bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural mechanisms of psychedelic visual imagery
Authors: Stoliker Devon , Preller Katrin H. , Novelli Leonardo , Anticevic Alan , Egan Gary F. , Vollenweider Franz X. , Razi Adeel
Published: September 2022

Visual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed imagery. Preclinical evidence suggests agonism of the 5-HT2A receptor may reduce synaptic gain to produce psychedelic-induced imagery. However, this has not been investigated in humans. To infer the directed connectivity changes to visual sensory connectivity underlying psychedelic visual imagery in healthy adults, a double-blind, randomised, placebo-controlled, cross-over study was performed, and dynamic causal modelling was applied to the resting state eyes-closed functional MRI scans of 24 subjects after administration of 0.2mg/kg of the serotonergic psychedelic drug, psilocybin (magic mushrooms), or placebo. The effective connectivity model included the early visual area, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus. We observed a pattern of increased self-inhibition of both early visual and higher visual-association regions under psilocybin that was consistent with preclinical findings. We also observed a pattern of reduced inhibition from visual-association regions to earlier visual areas that indicated top-down connectivity is enhanced during visual imagery. The results were associated with behavioural measures taken immediately after the scans, suggesting psilocybin-induced decreased sensitivity to neural inputs is associated with the perception of eyes-closed visual imagery. The findings inform our basic and clinical understanding of visual perception. They reveal neural mechanisms that, by affecting balance, may increase the impact of top-down feedback connectivity on perception, which could contribute to the visual imagery seen with eyes-closed during psychedelic experiences.
The Asgard archaeal ESCRT-III system forms helical filaments and remodels eukaryotic membranes, shedding light on the emergence of eukaryogenesis
Authors: Melnikov Nataly , Junglas Benedikt , Halbi Gal , Nachmias Dikla , Zerbib Erez , Upcher Alexander , Zalk Ran , Sachse Carsten , Bernheim-Groswasser Ann , Elia Natalie
Published: September 2022

The ESCRT machinery mediates membrane remodeling in numerous processes in cells including cell division and nuclear membrane reformation. The identification of ESCRT homologs in Asgard archaea, currently considered the closest ancestor of eukaryotes, implies a role for ESCRTs in the membrane remodeling processes that occurred during eukaryogenesis. Yet, the function of these distant ESCRT homologs is mostly unresolved. Here we show that Asgard ESCRT-III proteins of the Lokiarcheota self-assemble into helical filaments, a hallmark of the ESCRT system. We determined the cryo-EM structure of the filaments at 3.6 Å resolution and found that they share features of bacterial and eukaryotic ESCRT-III assemblies. Markedly, Asgard ESCRT-III filaments bound and deformed eukaryotic-like membrane vesicles. Oligonucleotides facilitated the assembly of ESCRT-III filaments and tuned the extent of membrane remodeling. The ability of Asgard archaeal ESCRTs to remodel eukaryotic-like membranes, which are fundamentally different from archaeal membranes, and the structural properties of these proteins places them at the junction between prokaryotes and eukaryotes, substantiating a role for ESCRTs in eukaryogenesis.

GRAPHICAL ABSTRACT
Turbulent adaptive landscape shaped size evolution in modern ocean giants
Authors: Burin Gustavo , Park Travis , James Tamora D. , Slater Graham J. , Cooper Natalie
Published: September 2022

Adaptive landscapes are central to evolutionary theory, forming a conceptual bridge between micro- and macro-evolution1–4. Evolution by natural selection across an adaptive landscape should drive lineages towards fitness peaks, shaping the distribution of phenotypic variation within and among clades over evolutionary timescales5. Constant shifts in selection pressures mean the peaks themselves also evolve through time4, thus a key challenge is to identify these ‘ghosts of selection past’. Here, we characterise the global and local adaptive landscape for total length in cetaceans (whales and dolphins) across their ~ 53 million year evolutionary history, using 345 living and fossil taxa. We analyse shifts in long-term mean size6and directional changes in average trait values7using cutting-edge phylogenetic comparative methods. We demonstrate that the global macroevolutionary adaptive landscape of cetacean body size is relatively flat, with very few peak shifts after cetaceans colonised the oceans. Local peaks represent trends along branches linked to specific adaptations such as deep diving. These results contrast with previous studies using only extant taxa8, highlighting the vital role of fossil data for understanding macroevolutionary dynamics. Our results indicate that adaptive peaks are constantly changing and are associated with subzones of local adaptations, resembling turbulent waters with waves and ripples, creating moving targets for species adaptation. In addition, we identify limits in our ability to detect some evolutionary patterns and processes, and suggest multiple approaches are required to characterise complex hierarchical patterns of adaptation in deep-time.
Are brain displacements and pressures within the parenchyma induced by surface pressure differences? A computational modelling study
Authors: Piersanti Eleonora , Rognes Marie E. , Vinje Vegard
Published: September 2022

