bluuebunny/crossref_metadata_2025 huggingface dataset:
Cinnamic acid and p-coumaric acid are metabolized to 4-hydroxybenzoic acid byYarrowia lipolytica
Authors: Konzock Oliver , Mohedano Marta Tous , Cibin Irene , Chen Yun , Norbeck Joakim
Published: May 2023

The transition towards a bioeconomy requires the microbial production of various products from renewable resources such as lignocellulosic hydrolysate.Yarrowia lipolyticahas been explored as a potential production host for flavonoid synthesis due to its high tolerance to aromatic acids and ability to supply malonyl-CoA. However, little is known about its ability to consume the precursors cinnamic andp-coumaric acid. In this study, we demonstrate thatY. lipolyticacan consume these precursors through multiple pathways that are partially dependent on the cultivation medium. We constructed a collection of 15 P450 protein knock-out strains to identify the genes responsible for the reaction and identified YALI1_B28430g as the gene encoding for a protein with a trans-cinnamate 4-monooxygenase activity that converts cinnamic acid top-coumaric acid and named it TCM1.p-Coumaric acid in turn is further converted to 4-hydroxybenzoic acid. Our findings provide new insight into the metabolic capabilities ofY. lipolyticaand will be essential for the future construction of better flavonoid production strains.
Applying genomic approaches to identify historic population declines in European forest bats
Authors: Razgour Orly , Montauban Cecilia , Festa Francesca , Whitby Daniel , Juste Javier , Ibáñez Carlos , Rebelo Hugo , Afonso Sandra , Bekaert Michael , Jones Gareth , Williams Carol , Boughey Katherine
Published: May 2023

Anthropogenically-driven environmental changes over the past two centuries have led to severe biodiversity loss, most prominently in the form of loss of populations and individuals. Better tools are needed to assess the magnitude of these wildlife population declines. Anecdotal evidence suggests European bat populations have suffered substantial declines in the past few centuries. However, there is little empirical evidence of these declines that can be used to put more recent population changes into historic context and set appropriate targets for species recovery.

This study is a collaboration between academics and conservation practitioners to develop molecular approaches capable of providing quantitative evidence of historic population changes and their drivers that can inform the assessment of conservation status and conservation management. We generated a genomic dataset for the Western barbastelle,Barbastella barbastellus,a globally Near Threatened and regionally Vulnerable bat species, including colonies from across the species’ British and Iberian ranges. We used a combination of landscape genetics and approximate Bayesian computation model-based inference of demographic history to identify both evidence of population size changes and possible drivers of these changes.

We found that levels of genetic diversity increased and inbreeding decreased with increasing broadleaf woodland cover around the colony location. Genetic connectivity was impeded by artificial lights and facilitated by the combination of rivers and broadleaf woodland cover.

The demographic history analysis showed that both the northern and southern British barbastelle populations have declined by 99% over the past 330-548 years. These declines may have been triggered by loss of large oak trees and native woodlands due to shipbuilding during the early colonial period.

Synthesis and applications.Genomic approaches can be applied to provide a better understanding of the conservation status of threatened species, within historic and contemporary context, and inform their conservation management. This study shows how we can bridge the implementation gap and promote the application of genomics in conservation management through co-designing studies with conservation practitioners and co-developing applied management targets and recommendations.
Orai mediated Calcium entry determines activity of central dopaminergic neurons by regulation of gene expression
Authors: Mitra Rishav , Richhariya Shlesha , Hasan Gaiti
Published: May 2023

Maturation and fine-tuning of neural circuits frequently requires neuromodulatory signals that set the excitability threshold, neuronal connectivity and synaptic strength. Here we present a mechanistic study of how neuromodulator stimulated intracellular Ca2+signals, through the store - operated Ca2+channel Orai, regulate intrinsic neuronal properties by control of developmental gene expression in flight promoting central dopaminergic neurons (fpDANs). The fpDANs receive cholinergic inputs for release of dopamine at a central brain tripartite synapse that sustains flight (Sharma and Hasan, 2020). Cholinergic inputs act on the muscarinic acetylcholine receptor to stimulate intracellular Ca2+release through the endoplasmic reticulum (ER) localised inositol 1,4,5-trisphosphate receptor followed by ER-store depletion and Orai mediated store-operated Ca2+entry (SOCE). Analysis of gene expression in fpDANs followed by genetic, cellular and molecular studies identified Orai-mediated Ca2+entry as a key regulator of excitability in fpDANs during circuit maturation. SOCE activates the transcription factor Trithorax-like (Trl) which in turn drives expression of a set of genes includingSet2, that encodes a histone 3 Lysine 36 methyltransferase (H3K36me3). Set2 function establishes a positive feedback loop, essential for receiving neuromodulatory cholinergic inputs and sustaining SOCE. Chromatin modifying activity of Set2 changes the epigenetic status of fpDANs and drives expression of key ion channel and signaling genes that determine fpDAN activity. Loss of activity reduces the axonal arborisation of fpDANS within the MB lobe, and prevents dopamine release required for maintenance of long flight.

Highlights

Store-operated Ca2+entry (SOCE) through Orai is required in a set of flight-promoting central dopaminergic neurons (fpDANs) during late pupae and early adults to establish their gene expression profile.

