bluuebunny/crossref_metadata_2025_split huggingface dataset:
ReDis: efficient metagenomic profiling via assigning ambiguous reads
Authors: Song Chun , Guo Zule , Gu Ju , Ren Yong , Guo Hao , Liu Junfeng 
Published: August 2023

AbstractSummaryMetagenomic profiling is one of the primary means of microbiome analysis, which includes classification of sequencing reads and quantification of their relative abundances. Although mang methods have been developed for metagenomic profiling, metagenomic profiling remains challenges on striking a delicate balance between accuracy and runtime as well as assigning the ambiguous reads. Here, we present a novel method, named ReDis, to overcome the above issues. ReDis combines Kraken2 with Minimap2 for aligning sequencing reads against a reference database with hundreds of gigabytes (GB) in size accurately within feasible time, and then uses a novel statistical model to assign the ambiguous reads for producing accurate abundance estimates. In contrast to the popular Kraken2+Bracken, ReDis improved the accuracy of abundance estimation on simulated reads from two highly similar genomes:Escherichia coliandShigella flexneri.Contacth.guo@foxmail.comorjlsljf0101@126.com
WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury
Authors: Liu Yu , Zhao Zongren , Zheng Jinyu 
Published: August 2023

AbstractBackgroundTraumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. However, there are no sensitive diagnostic or prognostic biomarkers to identify TBI, which leads to long-term consequences. In this study, we aim to identify genes that contribute to brain injury and to identify potential mechanisms for its progression in the early stages.MethodFrom the Gene Expression Omnibus (GEO) database, we downloaded GSE2871’s gene expression profiles. Weighted gene coexpression network analyses (WGCNA) were conducted on differentially expressed genes (DEGs), and the DEGs were analyzed by Gene Set Enrichment Analysis(GSEA). An enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed for understanding the biological functions of genes. The potential biomarkers were identified using 3 kinds of machine learning algorithms. Nomogram was constructed using the “rms” package. And the receiver operating characteristic curve (ROC) was plotted to detect and validate our prediction model sensitivity and specifificity.ResultsBetween samples with and without brain injury, 107 DEGs were identified, including 47 upregulated genes and 60 downregulated genes. On the basis of WGCNA and DEGs, 97 target genes were identified. In addition, biological function analysis indicated that target genes were primarily involved in the interaction of neuroactive ligands with receptors, taste transduction, cortisol synthesis and secretion, potassium ion transport. Based on machine learning algorithms, LOC103691092, Npw could be potentially useful biomarkers for TBI and showed good diagnostic values. Finally, a nomogram was constructed of the expression levels of these seven target genes to predict level of TBI, and the ROC showed that these genes can be used as hub genes after TBI.ConclusionLOC103691092, NPW, STK39, KCND3, APOC3, FOXE3, and CHRNB1 were identified as hub genes of TBI. These findings can provide a new direction for the diagnosis and treatment of TBI.
Integration of Mass Cytometry and Mass Spectrometry Imaging for Spatially Resolved Single Cell Metabolic Profiling
Authors: Nunes Joana B , Ijsselsteijn Marieke E , Abdelaal Tamim , Ursem Rick , van der Ploeg Manon , Everts Bart , Mahfouz Ahmed , Heijs Bram , de Miranda Noel FCC 
Published: August 2023

AbstractIntegration of spatial omics technologies can provide important insights into the biology of tissues. We combined mass spectrometry imaging-based metabolomics and imaging mass cytometry-based immunophenotyping on the same single tissue section to reveal metabolic heterogeneity within tissues and its association with specific cell populations like cancer cells or immune cells. This approach has the potential to greatly increase our understanding of tissue-level interplay between metabolic processes and their cellular components.
Altered reactivity to threatening stimuli inDrosophilamodels of Parkinson’s disease, revealed by a trial-based assay
Authors: Kajtor Márton , Billes Viktor A. , Király Bálint , Karkusova Patricia , Kovács Tibor , Stabb Hannah , Sviatkó Katalin , Vizi Andor , Ujvári Eszter , Balázsfi Diána , Seidenbecher Sophie E. , Kvitsiani Duda , Vellai Tibor , Hangya Balázs 
Published: August 2023