The intracranial pressure is implicated in many homeostatic processes in the brain and is a fundamental parameter in several diseases such as e.g. idiopathic normal pressure hydrocephalus (iNPH). The presence of a small but persistent pulsatile intracranial pulsatile transmantle pressure gradient (on the order of a few mmHg/m at peak) has recently been demonstrated in iNPH subjects. A key question is whether pulsatile ICP and displacements can be induced by a small pressure gradient originating from the brain surface e.g. pial arteries alone. In this study, we model the brain parenchyma as either a linearly elastic or a poroelastic medium and impose a pulsatile pressure gradient acting between the ventricular and the pial surfaces. Using this high-resolution physics-based model, we compute the effect of the pulsatile pressure gradient on parenchyma displacement, volume change, fluid pressure, and fluid flux. The resulting displacement field is pulsatile and in qualitatively and quantitatively good agreement with the literature, both with elastic and poroelastic models. However, the pulsatile forces on the boundaries are not sufficient for pressure pulse propagation through the brain parenchyma. Our results suggest that pressure differences originating over the brain surface via e.g. pial artery pulsatility are not sufficient to drive interstitial fluid (ISF) flow within the brain parenchyma and that potential pressure gradients found within the parenchyma rather arise from local pressure pulsations of blood vessels within the brain parenchyma itself.
Preclinical shortwave infrared tumor screening and resection via pHLIP ICG under ambient lighting conditions
Authors: Mc Larney Benedict Edward , Kim Mijin , Roberts Sheryl , Skubal Magdalena , Hsu Hsiao-Ting , Ogirala Anuja , Pillarsetty NagaVaraKishore , Heller Daniel , Lewis Jason S. , Grimm Jan
Published: September 2022

There is a critical need to improve optical imaging that will lead to its widespread acceptance for routine clinical procedures. Shortwave infrared (SWIR, 900–1700nm) imaging has demonstrated clear advantages over visible and near-infrared imaging (reduced autofluorescence with improved contrast, resolution, and sensitivity at tissue depth). Here we show that the previously reported compound, pH low insertion peptide (pHLIP) conjugated to indocyanine green (ICG, pHLIP ICG) currently in clinical trials, serves as an excellent candidate for SWIR imaging protocols. SWIR’s increased sensitivity enabled preclinical tumor screening and resection at exposure times as low as 0.1 ms with acceptable signal-to-noise and contrast-to-noise ratios. Imaging was performed under ambient lighting conditions, and SWIRs sensitivity enabled an extended surgical resection window up to 96 hrs post injection in an orthotopic breast cancer mouse model. This work provides a direct precedent for the clinical translation of SWIR pHLIP ICG imaging for cancer resection.

One Sentence Summary

SWIR imaging under ambient lighting is highly sensitive to pHLIP ICG, a cancer targeting fluorescent agent currently under clinical investigation.
Single-cell transcriptomics of resected human traumatic brain injury tissues reveals acute activation of endogenous retroviruses in oligodendroglia
Authors: Garza Raquel , Sharma Yogita , Atacho Diahann , Thiruvalluvan Arun , Hamdeh Sami Abu , Jönsson Marie , Horvath Vivien , Adami Anita , Ingelsson Martin , Jern Patric , Hammell Molly Gale , Englund Elisabet , Kirkeby Agnete , Jakobsson Johan , Marklund Niklas
Published: September 2022

Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used snRNA-seq to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linkedin vitrousing human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides a unique insight into the initiating events of the neuroinflammatory response in TBI, which has new therapeutic implications.
Distinguishing between histories of speciation and introgression using genomic data
Authors: Hibbins Mark S. , Hahn Matthew W.
Published: September 2022

Introgression creates complex, non-bifurcating relationships among species. At individual loci and across the genome, both introgression and incomplete lineage sorting interact to produce a wide range of different gene tree topologies. These processes can obscure the history of speciation among lineages, and, as a result, identifying the history of speciation vs. introgression remains a challenge. Here, we use theory and simulation to investigate how introgression can mislead multiple approaches to species tree inference. We find that arbitrarily low amounts of introgression can mislead both gene tree methods and parsimony methods if the rate of incomplete lineage sorting is sufficiently high. We also show that an alternative approach based on minimum gene tree node heights is inconsistent and depends on the rate of introgression across the genome. To distinguish between speciation and introgression, we apply supervised machine learning models to a set of features that can easily be obtained from phylogenomic datasets. We find that multiple of these models are highly accurate in classifying the species history in simulated datasets. We also show that, if the histories of speciation and introgression can be identified, PhyloNet will return highly accurate estimates of the contribution of each history to the data (i.e. edge weights). Overall, our results highlight the promise of supervised machine learning as a potentially powerful complement to phylogenetic methods in the analysis of introgression from genomic data.
Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
Authors: Zea Diego Javier , Mac Donagh Juan , Benitez Guillermo , Donadio Cristian Guisande , Marchetti Julia , Palopoli Nicolas , Fornasari María Silvina , Parisi Gustavo
Published: September 2022

