bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging Intra- and Extracellular Conductivity using MR based Conductivity Tensor Imaging
Authors: Rana Neha , Katoch Nitish 
Published: July 2024

AbstractImaging electrical conductivity may reveal relationships between biological tissues, cellular structures, and physiological processes. Biological tissues are primarily composed of major ions such as Na+ and K+, with varying concentrations and mobility within the cellular structures. These tissues consist of intracellular and extracellular fluids separated by cell membranes, and their electrical conductivity can be expressed as a function of ion concentration and mobility. This study introduces Conductivity Tensor Imaging (CTI) to independently reconstruct the electrical conductivity of intra- and extracellular compartments in biological tissues using MRI. We validated this method using a conductivity phantom with three compartments filled with electrolytes and/or giant vesicle suspensions. These vesicles mimic cell-like materials with thin insulating membranes, providing a realistic model for cellular structures. Measurements showed that high-frequency conductivity closely matched low-frequency conductivity in normal electrolytes. However, in the giant vesicle compartment, the conductivity of extracellular (EC) and intracellular (IC) regions correlated with cell volume fraction. In vivo human brain imaging using CTI revealed significant EC and IC conductivity variations across different brain regions, corresponding to underlying cellular compositions and structures. CTI introduces a novel MR contrast mechanism to distinctly measure IC and EC conductivities. Our findings highlight the potential of CTI to enhance our understanding of brain microstructure and its physiological processes through detailed conductivity mapping. This method signifies a notable advancement in non-invasive imaging, providing novel insights into the electrical properties of biological tissues and their implications for biophysical properties.
Aedes aegypti VLG-1challenges the assumed antiviral nature ofVagogenes
Authors: Couderc Elodie , Crist Anna B. , Daron Josquin , Varet Hugo , van Hout Femke A. H. , Miesen Pascal , Palatini Umberto , Dabo Stéphanie , Vial Thomas , Lambrechts Louis , Merkling Sarah H. 
Published: July 2024

ABSTRACTArthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, theAedes aegyptimosquito. In arthropods, genes of theVagofamily are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role ofVagogenes upon virus infection inAe. aegyptiis largely unknown. We conducted a phylogenetic analysis of theVagogene family in Diptera, which led us to focus on aVago-like gene that we namedVLG-1. Using CRISPR/Cas9-mediated gene editing, we generated aVLG-1mutant line ofAe. aegypti, which revealed a broad impact ofVLG-1on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of theVLG-1mutant line indicated a modest proviral role for this gene during DENV and ZIKV infectionsin vivo. In the absence ofVLG-1, virus dissemination throughout the mosquito’s body was slightly impaired, albeit not altering virus transmission rates. Our results challenge the conventional understanding ofVago-like genes as antiviral factors and underscore the need for furtherin vivoresearch to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.
Phosphodiesterase 3 inhibitors boost bone outgrowth
Authors: Kawabe Takaaki , Ichimura Atsuhiko , Yasue Tomoki , Li Jianhong , Kim Ga Eun , Ishikawa Haruki , Uda Yohei , Ito Hiromu , Nishi Miyuki , Takeshima Hiroshi 
Published: July 2024

ABSTRACTC-type natriuretic peptide (CNP) stimulates skeletal growth by acting on the growth plates of long bones, and a CNP variant is clinically used for achondroplasia treatment. We previously reported that CNP stimulates the autonomic Ca2+influx mediated by TRPM7 channels in growth plate chondrocytes to facilitate extracellular matrix synthesis for bone growth. Here, we report that phosphodiesterase 3 (PDE3) inhibitors facilitate the Ca2+influx and promote bone outgrowth. The representative PDE3 inhibitor cilostazol elevated cGMP levels and activated cell-surface K+channels probably due to protein kinase G-mediated phosphorylation in growth-plate chondrocytes. The resulting hyperpolarization likely facilitated TRPM7-mediated Ca2+influx by increasing the Ca2+-driving force. Moreover, cilostazol simulated the elongation of cultured bones and enlarged the body size of juvenile mice. Several PDE3 inhibitors have been used for clinical treatment of thrombosis, heart failure and asthma, while our observations suggest that the repositioning of PDE3 inhibitors would provide novel medications for syndromes involving short stature.
Characterisation of aphid antixenosis in aphid-resistant ancestor wheat,Triticum monococcum
Authors: Borg Alexander N. , Vuts József , Caulfield John C. , Withall David M. , Foulkes M. John , Birkett Michael A 
Published: July 2024

