bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung inflammation is associated with lipid deposition
Authors: Potashnikova Daria M , Tvorogova Anna V , Saidova Aleena A , Sotnikova Tatiana N , Arifulin Eugene A , Lipina Tatiana V , Shirokova Olesya M , Melnikov Eugene S , Rodina Tatiana A , Valyaeva Anna A , Zharikova Anastasia A , Zayratyants George O , Zayratyants Oleg V , Sheval Eugene V , Vasilieva Elena J
Published: January 2023

Lung inflammation, pneumonia, is an acute respiratory disease of varying etiology that has recently drawn much attention during the COVID-19 pandemic as lungs are among the main targets for SARS-CoV-2. Multiple other etiological agents are associated with pneumonias. Here, we describe a newly-recognized pathology, namely abnormal lipid depositions in the lungs of patients who died from COVID-19 as well as from non-COVID-19 pneumonias. Our analysis of both semi-thin and Sudan III-stained lung specimens revealed extracellular and intracellular lipid depositions irrespective of the pneumonia etiology. Most notably, lipid depositions were located within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Structurally, the lipid droplets in the inflamed lung tissue were homogeneous and lacked outer membranes as assessed by electron microscopy. Morphometric analysis of lipid droplet deposition area allowed us to distinguish the non-pneumonia control lung specimens from the macroscopically intact area of the pneumonia lung and from the inflamed area of the pneumonia lung. Our measurements revealed a gradient of lipid deposition towards the inflamed region. The pattern of lipid distribution proved universal for all pneumonias. Finally, lipid metabolism in the lung tissue was assessed by the fatty acid analysis and by expression of genes involved in lipid turnover. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared to that in control non-inflamed lung tissue from the same individual. The expression of genes involved in lipid metabolism was altered in pneumonia, as shown by qPCR and in silico RNA-seq analysis. Thus, pneumonias of various etiologies are associated with specific lipid abnormalities; therefore, lipid metabolism can be considered to be a target for new therapeutic strategies.
Predicting alcohol-related memory problems in older adults: A machine learning study with multi-domain features
Authors: Kamarajan Chella , Pandey Ashwini K. , Chorlian David B. , Meyers Jacquelyn L. , Kinreich Sivan , Pandey Gayathri , Subbie-Saenz de Viteri Stacey , Zhang Jian , Kuang Weipeng , Barr Peter B. , Aliev Fazil , Anokhin Andrey P. , Plawecki Martin H. , Kuperman Samuel , Almasy Laura , Merikangas Alison , Brislin Sarah J. , Bauer Lance , Hesselbrock Victor , Chan Grace , Kramer John , Lai Dongbing , Hartz Sarah , Bierut Laura J. , McCutcheon Vivia V. , Bucholz Kathleen K. , Dick Danielle M. , Schuckit Marc A. , Edenberg Howard J. , Porjesz Bernice
Published: January 2023

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (Memorygroup) were compared with a matchedControlgroup who did not have memory problems. The Random Forests model identified specific features from each domain that contributed to the classification of Memory vs. Control group (AUC=88.29%). Specifically, individuals from the Memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except some connections involving anterior cingulate cortex which were predominantly hypoconnected. Other significant contributing features were (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past 5 years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past 12 months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive “uplift” life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity collected ∼18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict alcohol-related memory problems that arise in later life.
Indoleamine Dioxygenase and Tryptophan Dioxygenase Activities are Regulated through Control of Cell Heme Allocation by Nitric Oxide
Authors: Biswas Pranjal , Stuehr Dennis J.
Published: January 2023

Indoleamine-2, 3-dioxygenase (IDO1) and Tryptophan-2, 3-dioxygenase (TDO) catalyze the conversion of L-tryptophan to N-formyl- kynurenine and thus play primary roles in metabolism, inflammation, and tumor immune surveillance. Because their activities depend on their heme contents which range from 30- 60% heme-saturated in biological settings and go up or down in a dynamic manner, we studied how their heme levels may be impacted by nitric oxide (NO) in mammalian cells. We utilized cells expressing TDO or IDO1 either naturally or via transfection and determined their activities, heme contents, and expression levels as a function of NO exposure. We found NO has a bimodal effect: A narrow range of very low NO exposure promoted cells to allocate heme into TDO and IDO1 and boosted their activities several fold, while beyond this range the NO exposure transitioned to have a negative impact on their heme contents and activities. NO did not alter dioxygenase protein expression levels and its bimodal impact was observed when NO was released by a chemical donor or was generated naturally by immune-stimulated macrophage cells. NO-driven heme allocations to IDO1 and TDO required participation of a GAPDH- heme complex and for IDO1 required chaperone Hsp90 activity. Thus, cells can up- or down-regulate their IDO1 and TDO activities through a bimodal control of heme allocation by NO. This mechanism has important biomedical implications and helps explain why the IDO1 and TDO activities in animals go up and down in response to immune stimulation.
Massive solubility changes of neuronal proteins upon simulated traumatic brain injury reveal the role of shockwave in irreversible damage
Authors: Saei Amir Ata , Gharibi Hassan , Lyu Hezheng , Nilsson Brady , Jafari Maryam , von Holst Hans , Zubarev Roman A.
Published: January 2023