The emerging picture of protein nature reveals its intrinsic metastability. According to this idea, although a protein is kinetically trapped in a local free energy minimum that defines its native state, those kinetic barriers can be overcome by a complex mixture of the protein’s intrinsic properties and environmental conditions, promoting access to more stable states such as the amyloid fibril. Proteins that are strongly driven towards aggregation in the form of these fibrils are called amyloidogenic. In this work we study the evolutionary rates of 81 human proteins for which an in vivo amyloid state is supported by experiment-based evidence. We found that these proteins evolve faster when compared with a large dataset of ∼16,000 reference proteins from the human proteome. However, their evolutionary rates were indistinguishable from those of secreted proteins that are already known to evolve fast. After analyzing different parameters that correlate with evolutionary rates, we found that the evolutionary rates of amyloidogenic proteins could be modulated by factors associated with metastable transitions such as supersaturation and conformational diversity. Our results showcase the importance of protein metastability in evolutionary studies.
The functional impact of rare variation across the regulatory cascade
Authors: Li Taibo , Ferraro Nicole , Strober Benjamin J. , Aguet Francois , Kasela Silva , Arvanitis Marios , Ni Bohan , van de Wiel Laurens , Hershberg Elliot , Ardlie Kristin , Arking Dan E. , Beer Rebecca L. , Brody Jennifer , Blackwell Thomas W , Clish Clary , Gabriel Stacey , Gerszten Robert , Guo Xiuqing , Gupta Namrata , Johnson W. Craig , Lappalainen Tuuli , Lin Henry J. , Liu Yongmei , Nickerson Deborah A. , Papanicolaou George , Pritchard Jonathan K. , Qasba Pankaj , Shojaie Ali , Smith Josh , Sotoodehnia Nona , Taylor Kent D. , Tracy Russell P. , Van Den Berg David , Wheeler Matthew , Rich Stephen S. , Rotter Jerome I. , Battle Alexis , Montgomery Stephen B.
Published: September 2022

Each human genome has tens of thousands of rare genetic variants; however, identifying impactful rare variants remains a major challenge. We demonstrate how use of personal multi-omics can enable identification of impactful rare variants by using the Multi-Ethnic Study of Atherosclerosis (MESA) which included several hundred individuals with whole genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, ten years apart. We evaluated each multi-omic phenotype’s ability to separately and jointly inform functional rare variation. By combining expression and protein data, we observed rare stop variants 62x and rare frameshift variants 216x as frequently as controls, compared to 13x to 27x for expression or protein effects alone. We developed a Bayesian hierarchical model to prioritize specific rare variants underlying multi-omic signals across the regulatory cascade. With this approach, we identified rare variants that exhibited large effect sizes on multiple complex traits including height, schizophrenia, and Alzheimer’s disease.
Structure and Function of Gli123 Involved in Mycoplasma mobile Gliding
Authors: Matsuike Daiki , Tahara Yuhei O , Nonaka Takahiro , Wu Heng Ning , Hamaguchi Tasuku , Kudo Hisashi , Hayashi Yuuki , Arai Munehito , Miyata Makoto
Published: September 2022

Mycoplasma mobile is a fish pathogen that glides on solid surfaces by means of a unique mechanism. The gliding machinery of M. mobile is composed of internal and surface structures. In the present study, we focused on the function and structure of Gli123, a surface protein that is essential for the localization of other surface proteins. The amino acid sequence of Gli123, which is 1128 amino acids long, contains lipoprotein-specific repeats. We isolated the native Gli123 protein from M. mobile cells and a recombinant protein, rGli123, from Escherichia coli. The isolated rGli123 complemented a non-binding and non-gliding mutant of M. mobile that lacked Gli123. Circular dichroism and rotary-shadowing electron microscopy (EM) showed that rGli123 has a structure that is not significantly different from that of the native protein. Rotary-shadowing EM suggested that the molecules changed their shape between globular and rod-like structures, depending on the ionic strength of the solution. Negative-staining EM coupled with single-particle analysis revealed that Gli123 forms a globular structure featuring a small protrusion with dimensions of 20.0, 14.5, and 16.0 nm. Small-angle X-ray scattering analyses indicated a rod-like structure composed of several tandem globular domains with total dimensions of approximately 34 nm length and 4 nm width. Both molecular structures were suggested to be dimers based on the predicted molecular size and structure. Gli123 may have evolved by multiplication of repeating lipoprotein units and acquired clumping role of surface proteins.

