bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel and highly specific Forssman antigen-binding protein from sheep polyomavirus
Authors: Rustmeier Nils H. , Silva Lisete M. , Di Maio Antonio , Müller Joshua C. , Herrmann Alexander , Feizi Ten , Liu Yan , Stehle Thilo 
Published: April 2023

AbstractPolyomaviruses are small, non-enveloped double-stranded DNA viruses of humans and other mammals, birds, and fish. Infections are usually asymptomatic and result in latency, however, some polyomaviruses can induce severe diseases, including cancer, in immunocompromised individuals. Established cellular receptors for polyomavirus infection are sialylated glycolipids (such as gangliosides), membrane proteins, and glycosaminoglycans. Polyomaviruses are usually highly host specific but the exact principles that govern host tropism remain unknown in many cases. Here, glycan array screening shows that the major capsid protein VP1 of sheep polyomavirus (ShPyV) binds to the Forssman glycolipid, an antigen of many vertebrates and a potential tumor marker in humans. Following closer investigation, we can report for the first time that a neutral, non-sialylated glycolipid acts as a polyomavirus receptor. Concurrently, we present the first report of a viral protein that specifically engages the Forssman antigen. We demonstrate that ShPyV VP1 binds to Forssman-positive erythrocytes but not those of human A, B and O blood groups, which is a clear distinction from features thus far described for Forssman lectins. X-ray crystallography and structural analysis of the VP1-Forssman glycan complex define the terminal Forssman disaccharide as the determinant of this protein-receptor interaction. These results strongly suggest that the sheep polyomavirus can use Forssman antigen for infectious cell entry. Furthermore, the ability of ShPyV VP1 to distinguish Forssman-positive from -negative cells may prove useful for monitoring the Forssman-‘status’ of normal, preneoplastic and neoplastic cells and tissues and establishing the antigen level as a biomarker.Author summaryElucidation of host cell receptor specificities of viral infection is crucial to understand the pathobiology of associated diseases and develop treatments. However, for many polyomaviruses the receptor engagement as the initial event in infection is poorly understood. In only a few cases polyomavirus tropism has been pinned down to a single type of glycan receptor. While many polyomaviruses utilize sialyl glycans to attach to host cells, the role of non-sialylated glycans as receptors is so far underestimated. Here, we show for the first time that a glycan of neutral charge, in this case the carbohydrate portion of the Forssman antigen, acts as a ligand for a polyomavirus capsid protein and may thus contribute to host tropism and infective cell entry. These results represent a significant addition to knowledge on polyomavirus-glycan interactions and complement general principles of carbohydrate engagement by viruses. Furthermore, as a specific binding protein of Forssman antigen, VP1 may help to determine levels of this antigen in healthy and malignant tissues in humans.
Impact of Zinc Pre-exposure on de novo Antibiotic Resistance Development
Authors: Suprenant Mark P. , Ching Carly , Sutradhar Indorica , Gross Neila , Anderson Jessica E. , El Sherif Nourhan , Zaman Muhammad H. 
Published: April 2023