The immediate molecular consequences of traumatic brain injuries or TBI are poorly understood. Here, we simulated TBI using an innovative laboratory apparatus that employs a 5.1 kg dummy head holding neuronal cells and generating a ≤4,000 g-force acceleration upon impact. Dynamic impact led to both reduction in neuron viability and massive solubility changes in the proteome profiled using Proteome Integral Solubility Alteration (PISA) assay. The affected proteins mapped not only to the expected pathways like cell adhesion, collagen and laminin structures, as well as response to stress, but also to other dense protein networks, such as immune response, complement and coagulation cascades. The cellular effects are found to be mainly due to the shockwave rather than the g-force acceleration. Soft materials could reduce the impact severity only until being fully compressed. This study shows way to develop a proteome-based meter for measuring irreversible shockwave-induced cell damage and provides a resource for identifying TBI protein biomarkers and potential drug targets for developing products aiming at primary prevention and intervention.
The (Limited?) Utility of Brain Age as a Biomarker for Capturing Fluid Cognition in Older Individuals
Authors: Tetereva Alina , Pat Narun
Published: January 2023

Fluid cognition usually declines as people grow older. For decades, neuroscientists have been on a quest to search for a biomarker that can help capture fluid cognition. One well-known candidate is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI data. Here we aim to formally evaluate the utility of Brain Age as a biomarker for capturing fluid cognition among older individuals. Using 504 aging participants (36-100 years old) from the Human Connectome Project in Aging, we created 26 age-prediction models for Brain Age based on different combinations of MRI modalities. We first tested how much Brain Age from these age-prediction models added to what we had already known from a person’s chronological age in capturing fluid cognition. Based on the commonality analyses, we found a large degree of overlap between Brain Age and chronological age, so much so that, at best, Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition. Next, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition, thus not improving the models’ utility to capture cognitive abilities. Lastly, we tested how much Brain Age missed the variation in the brain MRI that could explain fluid cognition. To capture this variation in the brain MRI that explained fluid cognition, we computed Brain Cognition, or a predicted value based on prediction models built to directly predict fluid cognition (as opposed to chronological age) from brain MRI data. We found that Brain Cognition captured up to an additional 11% of the total variation in fluid cognition that was missing from the model with only Brain Age and chronological age, leading to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.
Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP-2-mediated endocytosis
Authors: Matsubayashi Hideaki T. , Mountain Jack , Yao Tony , Peterson Amy F. , Roy Abhijit Deb , Inoue Takanari
Published: January 2023

Class IA phosphoinositide 3-kinase (PI3K) galvanizes fundamental cellular processes such as migration, proliferation, and differentiation. To enable multifaceted roles, the catalytic subunit p110 utilizes a multi- domain, regulatory subunit p85 through its inter SH2 domain (iSH2). In cell migration, their product PI(3,4,5)P3generates locomotive activity. While non-catalytic roles are also implicated, underlying mechanisms and its relationship to PI(3,4,5)P3signaling remain elusive. Here, we report that a disordered region of iSH2 contains previously uncharacterized AP-2 binding motifs which can trigger clathrin and dynamin-mediated endocytosis independent of PI3K catalytic activity. The AP-2 binding motif mutants of p85 aberrantly accumulate at focal adhesions and upregulate both velocity and persistency in fibroblast migration. We thus propose the dual functionality of PI3K in the control of cell motility, catalytic and non- catalytic, arising distinctly from juxtaposed regions within iSH2.
Population-level neural correlates of flexible avoidance learning in medial prefrontal cortex
Authors: Ehret Benjamin , Boehringer Roman , Amadei Elizabeth A. , Cervera Maria R. , Henning Christian , Galgali Aniruddh , Mante Valerio , Grewe Benjamin F.
Published: January 2023

The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a novel tone-signaled active avoidance paradigm in mice. We developed a novel analysis approach based on dimensionality reduction and decoding that allowed us to identify and isolate population activity patterns related the tone stimulus, learned avoidance actions and general motion. While tone-related activity was not informative about behavior, avoidance-related activity was predictive of upcoming avoidance actions. Moreover, avoidance-related activity distinguished between two different learned avoidance actions, consistent with a model in which mPFC contributes to the selection between different goal-directed actions. Overall, our results suggest that mPFC circuit dynamics transform sensory inputs into specific behavioral outputs through distributed population-level computations.
Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes
Authors: Wang Gaowei , Chiou Joshua , Zeng Chun , Miller Michael , Matta Ileana , Han Jee Yun , Kadakia Nikita , Okino Mei-Lin , Beebe Elisha , Mallick Medhavi , Camunas-Soler Joan , Santos Theodore dos , Dai Xiao-Qing , Ellis Cara , Hang Yan , Kim Seung K. , MacDonald Patrick E. , Kandeel Fouad R. , Preissl Sebastian , Gaulton Kyle J , Sander Maike
Published: January 2023

