bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partnership with both fungi and bacteria can protectOdontotermes obesusfungus gardens against fungal invaders
Authors: Agarwal Renuka , Gupta Manisha , Sen Ruchira , E.S. Nimisha , Raychoudhury Rhitoban 
Published: August 2023

AbstractFungus-growing termites, likeOdontotermes obesus, cultivateTermitomycesas their sole food source on fungus combs which are continuously maintained with foraged plant materials. This necessary augmentation also increases the threat of introducing pathogenic fungi capable of displacingTermitomyces. The magnitude of this threat and how termites prevent pathogens remain largely unknown. This study identifies this pathogenic load by establishing the pan-mycobiota ofO. obesusfrom the fungus comb and termite castes. Furthermore, to maximize the identification of such pathogenic fungi, the mycobiota of the decaying stages of the unattended fungus comb were also assessed. The simultaneous assessment of the microbiota and the mycobiota of these stages identified possible interactions between the fungal and bacterial members of this community. Based on these, we propose a possible interaction among the crop fungusTermitomyces, the weedy fungusPseudoxylariaand some bacterial mutualists. These possibilities were then tested within vitrointeraction assays which suggest thatTermitomyces,Pseudoxylariaand bacterial mutualists all possess anti-fungal capabilities. We propose a multifactorial interaction model of these microbes, under the care of the termites, to explain how their interactions can maintain a predominantlyTermitomycesmonoculture.
Platelet Factor 4 (PF4) Improves Survival in a Murine Model of Antibiotic-Susceptible and Methicillin-ResistantStaphylococcus AureusPeritonitis
Authors: Podolnikova Nataly P. , Lishko Valeryi K. , Roberson Robert , Koh Zhqian , Derkach Dmitry , Richardson David , Sheller Michael , Ugarova Tatiana P. 
Published: August 2023

ABSTRACTThe complement receptor CR3, also known as integrin Mac-1 (CD11b/CD18), is one of the major phagocytic receptors on the surface of neutrophils and macrophages. We previously demonstrated that in its protein ligands, Mac-1 binds sequences enriched in basic and hydrophobic residues and strongly disfavors negatively charged sequences. The avoidance by Mac-1 of negatively charged surfaces suggests that the bacterial wall and bacterial capsule possessing net negative electrostatic charge may repel Mac-1 and that the cationic Mac-1 ligands can overcome this evasion by acting as opsonins. Indeed, we previously showed that opsonization of Gram-negativeEscherichia coliwith several cationic peptides, including PF4 (Platelet Factor 4), strongly augmented phagocytosis by macrophages. Here, we investigated the effect of recombinant PF4 (rPF4) on phagocytosis of Gram-positiveStaphylococcus aureusin vitro and examined its impact in a mouse model ofS. aureusperitonitis. Characterization of the interaction of rPF4 with nonencapsulated and encapsulatedS. aureusshowed that rPF4 localizes on the bacterial surface, thus making it available for Mac-1. Furthermore, rPF4 did not have direct bactericidal and bacteriostatic activity and was not toxic to host cells. rPF4 enhanced phagocytosis ofS. aureusbioparticles by various primary and cultured Mac-1-expressing leukocytes by several folds. It also increased phagocytosis of live nonencapsulated and encapsulated bacteria. Notably, the augmentation of phagocytosis by rPF4 did not compromise the intracellular killing ofS. aureusby macrophages. Using a murineS. aureusperitonitis model, we showed that treatment of infected mice with rPF4 caused a significant increase in the clearance of antibiotic-susceptibleS. aureusand its methicillin-resistant (MRSA) variant and markedly improved survival. These findings indicate that rPF4 binding to the bacterial surface circumvents its antiphagocytic properties, improving host defense against antibiotic-susceptible and antibiotic-resistant bacteria.
Divergent Folding-Mediated Epistasis Among Unstable Membrane Protein Variants
Authors: Chamness Laura M. , Kuntz Charles P. , McKee Andrew G. , Penn Wesley D. , Hemmerich Christopher M. , Rusch Douglas B. , Woods Hope , Dyotima  , Meiler Jens , Schlebach Jonathan P. 
Published: August 2023