AbstractAntimicrobial resistance (AMR) is a global health crisis that is currently predicted to worsen. While the impact of improper antibiotics is an established driver, much less is known on the impacts of metal supplements. Here, we specifically probe the impact of zinc (Zn) on AMR. In conflict settings where diarrhea disease cases are high, Zn is both given as a supplement for treatment of these diseases prior to use of antibiotics such as ciprofloxacin and is associated with weapons of war. In this study, we find that the order with whichE. coliis exposed to zinc impacts resistance development, with increasing pre-exposure time leading to accelerated ciprofloxacin resistance, while combined exposure of zinc with ciprofloxacin delays ciprofloxacin resistance. We did not find evidence that zinc pre-exposure leads to genetic changes or change in antibiotic tolerance, though it does increase both the lag phase and doubling time ofE. coli, suggesting the mechanism may be due to changes in gene expression. While the zinc phenotype behavior is not permeant and would no longer be observed if ciprofloxacin exposure did not occur right after zinc pre-exposure, the elevated MIC phenotype resulting from the zinc pre-exposure was more stable than the zinc phenotype. These results are important as they highlight the need to reexamine the clinical role of zinc in treating diarrheal diseases and assess if changes in resistance development observed in vitro are also observed in vivo.ImportanceAntimicrobial resistance (AMR) is a global problem. According to a 2014 Review on Antimicrobial Resistance, it is projected to result in several million deaths by 2050 (Review on Antimicrobial Resistance, Tackling a Crisis for the Health and Wealth of Nations, 2014). While the improper usage of antibiotic treatments is an accepted driver of AMR, little work has focused on how non-antibiotic medication, such as supplements, might impact this when combined with antibiotics. One supplement of interest is the heavy metal zinc which is used in conjunction with ciprofloxacin to treat diarrheal diseases in children. We find that the order and duration of zinc exposure has significant impact on resistance development. More specifically, although the combined presence of zinc and ciprofloxacin delays the onset of resistance, when used successively as they often are in practice, zinc pre-exposure followed by ciprofloxacin exposure results in faster resistance development.
Hyperexcitability in the olfactory bulb and impaired fine odor discrimination in theFmr1KO mouse model of fragile X syndrome
Authors: Kuruppath Praveen , Xue Lin , Pouille Frederic , Jones Shelly T. , Schoppa Nathan E. 
Published: April 2023

AbstractFragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders in humans. FXS is caused by loss of expression of the Fragile X mental retardation protein (FMRP), an mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. Sensory processing deficits have been a major focus of studies of FXS in both humans and rodent models of FXS, but olfactory deficits remain poorly understood. Here we conducted experiments in wild-type andFmr1KO (Fmr1-/y) mice (males) that lack expression of the gene encoding FMRP to assess olfactory circuit and behavioral abnormalities. In patch-clamp recordings conducted in slices of the olfactory bulb, output mitral cells (MCs) inFmr1KO mice displayed greatly enhanced excitation, as evidenced by a much higher rate of occurrence of spontaneous network-level events known as long-lasting depolarizations (LLDs). The higher probability of LLDs did not appear to reflect changes in inhibitory connections onto MCs but rather enhanced spontaneous excitation of external tufted cells (eTCs) that provide feedforward excitation onto MCs within glomeruli. In addition, in a go/no-go operant discrimination paradigm, we found thatFmr1KO mice displayed impaired discrimination of odors in difficult tasks that involved odor mixtures but not altered discrimination of monomolecular odors. We suggest that the higher excitability of MCs inFmr1KO mice may impair fine odor discrimination by broadening odor tuning curves of MCs and/or altering synchronized oscillations through changes in transient inhibition.Significance StatementFragile X syndrome (FXS) in humans is associated with a range of debilitating deficits including aberrant sensory processing. One sensory system that has received comparatively little attention in studies in animal models of FXS is olfaction. Here, we report the first comprehensive physiological analysis of circuit defects in the olfactory bulb in the commonly-usedFmr1knockout (KO) mouse model of FXS. Our studies indicate thatFmr1KO alters the local excitation/inhibition balance in the bulb – similar to whatFmr1KO does in other brain circuits – but through a novel mechanism that involves enhanced feedforward excitatory drive. Furthermore,Fmr1KO mice display behavioral impairments in fine odor discrimination, an effect that may be explained by enhanced neural excitability.
Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma
Authors: Fitzsimmons Christina M. , Mandler Mariana D. , Lunger Judith C. , Chan Dalen , Maligireddy Siddhardha S. , Schmiechen Alexandra C. , Gamage Supuni Thalalla , Link Courtney , Jenkins Lisa M. , Crooks Daniel R. , Meier Jordan L. , Linehan W. Marston , Batista Pedro J. 
Published: April 2023

ABSTRACTMetabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) lead to fumarate accumulation and cause hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is a rare, inherited disease characterized by the development of non-cancerous smooth muscle tumors of the uterus and skin, and an increased risk of a highly metastatic and aggressive form of kidney cancer. Fumarate has been shown to inhibit 2-oxyglutarate-dependent dioxygenases (2OGDDs) involved in the hydroxylation of HIF1α, as well as in DNA and histone demethylation. However, the link between fumarate accumulation and changes in RNA post-transcriptional modifications has not been defined. Here, we determine the consequences of fumarate accumulation on the activity of different members of the 2OGDD family targeting RNA modifications. By evaluating multiple RNA modifications in patient-derived HLRCC cell lines, we show that mutation of FH selectively alters the activity of demethylases acting upon N6-methyladenosine (m6A), while the demethylase acting upon N1-methyladenosine (m1A) and 5-formylcytosine (f5C) in mitochondrial RNA are unaffected. The observation that metabolites modulate specific subsets of RNA-modifying enzymes offers new insights into the intersection between metabolism and the epitranscriptome.
Body size affects specialization and modularity in the global resin foraging meta-network of stingless bees
Authors: Nakamura Daniel Yudi Miyahara , Koffler Sheina , Francoy Tiago Mauricio 
Published: April 2023

ABSTRACTBees are in global decline and specialized species might be the most vulnerable to extinctions. Bee conservation can be studied using interaction networks, whose relative importance of nodes might correlate with morphological traits. Specifically, body size could affect flying range and thus influence the set of plant-bee interactions. Although several studies have reported botanical sources of resins in stingless bees, resin foraging networks were rarely assembled. Here we aim to describe the global resin-foraging meta-network of stingless bees, identify the most specialized species, and test how body size influences modularity and specialization. We found a modular and nested structure, in which some modules exhibit significant differences in body size and specialization.Melipona beecheiiis the most specialized stingless bee in collecting resins. Body size is positively correlated with specialization, in which larger bees are more specialized to collect resins from a subset of plants, possibly because larger bees with broader flying ranges avoid competition by collecting less disputed resources. Our results demonstrate how resin collection can be analyzed in a meta-network framework to test ecological hypotheses and identify specialized species as candidate priorities for the conservation of stingless bees.
Geochemical constraints on bacteriophage infectivity in terrestrial environments
Authors: Carlson Hans K. , Piya Denish , Moore Madeline L. , Magar Roniya Thapa , Elisabeth Nathalie H. , Deutschbauer Adam M. , Arkin Adam P. , Mutalik Vivek K. 
Published: April 2023

AbstractLytic phages can be potent and selective inhibitors of microbial growth and can have profound impacts on microbiome composition and function. However, there is uncertainty about the biogeochemical conditions under which phage predation can proceed and modulate microbial ecosystem function, particularly in terrestrial systems. Ionic strength is known to be critical for infection of bacteria by many phages, but there is limited quantitative data on ion thresholds for phage infection that can be compared with environmental ion concentrations. Similarly, while carbon composition varies in terrestrial environments, we know little of which carbon sources favor or disfavor phage infection and how these higher order interactions impact microbiome function. Here, we measured the half-maximal effective concentrations (EC50) of 80 different inorganic ions for the infection ofE. coliwith two canonical dsDNA and ssRNA phages, T4 and MS2, respectively. We found that many alkaline earth metals and alkali metals enabled successful lytic infection but that the ionic strength thresholds varied for different ions between phages. Additionally, using a freshwater nitrate reducing microbiome, we found that the ability of lytic phage to influence nitrate reduction end-products was dependent on the carbon source as well as the ion concentration. For all phage:host pairs we tested, the ion EC50s for phage infection we measured exceed the ion concentrations found in many terrestrial freshwater systems. Thus, our findings support a model where the influence of phages on terrestrial microbial functional ecology is greatest in hot spots and hot moments such as metazoan guts, drought influenced soils, or biofilms where ion concentration is locally or transiently elevated and carbon source composition is of a sufficiently low complexity to enrich for a dominant phage susceptible population.SignificanceViral-prokaryote dynamics greatly influence microbial ecology and the earth’s biogeochemical cycles. Thus, identifying the key environmental controls on phage predation is critical for predictive microbial ecology. Here we conduct laboratory experiments that implicate ionic strength and carbon composition as major controls on phage interactions with bacterial hosts in terrestrial microbiomes. We propose a model in which terrestrial phage predation is most favored in drought impacted soils and in higher ionic strength environments such as metazoan guts or between adjacent cells in biofilms.
A Predictive Coding Model of the N400
Authors: Eddine Samer Nour , Brothers Trevor , Wang Lin , Spratling Michael , Kuperberg Gina R. 
Published: April 2023