Altered function and gene regulation of pancreatic islet beta cells is a hallmark of type 2 diabetes (T2D), but a comprehensive understanding of mechanisms driving T2D is still missing. Here we integrate information from measurements of chromatin activity, gene expression and function in single beta cells with genetic association data to identify disease-causal gene regulatory changes in T2D. Using machine learning on chromatin accessibility data from 34 non-diabetic, pre-T2D and T2D donors, we robustly identify two transcriptionally and functionally distinct beta cell subtypes that undergo an abundance shift in T2D. Subtype-defining active chromatin is enriched for T2D risk variants, suggesting a causal contribution of subtype identity to T2D. Both subtypes exhibit activation of a stress-response transcriptional program and functional impairment in T2D, which is likely induced by the T2D-associated metabolic environment. Our findings demonstrate the power of multimodal single-cell measurements combined with machine learning for identifying mechanisms of complex diseases.
Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets
Authors: Tahti Elise F. , Blount Jadon M. , Jackson Sophie N. , Gao Melody , Gill Nicholas P. , Smith Sarah N. , Pederson Nick J. , Rumph Simone N. , Struyvenberg Sarah A. , Mackley Iain G. P. , Madden Dean R. , Amacher Jeanine F.
Published: January 2023

Protein-protein interactions that include recognition of short sequences of amino acids, or peptides, are critical in cellular processes. Protein-peptide interaction surface areas are relatively small and shallow, and there are often overlapping specificities in families of peptide-binding domains. Therefore, dissecting selectivity determinants can be challenging. PDZ domains are an example of a peptide-binding domain located in several intracellular signaling and trafficking pathways, which form interactions critical for the regulation of receptor endocytic trafficking, tight junction formation, organization of supramolecular complexes in neurons, and other biological systems. These domains are also directly targeted by pathogens, and a hallmark of many oncogenic viral proteins is a PDZ-binding motif. However, amidst sequences that target PDZ domains, there is a wide spectrum in relative promiscuity. For example, the viral HPV16 E6 oncoprotein recognizes over double the number of PDZ domain-containing proteins as the cystic fibrosis transmembrane conductance regulator (CFTR) in the cell, despite similar PDZ targeting-sequences and identical motif residues. Here, we determine binding affinities for PDZ domains known to bind either HPV16 E6 alone or both CFTR and HPV16 E6, using peptides matching WT and hybrid sequences. We also use energy minimization to model PDZ-peptide complexes and use sequence analyses to investigate this difference. We find that while the majority of single mutations had a marginal effect on overall affinity, the additive effect on the free energy of binding accurately describes the selectivity observed. Taken together, our results describe how complex and differing PDZ interactomes can be programmed in the cell.
Autophagy collaborates with apoptosis pathways to control myelination specificity and function
Authors: Zhang Tingxin , Bae Han-Gyu , Bhambri Aksheev , Zhang Yihe , Barbosa Daniela , Xue Jumin , Wazir Sabeen , Mulinyawe Sara B. , Kim Jun Hee , Sun Lu O.
Published: January 2023

Oligodendrocytes are the sole myelin producing cells in the central nervous system. Oligodendrocyte numbers are tightly controlled across diverse brain regions to match local axon type and number, but the underlying mechanisms and functional significance remain unclear. Here, we show that autophagy, an evolutionarily conserved cellular process that promotes cell survival under canonical settings, elicits premyelinating oligodendrocyte apoptosis during development and regulates critical aspects of nerve pulse propagation. Autophagy flux is increased in premyelinating oligodendrocytes, and its genetic blockage causes ectopic oligodendrocyte survival throughout the entire brain. Autophagy acts in the TFEB-Bax/Bak pathway and elevatesPUMAmRNA levels to trigger premyelinating oligodendrocyte apoptosis cell-autonomously. Autophagy continuously functions in the myelinating oligodendrocytes to limit myelin sheath numbers and fine-tune nerve pulse propagation. Our results providein vivoevidence showing that autophagy promotes apoptosis in mammalian cells under physiological conditions and reveal key intrinsic mechanisms governing oligodendrocyte number.

