bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially aware self-representation learning for tissue structure characterization and spatial functional genes identification
Authors: Zhang Chuanchao , Li Xinxing , Huang Wendong , Wang Lequn , Shi Qianqian 
Published: March 2023

AbstractSpatially resolved transcriptomics (SRT) enable the comprehensive characterization of transcriptomic profiles in the context of tissue microenvironments. Unveiling spatial transcriptional heterogeneity needs to effectively incorporate spatial information accounting for the substantial spatial correlation of expression measurements. Here, we develop a computational method, SpaSRL (spatially aware self-representation learning), which flexibly enhances and decodes spatial transcriptional signals to simultaneously achieve spatial domain detection and spatial functional genes identification. This novel tunable spatially aware strategy of SpaSRL not only balances spatial and transcriptional coherence for the two tasks, but also can transfer spatial correlation constraint between them based on a unified model. Additionally, this joint analysis by SpaSRL deciphers accurate and fine-grained tissue structures and ensures the effective extraction of biologically informative genes underlying spatial architecture. We verified the superiority of SpaSRL on spatial domain detection, spatial functional genes identification and data denoising using multiple SRT datasets obtained by different platforms and tissue sections. Our results illustrate SpaSRL’s utility in flexible integration of spatial information and novel discovery of biological insights from spatial transcriptomic datasets.
30S subunit recognition and G1405 modification by the aminoglycoside-resistance 16S ribosomal RNA methyltransferase RmtC
Authors: Srinivas Pooja , Nosrati Meisam , Zelinskaya Natalia , Dey Debayan , Comstock Lindsay R. , Dunham Christine M. , Conn Graeme L. 
Published: March 2023

AbstractAcquired ribosomal RNA (rRNA) methylation has emerged as a significant mechanism of aminoglycoside resistance in pathogenic bacterial infections. Modification of a single nucleotide in the ribosome decoding center by the aminoglycoside-resistance 16S rRNA (m7G1405) methyltransferases effectively blocks the action of all 4,6-deoxystreptamine ring-containing aminoglycosides, including the latest generation of drugs. To define the molecular basis of 30S subunit recognition and G1405 modification by these enzymes, we used aS-adenosyl-L-methionine (SAM) analog to trap the complex in a post-catalytic state to enable determination of an overall 3.0 Å cryo-electron microscopy structure of the m7G1405 methyltransferase RmtC bound to the matureEscherichia coli30S ribosomal subunit. This structure, together with functional analyses of RmtC variants, identifies the RmtC N-terminal domain as critical for recognition and docking of the enzyme on a conserved 16S rRNA tertiary surface adjacent to G1405 in 16S rRNA helix 44 (h44). To access the G1405 N7 position for modification, a collection of residues across one surface of RmtC, including a loop that undergoes a disorder to order transition upon 30S subunit binding, induces significant distortion of h44. This distortion flips G1405 into the enzyme active site where it is positioned for modification by two almost universally conserved RmtC residues. These studies expand our understanding of ribosome recognition by rRNA modification enzymes and present a more complete structural basis for future development of strategies to inhibit m7G1405 modification to re-sensitize bacterial pathogens to aminoglycosides.SignificanceIncreasing prevalence of bacterial antibiotic resistance threatens our ability to treat bacterial infections and with it, many other facets of modern healthcare. For the ribosome-targeting aminoglycoside antibiotics, diverse pathogenic bacteria have acquired ribosomal RNA (rRNA) methyltransferase enzymes that confer exceptionally high-level resistance through site-specific modification of the drug binding site. Here, we define the molecular basis for ribosomal substrate recognition and modification by an enzyme (RmtC) representing the most clinically prevalent methyltransferase family. Specifically, RmtC exploits a conserved rRNA surface for binding and induces significant disruption of the rRNA structure to capture the target nucleotide for modification via a “base flipping” mechanism. These insights also present a platform for methyltransferase inhibitor development to extend usefulness of aminoglycoside antibiotics.
Emergence of ISAba1-linked oxacillinase genes among carbapenem resistantAcinetobacter baumanniiisolates in a tertiary cardiac center, Nepal
Authors: Bista Shrijana , Yadav Bindeshwar , Syangtan Gopiram , Shakya Jivan , Tuladhar Reshma , Joshi Dev Raj , Lekhak Binod 
Published: March 2023