SOCE activates a homeobox transcription factor, ‘Trithorax-like’ and thus regulates expression of histone modifiers Set2 andE(z)to generate a balance between opposing epigenetic signatures of H3K36me3 and H3K27me3 on downstream genes.

SOCE drives a transcriptional feedback loop to ensure expression of key genes required for neuronal function including the muscarinic acetylcholine receptor (mAChR) and the inositol 1,4,5-trisphosphate receptor (itpr).

The transcriptional program downstream of SOCE is key to functional maturation of the dopaminergic neurons, enabling their neuronal excitability, axonal arborization and synaptic transmission required for adult flight.
Group BStreptococcusCas9 variants provide insight into programmable gene repression and CRISPR-Cas transcriptional effects
Authors: Gopalakrishna Kathyayini P , Hillebrand Gideon H , Bhavana Venkata H , Elder Jordan L , D’Mello Adonis , Tettelin Hervé , Hooven Thomas A
Published: May 2023

Group BStreptococcus(GBS;S. agalactiae) causes chorioamnionitis, neonatal sepsis, and can also cause disease in healthy or immunocompromised adults. GBS possesses a type II-A CRISPR-Cas9 system, which defends against foreign DNA within the bacterial cell. Several recent publications have shown that GBS Cas9 influences genome-wide transcription through a mechanism uncoupled from its function as a specific, RNA-programmable endonuclease. We examine GBS Cas9 effects on genome-wide transcription through generation of several isogenic variants with specific functional defects. We compare whole-genome RNA-seq from Δcas9GBS with a full-length Cas9 gene deletion;dcas9defective in its ability to cleave DNA but still able to bind to frequently occurring protospacer adjacent motifs; andscas9that retains its catalytic domains but is unable to bind protospacer adjacent motifs. Comparingscas9GBS to the other variants, we identify nonspecific protospacer adjacent motif binding as a driver of genome-wide, Cas9 transcriptional effects in GBS. We also show that Cas9 transcriptional effects from nonspecific scanning tend to influence genes involved in bacterial defense and nucleotide or carbohydrate transport and metabolism. While genome-wide transcription effects are detectable by analysis of next-generation sequencing, they do not result in virulence changes in a mouse model of sepsis. We also demonstrate that catalytically inactive dCas9 expressed from the GBS chromosome can be used with a straightforward, plasmid-based, single guide RNA expression system to suppress transcription of specific GBS genes without potentially confounding off-target effects. We anticipate that this system will be useful for study of nonessential and essential gene roles in GBS physiology and pathogenesis.
Modelling the effect of matrix metalloproteinases in dermal wound healing
Authors: Dari Sonia , Fadai Nabil T. , O’Dea Reuben D.
Published: May 2023

With over 2 million people in the UK suffering from chronic wounds, understanding the biochemistry and pharmacology that underpins these wounds and wound healing is of high importance. Chronic wounds are characterised by high levels of matrix metalloproteinases (MMPs), which are necessary for the modification of healthy tissue in the healing process. Overexposure of MMPs, however, adversely affects healing of the wound by causing further destruction of the surrounding extracellular matrix. In this work, we propose a mathematical model that focuses on the interaction of MMPs with dermal cells using a system of partial differential equations. Using biologically realistic parameter values, this model gives rise to travelling waves corresponding to a front of healthy cells invading a wound. From the arising travelling wave analysis, we observe that deregulated apoptosis results in the emergence of chronic wounds, characterised by elevated MMP concentrations. We also observe hysteresis effects when both the apoptotic rate and MMP production rate are varied, providing further insight into the management (and potential reversal) of chronic wounds.
RAPSYN-Mediated Neddylation of BCR-ABL Alternatively Determines the Fate of Philadelphia Chromosome-positive Leukemia
Authors: Zhao Mengya , Dai Beiying , Li Xiaodong , Zhang Yixin , Qiao Chun , Qin Yaru , Li Zhao , Li Qingmei , Wang Shuzhen , Yang Yong , Chen Yijun
Published: May 2023

Philadelphia chromosome-positive (Ph+) leukemia is a fatal hematological malignancy. Although standard treatments with tyrosine kinase inhibitors (TKI) have achieved remarkable success in prolonging patient survival, intolerance, relapse and TKI resistance remain serious issues for patients with Ph+leukemia. Here, we report a new leukemogenic process in which RAPSYN and BCR-ABL co-occur in Ph+leukemia, and RAPSYN mediates the neddylation of BCR-ABL. Consequently, neddylated BCR-ABL enhances the stability by competing its c-CBL-mediated degradation. Furthermore, SRC phosphorylates RAPSYN to activate its NEDD8 E3 ligase activity, promoting BCR-ABL stabilization and disease progression. Moreover, in contrast toin vivoineffectiveness of PROTAC-based degraders, depletion of RAPSYN expression or its ligase activity decreased BCR-ABL stability and, in turn, inhibited tumor formation and growth. Collectively, these findings represent an alternative to tyrosine kinase activity for the oncoprotein and leukemogenic cells and generate a rationale of targeting RAPSYN-mediated BCR-ABL neddylation for the treatment of Ph+leukemia.
Neural correlates of object identity and reward outcome in the corticohippocampal hierarchy: double dissociation between perirhinal and secondary visual cortex
Authors: Fiorilli J. , Marchesi P. , Ruikes T. , Huis in ‘t Veld G. , Buckton R. , Duque Quintero M. , Reiten I. , Bjaalie J. , Pennartz C.M.A.
Published: May 2023