HIGHLIGHTS

Autophagy flux increases in the premyelinating and myelinating oligodendrocytes

Autophagy promotes premyelinating oligodendrocyte (pre-OL) apoptosis to control myelination location and timing

Autophagy acts in the TFEB-PUMA-Bax/Bak pathway and elevatesPUMAmRNA levels to determine pre-OL fate

Autophagy continuously functions in the myelinating oligodendrocytes to limit myelin sheath thickness and finetune nerve pulse propagation
New mega dataset combined with deep neural network makes a progress in predicting impact of mutation on protein stability
Authors: Pak Marina A , Dovidchenko Nikita V , Sharma Satyarth Mishra , Ivankov Dmitry N
Published: January 2023

Prediction of proteins stability change (ΔΔG) due to single mutation is important for biotechnology, medicine, and our understanding of physics underlying protein folding. Despite the recent tremendous success in 3D protein structure prediction, the apparently simpler problem of predicting the effect of mutations on protein stability has been hampered by the low amount of experimental data. With the recent high-throughput measurements of mutational effects in ‘mega’ experiment for ~850,000 mutations [Tsuboyama et al., bioRxiv, 2022] it becomes possible to apply the state-of-the-art deep learning methods. Here we explore the ability of ESM2 deep neural network architecture with added Light Attention mechanism to predict the change of protein stability due to single mutations. The resulting method ABYSSAL predicts well the data from the ‘mega’ experiment (Pearson correlation 0.85) while the prediction of ΔΔG values from previous experiments is more modest (Pearson correlation 0.50). ABYSSAL also shows a perfect satisfaction of the antisymmetry property. The ABYSSAL training demonstrated that the dataset should contain around ~100,000 data points for taking advantage of the state-of-the-art deep learning methods. Overall, our study shows great perspectives for developing the deep learning ΔΔG predictors.
F-actin and Myosin F control apicoplast elongation dynamics which drive apicoplast-centrosome association inToxoplasma gondii
Authors: Devarakonda Parvathi Madhavi , Sarmiento Valeria , Heaslip Aoife T.
Published: January 2023

Toxoplasma gondiicontains an essential plastid organelle called the apicoplast that is necessary for fatty acid, isoprenoid, and heme synthesis. Perturbations affecting apicoplast function or inheritance lead to parasite death. The apicoplast is a single copy organelle and therefore must be divided so that each daughter parasite inherits an apicoplast during cell division. In this study we identify new roles for F-actin and an unconventional myosin motor, TgMyoF, in this process. First, loss of TgMyoF and actin lead to an accumulation of apicoplast vesicles in the cytosol indicating a role for this actomyosin system in apicoplast protein trafficking or morphological integrity of the organelle. Second, live cell imaging reveals that during division the apicoplast is highly dynamic, exhibiting branched, U-shaped and linear morphologies that are dependent on TgMyoF and actin. In parasites where movement was inhibited by the depletion of TgMyoF, the apicoplast fails to associate with the parasite centrosomes. Thus, this study provides crucial new insight into mechanisms controlling apicoplast-centrosome association, a vital step in the apicoplast division cycle, which ensures that each daughter inherits a single apicoplast.
On the correspondence between the transcriptomic response of a compound and its effects on its targets
Authors: Engler Hart Chloe , Ence Daniel , Healey David , Domingo-Fernández Daniel
Published: January 2023

Better understanding the transcriptomic response produced by a compound perturbing its targets can shed light on the underlying biological processes regulated by the compound. However, establishing the relationship between the induced transcriptomic response and the target of a compound is non-trivial, partly because targets are rarely differentially expressed. Thus, connecting both modalities requires orthogonal information (e.g., pathway or functional information). Here, we present a comprehensive study aimed at exploring this relationship by leveraging thousands of transcriptomic experiments and target data for over 2,000 compounds. Firstly, we confirmed that compound-target information does not correlate as expected with the transcriptomic signatures induced by a compound. However, we demonstrate how the concordance between both modalities can be increased by connecting pathway and target information. Additionally, we investigated whether compounds that target the same proteins induce a similar transcriptomic response and conversely, whether compounds with similar transcriptomic responses share the same target proteins. While our findings suggest that this is generally not the case, we did observe that compounds with similar transcriptomic profiles are more likely to share at least one protein target, as well as common therapeutic applications. Lastly, we present a case scenario on a few compound pairs with high similarity to demonstrate how the relationship between both modalities can be exploited for mechanism of action deconvolution.
Arginine limitation causes a directed DNA sequence evolution response in colorectal cancer cells
Authors: Hsu Dennis J. , Gao Jenny , Yamaguchi Norihiro , Pinzaru Alexandra , Mandayam Nandan , Liberti Maria , Heissel Søren , Alwaseem Hanan , Tavazoie Saeed , Tavazoie Sohail F.
Published: January 2023