AbstractInsertion sequence contributes to the emergence of carbapenem resistance by dissemination of carbapenemase genes and providing promoter for their overexpression. This study aims to ascertain the occurrence of ISAba1-linked OXA carbapenemase genes and its relevance to carbapenem resistance level inAcinetobacter baumannii. This hospital based descriptive study was conducted at Shahid Gangalal National Heart Center, Kathmandu, Nepal. An overall of 1,291 clinical specimens received for routine culture and antibiotic susceptibility testing throughout the study period were included in this study. Identification ofAcinetobacter baumanniiwas validated through detection of intrinsicblaOXA-51-likegene by polymerase chain reaction (PCR). Antibiotic susceptibility was tested by Kirby-Bauer disc diffusion approach and minimum inhibitory concentration (MIC) of meropenem was assessed through agar dilution method. Uniplex PCR assays were performed to detect genes encoding oxacillinases and ISAba1. Upstream association of insertion element, ISAba1to oxacillinase genes was assessed through PCR mapping strategy using ISAba1F and OXA-51R/OXA-23R primers. Out of the 340 bacteria isolated, only 40 (11.8%) wereAcinetobacter baumannii. All isolates were resistant against meropenem with MIC value ranging from 16-256 μg/ml.blaOXA-23-likegenes was present in every isolate butblaOXA-58in just two isolates (5%). All isolates had ISAba1either aboveblaOXA-23-likeorblaOXA-51-likegene. Higher MIC90value of meropenem (243.20 μg/ml) was found inA.baumanniicluster with ISAba1-linked upstream to bothblaOXA-23-likeandblaOXA-51-likegenes, thus depicting their eminent role to enhanced carbapenem resistance.Acinetobacter baumanniiisolates with ISAba1-linked oxacillinase genes are rapidly emerging in clinical settings of Nepal. Thus, medical communities need to be prepared and enable targeted approaches for managing burgeoning problem of carbapenem resistance.
Histone methyltransferase SUV39H1 regulates the Golgi complex via the nuclear envelope-spanning LINC complex
Authors: Nishino Miyu , Imaizumi Hiromasa , Yokoyama Yuhki , Katahira Jun , Kimura Hiroshi , Matsuura Nariaki , Matsumura Miki 
Published: March 2023

AbstractCell motility is related to the higher-order structure of chromatin. Stimuli that induce cell migration change chromatin organization; such stimuli include elevated histone H3 lysine 9 trimethylation (H3K9me3). We previously showed that depletion of histone H3 lysine 9 methyltransferase, SUV39H1, suppresses directional cell migration. However, the molecular mechanism underlying this association between chromatin and cell migration remains elusive. The Golgi apparatus is a cell organelle essential for cell motility. In this study, we show that loss of H3K9 methyltransferase SUV39H1 but not SETDB1 or SETDB2 causes dispersion of the Golgi apparatus throughout the cytoplasm. The Golgi dispersion triggered by SUV39H1 depletion is independent of transcription, centrosomes, and microtubule organization, but is suppressed by depletion of any of the following three proteins: LINC complex components SUN2, nesprin-2, or microtubule plus-end-directed kinesin-like protein KIF20A. In addition, SUN2 is closely localized to H3K9me3, and SUV39H1 affects the mobility of SUN2 in the nuclear envelope. Further, inhibition of cell motility caused by SUV39H1 depletion is restored by suppression of SUN2, nesprin-2, or KIF20A. In summary, these results show the functional association between chromatin organization and cell motility via the Golgi organization regulated by the LINC complex.
Imaging of plant calcium-sensor kinase conformation monitors real time calcium decodingin planta
Authors: Liese Anja , Eichstädt Bernadette , Lederer Sarah , Schulz Philipp , Oehlschläger Jan , Feijó José A , Schulze Waltraud X. , Konrad Kai R. , Romeis Tina 
Published: March 2023