AbstractMany membrane proteins are prone to misfolding, which compromises their functional expression at the plasma membrane. This is particularly true for the mammalian gonadotropin-releasing hormone receptor GPCRs (GnRHR). We recently demonstrated that evolutionary GnRHR modifications appear to have coincided with adaptive changes in cotranslational folding efficiency. Though protein stability is known to shape evolution, it is unclear how cotranslational folding constraints modulate the synergistic, epistatic interactions between mutations. We therefore compared the pairwise interactions formed by mutations that disrupt the membrane topology (V276T) or tertiary structure (W107A) of GnRHR. Using deep mutational scanning, we evaluated how the plasma membrane expression of these variants is modified by hundreds of secondary mutations. An analysis of 251 mutants in three genetic backgrounds reveals that V276T and W107A form distinct epistatic interactions that depend on both the severity and the mechanism of destabilization. V276T forms predominantly negative epistatic interactions with destabilizing mutations in soluble loops. In contrast, W107A forms positive interactions with mutations in both loops and transmembrane domains that reflect the diminishing impacts of the destabilizing mutations in variants that are already unstable. These findings reveal how epistasis is remodeled by conformational defects in membrane proteins and in unstable proteins more generally.Impact StatementMany of the synergistic interactions between mutations within a gene are modified in the context of unstable proteins in a manner that depends on how the variants promote misfolding in the cell.
α-catenin mechanosensitivity as a route to cytokinesis failure through sequestration of LZTS2
Authors: Wang Yuou , Yemelyanov Alex , Go Christopher D. , Kim Sun , Quinn Jeanne M. , Flozak Annette S. , Le Phuong M. , Liang Shannon , Claude-Gingras Anne , Ikura Mitsu , Ishiyama Noboru , Gottardi Cara J. 
Published: August 2023

ABSTRACTEpithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using α-catenin (α-cat) knock-out Madin Darby Canine Kidney (MDCK) cells reconstituted with wild-type and mutant forms of α-cat as a model system, we find that an established α-cat actin-binding domain unfolding mutant designed to reduce force-sensitive binding to F-actin (α-cat-H0-FABD+) can promote cytokinesis failure, particularly along epithelial wound-fronts. Enhanced α-cat coupling to cortical actin is neither sufficient nor mitotic cell-autonomous for cytokinesis failure, but critically requires the mechanosensitive Middle-domain (M1-M2-M3) and neighboring cells. Disease relevant α-cat M-domain missense mutations known to cause a form of retinal pattern dystrophy (α-cat E307K or L436P) are associated with elevated binucleation rates via cytokinesis failure. Similar binucleation rates are seen in cells expressing an α-cat salt-bridge destabilizing mutant (R551A) designed to promote M2-M3 domain unfurling at lower force thresholds. Since binucleation is strongly enhanced by removal of the M1 as opposed to M2-M3 domains, cytokinetic fidelity is most sensitive to α-cat M2-M3 domain opening. To identify α-cat conformation-dependent proximity partners that contribute to cytokinesis, we used a biotin-ligase approach to distinguished proximity partners that show enhanced recruitment upon α-cat M-domain unfurling (R551A). We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), an abscission factor previously implicated in cytokinesis. We confirm that LZTS2 enriches at the midbody, but discover it also localizes to tight and tricellular junctions. LZTS2 knock-down promotes binucleation in both MDCK and Retinal Pigmented Epithelial (RPE) cells. α-cat mutants with persistent M2-M3 domain opening showed elevated junctional enrichment of LZTS2 from the cytosol compared α-cat wild-type cells. These data implicate LZTS2 as a mechanosensitive effector of α-cat that is critical for cytokinetic fidelity. This model rationalizes how persistent mechano-activation of α-cat may drive tension-induced polyploidization of epithelia post-injury and suggests an underlying mechanism for how pathogenic α-cat mutations drive macular dystrophy.
Female germline expression of OVO transcription factor bridgesDrosophilagenerations
Authors: Benner Leif , Muron Savannah , Oliver Brian 
Published: August 2023