Neural circuits support behavioral adaptations by integrating sensory and motor information with reward and error-driven learning signals, but it remains poorly understood how these signals are distributed across different levels of the corticohippocampal hierarchy. We trained rats on a multisensory object-recognition task and compared visual and tactile responses of simultaneously recorded neuronal ensembles in somatosensory cortex, secondary visual cortex, perirhinal cortex and hippocampus. The sensory regions primarily represented unisensory information, while hippocampus was modulated by both vision and touch. Surprisingly, secondary visual cortex but not perirhinal neurons coded object-specific information, whereas perirhinal but not visual cortical neurons signaled trial outcome. A majority of outcome-related perirhinal cells responded to a negative outcome (reward omission), whereas a minority of other cells coded positive outcome (reward delivery). Our results support a distributed neural coding of multisensory variables in the cortico-hippocampal hierarchy, with a double dissociation between higher visual cortex and perirhinal cortex in coding of object identity versus feedback on trial outcome.
IL-36/IL-36R Signaling Promotes CD4+ T Cell-Dependent Colitis via Pro-Inflammatory Cytokine Production
Authors: Maarouf Maya , Kuczma Michal , Denning Timothy L.
Published: May 2023

Inflammatory bowel disease (IBD) is a multifactorial, chronic disease that affects approximately 1.5 million people in the United States [1]. It presents with inflammation of the intestine with unknown etiology and its two main forms are Crohn’s disease (CD) and ulcerative colitis (UC). Several important factors are implicated in the pathogenesis of IBD, one being dysregulation of the immune system resulting in the accumulation and stimulation of innate and adaptive immune cells and subsequent release of soluble factors, including pro-inflammatory cytokines. One of these cytokines is a member of the IL-36 cytokine family, IL-36γ, which is overexpressed in human IBD and experimental mouse models of colitis. In this study, we explored the role of IL-36γ in promoting CD4+T cell activation and cytokine secretion. We found that IL-36γ stimulation of naïve CD4+T cells significantly induced IFNγ expressionin vitroand was associated with augmented intestinal inflammationin vivousing naive CD4+cell transfer model of colitis. Using IFNγ-/- CD4+cells, we observed a dramatic decrease in the ability of TNFα production and delayed colitis. This data not only suggests that IL-36γ is a master regulator of a pro-inflammatory cytokine network involving IFNγ and TNFα, but also highlights the importance of targeting IL-36γ and IFNγ as therapeutic approaches. Our studies have broad implications in relation to targeting specific cytokines in human IBD.
Oxidative stress changes interactions between two bacterial species
Authors: Di Martino Rita , Picot Aurore , Mitri Sara
Published: May 2023

Knowing how species interact within microbial communities is crucial to predicting and controlling community dynamics, but interactions can depend on environmental conditions. The stress-gradient hypothesis (SGH) predicts that species are more likely to facilitate each other in harsher environments. Even if the SGH gives some intuition, quantitative modeling of the context-dependency of interactions requires understanding the mechanisms behind the SGH. In this study, we show with both experiments and a theoretical analysis, that varying the con-centration of a single compound, linoleic acid, modifies the interaction between two bacterial species from competitive at a low concentration, to facilitative at higher concentrations where linoleic acid becomes toxic for one of the two species. We demonstrate that the mechanism behind facilitation is that one species is able to reduce Reactive Oxygen Species (ROS) that are produced spontaneously at higher concentrations of linoleic acid, allowing for short-term rescue of the species that is sensitive to ROS and longer coexistence in serial transfers. In our system, competition and facilitation between species can occur simultaneously, and changing the concentration of a single compound can alter the balance between the two.
The novel spore-specific regulator SscA governsAspergillusconidiogenesis
Authors: Son Ye-Eun , Yu Jae-Hyuk , Park Hee-Soo
Published: May 2023

A major group of fungi produces asexual spores (conidia) for propagation and infection. Despite the critical role of conidia, the underlying mechanism of spore formation, integrity, and viability is not fully elucidated. In this study, we have identified and investigated the role of the spore-specific transcription factor (TF) SscA in three representativeAspergillusspecies. Comparative transcriptomic analyses have revealed that 25 TF encoding genes showed higher mRNA levels in conidia than in hyphae in three species. Functional and transcriptomic analyses of the 25 genes have identified SscA as a key TF for conidial formation, maturation, germination, integrity, amino acid production, and secondary metabolism inAspergillus nidulansconidia. Importantly, the roles of SscA are conserved in otherAspergillusspecies. Altogether, our study demonstrates that SscA is a novel spore-specific TF that governs production of intact and functional conidial formation inAspergillusspecies.

