) from 2000 to 2020 in the field of English Mobile Learning were analyzed using the VOSviewer and CiteSpace software tools. The WoS built-in functions, including “Refine” and “Analyze,” were employed to perform the bibliometric analysis. The study further analyzed a sample of the five most-cited articles to identify the previous studies with the highest quality or impact.

Findings

The results showed that research in English Mobile Learning is growing quickly and steadily with a noticeable emphasis on various device-based technologies and applications. The study also discusses the key implications for research institutions, education policymakers and academicians, and identifies the most prominent avenues for future research on English Mobile Learning. Moreover, the results shared in this review highlight the most important and emerging areas of research in the field.

Originality/value

This article is the most recent bibliographic review of literature that particularly addresses the English Mobile Learning research during the past two decades.