AbstractChanges in cytosolic calcium concentration are among the earliest reactions to a multitude of stress cues. Whereas a plethora of calcium-permeable channels may generate distinct calcium signatures and contribute to response specificities, the mechanisms by which calcium signatures are decoded is poorly understood. Here we develop a genetically encoded, FRET-based reporter that visualizes the conformational change of calcium-dependent protein kinases (CDPKs/CPKs), preceding kinase activation, for calcium-dependent AtCPK21 and calcium-independent AtCPK23. In pollen tubes, naturally displaying a physiological calcium range, CPK21-FRET, but not CPK23-FRET, report activity oscillations with similar features to cytosolic calcium, suggesting an isoform-specific calcium dependency and reversibility of the conformational change. In guard cells CPK21-FRET identifies CPK21 as a decoder of signal-specific calcium signatures in response to ABA and flg22. Based on this data, CDPK-FRET stands as a novel approach for tackling real-time live-cell calcium decoding in a multitude of plant developmental and stress responses.
A Dynamic population of prophase CENP-C is required for meiotic chromosome segregation
Authors: Fellmeth Jessica E. , Jang Janet , Persaud Manisha , Sturm Hannah , Changela Neha , Parikh Aashka , McKim Kim S. 
Published: March 2023

AbstractThe centromere is an epigenetic mark that is a loading site for the kinetochore during meiosis and mitosis. This mark is characterized by the H3 variant CENP-A, known as CID inDrosophila. InDrosophila, CENP-C is critical for maintaining CID at the centromeres and directly recruits outer kinetochore proteins after nuclear envelope break down. It is not known, however, if these two functions require the same CENP-C molecules. Furthermore, inDrosophilaand many other metazoan oocytes, centromere maintenance and kinetochore assembly are separated by an extended prophase. Consistent with studies in mammals, CID is relatively stable and does not need to be expressed during prophase to remain at high levels in metaphase I of meiosis. Expression of CID during prophase can even be deleterious, causing ectopic localization to non-centromeric chromatin, abnormal meiosis and sterility. In contrast to CID, maintaining high levels of CENP-C requires expression during prophase. Confirming the importance of this loading, we found CENP-C prophase loading is required for multiple meiotic functions. In early meiotic prophase, CENP-C loading is required for sister centromere cohesion and centromere clustering. In late meiotic prophase, CENP-C loading is required to recruit kinetochore proteins. CENP-C is one of the few proteins identified in which expression during prophase is required for meiotic chromosome segregation. An implication of these results is that the failure to maintain recruitment of CENP-C during the extended prophase in oocytes would result in chromosome segregation errors in oocytes.Author SummaryMeiosis in oocytes of diverse organisms, including humans andDrosophila,is characterized by a long prophase pause and a cell cycle arrest in meiosis I or meiosis II. These pauses could be a challenge for centromeres, whose components are replenished during G1, and then must remain with the chromosomes until the meiotic divisions. We have investigated the stability, prophase dynamics and function of centromere protein CENP-C. We show that CENP-C expression and loading onto centromeres during prophase is required for multiple meiotic functions. In contrast, the expression of other centromere partners CID/CENP-A and CAL1 is not required during meiotic prophase. Furthermore, expression of CID during prophase can be deleterious and result in ectopic kinetochore formation. CENP-C loading in prophase is required for sister centromere cohesion and kinetochore assembly. Our results provide the first description of CENP-C dynamics during meiosis and show that prophase expression is required for oocyte spindle assembly and function. CENP-C is among a small number of proteins that are required for the meiotic divisions but are loaded prior to prometaphase. Failure to maintain these proteins during the long prophase of oocyte meiosis may contribute to the increased aneuploidy associated with advanced maternal age.
Intermediate filament dysregulation and astrocytopathy in the human disease model ofKLHL16mutation in giant axonal neuropathy (GAN)
Authors: Battaglia Rachel , Faridounnia Maryam , Beltran Adriana , Robinson Jasmine , Kinghorn Karina , Ezzell J. Ashley , Bharucha-Goebel Diana , Bonnemann Carsten , Hooper Jody E. , Opal Puneet , Bouldin Thomas W. , Armao Diane , Snider Natasha 
Published: March 2023