Importance

Filamentous fungi produce myriads of asexual spores are main reproductive particles and act as infectious or allergenic agents. Although the serial of asexual sporogenesis is coordinated by various genetic regulators, there remain uncharacterized transcription factors inAspergillus. To understand the underlying mechanism of spore formation, integrity, and viability, we have performed comparative transcriptomic analyses on three representativeAspergillusspecies and found a novel spore-specific transcription factor, SscA. SscA has a major role in conidial formation, maturation and dormancy, and germination inAspergillus nidulans. Transcriptomic data indicate that SscA coordinates conidial wall integrity, amino acid production, and secondary metabolism inA. nidulansconidia. Furthermore, the roles of SscA are conserved in otherAspergillusspecies. Our findings that the novel SscA has broad functions inAspergillusconidia will help to understand conidiogenesis ofAspergillusspecies.
Single Cell Spatial Analysis and Biomarker Discovery in Hodgkin Lymphoma
Authors: Xu Alexander M , Jiang Aixiang , Aoki Tomohiro , Gamboa Alicia , Chong Lauren , Colombo Anthony , Yin Yifan , Lownik Joseph , Takata Katsuyoshi , Hav Monirath , Steidl Christian , Merchant Akil
Published: May 2023

The biology of tumors is suffused with spatial interactions, such as tumor-immune signaling through localized cytokine/ligand secretion, cell-cell contacts, and checkpoint ligand/receptor signaling. Hodgkin Lymphoma (HL) can serve as a study paradigm for tumor microenvironment (TME) architecture as the defining pathological feature is the scarcity of the malignant Hodgkin and Reed Sternberg (HRS) cells, leaving a diverse and predominantly immune cell rich tumor microenvironment (TME) with complex tumor-immune interactions. Previous studies have identified TME features that are prognostic and predictive, however these studies did not consider the entirety of TME cellular ecosystems, including precisely defined immune cell subsets with opposing inflammatory and immune-suppressive effects, as a determinant for differential clinical course of HL patients. Here we use Imaging Mass Cytometry (IMC) with 42 antibody markers to profile tumors from 93 patients with HL. Our cohort consists of relapsed/refractory HL with matched diagnostic and relapsed biopsies, and we present a bioinformatic pipeline to profile 10 major cell lineages and their subtypes including spatial interaction mapping. Our pipeline identifies putative biomarker candidates with a focus on “rosettes” – local aggregates of immune cells around single tumor cells. In addition to validating existing biomarkers centered on CD68+ macrophages, GranzymeB+CD8+ T cells, and others in HL, we propose new biomarkers based on localized interactions between HRS cells and aggregating CD4+ and CD8+ T cells and macrophages involving the immune checkpoints PD1/PDL1, LAG3, and Galectin9. This study serves as a broad tissue imaging resource for multi-timepoint biopsies in HL, and a computational resource and pipeline for users of IMC and other multiplexed imaging studies to perform tissue analysis and biomarker candidate testing with any tissue type.
A mechanistically novel peptide agonist of the IL-7 receptor that addresses limitations of IL-7 cytokine therapy
Authors: Dower William J. , Park Angie Inkyung , Bakker Alice V. , Cwirla Steven E. , Pongtornpipat Praechompoo , Williams Blake M. , Joshi Prarthana , Baxter Bryan A. , Needels Michael C. , Barrett Ronald W.
Published: May 2023

Interleukin (IL)-7 is broadly active on T-cell populations, and modified versions have been clinically evaluated for a variety of therapeutic applications, including cancer, lymphopenia and infectious diseases; and found to be relatively well-tolerated and biologically active. Here we describe novel IL-7R agonists that are unrelated in structure to IL-7, bind to the receptor subunits differently from IL-7, but closely emulate IL-7 biology. The small size, low structural complexity, and the natural amino acid composition of the pharmacologically active peptide MDK1472 allows facile incorporation into protein structures, such as the IgG2-Fc fusion MDK-703. This molecule possesses properties potentially better suited to therapeutic applications than native IL-7 or its derivatives. We compared these compounds with IL-7 for immune cell selectivity, induction of IL-7R signaling, receptor-mediated internalization, proliferation, and generation of immune cell phenotypes in human and non-human primate (NHP) peripheral blood cells in vitro; and found them to be similar in biological activity to IL-7.

In cynomolgus macaques, MDK-703 exhibits a circulating half-life of 46 hr, and produces sustained T-cell expansion characteristic of IL-7 treatment. In the huCD34+-engrafted NSG mouse model of the human immune system, MDK-703 induces an immune cell profile very similar to that generated by IL-7-derived compounds; including the pronounced expansion of memory T-cells, particularly the population of stem-like memory T-cells (Tscm), which may be important for anti-tumor activities reported with IL-7 treatment.

Clinical administration of IL-7 and modified variants has been reported to induce anti-drug antibodies (ADAs), including IL-7 neutralizing antibodies. The novel peptide agonist reported here scores very low in predicted immunogenicity, and because the peptide lacks sequence similarity with IL-7, the problematic immunogenic neutralization of endogenous cytokine should not occur.
Primacy of vision shapes behavioral strategies and neural substrates of spatial navigation in the hippocampus of the common marmoset
Authors: Piza Diego B. , Corrigan Benjamin W. , Gulli Roberto A. , Carmo Sonia Do , Cuello A. Claudio , Muller Lyle , Martinez-Trujillo Julio
Published: May 2023