AbstractThe N400 event-related component has been widely used to investigate the neural mechanisms underlying real-time language comprehension. However, despite decades of research, there is still no unifying theory that can explain both its temporal dynamics and functional properties. In this work, we show that predictive coding – a biologically plausible algorithm for approximating Bayesian inference – offers a promising framework for characterizing the N400. Using an implemented predictive coding computational model, we demonstrate how the N400 can be formalized as the lexico-semantic prediction error produced as the brain infers meaning from linguistic form of incoming words. We show that the magnitude of lexico-semantic prediction error mirrors the functional sensitivity of the N400 to various lexical variables, priming, contextual effects, as well as their higher-order interactions. We further show that the dynamics of the predictive coding algorithm provide a natural explanation for the temporal dynamics of the N400, and a biologically plausible link to neural activity. Together, these findings directly situate the N400 within the broader context of predictive coding research, and suggest that the brain may use the same computational mechanism for inference across linguistic and non-linguistic domains.
Tree diversity increases productivity through enhancing structural complexity across mycorrhizal types
Authors: Ray Tama , Delory Benjamin M. , Bruelheide Helge , Eisenhauer Nico , Ferlian Olga , Quosh Julius , Oheimb Goddert von , Fichtner Andreas 
Published: April 2023

AbstractTree species diversity plays a central role for forest productivity, but factors driving positive biodiversity-productivity relationships remain poorly understood. In a biodiversity experiment manipulating tree diversity and mycorrhizal associations, we examined the roles of above- and belowground processes in modulating wood productivity in young temperate tree communities, as well as potential underlying mechanisms. We found that tree species richness increased forest productivity indirectly by enhancing structural complexity within communities. After six years, structurally complex communities were twice as productive as structurally simple stands. This pattern was consistent across stands with different mycorrhizal associations. Our results also demonstrate that taxonomic diversity and functional variation in shade tolerance, but not phenotypic plasticity, are key drivers of structural complexity in mixtures, which in turn lead to overyielding. Consideration of stand structural complexity appears to be a crucial element in predicting carbon sequestration in the early successional stages of mixed-species forests.
Strategic change in the health sector: a literature review and future challenges
Authors: Pereira Sérgio A.F. , Ferreira João J. , Rammal Hussain Gulzar , Peris-Ortiz Marta 
Published: April 2023

PurposeThe health sector is increasingly dynamic and complex, in which (strategic) change has become a constant in the sector's adaptation to different challenges. This study aims to meet the need to understand which trends in the literature on strategic change in the health sector and which elements comprise it.Design/methodology/approachTo advance research in this area, the authors systematically review 285 articles collected from the Scopus database. The authors conducted a bibliometric analysis using the VOSviewer software by applying the bibliographic matching method to understand how these articles were grouped and thus characterise the literature trends.FindingsThrough a systematic literature review (SLR), this study analyses the various lenses of literature on strategic change in the context of the health sector, classifying and conceptually mapping existing research into four thematic groups: key factors in strategic change, theories and models underlying strategic change, decentralisation in strategic change and the challenges to strategic change in this millennium.Research limitations/implicationsThe trends in the literature on strategic change in the health sector explore strategic change from different perspectives. Key features in strategic change suffered reciprocal influence from the theories/models of strategic change and decentralisation of health care so that the health sector could define strategies to respond to the challenges it faced.Originality/valueThe health sector has been in great prominence worldwide, specifically due to the recent events that have occurred on a planetary scale. Therefore, a systematic review is essential to help understand the strategic changes that have occurred in the health sector and their impact. The authors did not find any SLR that focuses on global strategic changes in the health sector, so this study will fill this gap, systematising the main topics on strategic change in the health sector. The authors also suggest an integrative research framework and a future research agenda.
Sin versus green investment: A retrospective study on investor choice during pre- and through COVID regime
Authors: Bhatnagar Chandra Shekhar , Bhatnagar Dyal , Kumari Vineeta , Bhullar Pritpal Singh 
Published: April 2023