Utilization of specific codons varies significantly across organisms. Cancer represents a model for understanding DNA sequence evolution and could reveal causal factors underlying codon evolution. We found that across human cancer, arginine codons are frequently mutated to other codons. Moreover, arginine restriction—a feature of tumor microenvironments—is sufficient to induce arginine codon-switching mutations in human colon cancer cells. Such DNA codon switching events encode mutant proteins with arginine residue substitutions. Mechanistically, arginine limitation caused rapid reduction of arginine transfer RNAs and the stalling of ribosomes over arginine codons. Such selective pressure against arginine codon translation induced a proteomic shift towards low arginine codon containing genes, including specific amino acid transporters, and caused mutational evolution away from arginine codons—reducing translational bottlenecks that occurred during arginine starvation. Thus, environmental availability of a specific amino acid can influence DNA sequence evolution away from its cognate codons and generate altered proteins.
Early infection response of the first trimester human placenta at single-cell scale
Authors: Hoo Regina , Ruiz-Morales Elias R. , Kelava Iva , Sancho-Serra Carmen , Mazzeo Cecilia Icoresi , Chelaghma Sara , Tuck Elizabeth , Predeus Alexander V. , Fernandez-Antoran David , Waller Ross F. , Lee Marcus , Vento-Tormo Roser
Published: January 2023

Placental infections are a major worldwide burden, particularly in developing countries. The placenta is a transient tissue located at the interface between the mother and the fetus. Some pathogens can access the placental barrier resulting in pathological transmission from mother to fetus, which may have a profound impact on the health of the developing fetus. Limited tissue accessibility, critical differences between humans and mice, and, until recently, lack of properin vitromodels, have hampered our understanding of the early placental response to pathogens. Here we use single-cell transcriptomics to describe the placental primary defence mechanisms against three pathogens that are known to cause fetal and maternal complications during pregnancy -Plasmodium falciparum, Listeria monocytogenesandToxoplasma gondii. We optimiseex vivoplacental explants of the first-trimester human placenta and show that trophoblasts (the epithelial-like cells of the placenta), and Hofbauer cells (placental macrophages) orchestrate a coordinated inflammatory response after 24 hours of infection. We show that hormone biosynthesis and transport are downregulated in the trophoblasts, suggesting that protective responses are promoted at the expense of decreasing other critical functions of the placenta, such as the endocrine production and the nourishment of the fetus. In addition, we pinpoint pathogen-specific effects in some placental lineages, including a strong mitochondrial alteration in the Hofbauer cells in response toT. gondii. Finally, we identify adaptive strategies and validate nutrient acquisition employed by theP. falciparumduring placental malaria infection. This study provides the first detailed cellular map of the first-trimester placenta upon infection and describes the early events that may lead to fetal and placental disorders if left unchecked.
Early life drought predicts components of adult body size in wild female baboons
Authors: Levy Emily J. , Lee Anna , Siodi I. Long’ida , Helmich Emma C. , McLean Emily M. , Malone Elise J. , Pickard Maggie J. , Ranjithkumar Riddhi , Tung Jenny , Archie Elizabeth A. , Alberts Susan C.
Published: January 2023

Objectives

In many taxa, adverse early-life environments are associated with reduced growth and smaller body size in adulthood. However, in wild primates, we know very little about whether, where, and to what degree trajectories are influenced by early adversity, or which types of early adversity matter most. Here, we use parallel-laser photogrammetry to assess inter-individual predictors of three measures of body size (leg length, forearm length, and shoulder-rump length) in a population of wild female baboons studied since birth.

Materials and Methods

Using >2,000 photogrammetric measurements of 127 females, we present a cross-sectional growth curve of wild female baboons (Papio cynocephalus) from juvenescence through adulthood. We then test whether females exposed to three important sources of early-life adversity - drought, maternal loss, or a cumulative measure of adversity – were smaller for their age than females who experienced less adversity. Using the ‘animal model’, we also test whether body size is heritable in this study population.

Results

Prolonged early-life drought predicted shorter limbs but not shorter torsos (i.e., shoulder-rump lengths). Our other two measures of early-life adversity did not predict any variation in body size. Heritability estimates for body size measures were 36%-58%. Maternal effects accounted for 13%-22% of the variance in leg and forearm length, but no variance in torso length.

Discussion

Our results suggest that baboon limbs, but not torsos, grow plastically in response to maternal effects and energetic early-life stress. Our results also reveal considerable heritability for all three body size measures in this study population.
Structural insights into ubiquitin chain cleavage byLegionellaovarian tumor deubiquitinases
Authors: Kang Sangwoo , Kim Gyuhee , Choi Minhyung , Jeong Minwoo , van der Heden van Noort Gerbrand J. , Roh Soung-Hun , Shin Donghyuk
Published: January 2023