IMPORTANCE

Mycoplasmas are pathogenic bacteria that are widespread in animals. They are characterized by small cell and genome sizes but are equipped with unique abilities to escape host immunity, such as surface variation and gliding. Here, we focused on a surface-localizing protein that is essential for Mycoplasma mobile gliding. The findings of this study suggested that the protein undergoes drastic conformational changes between its rod-like and globular structures. These changes may be caused by a repetitive structure common in the surface proteins that is responsible for the modulation of the cell surface structure and related to the assembly process for the surface gliding machinery. An evolutionary process for this unique mycoplasma gliding mechanism has also been suggested in the present study.
More than 90% of nacre matrix proteins are composed of silk-like proteins
Authors: Liu Xiaojun , Yin Zehui , Ma Zhuojun , Liang Jian , Yao Liping , Zhang Rongqing
Published: September 2022

A proteome is a powerful tool to study nacre biomineralization that occurs in an ordered microenvironment composed mainly of proteins and polysaccharides. As more and more proteins are detected, new questions arise about which proteins are responsible for forming this microenvironment. In this study, shell matrix proteins (SMPs) of nacre were analyzed using label-free quantitative proteome. A total of 99.89% of the insoluble nacre SMPs were composed of silk-like proteins, chitin-binding proteins, and cysteine-rich SMPs, which were responsible for organic framework assembly. A total of 99.34% of the soluble nacre SMPs were composed of silk-like proteins and chitin-binding proteins, which were responsible for forming protein gel filling in organic frameworks. The content of silk-like proteins was more than 90% in both insoluble and soluble nacre SMPs. As organic frameworks and protein gel together constructed a microenvironment for calcium carbonate biomineralization, these results provided a novel understanding of nacre formation.
Effect of cognitive reserve on physiological measures of cognitive workload in older adults with cognitive impairments
Authors: Devos Hannes , Gustafson Kathleen , Liao Ke , Ahmadnezhad Pedram , Kuhlmann Emily , Estes Bradley , Martin Laura E. , Mahnken Jonathan D. , Brooks William M. , Burns Jeffrey M.
Published: September 2022

Background

Cognitive reserve may protect against cognitive decline. However, its effect on physiological measures of cognitive workload in adults with cognitive impairments is unclear.

Objective

The aim was to determine the association between cognitive reserve and physiological measures of cognitive workload in older adults with and without cognitive impairments.

Methods

29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MOCA scores 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MOCA 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve.

Results

Higher CRIq total scores were associated with larger P3 ERP amplitude (p=0.048), independent of cognitive status (p=0.80), task demand (p=0.003), and electrode site (p<0.0001). This relationship was mainly driven by Work Activity (p=0.0005). Higher CRIq total scores also correlated with higher mean ICA (p = 0.002), regardless of cognitive status (p=0.29) and task demand (p=0.12). Both Work Activity (p=0.0002) and Leisure Time (p=0.045) impacted ICA. No relationship was found between CRIq and P3 latency.

Conclusion

Cognitive reserve affects cognitive workload and neural efficiency, regardless of cognitive status. Future longitudinal studies should investigate the causal relationship between cognitive reserve and physiological processes of neural efficiency across cognitive aging.
Distinct selection signatures during domestication and improvement in crops: a tale of two genes in mungbean
Authors: Lin Ya-Ping , Chen Hung-Wei , Yeh Pei-Min , Anand Shashi S. , Lin Jiunn , Li Juan , Noble Thomas , Nair Ramakrishnan , Schafleitner Roland , Samsonova Maria , Bishop-von-Wettberg Eric , Nuzhdin Sergey , Ting Chau-Ti , Lawn Robert J. , Lee Cheng-Ruei
Published: September 2022

Domestication and improvement are two crucial processes underlying the evolution of crops. Domestication transformed wild plants into a utilizable form for humans; improvement refined cultivars adapting to distinct environments and local preferences. Using whole-genome re-sequencing of Vigna radiata, we investigated the demographic history and compared the genetic footprints of domestication and improvement. The Asian wild population migrated to Australia at about 50 kya, and domestication happened in Asia about 9 kya selecting for non-shattering pods. The key candidate gene for this trait, VrMYB26a, has lower expression in cultivars, consistent with the reduced polymorphism in the promoter region reflecting hard selective sweep. The determinate stems were later selected as an improvement phenotype and associated with the gene VrDet1. Two ancient haplotypes reducing gene expression exhibit intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in soft selective sweep. Our results suggest domestication and improvement may leave different genomic signatures of selection, reflecting the fundamental differences in the two processes and highlighting the limitations of genome-scan methods relying on hard selective sweep.
When Abstract Becomes Concrete: Naturalistic Encoding of Concepts in the Brain
Authors: Kewenig Viktor , Vigliocco Gabriella , Skipper Jeremy I
Published: September 2022

Language is acquired and processed in complex and dynamic naturalistic contexts, involving simultaneous processing of connected speech, faces, bodies, objects, etc.. How words and their associated concepts are encoded in the brain during real-world processing is still unknown. Here, the representational structure of concrete and abstract concepts was investigated during movie watching to address the extent to which brain responses dynamically change depending on visual context. First, across contexts, concrete and abstract concepts are shown to encode different experience-based information in separable sets of brain regions. However, these differences are reduced when multimodal context is considered. Specifically, the response profile of abstract words becomes more concrete-like when these are processed in visual scenes highly related to their meaning. Conversely, when the visual context is unrelated to a given concrete word, the activation pattern resembles more that of abstract conceptual processing. These results suggest that while concepts generally encode habitual experiences, the underlying neurobiological organisation is not fixed but depends dynamically on available contextual information.
A widespread family of phage-inducible chromosomal islands only steals bacteriophage tails to spread in nature
Authors: Alqurainy Nasser , Miguel-Romero Laura , Moura de Sousa Jorge , Chen John , Rocha Eduardo P.C. , Fillol-Salom Alfred , Penadés José R
Published: September 2022

