bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma extracellular vesicles influence glial cell hyaluronic acid deposition to promote invasiveness
Authors: Koessinger Dominik , Novo David , Koessinger Anna , Campos America , Peters Jasmine , Dutton Louise , Paschke Peggy , Zerbst Désirée , Moore Madeleine , Mitchell Louise , Neilson Matthew , Stevenson Katrina , Chalmers Anthony , Tait Stephen , Birch Joanna , Norman Jim 
Published: May 2023

Abstract

Background
Infiltration of glioblastoma (GBM) throughout the brain leads to its inevitable recurrence following standard-of-care treatments, such as surgical resection, chemo-, and radiotherapy. A deeper understanding of the mechanisms invoked by GBM to infiltrate the brain is needed to develop approaches to contain the disease and reduce recurrence. The aim of this study was to discover mechanisms through which extracellular vesicles (EVs) released by GBM influence the brain microenvironment to facilitate infiltration, and to determine how altered extracellular matrix (ECM) deposition by glial cells might contribute to this.

Methods
CRISPR was used to delete genes, previously established to drive carcinoma invasiveness and EV production, from patient-derived primary and GBM cell lines. We purified and characterized EVs released by these cells, assessed their capacity to foster pro-migratory microenvironments in mouse brain slices, and evaluated the contribution made by astrocyte-derived ECM to this. Finally, we determined how CRISPR-mediated deletion of genes, which we had found to control EV-mediated communication between GBM cells and astrocytes, influenced GBM infiltration when orthotopically injected into CD1-nude mice.

Results
GBM cells expressing a p53 mutant (p53R273H) with established pro-invasive gain-of-function release EVs containing a sialomucin, podocalyxin (PODXL), which encourages astrocytes to deposit ECM with increased levels of hyaluronic acid (HA). This HA-rich ECM, in turn, promotes migration of GBM cells. Consistently, CRISPR-mediated deletion of PODXL opposes infiltration of GBM in vivo.

Conclusions
This work describes several key components of an EV-mediated mechanism though which GBM cells educate astrocytes to support infiltration of the surrounding healthy brain tissue.
Assessing bird diversity in Neotropical rainforests: A comparative study of camera traps and mist nets reveals complementary sampling approaches
Authors: Vargas-Daza Angela M , Betancurt-Grisales Juan F , Cardona-Salazar Leydy J , Benavides-Ossa Yeny A , Fontúrbel Francisco E , Castaño-Villa Gabriel J 
Published: May 2023

Abstract
Different sampling methods are used to study bird diversity in the tropics, mist nets being one of the most common approaches. However, camera traps have been used for this purpose in the last 20 years. We compared the performance of mist nets and camera traps in sampling the diversity of understory and sub-canopy birds in a Neotropical rainforest. Given its high biodiversity, obtaining accurate bird diversity estimates in these forests is a challenging task. We sampled secondary forest patches in the Colombian central Andes between 2019 and 2021. We compared the effectiveness of both methods based on six comparison criteria (body size, foraging stratum, detection difficulty, habitat specialization, population trend, and migratory status). We recorded a total of 99 bird species: 92 species were captured using mist nets and 37 species using camera traps; 30 species were detected using both methods (mainly generalist and abundant birds). Mist net’s effectiveness was 83%, while camera trap effectiveness was 68%. Differences in sampling effectiveness were mainly determined by body size, as small birds were captured using mist nets, while camera traps often recorded large birds. However, detection difficulty and habitat specialization were also relevant. Camera traps effectively recorded ground-dwelling species that were not captured in mist nets. In contrast, those birds that forage in the sub-canopy stratum were mainly captured in the mist nets but not detected in camera traps. Although both methods detected different species, we found similar patterns regarding estimated species richness among different categories of body size, detection difficulty, population trend, and behavior, but not for habitat specialization. As both methods have advantages and limitations, using mist nets and camera traps together would improve bird diversity estimations. We urge investigators to explore canopy ecology with camera traps, as they provide long-term information that cannot be obtained with other methods.
Glutamine Metabolism, Sensing and Signaling in Plants
Authors: Lee Kim-Teng , Liao Hong-Sheng , Hsieh Ming-Hsiun 
Published: May 2023