AbstractOVO is required for karyotypically female germ cell viability but has no known function in the male germline in Drosophila.ovois autoregulated by two antagonistic isoforms, OVO-A and OVO-B. Allovo-alleles were created as partial revertants of the antimorphicovoD1allele. Creation of new targeted alleles in anovo+background indicated that disrupting the germline-specific exon extension ofovo-Bleads to an arrested egg chamber phenotype, rather than germ cell death. RNA-seq analysis, including >1K full length cDNAs, indicates thatovoutilizes a number of unannotated splice variations in the extended exon and a minor population ofovo-Btranscripts utilizes an alternative splice. This indicates that classicalovoalleles such asovoD1rv23, are not truly null forovo, and are likely to be weak antimorphs. To generate bonafide nulls, we deleted theovo-Aandovo-Bpromoters showing that onlyovo-Bis required for female germ cell viability and there is an early and polyphasic developmental requirement forovo-Bin the female germline. To visualize OVO expression and localization, we endogenously taggedovoand found nuclear OVO in all differentiating female germ cells throughout oogenesis in adults. We also found that OVO is maternally deposited into the embryo, where it showed nuclear localization in newly formed pole cells. Maternal OVO persisted in embryonic germ cells until zygotic OVO expression was detectable, suggesting that there is continuous nuclear OVO expression in the female germline in the transition from one generation to the next.Article Summaryovohas long been considered to be at the top of the female germline sex determination pathway. We utilized updated genetic methods to determine OVO expression, localization, and requirement in the embryonic and adult germline. Our results indicate that OVO is always present, and likely required, in the Drosophila female germline.
Cytoskeletal adaptation following long-term dysregulation of actomyosin in neuronal processes
Authors: Cisterna Bruno A. , Skruber Kristen , Jane Makenzie L. , Camesi Caleb I. , Nguyen Ivan D. , Warp Peyton V. , Black Joseph B. , Butler Mitchell T. , Bear James E. , Read Tracy-Ann , Vitriol Eric A. 
Published: August 2023

AbstractMicrotubules, intermediate filaments, and actin are cytoskeletal polymer networks found within the cell. While each has unique functions, all the cytoskeletal elements must work together for cellular mechanics to be fully operative. This is achieved through crosstalk mechanisms whereby the different networks influence each other through signaling pathways and direct interactions. Because crosstalk can be complex, it is possible for perturbations in one cytoskeletal element to affect the others in ways that are difficult to predict. Here we investigated how long-term changes to the actin cytoskeleton affect microtubules and intermediate filaments. Reducing F-actin or actomyosin contractility increased acetylated microtubules and intermediate filament expression, with the effect being significantly more pronounced in neuronal processes. Changes to microtubules were completely reversible if F-actin and myosin activity is restored. Moreover, the altered microtubules in neuronal processes resulting from F-actin depletion caused significant changes to microtubule-based transport, mimicking phenotypes that are linked to neurodegenerative disease. Thus, defects in actin dynamics cause a compensatory response in other cytoskeleton components which profoundly alters cellular function.
Adrenergic Reprogramming of Preexisting Adipogenic Trajectories Steer Naïve Mural Cells Toward Beige Differentiation
Authors: Desevin Kathleen , Cortez Briana N. , Lin Jean Z , Lama Dechen , Layne Matthew D. , Farmer Stephen R. , Rabhi Nabil 
Published: August 2023

SUMMARYIn adult white adipose tissue, cold or β3-adrenoceptor activation promotes the appearance of thermogenic beige adipocytes. Our comprehensive single-cell analysis revealed that these cells arise through the reprogramming of existing adipogenic trajectories, rather than from a single precursor. These trajectories predominantly arise from SM22-expressing vascular mural progenitor cells. Central in this transition is the activation of Adrb3 in mature adipocytes, leading to subsequent upregulation of Adrb1 in primed progenitors. Under thermoneutral conditions, synergistic activation of both Adrb3 and Adrb1 recapitulates the pattern of cold-induced SM22+ cell recruitment. Lipolysis-derived eicosanoids, specifically docosahexaenoic acid (DHA) and arachidonic acid (AA) prime these processes and in vitro, were sufficient to recapitulate progenitor cells priming. Collectively, our findings provide a robust model for cold-induced beige adipogenesis, emphasizing a profound relationship between mature adipocytes and mural cells during cold acclimation, and revealing the metabolic potential of this unique cellular reservoir.
Functional Organization of Glycolytic Metabolon on Mitochondria
Authors: Wang Haoming , Vant John , Wu Youjun , Sánchez Richard , Micou Mary Lauren , Zhang Andrew , Luczak Vincent , Yu Seungyoon Blenda , Jabbo Mirna , Yoon Seokjun , Abushawish Ahmed Abdallah , Ghassemian Majid , Griffis Eric , Hammarlund Marc , Singharoy Abhishek , Pekkurnaz Gulcin 
Published: August 2023