AbstractBACKGROUNDDue to the increasing presence of insecticide resistance across cereal aphid populations, new aphid management strategies, including the engineering of host resistance to aphids into commercial wheat varieties, are required. Previous studies have identified ancestor wheat,Triticum monococcumaccessions MDR045 and MDR049, with resistance against the grain aphid,Sitobion avenae. To test the hypothesis that resistance can be accounted for by antixenosis (reduced attractiveness of host plants)viathe release of repellent volatile organic compounds (VOCs), we explored the response ofS. avenaeto MDR045 and MDR049 followingS. avenaeherbivory, using behaviour and electrophysiology experiments.RESULTSIn four-arm olfactometry assays, alateS. avenaeshowed aphid-density dependent reduced preference to VOC extracts fromT. monococcumMDR045 and MDR049. By contrast, alateS. avenaeshowed aphid-density dependent increased preference to extracts from hexaploid wheat,T. aestivumvar Solstice andT. monococcumMDR037. Coupled gas chromatography-electroantennography (GC- EAG), using the antennae of alateS. avenae, located 24 electrophysiologically active compounds across all tested accessions. Synthetic blends created from 21 identified EAG-active compounds confirmed bioactivity of corresponding VOC extracts in four-arm olfactometry assays against alateS. avenae.CONCLUSIONOur data suggest that resistance ofT. monococcumMDR045 and MDR049 toS. avenaecan be at least partially accounted for by antixenosis, through antennal perception of specific repellent VOC blends induced byS. avenaefeeding behaviour.
Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors
Authors: Astarloa-Pando Gabirel , Polanco-Alonso Diego , Sandá Víctor , Orrantia Ane , Amarilla-Irusta Ainhoa , Pérez-Fernández Silvia , Pérez-Garay Raquel , Sevilla Arrate , Lopez-Pardo Ainara , Tijero Aritz , Úriz José J. , Rey Mercedes , Astigarraga Itziar , Manzanares-Martin Bárbara , Bediaga Naiara G. , Amo Laura , Zenarruzabeitia Olatz , Borrego Francisco 
Published: July 2024

SUMMARYEarly immune reconstitution after autologous hematopoietic stem cell transplantation (autoHSCT) is associated with a better outcome in a variety of cancers. NK cells constitute the first lymphocyte subset to recover in the blood after autoHSCT. We have in-depth characterized them in pediatric patients with different tumors and found that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, were more immature and activated, and exhibited an increased expression of inhibitory receptors, while activating receptors levels were diminished. This activated and decidual-like phenotype was characterized by increased CD56, CD9, CD49a, CD151, CD38, HLA-DR and CD55 expression. We also determined plasma levels of several cytokines and found that their concentrations were associated with the observed changes in NK cells phenotype.In vitroexperiments, including flow cytometry and single-cell RNA sequencing (scRNA-seq), recapitulated the changes observed in NK cells early after autoHSCT. Specifically, results revealed that the combination of IL-15 and TGF-β induced, at least partially, this distinctive phenotype on NK cells after autoHSCT. Finally, we have observed a positive correlation between relapse and the percentage of CD56dimNK cells shortly after autoHSCT in our cohort of pediatric patients. Altogether, our work is of relevance to understand the physiopathology of NK cells during the immune system reconstitution after autoHSCT in children and potentially help in the management of these patients.
Upregulation of a nonsense mediated decay (NMD) insensitive CFTR mRNA isoform has therapeutic potential for the treatment of 3’ CFTR PTC variants
Authors: Allaire Normand E. , Armstrong Mathew , Yoon Jae Seok , Bhatt Priyanka , Harrington Jan , Cheng Yi , Valley Hillary , Macadino Caitlin , Bihler Hermann , Sivachenko Andrey , Mense Martin , Cotton Calvin 
Published: July 2024