AbstractThe fruit flyDrosophila melanogasteremerges as an affordable, genetically tractable model of behavior and brain diseases. However, despite the surprising level of evolutionary conservation from flies to humans, significant genetic, circuit-level and behavioral differences hinder the interpretability of fruit fly models for human disease. Therefore, to allow a more direct fly-versus-human comparison, we surveyed the rarely exploited, rich behavioral repertoire of fruit flies with genetic alterations relevant to Parkinson’s disease (PD), including overexpression of human mutant Parkin or α-synuclein proteins and mutations in dopamine receptors. Flies with different genetic backgrounds displayed variable behaviors, including freezing, slowing and running, in response to predator-mimicking passing shadows used as threatening stimuli in a single-animal trial-based assay. We found that the expression of human mutant Parkin in flies resulted in reduced walking speed and decreased reactivity to passing shadows. Flies with dopamine receptor mutations showed similar alterations, consistent with the motor and cognitive deficits typical in humans with PD. We also found age-dependent trends in behavioral choice during the fly lifespan, while dopamine receptor mutant flies maintained their decreased general reactivity throughout all age groups. Our data demonstrate that single-trial behavioral analysis can reveal subtle behavioral changes in mutant flies that can be used to further our understanding of disease pathomechanisms and help gauge the validity of geneticDrosophilamodels of neurodegeneration, taking us one step closer to bridging the gap in fly-to-human translation.
Extinction risk predictions for the world’s flowering plants to support their conservation
Authors: Bachman Steven P. , Brown Matilda J.M. , Leão Tarciso C.C. , Lughadha Eimear Nic , Walker Barnaby E. 
Published: August 2023

SummaryMore than 70% of all vascular plants lack conservation status assessments. We aimed to address this shortfall in knowledge of species extinction risk by using the World Checklist of Vascular Plants to generate the first comprehensive set of predictions for a large clade: angiosperms (flowering plants, ∼330,000 species).We used Bayesian Additive Regression Trees (BART) to predict the extinction risk of all angiosperms using predictors relating to range size, human footprint, climate, and evolutionary history and applied a novel approach to estimate uncertainty of individual species level predictions.From our model predictions we estimate 45.1% of angiosperm species are potentially threatened with a lower bound of 44.5% and upper bound of 45.7%.Our species-level predictions, with associated uncertainty estimates, do not replace full Red List assessments, but can be used to prioritise predicted threatened species for full Red List assessment and fast-track predicted non-threatened species for Least Concern assessments. Our predictions and uncertainty estimates can also guide fieldwork, inform systematic conservation planning and support global plant conservation efforts and targets.
Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR
Authors: Deng Jiahua , Yuan Yuchen , Cui Qiang 
Published: August 2023

AbstractModulating allosteric coupling offers unique opportunities for biomedical applications. Such efforts can benefit from efficient prediction and evaluation of allostery hotspot residues that dictate the degree of co-operativity between distant sites. We demonstrate that effects of allostery hotspot mutations can be evaluated qualitatively and semi-quantitatively by molecular dynamics simulations in a bacterial tetracycline repressor (TetR). The simulations recapitulate the effects of these mutations on abolishing the induction function of TetR and provide a rationale for the different degrees of rescuability observed to restore allosteric coupling of the hotspot mutations. We demonstrate that the same non-inducible phenotype could be the result of perturbations in distinct structural and energetic properties of TetR. Our work underscore the value of explicitly computing the functional free energy landscapes to effectively evaluate and rank hotspot mutations despite the prevalence of compensatory interactions, and therefore provide quantitative guidance to allostery modulation for therapeutic and engineering applications.Abstract FigureTOC Graphic
Earliest observation of the tetracycline destructasetet(X3)
Authors: Grenier Frédéric , Lévesque Simon , Rodrigue Sébastien , Haraoui Louis-Patrick 
Published: August 2023