AbstractGiant Axonal Neuropathy (GAN) is a pediatric neurodegenerative disease caused byKLHL16mutations.KLHL16encodes gigaxonin, a regulator of intermediate filament (IF) protein turnover. Previous neuropathological studies and our own examination of postmortem GAN brain tissue in the current study revealed astrocyte involvement in GAN. To study the underlying mechanisms, we reprogrammed skin fibroblasts from seven GAN patients carrying differentKLHL16mutations to iPSCs. Isogenic controls with restored IF phenotypes were derived via CRISPR/Cas9 editing of one patient carrying a homozygous missense mutation (G332R). Neural progenitor cells (NPCs), astrocytes, and brain organoids were generated through directed differentiation. All GAN iPSC lines were deficient for gigaxonin, which was restored in the isogenic control. GAN iPSCs displayed patient-specific increased vimentin expression, while GAN NPCs had decreased nestin expression compared to isogenic control. The most striking phenotypes were observed in GAN iPSC-astrocytes and brain organoids, which exhibited dense perinuclear IF accumulations and abnormal nuclear morphology. GAN patient cells with large perinuclear vimentin aggregates accumulated nuclearKLHL16mRNA. In over-expression studies, GFAP oligomerization and perinuclear aggregation were potentiated in the presence of vimentin. As an early effector ofKLHL16mutations, vimentin may serve as a potential therapeutic target in GAN.
Metabolomics of bacterial-fungal pairwise interactions reveal conserved molecular mechanisms
Authors: Luu Gordon T. , Little Jessica C. , Pierce Emily C. , Morin Manon , Ertekin Celine A. , Wolfe Benjamin E. , Baars Oliver , Dutton Rachel J. , Sanchez Laura M. 
Published: March 2023

AbstractBacterial-fungal interactions (BFIs) can shape the structure of microbial communities, but the small molecules mediating these BFIs are often understudied. We explored various optimization steps for our microbial culture and chemical extraction protocols for bacterial-fungal co-cultures, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that metabolomic profiles are mainly comprised of fungi derived features, indicating that fungi are the key contributors to small molecule mediated BFIs. LC-inductively coupled plasma MS (LC-ICP-MS) and MS/MS based dereplication using database searching revealed the presence of several known fungal specialized metabolites and structurally related analogues in these extracts, including siderophores such as desferrichrome, desferricoprogen, and palmitoylcoprogen. Among these analogues, a novel putative coprogen analogue possessing a terminal carboxylic acid motif was identified fromScopulariopsisspp. JB370, a common cheese rind fungus, and its structure was elucidated via MS/MS fragmentation. Based on these findings, filamentous fungal species appear to be capable of producing multiple siderophores with potentially different biological roles (i.e. various affinities for different forms of iron). These findings highlight that fungal species are important contributors to microbiomes via their production of abundant specialized metabolites and their role in complex communities should continue to be a priority.
Bacterial contact induces polar plug disintegration to mediate whipworm egg hatching
Authors: Robertson Amicha , Sall Joseph , Venzon Mericien , Olivas Janet J. , Zheng Xuhui , Cammer Michael , Antao Noelle , Thur Rafaela Saes , Bethony Jeffrey , Nejsum Peter , Torres Victor J. , Liang Feng-Xia , Cadwell Ken 
Published: March 2023

AbstractThe bacterial microbiota promotes the life cycle of the intestine-dwelling whipwormTrichurisby mediating hatching of parasite eggs ingested by the mammalian host. Despite the enormous disease burden associated withTrichuriscolonization, the mechanisms underlying this transkingdom interaction have been obscure. Here, we used a multiscale microscopy approach to define the structural events associated with bacteria-mediated hatching of eggs for the murine model parasiteTrichuris muris. Through the combination of scanning electron microscopy (SEM) and serial block face SEM (SBFSEM), we visualized the outer surface morphology of the shell and generated 3D structures of the egg and larva during the hatching process. These images revealed that exposure to hatching-inducing bacteria catalyzed asymmetric degradation of the polar plugs prior to exit by the larva. Although unrelated bacteria induced similar loss of electron density and dissolution of the structural integrity of the plugs, egg hatching was most efficient in the presence of bacteria that bound poles with high density such asStaphylococcus aureus. Consistent with the ability of taxonomically distant bacteria to induce hatching, additional results suggest chitinase released from larva within the eggs degrade the plugs from the inside instead of enzymes produced by bacteria in the external environment. These findings define at ultrastructure resolution the evolutionary adaptation of a parasite for the microbe-rich environment of the mammalian gut.
A mathematical framework for the emergence of winners and losers in cell competition
Authors: Pak Thomas F. , Pitt-Francis Joe M. , Baker Ruth E. 
Published: March 2023