PurposeIncreasing focus on socially responsible investments (SRIs) and green projects in recent times, coupled with the arrival of COVID pandemic, are the main drivers of this study. The authors conduct a post-factum analysis of investor choice between sin and green investments before and through the COVID outbreak.Design/methodology/approachA passive investor is introduced who seeks maximum risk-adjusted return and/or investment variance. When presented an opportunity to add sin and/or green investments to her initial one-asset market-only investment position, she views and handles this issue as a portfolio problem (MPT). She estimates value-at-risk (VaR) and conditional-value-at-risk (CVaR) for portfolios to account for downside risk.FindingsGreen investments offer better overall risk-return optimization in spite of major inter-period differences in return-risk dynamics and substantial downside risk. Portfolios optimized for minimum variance perform just as well as the ones optimized for minimum downside risk. Return and risk have settled at higher levels since the onset of COVID, resulting in shifting the efficient frontier towards north-east in the return-risk space.Originality/valueThe study contributes to the literature in two ways: One, it examines investor choice between sin and green investments during a global health emergency and views this choice against the one made during normal times. Two, instead of using the principles of modern portfolio theory (MPT) explicitly for diversification, the study uses them to identify investor preference for one over the other investment type. This has not been widely done thus far.
Meadow transformations alter above‐ and below‐ground ecological networks and ecosystem multifunctionality
Authors: Gao Erliang , Ma Hui , Yang Ting , Kaiser‐Bunbury Christopher N. , Zhao Zhigang 
Published: April 2023

AbstractHuman‐mediated environmental change transforms ecosystems worldwide. Understanding the detailed impact of these unprecedented changes on biodiversity and ecosystem functioning, however, is challenging. Meadow ecosystems on the Tibetan Plateau transform as a result of climate change and anthropogenic disturbances. Evaluating the consequences of these meadow transformations on above‐ and below‐ground community structure, ecological network and ecosystem functioning is critical for predicting the impact on biodiversity and developing mitigation strategies.Here, we used a natural experiment across replicated sites to assess the responses of ecological networks of soil microbial communities and plant‐pollinator communities to meadow transformations and investigate the impacts of these changes on ecosystem multifunctionality.As a result of swampy meadow desiccation, species richness and ecological network complexity at multiple trophic levels increased, pollination networks became more robust while soil microbial networks became more vulnerable to species loss. Pollination function appeared to benefit from increased diversity in resources and the formation of dry soil, but important below‐ground functions decreased. When alpine meadows degraded further because of extensive grazing pressure, above‐ground diversity and network complexity tended to decline. Soil microbial richness and composition remained unchanged but associations among soil microbes homogenized, and ecosystem productivity and pollination function decreased.Our study provides empirical evidence that human‐mediated meadow transformations influence above‐ and below‐ground ecological networks and ecosystem functioning simultaneously. The findings highlight that ecosystem transformations can have contrasting effects on above‐ and below‐ground diversity and ecological networks, as well as ecosystem functions. Such contrasting responses call for targeted and nuanced management strategies to conserve biodiversity and ecosystem functioning in the Tibetan Plateau.Read the freePlain Language Summaryfor this article on the Journal blog.