Although ubiquitin is found only in eukaryotes, several pathogenic bacteria and viruses possess proteins that hinder the host ubiquitin system.Legionella, a gram-negative intracellular bacterium, possesses an ovarian tumor (OTU) family of deubiquitinases (Lot DUBs). Herein, we describe the molecular characteristics of Lot DUBs. We elucidated the structure of LotA OTU1 domain and revealed that entire Lot DUBs possess a characteristic extended helical lobe (EHL) that is not found in other OTU-DUBs. The structural topology of EHL is the same throughout the Lot family, and it provides an S1′ ubiquitin-binding site. Moreover, the catalytic triads of Lot DUBs resemble those of the A20-type OTU-DUBs. Furthermore, we revealed a unique mechanism by which LotA OTU domains cooperate together to distinguish the length of the chain and preferentially cleaves longer K48-linked polyubiquitin chains. The LotA OTU1 domain itself cleaves K6-linked ubiquitin chains, while it is also essential for assisting the cleavage of longer K48-linked polyubiquitin chains by the OTU2 domain. Thus, this study provides novel insights into the structure and mechanism of action of Lot DUBs.
Genomics of the “tumorigenes” clade of the familyRhizobiaceaeand description ofRhizobium rhododendrisp. nov.
Authors: Kuzmanović Nemanja , diCenzo George C. , Bunk Boyke , Spröer Cathrin , Frühling Anja , Neumann-Schaal Meina , Overmann Jörg , Smalla Kornelia
Published: January 2023

Tumorigenic members of the familyRhizobiaceae, known as agrobacteria, are responsible for crown and cane gall diseases of various agricultural crops worldwide. Tumorigenic agrobacteria are commonly found in the generaAgrobacterium,Allorhizobium, andRhizobium. In this study, we analyzed a distinct “tumorigenes” clade of the genusRhizobium, which includes the tumorigenic speciesRhizobium tumorigenes, as well as strains causing crown gall disease on rhododendron. Here, high quality, closed genomes of representatives of the “tumorigenes” clade were generated, followed by comparative genomic and phylogenomic analyses. Additionally, phenotypic characteristics of representatives of the “tumorigenes” clade were analyzed. Our results showed that the tumorigenic strains isolated from rhododendron represent a novel species of the genusRhizobiumfor which the nameRhizobium rhododendrisp. nov. is proposed. This species also includes additional strains originating from blueberry and Himalayan blackberry in USA, whose genome sequences were retrieved from GenBank. BothR. tumorigenesandR. rhododendricontain multipartite genomes, including a chromosome, putative chromids, and megaplasmids. Synteny and phylogenetic analyses indicated that a large putative chromid ofR. rhododendriresulted from the cointegration of an ancestral megaplasmid and two putative chromids, following its divergence fromR. tumorigenes. Moreover, gene clusters specific for both species of the “tumorigenes” clade were identified, and their biological functions and roles in ecological diversification ofR. rhododendriandR. tumorigeneswere predicted and discussed.
CAS12e (CASX2) CLEAVAGE OF CCR5: IMPACT OF GUIDE RNA LENGTH AND PAM SEQUENCE ON CLEAVAGE ACTIVITY
Authors: Armstrong David A. , Hudson Taylor R. , Hodge Christine A. , Hampton Thomas H. , Howell Alexandra L. , Hayden Matthew S.
Published: January 2023

CRISPR/Cas is under development as a therapeutic tool for the cleavage, excision, and/or modification of genes in eukaryotic cells. While much effort has focused on CRISPR/Cas fromStreptococcus pyogenes(SpCas9) andStaphylococcus aureus(SaCas9), alternative CRISPR systems have been identified using metagenomic datasets from non-pathogenic microbes, including previously unknown class 2 systems, adding to a diverse toolbox of gene editors. The Cas12e (CasX1, CasX2) endonucleases from non-pathogenic Deltaproteobacteria (DpeCas12e) and Planctomycetes (PlmCas12e) are more compact than SpCas9, have a more selective protospacer adjacent motif (PAM) requirement, and deliver a staggered cleavage cut with 5-7 base overhangs. We investigated varying guide RNA (spacer) lengths and alternative PAM sequences to determine optimal conditions for PlmCas12e cleavage of the cellular geneCCR5(CC-Chemokine receptor-5).CCR5encodes one of two chemokine coreceptors required by HIV-1 to infect target cells, and a mutation ofCCR5(delta-32) is responsible for HIV-1 resistance and reported cures following bone marrow transplantation. Consequently,CCR5has been an important target for gene editing utilizing CRISPR, TALENs, and ZFNs. We determined thatCCR5cleavage activity varied with the target site, guide RNA length, and the terminal nucleotide in the PAM sequence. Our analyses demonstrated a PlmCas12e PAM preference for purines (A, G) over pyrimidines (T, C) in the fourth position of the CasX2 PAM (TTCN). These analyses have contributed to a better understanding of CasX2 cleavage requirements and will position us more favorably to develop a therapeutic that creates the delta-32 mutation in theCCR5gene in hematopoietic stem cells.
Productivity determinants in the service industry: differences between high and low knowledge intensive sectors
Authors: Guevara-Rosero Grace , Carrión-Cauja Cristian , Simbaña-Landeta Lizbeth , Camino-Mogro Segundo
Published: January 2023

Purpose

The service industry has become an important sector for the economic growth, particularly in developing countries. In this context, the aim of this article is to compare the productivity determinants across firms operating in low and high knowledge intensity service sectors (low knowledge intensive sectors (LKIS) and high knowledge intensive sectors (HKIS)) in Ecuador.