The mammalian hippocampus has been compared to a Global Positioning System (GPS) that enables spatial navigation. This notion has been primarily drawn from studies conducted in nocturnal mammals, such as rats; that lack many adaptations to daylight vision compared to diurnal primates. Here we demonstrate that during foraging in a 3D maze, the common marmoset, a new world diurnal primate with foveal, stereo-color vision, predominantly uses rapid head-gaze shifts to visually explore their surroundings while remaining stationary, and then minimizes head movements to navigate towards goals. On the other hand, rats, mainly move their head at low velocities while locomoting to explore the environment using their whiskers. These differences in exploration-navigation strategies reflect the species’ sensory adaptations to different ecological niches. In the marmoset hippocampus CA3/CA1 regions putative pyramidal neurons show selectivity for 3D view, head direction, and less for place, but mainly mixed selectivity for combinations of these variables. Despite weak place selectivity, the spatial position of the animal in the maze can be decoded from the activity of small ensembles of mixed selective neurons. Inhibitory interneurons are tuned to 3D angular head velocity and translation speed, with most cells showing mixed selectivity for both variables. Finally, marmosets lack the rhythmic theta oscillations of local field potentials seen during locomotion in rats. Instead, they show resetting of theta oscillations triggered by head-gaze shifts that co-occurred with the activation of inhibitory interneurons, followed by various modulations in the activity of pyramidal cells. Our results show that the marmoset visual exploration/navigation strategies and the hippocampal neuronal specializations supporting them diverge from those observed in rats, reflecting the far-sensing capabilities of the marmoset visual system adapted to diurnal lifestyle.
Macrophage Receptor with collagenous structure (MARCO) recognizes the cellular protein corona formed on environmental particles
Authors: Hirano Seishiro , Kanno Sanae
Published: May 2023

Several difficulties hamper the toxicological evaluation of particulate substancesin vitro. One of the most serious difficulties is that most particles are insoluble in water, and easily agglomerate during the assay. Albumin and some detergents have been used to disperse the particles in the culture medium. However, effects of these additives on the cellular uptake of particles and the following biological consequences are unknown. The first event when phagocytic cells encounter particulate substances is an association of the plasma membrane with the particle surface. Macrophage receptor with collagenous structure (MARCO) has been identified as a receptor for environmental particles such as titanium dioxide (TiO2) and carbonaceous particles. However, it remained to be revealed how MARCO recognizes the unopsonized particles. While investigating the particle surface-cell membrane interaction using GFP-tagged MARCO-expressing cells, we found that cytosolic proteins were released from the cells and rapidly adsorbed on the surface of TiO2particles. The GFP-tagged MARCO-overexpressing cells were further engineered to express RFP-tagged LC3 (cytosolic protein) to visualize adsorption of proteins on the surface of titanium dioxide (TiO2) particles. We found that cytosolic proteins including LC3 were released in the culture medium from intact cells and adsorbed on the particle surface quickly in the cell culture system. These results indicate that MARCO probably recognizes adsorbed intracellular proteins rather than the uncoated inorganic surface of environmental particles.
Genetic profiling andin silicosequence analysis ofCSN2(β-casein) andCSN3(κ-casein) genes in the indian buffalo (Bubalus bubalis)
Authors: Mehra Vinay Kumar , Kumar Satish
Published: May 2023

Buffalo rank second for milk production in the world and play important role in Indian economy. There are four types of caseins α-S1-casein, α-S2-casein, β-casein and κ-casein in milk. The major function of the casein protein in milk is to chelate colloidal calcium phosphate and serves as a major source of amino acids, calcium and phosphate. In buffalo milk all four casein proteins (αs1, αs2, β and κ) are encoded by four closely linked autosomal genes (CSN1S1, CSN1S2, CSN2 and CSN3 respectively) that are present on chromosome 7. Bovine CSN2 (β-casein) gene is 8.5 kb long and contains nine exons and CSN3 (κ-casein) is ∼ 13 kb long. The aim of the study was to characterize CSN2 and CSN3 genes,In-silicoanalysis of β-casein and κ-casein protein and evolutionary relationship with other species. Buffalo mammary gland tissue was collected from local slaughterhouse (New Delhi, India) and total RNA was isolated from Buffalo Mammary Epithelial Cells. The ORF region of CSN2 and CSN3 genes were amplified and sequenced for characterization. Physiochemical properties showed that both buffalo β-casein (Bu_CSN2) and κ-casein (Bu_CSN3) proteins are stable and hydrophobic in nature.The presence of high phosphorylated residues in both β-casein and κ-casein proteins residues suggested that they are involved in signal transduction processes, cell growth and metabolism. The N-glycosylation result showed that both proteins are less in foldable state. The presence of methylation and acetylation sites in both protein revealed that they are involved in different cellular process. The evolutionary analysis showed that both buffalo genes more closely toBos grunniens (yak).
Vaccination withHelicobacter pyloriattachment proteins protects against gastric cancer
Authors: Bugaytsova Jeanna A. , Piddubnyi Artem , Tkachenko Iryna , Rakhimova Lena , Edlund Johan Olofsson , Thorell Kaisa , Marcotte Harold , Lundquist Anders , Schön Karin , Lycke Nils , Suerbaum Sebastian , Schulz Christian , Malfertheiner Peter , Hansen Lori M. , Solnick Jay V. , Moskalenko Roman , Hammarström Lennart , Borén Thomas
Published: May 2023