SUMMARYGlucose, the primary cellular energy source, is metabolized through glycolysis initiated by the rate-limiting enzyme Hexokinase (HK). In energy-demanding tissues like the brain, HK1 is the dominant isoform, primarily localized on mitochondria, crucial for efficient glycolysis-oxidative phosphorylation coupling and optimal energy generation. This study unveils a unique mechanism regulating HK1 activity, glycolysis, and the dynamics of mitochondrial coupling, mediated by the metabolic sensor enzyme O-GlcNAc transferase (OGT). OGT catalyzes reversible O-GlcNAcylation, a post-translational modification, influenced by glucose flux. Elevated OGT activity induces dynamic O-GlcNAcylation of HK1’s regulatory domain, subsequently promoting the assembly of the glycolytic metabolon on the outer mitochondrial membrane. This modification enhances HK1’s mitochondrial association, orchestrating glycolytic and mitochondrial ATP production. Mutations in HK1’s O-GlcNAcylation site reduce ATP generation, affecting synaptic functions in neurons. The study uncovers a novel pathway that bridges neuronal metabolism and mitochondrial function via OGT and the formation of the glycolytic metabolon, offering new prospects for tackling metabolic and neurological disorders.
Regulation of Non-Canonical Proteins Encoded by Small Open Reading Frames via the Nonsense-Mediated Decay Pathway
Authors: Periasamy Parthiban , Joseph Craig , Campos Adrian , Rajandran Sureka , Batho Christopher , Hudson James E. , Sivakumaran Haran , Kore Hitesh , Datta Keshava , Yeong Joe , Gowda Harsha 
Published: August 2023

AbstractImmunotherapy interventions relies heavily on neoantigen availability. The human genome encodes non-canonical/mutant proteins that potentially contain neoantigenic peptides. Nevertheless, their typically low expression, potentially moderated by the Nonsense-Mediated Decay (NMD) pathway, restricts their therapeutic utility. In this study, we explored the NMD pathway influence on non-canonical/mutant protein expression, specifically focusing onUPF1knockdown. We implemented proteogenomic approaches to ascertain if the encoding transcripts and their respective proteins were upregulated post-knockdown. Complementary to this, we conducted a comprehensive pan-cancer survey ofUPF1expression and anin vivoevaluation ofUPF1expression in Triple-Negative Breast Cancer (TNBC) tissue. Our empirical results delineated thatUPF1knockdown precipitates an increase in the transcription of non-canonical/mutant proteins, especially those originating from retained-introns, pseudogenes, long non-coding RNAs, and unannotated biotypes. Furthermore, the analysis revealed thatUPF1expression was conspicuously high across a range of neoplastic tissues, with protein levels notably amplified in patient derived TNBC tumours in comparison to adjacent tissues. Our study elucidatesUPF1functional role in attenuating transcriptional noise through the degradation of transcripts encoding non-canonical/mutant proteins. Interestingly, we observed an upregulation of the NMD pathway in cancer, potentially functioning as a “neoantigen masking” mechanism that subdues non-canonical/mutant protein expression. Suppressing this mechanism may unveil a new cadre of neoantigens accessible to the antigen presentation pathway. Our novel findings proffer a solid base for devising therapeutic strategies targetingUPF1or the NMD pathway, given the pronounced presence ofUPF1in malignant cells, thus potentially augmenting immunotherapeutic responses in cancer.
Policies and politics development of vocational education in Indonesia: a historical perspective
Authors: Yasdin Yasdin , Parenrengi Syafiuddin , Hasriani Hasriani , Mahande Ridwan Daud 
Published: August 2023