Design/methodology/approach

The authors use a two-step estimation method. The firm productivity is estimated in the first step and the productivity determinants in the second step. To achieve the objective, the authors use an unbalanced panel database on the financial statements from formal Ecuadorian firms for the period 2007–2018.

Findings

The authors’ results show that LKIS firms are slightly more labor-intensive compared to HKIS firms. Productivity determinants are similar across HKIS and LKIS firms, except for exports and market concentration. HKIS firms are more productive when the competition level is low, indicating that higher market power is associated with higher productivity. The influence of taxes on productivity depends on firm size. Small and medium-sized firms are more negatively affected than large firms.

Practical implications

Taxes should be designed considering the size of the companies, since these could affect their productivity. Thus, lower taxes to small and medium firms may reduce firm size inequality. In addition, the acquired knowledge of HKIS should be spread to other firms becoming a positive externality instead of an entry barrier.

Originality/value

Despite the productivity determinants of the service sector has been recently explored, in contrast to the manufacturing sector, individual and contextual determinants are less identified. In this paper the authors use a large set of firm characteristics that might affect productivity in service firms.
Heavy metals, rare earth elements and isotopic fingerprint of Venetian Protected Designation of Origin sparkling wines
Authors: Rapa Mattia , Ferrante Marco , Rodushkin Ilia , Paulukat Cora , Conti Marcelo Enrique
Published: January 2023

Purpose

World imports of Italian sparkling wines fell by 9% in value and 5% in quantities. In view of this, the quality characterisation of these products is desirable to increase their market value and restore their global visibility.

Design/methodology/approach

For this purpose, in this paper, heavy metals (Cd, Co, Cr, Cu, Fe, Ga, Hf, Hg, Mn, Mo, Nb, Ni, Pb, Re, Sb, Sn, Ta, Th, Tl, U, W, V, Zn, Zr), rare Earth elements (REEs) (Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Sm, Tb, Tm, Yb) and isotopes ratio (208Pb/206Pb, 207Pb/206Pb, 206Pb/204Pb, 208Pb/207Pb, 87Sr/86Sr) were analysed in Italian sparkling wines with Protected Designation of Origin (PDO) certification by High Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICP-MS) and MultiCollector Inductively Coupled Plasma Mass Spectrometer (MC-ICP-MS). The samples were produced in the Veneto region, and they were compared to white and red wines from the same area.

Findings

Sparkling wines present a characteristic elemental pattern compared to white and red ones, with lower content of heavy metals and higher content in REEs. The ratio 87Sr/86Sr resulted in a powerful micro-scale geographical origins marker while Pb ratios as winemaking process one, both useful to prevent possible frauds. Multivariate data analyses, such as PCA and PLS-DA, were used to develop a model of recognition of Venetian sparkling wines.

Originality/value

The good classification of sparkling wines was achieved (95%), proving the suitable use of these analytes as markers for recognising sparkling wines and their geographical origin verification. To the best of the authors’ knowledge, this is the first study investigating heavy metals, REEs and isotopes in Venetian sparkling wine for their recognition.
Activating the right hemisphere in business minds
Authors: Marques Joan F. , Dhiman Satinder , Holt Svetlana , Wood Adam
Published: January 2023

Purpose

Strengthening awareness about the importance of mindfulness practices in business education and performance toward greater societal appreciation and compassion.

Design/methodology/approach

General Review: A Synthesis of Literature and Practice

Findings

The need to include mindfulness practices is not merely a wave in today’s era, but a well-considered shift that has already proven its advantage to business entities and their leaders.

Practical implications

The examples shared in this article are aimed to ignite interest about ways we can move toward cultivating awareness in making business a practice that is not merely profitable, but also socially constructive.

Originality/value

Four mindfulness enhancing practices are shared for possible implementation
Reflexivity, habitus and vulnerability: Vietnamese farmers' attribution of responsibility in a post-disaster context
Authors: Nguyen-Trung Kien
Published: January 2023

Purpose

This article examines how farmers' assignment of responsibility for the disaster in late 2015 – early 2016 connects with reflexivity, habitus and local vulnerability.

Design/methodology/approach

This article uses semi-structured interviews with 28 disaster-affected households in the Vietnamese Mekong Delta to answer the question.

Findings

This article finds out that Vietnamese farmers actively accepted their responsibility for the disaster. In their explanation, they link their action with the root causes of vulnerability embedded in their socio-cultural traditions and collective identity.

Research limitations/implications

This article makes a case for the importance of local culture and epistemologies in understanding disaster vulnerability and responsibility attribution.