Most cases of gastric cancer are caused by chronicHelicobacter pyloriinfection, but the lack of early onco-diagnostics and a high risk for antibiotic resistance hampers early intervention through eradication ofH. pyloriinfection by antibiotics. We reported on a protective mechanism whereH. pylorigastric mucosal attachment can be reduced by natural antibodies that block the binding of its attachment protein BabA. Here we show that challenge infection withH. pyloriinduced response of such blocking antibodies in both human volunteers and in rhesus macaques, that mucosal vaccination with BabA protein antigen induced blocking antibodies in rhesus macaques, and that vaccination in a mouse model induced blocking antibodies that reduced gastric mucosal inflammation, preserved the gastric juice acidity, and fully protected the mice from gastric cancer caused byH. pylori.
Combining Low toxic dose Tramadol and smoking is relatively safe unless you stop them: An Animal model evidence of Endoplasmic reticulum stress
Authors: Ghorab Doaa , Abuelrub Ejlal M. , Gharaibeh Mohamed Hamdi , Yehya Alaa , Khasawneh Ramada R , Matalgah Laila M , Helaly Ahmed Mohamed
Published: May 2023

Low toxic doses of tramadol induced animal brain cortex apoptosis and hippocampus injury. Adding nicotine reverted hippocampus pathological changes without triggering brain injury. The expression of CHOP protein in real-time PCR showed mild Endoplasmic reticulum stress (ER) in rats’ brains. Histological, immunohistochemical, and western blotting analysis of CHOP and BIP chaperones demonstrated Endoplasmic reticulum stress in brain and liver tissue samples. Furthermore, the levels of apoptosis and autophagy markers demonstrated a mild increase. Adding Nicotine relatively decreasedbrain and liver ER stress. The combined profile was considerably protective in comparison to administering each drug separately. Mild ER stress is essential for normal cell functions. The blood level of serotonin was high in all study groups with a marked increase in its level when tramadol and nicotine were combined. Low toxic doses of tramadol in combination with nicotine were safe at the reproductive system level which was evaluated by histological examination and animal blood androgen assay. Generally, combining low-dose tramadol with smoking was found to be safe in various animal tissues and organs, however, the high serotonin level in the blood can be critical and associated with a high risk of serious withdrawal and pathological consequences. Serotonin receptor blockers such as olanzapine may increase systemic serotonin levels and need further investigation to utterly pinpoint their roles in managing mood disorders.
Mapping of centriolar proteins onto the post-embryonic lineage ofC. elegans
Authors: Kalbfuss Nils , Berger Antonin , Gönczy Pierre
Published: May 2023

Centrioles, together with the surrounding peri-centriolar material (PCM), constitute the centrosome, a major microtubule-organizing center of animal cells. Despite being critical in many cells for signaling, motility and division, centrioles can be eliminated in some systems, including in the vast majority of differentiating cells during embryogenesis inCaenorhabditis elegans. Whether the cells retaining centrioles in the resulting L1 larvae do so because they lack an activity that eliminates centrioles in the other cells is not known. Moreover, the extent to which centrioles and PCM remain present in later stages of worm development, when all cells but those of the germ line are terminally differentiated, is not known. Here, by fusing cells that lack centrioles with cells that retain them, we established that L1 larvae do not possess a diffusible elimination activity sufficient to remove centrioles. Moreover, analyzing PCM core proteins in L1 larval cells that retain centrioles, we found that some such proteins, but not all, are present as well. Furthermore, we uncovered that foci of centriolar proteins remain present in specific terminally differentiated cells of adult hermaphrodites and males, in particular in the somatic gonad. Correlating the time at which cells were born with the fate of their centrioles revealed that it is not cell age, but instead cell fate, that determines whether and when centrioles are eliminated. Overall, our work maps the localization of centriolar and PCM core proteins in the post-embryonicC. eleganslineage, thereby providing an essential blueprint for uncovering mechanisms modulating their presence and function.
Phototriggered profiling of receptor-proximal proteins in vivo in minutes
Authors: Takato Mikiko , Sakamoto Seiji , Nonaka Hiroshi , Tamura Tomonori , Hamachi Itaru
Published: May 2023

Neurotransmitter receptors are regulated by an extensive and dynamic network of protein-protein interactions. Understanding how these networks control synaptic transmission and give rise to higher-order brain functions necessitates their investigation in the live mammalian brain. However, tools available for this purpose lack the temporal resolution necessary to capture rapid changes in the interactome in live animals and require potentially disruptive genetic modifications to the animal under study. Here, we describe a method for light-activated proximity labelling in the live mouse brain that relies solely on small-molecule reagents and achieves a minute-order temporal resolution. Named PhoxID (photooxidation-driven proximity labelling for protein identification), this method involves selectively tethering a chemical photosensitiser to neurotransmitter receptors of interest and enabled us to identify characteristic as well as less studied interactors of the endogenous α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and the ψ-aminobutyric acid type A receptor (GABAAR) with just minutes of in-brain green light irradiation. Furthermore, PhoxID’s temporal precision allowed us to capture molecular snapshots of the AMPAR-proximal proteome in the postnatal developing cerebellum, leading to the discovery of age-dependent shifts. Overall, this work establishes a highly flexible and generalisable platform to study receptor interactomes and proximal microenvironments in genetically intact specimens with an unprecedented temporal resolution.
RNA Targets and Physiological Role of Topoisomerase 3β
Authors: Teimuri Shohreh , Suter Beat
Published: May 2023