AbstractTigecycline is an antibiotic of last resort for infections with carbapenem-resistantAcinetobacter baumannii. Plasmids harboring variants of the tetracycline destructasetet(X)promote rising tigecycline resistance rates. We report the earliest observation oftet(X3)in a clinical strain predating tigecycline’s commercialization, suggesting selective pressures other than tigecycline contributed to its emergence.
Acute hyperoxia improves spinal cord oxygenation and circulatory function following cervical spinal cord injury in the rat
Authors: Lin Yen-Ting , Lee Kun-Ze 
Published: August 2023

AbstractSpinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague–Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1–2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats via the optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) breathing. The results showed that contused animals had a significantly lower spinal cord oxygenation level than uninjured animals during normoxia. Cervical spinal cord contusion also significantly reduced peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure. Notably, the spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia could elevate blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function during acute cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.
Novel YAP1/TAZ pathway inhibitors identified through phenotypic screening with potent anti-tumor activity via blockade of GGTase-I / Rho-GTPase signaling
Authors: Graham Keith , Lienau Philip , Bader Benjamin , Prechtl Stefan , Naujoks Jan , Lesche Ralf , Weiske Joerg , Kuehnlenz Julia , Brzezinka Krzysztof , Potze Lisette , Zanconato Francesca , Nicke Barbara , Montebaur Anna , Bone Wilhelm , Golfier Sven , Kaulfuss Stefan , Kopitz Charlotte , Pilari Sabine , Steuber Holger , Hayat Sikander , Kamburov Atanas , Steffen Andreas , Schlicker Andreas , Buchgraber Philipp , Braeuer Nico , Font Nuria Aiguabella , Heinrich Tobias , Kuhnke Lara , Nowak-Reppel Katrin , Stresemann Carlo , Steigemann Patrick , Walter Annette O. , Blotta Simona , Ocker Matthias , Lakner Ashley , Mumberg Dominik , Eis Knut , Piccolo Stefano , Lange Martin 
Published: August 2023

SUMMARYThis study describes the identification and target deconvolution of novel small molecule inhibitors of oncogenic YAP1/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay. Target deconvolution studies identified the geranylgeranyltransferase-I (GGTase-I) complex, as the direct target of YAP1/TAZ pathway inhibitors. The novel small molecule inhibitors block the activation of Rho-GTPases, leading to subsequent inactivation of YAP1/TAZ and inhibition of cancer cell proliferation in vitro. Multi-parameter optimization resulted in BAY-593, an in vivo probe with favorable PK properties, which demonstrated anti-tumor activity and blockade of YAP1/TAZ signalingin vivo.SIGNIFICANCEYAP1/TAZ have been shown to be aberrantly activated oncogenes in several human solid tumors, resulting in enhanced cell proliferation, metastasis and provision of a pro-tumorigenic microenvironment, making YAP1/TAZ targets for novel cancer therapies. Yet, the development of effective inhibitors of these potent oncogenes has been challenging. In this work, we break new ground in this direction through the identification of novel inhibitors of YAP1/TAZ activity.Graphical abstractHIGHLIGHTSNovel YAP1/TAZ pathway inhibitors identified by phenotypic high-throughput screenTarget deconvolution identifies GGTase-I as the direct target of the novel YAP1/TAZ pathway inhibitorsGGTase-I inhibitors block Rho-GTPase signaling and downstream YAP1/TAZGGTase-I inhibitor BAY-593 demonstrates potent anti-tumor activityin vivo
Stumpy forms are the predominant transmissible forms ofTrypanosoma brucei
Authors: Ngoune Jean Marc Tsagmo , Sharma Parul , Crouzols Aline , Petiot Nathalie , Rotureau Brice 
Published: August 2023