PurposeThe purpose of this study was to discuss the history and political development of vocational education in Indonesia began before independence until independence era.Design/methodology/approachAnalysis of related documents and literature was used to explore the policies and politics of vocational education in Indonesia. Some documents traced were in the form of laws and regulations and previous writings related to the politics and policies of vocational education in Indonesia.FindingsThe politics of vocational education at this time reinforces identity politics in the form of the language of instruction in the politics of vocational education. In addition, the school curriculum at this time tried to accommodate the interests of the colonizers. Change slowly occurred when Indonesia declared independence, and vocational education slowly underwent changes and development. Apart from still strengthening its identity in the form of language, culture and social structure, Indonesian vocational education has also been oriented toward the development of the country.Research limitations/implicationsAlthough the author has identified Indonesia's vocational education policies and politics, several things still require further investigation, especially the impact of culture in politics and vocational education policies including the contribution of community conditions.Practical implicationsThe findings of this paper can potentially raise interest in the politics of vocational education because of the many interest groups involved.Social implicationsThe findings can contribute in the conversion of interests between interest groups to allocated educational resources, both human resources and budgetary resources.Originality/valueThis paper not only describes aspects of Indonesian history and identity in vocational education and the politics of vocational education which were conducted previous studies but also provides information on strategies for converting interests between groups in the interests of vocational education.
Impact of service agents on customer satisfaction and loyalty: mediating role of Chatbots
Authors: Naqvi Muhammad Hasnain Abbas , Hongyu Zhang , Naqvi Mishal Hasnain , Kun Li 
Published: August 2023

PurposeThis study aims to determine whether or not fashion retail brands can maintain their essence by providing personalized care through conventional face-to-face interactions or the use of e-services.Design/methodology/approachAn exploratory investigation is being conducted to attain this goal. According to the findings of this research, Chatbots have an impact on consumer loyalty. The quality of a Chatbot’s system, service and information are all critical to providing a positive consumer experience.FindingsThe study concluded that Chatbot e-services might potentially enable dynamic and fascinating interactions between firms and their consumers. To personalize a Chatbot, firms might change the tone of the language used. Customers are more likely to use a Chatbot if it resembles a real person, which increases their pleasure and confidence in the product.Originality/valueMore precisely, the emphasis of the inquiry was on Chatbot, a relatively new digital tool that offers user-friendly, personalized and one-of-a-kind support to customers. Using information supplied by consumers, the authors examine a five-dimensional model that gauges how customers feel about Chatbots in terms of their ability to communicate with users, offer amusement, be trendy, personalize interactions and solve problems.
Leaving child and adolescent mental health services (CAMHS): the impact of diagnosis and medication management on optimal discharge or transition
Authors: Street Cathy , Ni Chinseallaigh Ellen , Holme Ingrid , Appleton Rebecca , Tah Priya , Tuomainen Helena , Leijdesdorff Sophie , van Bodegom Larissa , van Amelsvoort Therese , Franic Tomislav , Tomljenovic Helena , McNicholas Fiona 
Published: August 2023

PurposeThis study aims to explore how young people in child and adolescent mental health services (CAMHS) in the UK, Ireland, The Netherlands and Croatia, experienced leaving CAMHS and identified a range of factors impeding optimal discharge or transition to adult mental health services (AMHS).Design/methodology/approachInterviews about discharge or transition planning, including what information was provided about their ongoing mental health needs, undertaken with 34 young people aged 17–24, all previous or current attendees of CAMHS. Some interviews included accounts by parents or carers. Data were thematically analysed.FindingsA number of previously well-documented barriers to a well-delivered discharge or transition were noted. Two issues less frequently reported on were identified and further discussed; they are the provision of an adequately explained, timely and appropriately used diagnosis and post-CAMHS medication management. Overall, planning processes for discharging or transitioning young people from CAMHS are often sub-optimal. Practice with regard to how and when young people are given a diagnosis and arrangements for the continuation of prescribed medication appear to be areas requiring improvement.Originality/valueStudy participants came from a large cohort involving a wide range of different services and health systems in the first pan-European study exploring the CAMHS to adult service interface. Two novel and infrequently discussed issues in the literature about young people’s mental health transitions, diagnosis and medication management were identified in this cohort and worthy of further study.