AbstractCell competition is a process in multicellular organisms where cells interact with their neighbours to determine a “winner” or “loser” status. The loser cells are eliminated through programmed cell death, leaving only the winner cells to populate the tissue. Cell competition is context-dependent; the same cell type can win or lose depending on the cell type it is competing against. Hence, winner/loser status is anemergentproperty. A key question in cell competition is: how do cells acquire their winner/loser status? In this paper, we propose a mathematical framework for studying the emergence of winner/loser status based on a set of quantitative criteria that distinguishes competitive from non-competitive outcomes. We apply this framework in a cell-based modelling context, to both highlight the crucial role of active cell death in cell competition and identify the factors that drive cell competition.HighlightsEmergent winner/loser status tests for competitive outcomes in cell-based modelsDifferences in biomechanical properties alone are not sufficient for cell competitionWinners have both higher tolerance and higher emission of death signals than losers
Statistical analysis of the circular economy for the intervention policies of the NRRP
Authors: Passaro Pierluigi , Perchinunno Paola , Rotondo Francesco 
Published: March 2023

PurposeThis paper deals with analyzing the relationships between the domains of the Sustainable Development Goals (SDGs) and the Missions envisaged by the National Recovery and Resilience Plan (NRRP). Specifically, the authors refer to Mission 2 (Green revolution and ecological transition) and to the statistical indicators related to the M2C1 component (Circular economy and sustainable agriculture).Design/methodology/approachThe numerous data available were analyzed at a regional level using multivariate statistical methodologies (Totally Fuzzy and Relative method) capable of summarizing the various information to evaluate the current situation relating to the “circular economy and sustainable agriculture” component. The presence of multiple updated data allows for the development of a holistic approach to the evaluation of the local government policies in place and to be able to monitor the progress of the subsequent intervention policies of the Italian government.FindingsNo Findings.Originality/value NRRP represents an opportunity for development for the area, providing for reforms and substantial investments for the promotion of circular economy solutions, the improvement of the capacity for efficient and sustainable waste management, the strengthening of the infrastructures for treatment of waste and separate collection, the reduction of the North/South gap.
Perceptions, use and perceived value of nutrition and health claims among Australian consumers: a cross-sectional survey
Authors: Hughes Jaimee , McMahon Anne , Houston Lauren , Neale Elizabeth 
Published: March 2023

PurposeNutrition and health claims are used widely on food labels and are known to influence food choice, however research has found that consumer perceptions of such claims are mixed. The study aimed to explore the perceptions, use and perceived value of nutrition and health claims among consumers and investigate barriers for the use of claims in guiding food choice.Design/methodology/approachAn online cross-sectional survey conducted in May-July 2019 collected information on participant demographics, reported use and perceptions of nutrition and health claims, and barriers to the use of claims for 150 Australian consumers.FindingsWhile the majority (73.5%) of respondents were aware of nutrition and health claims on food labels and were largely confident in interpreting claims, 29% of respondents “often” or “always” used claims to guide food choices. More than one-quarter (27.3%) of respondents found nutrition and health claims “not very useful” or “not at all useful” for guiding food choice, while only 12.7% perceived claims as “very trustworthy” or “extremely trustworthy”. The ingredients list and nutrition information panel were the preferred sources of on-pack nutrition information for guiding food choice.Originality/valueFindings suggest there remains a role for nutrition and health claims to help consumers make healthier dietary decisions however, it appears that trust in claims and regulations must firstly be addressed. There is a need to develop strategies to increase the perceived trustworthiness of these claims, including clearer promotion of the current regulatory requirements for making nutrition and health claims.