AbstractSchusteret al. demonstrated that bloodstream slender forms of African trypanosomes are readily transmissible to young tsetse flies where they can complete their complex life cycle (1). In their experimental conditions, a single slender parasite was sufficient for productive infection. Here, we compared the infectivity of slender and stumpy bloodstream forms in adult flies with a mature immune system, and without using any chemical compounds that would alter the insect immune response and/or promote the infection. After ingestion of slender forms, infected flies were observed only in one out of 24 batches of non-immunocompetent teneral flies and with a high number of parasites. In contrast, infected flies were detected in 75% (18/24) of the batches infected with stumpy parasites, and as few as 10 stumpy parasites produced mature infections in immune adult flies. We discuss that, although Schusteret al. have demonstrated the intrinsic capacity of slender form trypanosomes to infect young and naive tsetse flies, highlighting the remarkable plasticity and adaptability of these protists, this phenomenon is unlikely to significantly contribute to the epidemiology of African trypanosomiases. According to both experimental and field observations, stumpy forms appear to be the most adapted forms for African trypanosome transmission from the mammalian host to the tsetse fly vector in natural conditions.
A novel glideosome-associated protein S14 coordinates sporozoite gliding motility and infectivity in mosquito and mammalian hosts
Authors: Ghosh Ankit , Varshney Aastha , Narwal Sunil Kumar , Nirdosh  , Gaurav Sachin , Gupta Roshni , Ahmed Shakil , Mishra Satish 
Published: August 2023

AbstractPlasmodiumsporozoites are the infective forms of the malaria parasite in the vertebrate host. Gliding motility allows sporozoites to migrate and invade the salivary gland and hepatocytes. Invasion is powered by an actin-myosin motor complex linked to glideosome. However, the gliding complex and the role of several glideosome-associated proteins (GAPs) are poorly understood. In silico analysis of a novel protein, S14, which is uniquely upregulated in salivary gland sporozoites, suggested its association with glideosome-associated proteins. We confirmedS14expression in sporozoites using real-time PCR. Further, theS14gene was endogenously tagged with 3XHA-mCherry to study expression and localization. We found its expression and localization on the inner membrane of sporozoites. By targeted gene deletion, we demonstrate that S14 is essential for sporozoite gliding motility, salivary gland, and hepatocyte invasion. The gliding and invasion-deficientS14KO sporozoites showed normal expression and organization of IMC and surface proteins. Using in silico and the yeast two-hybrid system, we showed the interaction of S14 with the glideosome-associated proteins GAP45 and MTIP. Together, our data show that S14 is a glideosome-associated protein and plays an essential role in sporozoite gliding motility, which is critical for the invasion of the salivary gland, hepatocyte, and malaria transmission.
A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease
Authors: Lim Kyungtae , Rutherford Eimear N. , Sun Dawei , Van den Boomen Dick J. H. , Edgar James R. , Bang Jae Hak , Matesic Lydia E. , Lee Joo-Hyeon , Lehner Paul J. , Marciniak Stefan J. , Rawlins Emma L. , Dickens Jennifer A. 
Published: August 2023

AbstractAlveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant1–3. AT2 dysfunction underlies many lung diseases including interstitial lung disease (ILD), in which some inherited forms result from mislocalisation of surfactant protein C (SFTPC) variants4,5. Disease modelling and dissection of mechanisms remains challenging due to complexities in deriving and maintaining AT2 cellsex vivo.Here, we describe the development of expandable adult AT2-like organoids derived from human fetal lung which are phenotypically stable, can differentiate into AT1-like cells and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH, demonstrating that their depletion phenocopies the pathological SFTPC redistribution seen for the SFTPC-I73T variant. In summary, we demonstrate the development of a novel alveolar organoid model and use it to identify effectors of SFTPC maturation necessary for AT2 health.
Are shadow banks a threat to the financial stability of EMEs?
Authors: Arora Dhulika , Kashiramka Smita 
Published: August 2023