Phage satellites interfere with helper phage packaging through the production of small-capsids, where only satellites can be packaged. So far, in all the analysed systems, the satellite-sized capsids are composed of phage proteins. Here we report the first demonstration that a family of phage-inducible chromosomal island (PICIs), a type of satellites, encodes all the proteins required for both the production of the small-sized capsids and the exclusive packaging of the PICIs into these capsids. Therefore, this new family, that we have named cf-PICIs (capsid forming PICIs), only requires phage tails to generate infective PICI particles. Remarkably, the representative cf-PICI reproduces without cost for their helper phages, suggesting that the relationship between these elements is not parasitic but commensalistic. Finally, our phylogenomic studies indicate that cf-PICIs are present both in Gram-positive and Gram-negative bacteria and have evolved at least three times independently to spread widely into the satellite universe.
A link between genotype and cellular architecture in microbiome members as revealed by cryo-EM
Authors: Wimmer Benedikt H , Moraïs Sarah , Zalk Ran , Mizrahi Itzhak , Medalia Ohad
Published: September 2022

Microbial taxonomy is not yet sufficient to describe microbe functionality and ecology. Since function is often linked to structure, we sought here to use cryo-electron microscopy and tomography to analyze microbial cellular architecture and correlate it to specific phylogenies and genomes. We cultured and imaged a large collection of microbiota covering 90% of the richness of the core rumen microbiome at the family level, which we selected as a model for our analyses. Based on measurements of several parameters, we found that the structural similarity of microbiota is significantly related to their taxonomic distance, i.e., closely related microbes have similar cellular architectures. However, above the Family level, these similarities end: the structural diversity stops increasing with phylogenetic distance. Our results highlight that cellular architectures could serve as an important parameter in microbial ecology and microbial ecosystems.
Expression of m6A RNA methylation markers in the hypothalamus of Atlantic salmon
Authors: Ahi Ehsan Pashay , Frapin Morgane , Hukkanen Mikaela , Primmer Craig R.
Published: September 2022

Methylation at the N6-position of adenosine, m6A, is the most abundant mRNA modification in eukaryotes. It is a highly conserved universal regulatory mechanism controlling gene expression in a myriad of biological processes. The role of m6A methylation in sexual maturation, however, has remained largely unexplored. While the maturation process is known to be affected by many genetic and environmental factors, the molecular mechanisms causing variation in the timing of maturation are still poorly understood. Hence, investigation of whether a widespread mechanism like m6A methylation could be involved in controlling of the maturation timing is warranted. In Atlantic salmon (Salmo salar), two genes associated with the age at maturity in human,vgll3andsix6, have been shown to play an important role in maturation timing. In this study, we investigated the expression of 16 genes involved in the regulation of m6A RNA methylation in the hypothalamus of Atlantic salmon with different homozygous combinations oflate(L) andearly(E) alleles forvgll3andsix6genes. We found differential expression ofythdf2.2which encodes an m6A modification reader and promotes mRNA degradation. Its expression was higher insix6*LLcompared to other genotypes as well as immature males compared to matures. In addition, we found that the expression levels of genes coding for an eraser,alkbh5, and for a reader,ythdf1, were higher in the hypothalamus of females than in males across all the different genotypes studied. Our results indicate a potential role of the m6A methylation process in sexual maturation of Atlantic salmon, and therefore, provide the first evidence for such regulatory mechanism in the hypothalamus of any vertebrate. Investigation of additional vertebrate species is warranted in order to determine the generality of these findings.
Various tomato cultivars display contrasted morphological and molecular responses to a heat wave
Authors: Bollier N. , Micol-Ponce R. , Dakdaki A. , Maza E. , Zouine M. , Djari A. , Bouzayen M. , Chevalier C. , Delmas F. , Gonzalez N. , Hernould M.
Published: September 2022

Climate change is one of the biggest threats that human society currently needs to face. Heat waves associated with global warming negatively affect plant growth and development and will increase in frequency. Tomato is one of the most produced and consumed fruit in the world but remarkable yield losses occur every year due to the sensitivity of many cultivars to heat stress. New insights into how tomato plants are responding to heat waves will contribute to the development of new cultivars with high yields under harsh temperature conditions. In this study, the analysis of microsporogenesis and pollen germination rate of eleven tomato cultivars after exposure to a simulated heat wave revealed differences between genotypes. The transcriptome of floral buds at two developmental stages of five cultivars selected based on their pollen germination tolerance or sensitivity, revealed common and specific molecular responses implemented by tomato cultivars to cope with heat waves. These data provide valuable insights into the underlying molecular adaptation of floral buds to heat stress and will contribute to the development of future climate resilient tomato varieties.
Mitotic tethering enables en masse inheritance of a shattered micronuclear chromosome
Authors: Trivedi Prasad , Steele Christopher D. , Alexandrov Ludmil B. , Cleveland Don W.
Published: September 2022