Originality/value

This article is original in researching Vietnamese farmers' responsibility attribution, their aesthetic reflexivity, collective habitus and the socio-cultural root causes of disaster.
An integrated risk assessment method for cross-regional mega construction projects
Authors: Xiang Pengcheng , Xia Xin , Pang Xianya
Published: January 2023

Purpose

The purpose of this paper is to develop a novel integrated risk assessment method from the system perspective to evaluate the risk of the cross-regional mega construction project (CMCP). Furthermore, this paper aims to confirm the core risk source factors and refine the risk management strategies of CMCPs through a case study.

Design/methodology/approach

Based on the analysis of the risk system of CMCPs, the concept model and risk assessment principles of integrated risk assessment were confirmed. The risk source factors and project objectives of the CMCP were identified from a literature review, export interview and case analysis. According to the vulnerability theory, the integrated risk assessment model was developed by involving vulnerabilities, threats, objectives and interaction of those factors synthetically. Then, ZW high-speed railway from China was analyzed to verify the feasibility and effectiveness of the proposed method.

Findings

As a result, 12 threat factors and 12 vulnerability factors were identified. Based on the case study, the main external threat comes from T13 (conflicts of interest between local governments) and T23 (harsh natural environment); the most easily exploited internal vulnerabilities were V11 (complexity of technology), V13 (lack of experience in technical application), V21 (inadequate experience) and V23 (lack of interest coordination mechanism). Moreover, the economic objective was most affected.

Practical implications

It is essential to develop an interest coordination mechanism for CMCPs. The harsh natural environment is a critical factor, but it also promotes technological innovation and iteration. Public opinions in different regions are critical for CMCPs, and more emphasis should be placed on public opinion surveys of CMCPs. Moreover, diverse and flexible environmental protection strategies should apply in CMCPs.

Originality/value

This research has the following three contributions. First, based on vulnerability theory, an integrated risk assessment approach of CMCPs is developed, which enriches the risk measurement method system and provides inspiration for future research on risk in the construction industry. Second, the risk sources of CMCPs are identified from the perspective of vulnerability and threat to provide clear guidance for the risk management of CMCPs. Third, the core risk source factors and management strategies confirmed by the case study will be beneficial for various governments in different regions and project managers to optimize the project management scheme, as they are transferable management experiences.
The effect of construction sustainability system interactions on financial performance: a sociotechnical perspective
Authors: Orr Stuart , Jadhav Akshay
Published: January 2023

Purpose

Construction sustainability (CS) is a strategic reaction to the sustainability expectations of the construction industry's external stakeholders. The extant literature has viewed the environmental, social and economic dimensions of CS as having independent effects on financial performance. Due to the influence of common stakeholders, however, interactions in these dimensions will be present in their effect on financial performance. Accordingly, this study identifies the mechanisms of the interactions between the three CS dimensions and how they jointly affect financial performance.

Design/methodology/approach

Content analysis of GRI reports of 60 large construction organisations, followed by a hierarchical regression analysis was used to identify the interactions between environmental, social and economic CS in their effect on financial performance.

Findings

Economic CS was found to indirectly, and not directly, affect financial performance, the effect being mediated by both environmental and social CS. Environmental CS was found to have a strong negative effect on financial performance, whilst social CS was found to have a strongly significant positive effect on financial performance.

Practical implications

The motivation for engaging in CS is that investment in economic CS will have a positive effect on both environmental and social CS outcomes, which, in turn can have a combined effect on financial performance.

Originality/value

This is one of the first studies investigating the effect of interactions between the environmental, social and economic CS dimensions on the financial performance of construction organisations. It is also one of the first studies that applies a sociotechnical framework to this relationship.
Identifying computational thinking in students through project-based problem-solving activities
Authors: Yang Dazhi , Snelson Chareen , Feng Shi
Published: January 2023

Purpose

This paper aims to identify computational thinking (CT) in 4th to 6th grade students in the context of project-based problem-solving while engaged in an after-school program.

Design/methodology/approach

This case study approach was selected due to its suitability for answering “how” or “why” questions about real-world phenomena within a set context (Creswell and Poth, 2018; Yin, 2018). This was an appropriate fit given the context of an after-school program and the research question asked how to identify learners’ demonstrated CT through project-based learning hands-on activities and problem-solving in a naturalistic environment.

Findings

Results show that heuristics, algorithms and conditional logic were observed more than other components of CT such as data collection, simulations and modeling. Descriptions of common activities in a naturalistic learning environment are presented to illustrate how the students practiced CT over time, which could help readers develop an understanding of CT in conjunction with hands-on problem-solving activities in elementary students. Identifying and classifying CT in this study focused on students’ learning process.

Originality/value

This study contributes to the challenging field of evaluating CT while focusing on observable behaviors and problem-solving activities with various degrees of teacher’s facilitation instead of final artifacts. Implications for researchers and educators interested in integrating CT in K-12 learning and its assessment are discussed.