Topoisomerase 3β (Top3β) works not only on DNA but also RNA. We isolated and identified the naturally cross-linked RNA targets of Drosophila Top3β from an early embryonic stage that contains almost exclusively maternal mRNAs. Favorite targets were longer RNAs, RNAs with many splice sites, and RNAs that become localized in large cells. Demonstrating the importance of its enzymatic activity, Top3β without the hydroxyl group that makes the covalent bond to the RNA, did not allow normal expression and subcellular localization of tested gene products of the identified targets.Top3βis not essential for development to the adult stage but to maintain the morphology of the neuromuscular junction in adult flies and to prevent premature loss of coordinated movement and aging. Alterations in humanTop3βhave been associated with several neurological diseases and cancers. The homologs of genes and (pre)mRNAs mis-expressed in these conditions show the same characteristics identified in the DrosophilaTop3βtargets, suggesting that Drosophila could model the function of humanTop3β. Indeed, anin vivotest of this model showed that the enzymatic activity of Top3β reduces the neurodegeneration caused by the human (G4C2)49RNA. Together, these studies show thatTop3βplays important roles in normal gene expression, particularly for large genes and long and complex transcripts that need to be transported and translationally controlled. Its absence stresses the cells, seemingly increasing the chances of contracting various neuronal and neurodegenerative diseases and cancers.
Changes in the Type 2 diabetes gut mycobiome associate with metformin treatment across populations
Authors: Syoc Emily Van , Nixon Michelle Pistner , Silverman Justin D. , Luo Yuhong , Gonzalez Frank J. , Elbere Ilze , Klovins Janis , Patterson Andrew D. , Rogers Connie J. , Ganda Erika
Published: May 2023

The human gut teems with a diverse ecosystem of microbes, yet non-bacterial portions of that community are overlooked in studies of metabolic diseases firmly linked to gut bacteria. Type 2 diabetes mellitus (T2D) associates with compositional shifts in the gut bacterial microbiome and fungal mycobiome, but whether T2D and/or pharmaceutical treatments underpin the community change is unresolved. To differentiate these effects, we curated a gut mycobiome cohort to-date spanning 1,000 human samples across 5 countries and a murine experimental model. We use Bayesian multinomial logistic normal models to show that metformin and T2D both associate with shifts in the relative abundance of distinct gut fungi. T2D associates with shifts in the Saccharomycetes and Sordariomycetes fungal classes, while the generaFusariumandTetrapisiporamost consistently associate with metformin treatment. We confirmed the impact of metformin on individual gut fungi by administering metformin to healthy mice. Thus, metformin and T2D account for subtle, but significant and distinct variation in the gut mycobiome across human populations. This work highlights for the first time that oral pharmaceuticals can confound associations of gut fungi with T2D and warrants the need to consider pharmaceutical interventions in investigations of linkages between metabolic diseases and gut microbial inhabitants.
Prenatal experience with language shapes the brain
Authors: Mariani Benedetta , Nicoletti Giorgio , Barzon Giacomo , Ortíz Barajas María Clemencia , Shukla Mohinish , Guevara Ramón , Suweis Samir Simon , Gervain Judit
Published: May 2023

Human infants acquire language with striking ease compared to adults, but the neural basis of their remarkable brain plasticity for language remains little understood. Applying a scaling analysis of neural oscillations for the first time to address this question, we show that newborns’ electrophysiological activity exhibits increased long-range temporal correlations after stimulation with speech, particularly in the prenatally heard language, indicating the early emergence of brain specialization for the native language.
Synthesis and crystal structure of bis(2-phthalimidoethyl)ammonium chloride dihydrate
Authors: Young Barry S. , Lee Jamie L. , Gembicky Milan , Bailey Jake , Smith Gary L. N.
Published: May 2023

The title compound {systematic name: bis[2-(1,3-dioxoisoindol-2-yl)ethyl]azanium chloride dihydrate}, C20H18N3O4
+·Cl−·2H2O, is a phthalimide-protected polyamine that was synthesized by a previous method. It was characterized by ESI–MS, 1H NMR, and FT–IR. Crystals were grown from a solution of H2O and 0.1 M HCl. The central nitrogen atom is protonated and forms hydrogen bonds with the chloride ion and a water molecule. The two phthalimide units make a dihedral angle of 22.07 (3)°. The crystal packing features a hydrogen-bond network, two-coordinated chloride, and off-set π–π stacking.
What are the key factors of enterprises' greenwashing behaviors under multi-agent interaction? A grey-DEMATEL analysis from Chinese construction materials enterprises
Authors: Li Xingwei , Li Jingru , He Jinrong , Huang Yicheng , Liu Xiang , Dai Jiachi , Shen Qiong
Published: May 2023

Purpose

The surging market demand for green construction materials has brought opportunities for construction materials enterprises' greenwashing behavior (GWB). This study aims to establish the causal relationship among the influencing factors of GWB and reveal the key influencing factors from the perspective of Chinese construction materials enterprises under multi-agent interactions.

Design/methodology/approach

This study is based on stakeholder theory, resource-based theory and the green development behavior and performance of industrial enterprises (GDBP-IE). First, with the literature analysis, an index framework of the influencing factors of enterprises' GWB was constructed from five dimensions (including 15 factors): environmental regulation, public scrutiny, market environment, corporate resources and corporate green development (GD) performance. Second, the interactive relationship among influencing factors was obtained by a questionnaire survey. Finally, the data are processed and analyzed with the grey-DEMATEL (Decision-making Trial and Evaluation Laboratory) method.