PurposeShadow banks or non-bank financial intermediaries (NBFIs) are facilitators of credit, especially in emerging market economies (EMEs). However, there are certain risks associated with them, such as their unchecked leverage and interconnectedness with the rest of the financial system. In light of this, the present study analyses the impact of the growth of shadow banks on the stability of the banking sector and the overall stability of the financial system. The authors further examine the effect of the growth of finance companies (a type of NBFIs) on financial stability.Design/methodology/approachThe study employs data of 11 EMEs (monitored by the Financial Stability Board (FSB)) for the period 2002–2020 to examine the above relationships. Panel-corrected standard errors method and Driscoll–Kray standard error estimation are deployed to conduct the analysis.FindingsThe results signify that the growth of the shadow banking sector and the growth of lending to the shadow banking sector are negatively associated with the stability of the banking sector and increases the vulnerability of the financial system (overall instability). This implies that the higher the growth of the shadow banks, the higher the financial fragility. Finance companies are also found to negatively affect financial stability. These findings are validated by different estimation methods and point out the risks posed by the NBFI sector.Originality/valueThe extant study builds a composite index (Financial Vulnerability Index (FVI)) to measure financial stability; thus, the findings contribute to the evolving literature on shadow banks.
Examine the impact of green methods and technologies on the environmental sustainability of supportive education buildings, perspectives of circular economy and net-zero carbon operation
Authors: Moghayedi Alireza , Michell Kathy , Hübner Dylan , Le Jeune Karen , Massyn Mark 
Published: August 2023

Purpose
This study investigates the barriers and drivers of using green methods and technologies (GMTs) in supportive educational buildings (SEBs) in South Africa, and assesses their impact on the circular economy (CE) in achieving net-zero carbon goals. While there has been extensive literature on green building technologies, there is limited research on the barriers and drivers of using GMT in SEBs, as well as their impact on the circular economy (CE) in achieving net-zero carbon goals.

Design/methodology/approach
This study adopts an interpretivist approach with an ontological basis, using an overarching case study of a SEB at the University of Cape Town (UCT). Semistructured interviews were conducted with executive UCT management, and a field survey of a UCT supportive education building was performed.

Findings
At UCT, multiple GMTs have been installed across various buildings to enhance monitoring and management of water and energy consumption. Moreover, initiatives to positively influence student behavior, such as water and energy-saving campaigns around UCT premises, have been introduced. The findings further indicate that UCT has recently emphasized the implementation of GMTs, resulting in improved resource efficiency, CE practices and progress toward achieving net-zero carbon targets for supportive education buildings and the university as a whole.

Originality/value
This research highlights the positive impact of GMTs on a SEB’s CE and net-zero carbon operations. As a result, facility managers should consider incorporating GMTs when planning the development or refurbishment of SEBs.
Leveraging autonomous mobile robots for Industry 4.0 warehouses: a multiple case study analysis
Authors: Grover Abhay Kumar , Ashraf Muhammad Hasan 
Published: August 2023

PurposeDespite its potential, warehouse managers still struggle to successfully assimilate autonomous mobile robots (AMRs) in their operations. This paper means to identify the moderating factors of AMR assimilation for production warehouses that influence the digital transformation of their intralogistics via AMRs.Design/methodology/approachDrawing on innovation of assimilation theory (IAT), this study followed an explorative approach using the principles of the case study method in business research. The cases comprised of four AMR end users and six AMR service providers. Data were collected through semi-structured interviews.FindingsFour clusters of moderators that affect each stage of AMR assimilation were identified. These clusters include organizational attributes of end users (i.e. production warehouses), service attributes of service providers, technology attributes of AMRs and relational attributes between the AMR service providers and the AMR end users.Originality/valueThe authors extend the IAT framework by identifying various moderating factors between different stages of the AMR assimilation process. To the authors' knowledge, this is the first study to introduce the perspective of AMR end users in conjunction with AMR service providers to the “Industry 4.0” technology assimilation literature. The study propositions regarding these factors guide future intralogistics and AMR research.