Chromothripsis, the shattering and imperfect reassembly of one (or a few) chromosome(s)1, is an ubiquitous2 mutational process generating localized complex chromosomal rearrangements that drive genome evolution in cancer. Chromothripsis can be initiated by missegregation errors in mitosis3,4 or DNA metabolism5-7 that lead to entrapment of chromosomes within micronuclei and their subsequent fragmentation in the next interphase or upon mitotic entry6,8-10. Here, we use inducible degrons to demonstrate that chromothriptically produced pieces of a micronucleated chromosome are tethered together in mitosis by a protein complex consisting of Mediator of DNA damage checkpoint 1 (MDC1), DNA Topoisomerase II Binding Protein 1 (TOPBP1), and Cellular Inhibitor of PP2A (CIP2A), thereby enabling en masse segregation to the same daughter cell. Such tethering is shown to be crucial for the viability of cells undergoing chromosome missegregation and shattering after transient inactivation of the spindle assembly checkpoint. Pan-cancer analysis of transcriptome and whole-genome sequencing data revealed that chromothriptic genome rearrangements were accompanied by elevated expression of MDC1, TOPBP1, and CIP2A. Thus, chromatin-bound tethers maintain proximity of fragments of a shattered chromosome enabling their re-encapsulation into, and religation within, a daughter cell nucleus to form heritable, chromothriptically rearranged chromosomes found in the majority of human cancers.
FRIZZLED 2 regulates limb development by mediating both β-catenin-dependent and independent Wnt signaling pathways
Authors: Zhu Xuming , Xu Mingang , Leu N. Adrian , Morrisey Edward E. , Millar Sarah E.
Published: September 2022

Human Robinow Syndrome and omodysplasia, characterized by skeletal limb and craniofacial defects, are associated with mutations in the Wnt receptor FZD2. However, as FZD2 can activate both canonical and non-canonical Wnt pathways, its precise functions and mechanisms of action in limb development are unclear. To address these questions, we generated mice harboring a single nucleotide insertion in the Dishevelled-interacting domain of Fzd2 (Fzd2em1Smill), causing a frameshift mutation similar to the effects of human syndromic FZD2 mutations. Fzd2em1Smill mutant mice had shortened limbs resembling those of Robinow Syndrome and omodysplasia patients. Fzd2em1Smill mutant embryos displayed decreased canonical Wnt signaling in developing limb mesenchyme and disruption of digit chondrocyte elongation and orientation, which is controlled by the WNT5A/PCP pathway. In line with this, we found that tissue-specific disruption of Fzd2 function in limb mesenchyme caused formation of shortened bone elements and was associated with deficiency in both Wnt/β-catenin and WNT5A/PCP signaling. These findings indicate that FZD2 controls limb development by mediating both canonical and non-canonical Wnt pathways and reveal causality of pathogenic FZD2 mutations in Robinow Syndrome and omodysplasia patients.

Summary statement

Human FZD2 mutations are associated with limb defects; using genetic mouse models we revealed causality of these mutations and showed that they disrupt both canonical and non-canonical Wnt signaling.
Contact patterns of UK home delivery drivers and their use of protective measures during the COVID-19 pandemic: a cross-sectional study
Authors: Bridgen Jessica RE , Wei Hua , Whitfield Carl , Han Yang , Hall Ian , Jewell Chris P , van Tongeren Martie JA , Read Jonathan M
Published: September 2022

Objectives

To quantify contact patterns of UK home delivery drivers and identify protective measures adopted during the pandemic.

Methods

We conducted a cross-sectional online survey to measure the interactions of 170 UK delivery drivers during a working shift between 7 December 2020 and 31 March 2021.

Results

Delivery drivers had a mean number of 71.6 (95% Confidence Interval (CI) 61.0 to 84.1) customer contacts per shift and 15.0 (95%CI 11.19 to 19.20) depot contacts per shift. Maintaining physical distancing with customers was more common than at delivery depots. Prolonged contact (more than 5 minutes) with customers was reported by 5.4% of drivers on their last shift. We found 3.0% of drivers had tested positive for SARS-CoV-2 since the start of the pandemic and 16.8% of drivers had self-isolated due to a suspected or confirmed case of COVID-19. Additionally, 5.3% (95%CI 2.3% to 10.2%) of participants reported having worked whilst ill with COVID-19 symptoms, or with a member of their household having a suspected or confirmed case of COVID-19.