AbstractBackgroundNonsense or Premature Termination Codon (PTC) mutations of theCFTRgene are pathogenic and found in ∼10% of North American people with cystic fibrosis. PTC mutations induce Nonsense-Mediated mRNA Decay (NMD), leading to a substantial (∼80-90%) reduction in full-length mRNA. This reduction is a key contributor to PTC mutation-related pathology. Various approaches to evade NMD and preserve the impacted mRNA transcript have been explored but have not progressed to clinical development, leaving NMD a significant hurdle for PTC readthrough therapy.MethodsAntisense oligonucleotides (ASOs) were tiled across intron 22 splice donor (SD) and acceptor (SA) sites of theCFTRgene. Immortalized airway cells were treated with SD and SA ASOs, and those yielding the greatest increase in aCFTRNMD-insensitive mRNA isoform (e22 trunc mRNA) were tested in combinations. Top SD/SA ASO pairs were assessed for their impact on e22 trunc mRNA via ddPCR, e22 trunc protein via western blot, and CFTR-mediated chloride (Cl-) transport via transepithelial electrophysiological measurements in immortalized and primary human bronchial epithelial (hBE) cell cultures.ResultsWe demonstrate that e22 trunc mRNA generates a truncated CFTR protein whose Cl-transport function can be enhanced with elexacaftor/tezacaftor/ivacaftor (ETI) treatment. ASO and ETI treatment in combination restore ∼20% and 25% of wild-type CFTR Cl-transport function in immortalized epithelial and primary hBE cells homozygous forCFTRW1282X, respectively.ConclusionsThis study lays the groundwork for advancing ASO-mediated upregulation of e22 trunc mRNA and protein as a therapeutic approach for cystic fibrosis caused by 3’-terminalCFTRPTC mutations.
PENGUIN: A rapid and efficient image preprocessing tool for multiplexed spatial proteomics
Authors: Sequeira A. M. , Ijsselsteijn M. E. , Rocha M. , de Miranda Noel F.C.C. 
Published: July 2024

AbstractMultiplex spatial proteomic methodologies can provide a unique perspective on the molecular and cellular composition of complex biological systems. Several challenges are associated to the analysis of imaging data, in particular regarding the normalization of signal-to-noise ratios across images and background noise subtraction. However, straightforward and user-friendly solutions for denoising multiplex imaging data that are applicable to large datasets are still lacking. We have developed PENGUIN –Percentile Normalization GUI Image deNoising: a rapid and efficient image preprocessing tool for multiplexed spatial proteomics. In comparison to existing approaches, PENGUIN stands out by eliminating the need for manual annotation or machine learning model training. It effectively preserves signal intensity differences and reduces noise, thereby enhancing downstream tasks like cell segmentation and phenotyping. PENGUIN’s simplicity, speed, and user-friendly interface, deployed both as script and as a Jupyter notebook, facilitate parameter testing and image processing. We illustrate the effectiveness of PENGUIN by comparing it with conventional image processing techniques and solutions tailored for multiplex imaging data. This comparison underscores PENGUIN’s capability to produce high-quality imaging data efficiently and consistently.
Dsg2 truncation causes a lethal barrier breakdown in mice
Authors: Kugelmann Daniela , Butz Elisabeth S. , Ponce Alexander Garcia , Radeva Mariya Y. , Neubauer Jessica , Hiermaier Matthias , Siadjeu Christian , Burkard Natalie , Egu Desalegn , Horn Anja K. E. , Schmitz Christoph , Vuopala Katri S. , Kuismin Outi , Schlegel Nicolas , Waschke Jens 
Published: July 2024

AbstractInflammatory bowel diseases (IBD) such as Crohn’s disease (CD) have a complex aetiology with alterations of both the intestinal epithelial barrier and the IL23/IL17 immune response. Here, we investigated the role of a novel mutation in the desmosomal cadherin desmoglein 2 gene (DSG2) in the pathogenesis of IBD. DSG2 is known to regulate intestinal epithelial barrier integrity. Genetic analysis of a CD patient revealed a novel likely pathogenicDSG2mutation leading to a truncated protein lacking part of the intracellular domain. We generated an enterocyte-specific mouse model, recapitulating the human mutation to study how the cytoplasmic truncation ofDsg2affects intestinal barrier properties systemically. Moreover, we analysed the intestinal genetic profile in these mice and compared it to IBD patients. We describe a first CD patient with a rare mutation in theDSG2gene causing cytoplasmic truncation with affects Dsg2 mobility. Mice with enterocyte-specific Dsg2 truncation suffered from a lethal intestinal barrier defect and presented a skewed IL17 response similar to CD patients. We identified the desmosomal cadherin Dsg2 as a regulator of the skewed IL17 response. These data indicate that desmosomes regulate inflammation similar to psoriasis which explains why the same novel immune therapies are effective for both diseases.
The Soybean Cyst Nematode Effector Cysteine Protease 1 (CPR1) Targets a Mitochondrial Soybean Branched-Chain Amino Acid Aminotransferase (GmBCAT1) for Degradation
Authors: Margets Alexandra , Foster Jessica , Kumar Anil , Maier Tom R. , Masonbrink Rick , Mejias Joffrey , Baum Thomas J. , Innes Roger W. 
Published: July 2024