Findings

Among the factors, corporate information transparency has the greatest impact on the other factors, and consumer green preferences are most influenced by others. The most critical and important factor is the corporate social performance factor. In China, corporate social performance, corporate information transparency, corporate size and media supervision are the key factors influencing the GWB of construction materials enterprises.

Originality/value

This study provides a new perspective on the literature related to GWB by considering multi-agent interactions and extends the evidence from the construction materials industry for research on the drivers or influencing factors of enterprises' bad environmental behavior. Furthermore, it adds insights from China for further research on the governance strategies of GWB in other countries.
Perception of sponge city for achieving circularity goal and hedge against climate change: a study on Weibo
Authors: Zeng Liyun , Li Rita Yi Man , Zeng Huiling , Song Lingxi
Published: May 2023

Purpose

Global climate change speeds up ice melting and increases flooding incidents. China launched a sponge city policy as a holistic nature-based solution combined with urban planning and development to address flooding due to climate change. Using Weibo analytics, this paper aims to study public perceptions of sponge city.

Design/methodology/approach

This study collected 53,586 sponge city contents from Sina Weibo via Python. Various artificial intelligence tools, such as CX Data Science of Simply Sentiment, KH Coder and Tableau, were applied in the study.

Findings

76.8% of public opinion on sponge city were positive, confirming its positive contribution to flooding management and city branding. 17 out of 31 pilot sponge cities recorded the largest number of sponge cities related posts. Other cities with more Weibo posts suffered from rainwater and flooding hazards, such as Xi'an and Zhengzhou.

Originality/value

To the best of the authors’ knowledge, this study is the first to explore the public perception of sponge city in Sina Weibo.
Linking employees’ challenge-hindrance appraisals toward AI to service performance: the influences of job crafting, job insecurity and AI knowledge
Authors: He Changqing , Teng Rongrong , Song Jun
Published: May 2023

Purpose

This study aims to explore the associations linking employees’ challenge-hindrance appraisals toward artificial intelligence (AI) to service performance while considering the dual mediating roles of job crafting and job insecurity, as well as the moderating role of AI knowledge.

Design/methodology/approach

A survey was administered to a sample of 297 service industry employees. This study examined all the hypotheses with Mplus 8.0.

Findings

This study confirms that challenge appraisal toward AI has an indirect positive influence on service performance via job crafting (motivation process), whereas hindrance appraisal toward AI has an indirect negative influence on service performance via job insecurity (strain process). Meanwhile, AI knowledge, serving as a key personal resource, could strengthen the positive impacts of challenge appraisal toward AI on job crafting and of hindrance appraisal toward AI on job insecurity.

Practical implications

Organizational decision-makers should first survey employees’ appraisals toward AI and then adopt targeted managerial strategies. From the perspective of service industry employees, employees should adopt proactive coping strategies and enrich their knowledge of AI to meet the challenges brought by this technology.

Originality/value

The primary contribution of this study is that we enrich the literature on AI by exploring the dual mediators (i.e. job crafting and job insecurity) through which AI awareness affects service performance. Moreover, this study advances our understanding of when appraisals toward AI influence job outcomes by identifying the moderating role of AI knowledge.
Local government's failure to recover loans from groups of women, youth, and people with disabilities in Tanzania
Authors: Rugeiyamu Rogers
Published: May 2023

Purpose

The purpose of this study is to assess reasons behind experienced challenges by local government authorities (LGAs) in operating Women, Youth and People with Disabilities Fund (WYDF) in Tanzania. Specifically, it assesses the reasons behind failures to recover loan by LGAs and groups of Women, Youth and People with Disability (WYPWD).

Design/methodology/approach

The qualitative approach was recruited in this study involving Tunduru District Council as a case study. Data were collected through Interviews, Focus Group Discussion and Documentary Review. Interviews were administered to Community Development Officers (CDOs) while FGD to WYPWD groups. Reviewed documents include laws, regulations and publications on social development funds. Data were analyzed using content analysis approach and backed up by quotations during presentation.

Findings

Failures to recover loans from beneficiaries is attributed to weaknesses of both groups and LGAs. LGAs suffer from lack of capability to manage the fund, poor governance practices and misuse of public funds, and groups lack awareness of the fund's goals.

Research limitations/implications

Due to experienced challenges, efforts by groups and LGAs to reclaim loan have been unsuccessful, which has prevented the fund from achieving its goals.

Practical implications

The central government should concentrate on ongoing LGAs capacity building so that they can successfully handle the fund, it is advised for improvement. Again, LGAs should establish an information system linked with groups to track their projects implementation. Once more, groups should be informed about the purpose of creating the fund and the advantages of the loan to them and to local economic development (LED). Furthermore, groups need entrepreneurial abilities to be able to participate in businesses that they can manage. Moreover, organizations should receive ongoing education so that they may repay the loan voluntarily.

Social implications

Community awareness on the aims of the fund should be provided to impact LED.

Originality/value

Recommendations given can be applied by other developing countries struggling to uplift citizens economically through social development funds.