Conclusion

Delivery drivers had a large number of face-to-face customer and depot contacts per shift compared to other working adults during this time. However, transmission risk may be curtailed as contact with customers was of short duration. Most drivers were unable to maintain physical distance with customers and at depots at all times. Usage of protective items such as face masks and hand sanitizer was widespread.
Genome-wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression
Authors: Holen Børge , Shadrin Alexey A. , Icick Romain , Hindley Guy , Rødevand Linn , O’Connell Kevin S. , Frei Oleksandr , Bahrami Shahram , Cheng Weiqiu , Parker Nadine , Tesfaye Markos , Jahołkowski Piotr , Karadag Naz , Dale Anders M. , Djurovic Srdjan , Smeland Olav B. , Andreassen Ole A.
Published: September 2022

Opioid use disorder (OUD) and mental disorders are often comorbid, with increased morbidity and mortality. The causes underlying this relationship are poorly understood. Although these conditions are highly heritable, their shared genetic vulnerabilities remain unaccounted for. We applied the conditional/conjunctional false discovery rate (cond/conjFDR) approach to analyse summary statistics from independent genome wide association studies of OUD, SCZ, BD and MD. Next, we characterized the identified shared loci using biological annotation resources. OUD data was obtained from the Million Veteran Program (15,756 cases 99,039 controls). SCZ (53,386 cases 77,258 controls), BD (41,917 cases 371,549 controls) and MD (170,756 cases 329,443 controls) data was provided by the Psychiatric Genomics Consortium. We discovered genetic enrichment for OUD conditional on associations with SCZ, BD, MD and vice versa, indicating polygenic overlap with identification of 14 novel OUD loci at condFDR<0.05 and 7 unique loci shared between OUD and SCZ (n=2), BD (n=2) and MD (n=7) at conjFDR<0.05 with concordant effect directions, in line with estimated positive genetic correlations. Two loci were novel for OUD, one for BD and one for MD. Three OUD risk loci were shared with more than one psychiatric disorder, at DRD2 on chromosome 11 (BD and MD), at FURIN on chromosome 15 (SCZ, BD and MD), and at the major histocompatibility complex region (SCZ and MD). Our findings provide new insights into the shared genetic architecture between OUD and SCZ, BD, and MD, indicating a complex genetic relationship, suggesting overlapping neurobiological pathways.
Loss of ANT1 Increases Fibrosis and Epithelial Cell Senescence in Idiopathic Pulmonary Fibrosis
Authors: Boatz Jennifer C. , Sui Justin , Hu Qianjiang , Li Xiaoyun , Zhang Yingze , Königshoff Melanie , Kliment Corrine R.
Published: September 2022

Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by progressive lung scarring and remodeling. Although treatments exist that slow disease progression, IPF is irreversible and there is no cure. Cellular senescence, a major hallmark of aging, has been implicated in IPF pathogenesis, and mitochondrial dysfunction is increasingly recognized as a driver of senescence. Adenine nucleotide translocases (ANTs) are abundant mitochondrial ATP-ADP transporters critical for regulating cell fate and maintaining mitochondrial function. We sought to determine how alterations in ANTs influence cellular senescence in pulmonary fibrosis. We found SLC25A4 (ANT1) and SLC25A5 (ANT2) expression is reduced in the lungs of IPF patients and particularly within alveolar type II cells by single cell RNA sequencing. Loss of ANT1 by siRNA in lung epithelial cell lines resulted in increased senescence markers such as beta-galactosidase staining and p21 by Western Blot and RT-qPCR. Bleomycin treated ANT1 knockdown cells also had increased senescence markers when compared to bleomycin treated control cells. Global loss of ANT1 resulted in worse lung fibrosis and increased senescence in the bleomycin and asbestos-induced mouse models of pulmonary fibrosis. This data supports the concept that loss of ANT1 drives IPF pathogenesis through mitochondrial dysfunction associated cellular senescence (MiDaS). In summary, loss of ANT1 induces cellular senescence, leading to abnormal tissue remodeling and enhanced lung fibrosis in IPF. Modulation of ANTs presents a new therapeutic avenue that may alter cellular senescence pathways and limit pulmonary fibrosis.
Optimal Covid-19 vaccine stations location and allocation strategies
Authors: Kumar Akhilesh , Kumar Gaurav , Ramane Tanaya Vijay , Singh Gurjot
Published: September 2022

Purpose

This study proposes strategies for vaccine center allocation for coronavirus disease (COVID) vaccine by determining the number of vaccination stations required for the vaccination drive, location of vaccination station, assignment of demand group to vaccination station, allocation of the scarce medical professional teams to station and number of optimal days a vaccination station to be functional in a week.

Design/methodology/approach

The authors propose a mixed-integer nonlinear programming model. However, to handle nonlinearity, the authors devise a heuristic and then propose a two-stage mixed-integer linear programming (MILP) formulation to optimize the allocation of vaccination centers or stations to demand groups in the first stage and the allocation of vaccination centers to cold storage links in the second stage. The first stage optimizes the cost and average distance traveled by people to reach the vaccination center, whereas the second stage optimizes the vaccine’s holding and storage and transportation cost by efficiently allocating cold storage links to the centers.

Findings

The model is studied for the real-world case of Chandigarh, India. The results obtained validate that the proposed approach can immensely help government agencies and policymaking body for a successful vaccination drive. The model tries to find a tradeoff between loss due to underutilized medical teams and the distance traveled by a demand group to get the vaccination.