AbstractThe soybean cyst nematode (SCN;Heterodera glycines) facilitates infection by secreting a repertoire of effector proteins into host cells to establish a permanent feeding site composed of a syncytium of root cells. Among the diverse proteins secreted by the nematode, we were specifically interested in identifying proteases to pursue our goal of engineering decoy substrates that elicit an immune response when cleaved by an SCN protease. We identified a cysteine protease that we named Cysteine Protease 1 (CPR1), which was predicted to be a secreted effector based on transcriptomic data obtained from SCN esophageal gland cells, presence of a signal peptide, and lack of transmembrane domains. CPR1 is conserved in all isolates of SCN sequenced to date, suggesting it is critical for virulence. Transient expression of CPR1 inNicotiana benthamianaleaves suppressed cell death induced by a constitutively active nucleotide binding leucine-rich repeat protein, RPS5, indicating that CPR1 inhibits effector-triggered immunity. CPR1 localizes in part to the mitochondria when expressedin planta. Proximity-based labeling in transgenic soybean roots, co-immunoprecipitation, and cleavage assays identified a branched-chain amino acid aminotransferase from soybean (GmBCAT1) as a substrate of CPR1. Silencing of theCPR1transcript in the nematode reduced penetration frequency in soybean roots while the expression ofCPR1in soybean roots enhanced susceptibility. Our data demonstrates that CPR1 is a conserved effector protease with a direct target in soybean roots, highlighting it as a promising candidate for decoy engineering.
Comparison of Conventional Cytomorphology, Automated Cell Counting, and FTIR Spectroscopy for Detection of CNS Involvement in Acute Leukaemia
Authors: esohe lasaki abiodun , ADEGBE Samson 
Published: July 2024

AbstractBackgroundThe incidence of central nervous system (CNS) involvement in pediatric leukemia patients presents significant diagnostic challenges. This study compares the diagnostic capabilities of Fourier Transform Infrared (FTIR) Spectroscopy with conventional cytomorphology and automated cell counting to detect CNS involvement in pediatric leukemia.MethodsA cohort of pediatric patients diagnosed with leukemia was assessed at Altınbaş University Medical Park Hospital. Cerebrospinal fluid (CSF) samples were analyzed using FTIR spectroscopy and compared with outcomes from conventional cytomorphology and automated cell counting to evaluate diagnostic efficacy and accuracy.ResultsFTIR spectroscopy demonstrated a higher sensitivity in detecting biochemical markers of CNS involvement than conventional methods. Distinct spectral profiles enabled the identification of specific biochemical changes associated with CNS leukemia.ConclusionsFTIR spectroscopy offers a promising alternative to traditional diagnostic methods, providing rapid, non-invasive, and accurate detection of CNS involvement, which is crucial for timely and effective treatment of pediatric leukemia.
Multiomics data analysis identifies TM4SF4 as a cell surface target in hepatocellular carcinoma
Authors: Wong Kah Keng , Ab. Hamid Suzina Sheikh 
Published: July 2024

ABSTRACTThe clinical application of cellular immunotherapy in hepatocellular carcinoma (HCC) is impeded by the lack of a cell surface target frequently expressed in HCC cells and with minimal presence in normal tissues to reduce on-target, off-tumor toxicity. In thisin silicoanalysis, a longlist of genes (n=12,948) expressed in HCCs according to The Human Protein Atlas database were examined. The aim was to identify the optimal cell surface target, without being shed into circulation, in HCCs and with restrictive expression profile in other normal human tissues. A total of eight genes were shortlisted and they were subsequently ranked according to the combination of their transcript and protein expression levels in HCC cases (n=791) derived from four independent datasets (TCGA, CNHPP, GSE14520, and CHCC). TM4SF4 was the top-ranked target with the highest expression in HCCs. TM4SF4 demonstrated more favorable expression profile with significantly lower expression in normal human tissues but more highly expressed in HCC cases compared with seven other common HCC therapeutic targets. Furthermore, scRNA-seq (GSE149614 and GSE134355) and immunohistochemistry (HPA) datasets showed that TM4SF4 was absent in immune cell populations but highly expressed in the bile duct canaliculi of hepatocytes, a region that is inaccessible to immune cells. In scRNA-seq dataset of HCCs (GSE149614),TM4SF4expression was positively associated with mitochondrial components and oxidative phosphorylation Gene Ontologies in HCC cells (n=15,787 cells), suggesting its potential roles in mitochondrial-mediated oncogenic effects in HCC. Taken together, TM4SF4 is proposed as a promising cell surface target in HCC.
EFL-3/E2F7 modulates Wnt signalling through repressing the LIT-1 Nemo-like kinase during asymmetric epidermal cell division inCaenorhabditis elegans
Authors: Ferrando-Marco Mar , Barkoulas Michalis 
Published: July 2024