Originality/value

To the best of our knowledge, there are hardly any studies on a vaccination program at such a scale due to sudden outbreaks such as Covid-19.
A bibliometric analysis of obesity in marketing research
Authors: Onjewu Adah-Kole , Sadraei Razieh , Jafari-Sadeghi Vahid
Published: September 2022

Purpose

In spite of wide civic and academic interest in obesity, there are no bibliometric records of this issue in the marketing corpus. Thus, this inquiry is conceived to address this shortcoming with a bibliometric analysis of Scopus indexed articles published on the subject.

Design/methodology/approach

The analysis followed a five-step science mapping approach of study design, data collection, data analysis, data visualisation and data interpretation. R programming software was used to review 88 peer reviewed journals published between 1987 and 2021.

Findings

A sizable stream of literature exploring obesity has accrued in the marketing area as authors have drawn parallels between the influence of persuasive communication and advertising on human wellbeing and child health. The United States of America is found to be by far the country with the highest number of publications on obesity, followed by Australia and the United Kingdom. The topic dendrogram indicates two strands of obesity discourse: (1) social and policy intervention opportunities and (2) the effects on social groups in the population.

Research limitations/implications

This review will shape future enquiries investigating obesity. Beyond the focus on children, males and females, an emerging focus on cola, ethics, food waste, milk, policy-making and students is highlighted.

Originality/value

This is the first bibliometric review of obesity in the marketing literature. This is especially timely for weighing up the utility of research aimed at understanding and reporting the trends, influences and role of stakeholders in addressing obesity.
Walking on a thin line! Empirical examination of work–home boundary violations faced by employees during forced work from home
Authors: Ramya S.M. , Banu Jasmine , Asokan Ajitha Aswathy , Baral Rupashree
Published: September 2022

Purpose

This research aims to study employees' pandemic-induced work–home boundary violations using the work–home boundary model. Boundary theory and social theories provide the theoretical underpinnings for this study. The authors study the role of gender, gender role ideology, and fear of COVID-19 in explaining the relationship between work–home boundary violations, work–family conflict (WFC), and subjective well-being (SWB) among working professionals.

Design/methodology/approach

Data were gathered using an online survey on married and working individuals (N = 354) and analyzed using the multi-group analysis technique in structural equation modeling (SEM).

Findings

Results show that men faced higher WFC due to job insecurity, while women reported higher WFC due to traditional gender role ideology. Surprisingly, men reported lower subjective well-being due to WFC compared to women, when fear of COVID-19 was low. One promising finding is the potential in using problem-focused coping strategy (PCS) as a boundary-work tactic for both men and women to ensure boundary control (BC) to reduce WFC and improve SWB during the new normal.

Practical implications

This study contributes to boundary theory, social role theory, and social support resource theory, along with practical implications for employees, organizations, and policymakers.

Originality/value

This study dissects the primary role of problem-focused coping as a valid coping mechanism for managing the issues arising from the pandemic-induced unfavorable working conditions.
Does practice make perfect? Assessing the formation of expertise amongst new venture founders
Authors: Nogueira Tadeu F. , Clausen Tommy H. , Corbett Andrew C.
Published: September 2022

Purpose

Prior research has theorised that entrepreneurs use deliberate practice (DP) in the start-up process to improve their competences and achieve new venture success. However, does DP truly lead to an increase in entrepreneurial expertise? This article advances the understanding of DP for entrepreneurship scholars by answering the following question: to what extent does DP influence the formation of entrepreneurial expertise amongst business founders?

Design/methodology/approach

The study employs a sample of founders of limited-liability firms. Data were collected mainly through a web-based survey designed specifically for this research. Regression analysis was used to investigate the relationship between DP and entrepreneurial expertise amongst business founders.

Findings

The results show that DP is positively associated with entrepreneurial expertise, which provides us with an improved understanding of DP and expertise in the entrepreneurship context.

Originality/value

The article offers empirical evidence linking DP to the achievement of entrepreneurial expertise. Further, the article emphasises DP as key to experiential learning, representing a predominant mode by which entrepreneurs’ experiences are transformed into expertise. Finally, the article highlights the important role of learning through DP in opportunity development.
The effectiveness of improvisational behavior on sales performance during the COVID-19 pandemic: the moderating effect of functional customer orientation
Authors: Charoensukmongkol Peerayuth , Pandey Arti
Published: September 2022

Purpose

This research aims to apply the contingency approach to explore the effectiveness of the improvisational behavior of salespeople on their sales performance by considering the moderating role of functional customer orientation.

Design/methodology/approach

Survey data were obtained from a sample of 227 salespeople in Bangkok, Thailand. The data analysis was implemented by partial least squares structural equation modeling.

Findings

The overall results indicate that the association between improvisational behavior and sales performance is significantly contingent on the level of functional customer orientation that salespeople exhibit. For salespeople with high functional customer orientation, improvisational behavior clearly shows a positive association with sales performance. In contrast, for salespeople with low functional customer orientation, improvisational behavior appears to have a negative association with sales performance.

Originality/value

This research broadens the knowledge in the literature by showing that improvisational behavior of salespeople needs to be combined with functional customer orientation to yield a benefit to their sales performance.