AbstractThe E2F family of transcription factors is conserved in higher eukaryotes and plays pivotal roles in controlling gene expression during the cell cycle. Most canonical E2Fs associate with members of the Dimerisation Partner (DP) family to activate or repress target genes. However, atypical repressors, such as E2F7 and E2F8, lack DP interaction domains and their functions are less understood. We report here that EFL-3, the E2F7 homologue ofC. elegans, regulates epidermal stem cell differentiation. We show that phenotypic defects inefl-3mutants depend on the Nemo-like kinaselit-1.EFL-3 represseslit-1expression through direct binding to alit-1intronic element. Increased LIT-1 expression inefl-3mutants reduces POP-1/TCF nuclear distribution, and consequently alters Wnt pathway activation. Our findings provide a mechanistic link between an atypical E2F family member and NLK duringC. elegansasymmetric cell division, which may be conserved in other animals.HighlightsEFL-3 is enriched in anterior daughter cells following asymmetric seam cell division.efl-3mutants show defects in cell differentiation and seam cell fate maintenance.EFL-3 directly represseslit-1/NLK expression.EFL-3-mediatedlit-1repression alters POP-1 nuclear levels, linking EFL-3 to Wnt signalling.
Responses to visual motion of neurons in the extrastriate visual cortex of macaque monkeys with experimental amblyopia
Authors: Van Grootel Tom J. , Raghavan R. T. , Kelly Jenna G. , Movshon J. Anthony , Kiorpes Lynne 
Published: July 2024

AbstractAmblyopia is a developmental disorder that results from abnormal visual experience in early life. Amblyopia typically reduces visual performance in one eye. We studied the representation of visual motion information in area MT and nearby extrastriate visual areas in two monkeys made amblyopic by creating an artificial strabismus in early life, and in a single age-matched control monkey. Tested monocularly, cortical responses to moving dot patterns, gratings, and plaids were qualitatively normal in awake, fixating amblyopic monkeys, with primarily subtle differences between the eyes. However, the number of binocularly driven neurons was substantially lower than normal; of the neurons driven predominantly by one eye, the great majority responded only to stimuli presented to the fellow eye. The small population driven by the amblyopic eye showed reduced coherence sensitivity and a preference for faster speeds in much the same way as behavioral deficits. We conclude that, while we do find important differences between neurons driven by the two eyes, amblyopia does not lead to a large scale reorganization of visual receptive fields in the dorsal stream when tested through the amblyopic eye, but rather creates a substantial shift in eye preference toward the fellow eye.
Evolutionarily conserved principles of ESCRT-III-mediated membrane remodelling revealed by a two-subunit Asgard archaeal system
Authors: Souza Diorge P. , Espadas Javier , Chaaban Sami , Moody Edmund R. R. , Hatano Tomoyuki , Balasubramanian Mohan , Williams Tom A. , Roux Aurélien , Baum Buzz 
Published: July 2024

SummaryESCRT-III proteins assemble into composite polymers that undergo stepwise changes in composition and structure to deform membranes across the tree of life. Here, using a phylogenetic analysis we demonstrate that the two ESCRT-III proteins present in our closest archaeal relatives are evolutionarily related to B-type and A-type eukaryotic paralogues, which initiate and execute membrane remodelling, respectively. This deep homology is reflected in ESCRT-III structure and function as demonstrated by the fact that ESCRT-IIIB assembles into parallel arrays on planar membranes to initiate membrane deformation, and is required to recruit ESCRT-IIIA to generate composite polymers. ESCRT-IIIA homopolymers can then remodel membranes into tubes, as a likely prelude to scission. Taken together, this analysis reveals a set of conserved principles governing ESCRT-III-dependent membrane remodelling that first emerged with the evolution of a two-component ESCRT-III system in the Asgard archaea, and which continue to underlie complex multi-component, ESCRT-III-dependent membrane remodelling in eukaryotes.