Abstract
Glutamine (Gln) is the first amino acid synthesized in nitrogen (N) assimilation in plants. Gln synthetase (GS), converting glutamate (Glu) and NH4+ into Gln at the expense of ATP, is one of the oldest enzymes in all life domains. Plants have multiple GS isoenzymes that work individually or cooperatively to ensure that the Gln supply is sufficient for plant growth and development under various conditions. Gln is a building block for protein synthesis and an N-donor for the biosynthesis of amino acids, nucleic acids, amino sugars and vitamin B coenzymes. Most reactions using Gln as an N-donor are catalyzed by Gln amidotransferase (GAT) that hydrolyzes Gln to Glu and transfers the amido group of Gln to an acceptor substrate. Several GAT domain–containing proteins of unknown function in the reference plant Arabidopsis thaliana suggest that some metabolic fates of Gln have yet to be identified in plants. In addition to metabolism, Gln signaling has emerged in recent years. The N regulatory protein PII senses Gln to regulate arginine biosynthesis in plants. Gln promotes somatic embryogenesis and shoot organogenesis with unknown mechanisms. Exogenous Gln has been implicated in activating stress and defense responses in plants. Likely, Gln signaling is responsible for some of the new Gln functions in plants.
Revisiting Atiyah–Hitchin manifold in the generalized Legendre transform
Authors: Arai Masato , Baba Kurando , Ionaş Radu A 
Published: May 2023

Abstract
We revisit construction of the Atiyah–Hitchin manifold in the generalized Legendre transform approach. This was originally studied by Ivanov and Roček [I. T. Ivanov, M. Roček, Commun. Math. Phys. 182, 291 (1996)] and subsequently investigated more by Ionas [R. A. Ionas, arXiv:0712.3598] , in the latter of which the explicit forms of the Kähler potential and the Kähler metric are calculated. There is a difference between the former and the latter. In the generalized Legendre transform approach, a Kähler potential is constructed from the contour integration of one function with holomorphic coordinates. The choice of the contour in the latter is different from that in the former; this difference may yield a discrepancy in the Kähler potential and eventually in the Kähler metric. We show that the former only gives the real Kähler potential, which is consistent with its definition, while the latter yields the complex one. We derive the Kähler potential and the metric for the Atiyah–Hitchin manifold in terms of holomorphic coordinates for the contour considered by Ivanov and Roček for the first time.
Effect of lactation and nursery diets supplemented with a feed flavor on sow feed intake and lactation performance and subsequent weaned pig nursery performance
Authors: Spinler Mikayla S , Gebhardt Jordan T , Tokach Mike D , Goodband Robert D , DeRouchey Joel M , Kyle Josh M , Woodworth Jason C 
Published: May 2023

Abstract
A total of 105 sows (Line 241, DNA, Columbus, NE) were used across four batch farrowing groups to evaluate the effects of feeding a feed flavor in lactation diets on sow and litter performance. Sow groups 1 and 2 farrowed in an old farrowing facility during the summer months and groups 3 and 4 farrowed in a new farrowing facility during the winter months. Sows were blocked by body weight (BW) within parity on days 110 of gestation and allotted to 1 of 2 dietary treatments. Dietary treatments were a standard corn–soy-based lactation diet (control) or the control diet with the addition of a feed flavor at 0.05% of diet (Krave AP, Adisseo, Alpharetta, GA, USA). Farrowing facility environment had a large impact and resulted in many interactions with the feed flavor treatment. From farrowing to weaning, sows fed the feed flavor in the old farrowing house tended to have a higher (P = 0.058) lactation feed intake, while no difference in average daily feed intake (ADFI) was observed in the new farrowing house. Pigs weaned from sows fed with the feed flavor in the old farrowing facility had a higher (P = 0.026) BW at weaning and piglet average daily gain (ADG) from day 2 to weaning (P = 0.001) compared to piglets from sows not fed with the feed flavor; whereas the opposite occurred in the new farrowing house. Progeny from one farrowing group in the old farrowing facility was followed into the nursery. A total of 360 weaned pigs (DNA 241 × 600: initially 5.7 kg) were used in a 2 × 2 factorial in the nursery portion of the study to evaluate the effects of previous sow feed flavoring treatment (control vs. flavor) and nursery diets formulated with or without a feed flavor on growth performance in a 38-d trial. Nursery treatments were either a control diet or a diet containing a feed flavor (Delistart #NA 21, Adisseo). Offspring from sows fed with the flavor diet were heavier at weaning (P &lt; 0.001) which was maintained throughout the study. Overall, progeny from sows fed with a diet containing a feed flavor had greater (P &lt; 0.05) ADG, ADFI, and final BW during the trial. The presence of a feed flavor in the nursery did not improve overall nursery performance. In conclusion, when sow lactation feed intake was increased in the old farrowing house, pigs weaned from sows fed with the flavor diet were heavier (P = 0.039) at weaning compared to pigs weaned from sows fed with the control diet. Adding the feed flavor increased sow feed intake and piglet ADG in a warm environment, but not in a cool environment.
Refining risk estimates for lead in drinking water based on the impact of genetics and diet on blood lead levels using the Collaborative Cross mouse population
Authors: Cuomo Danila , Nitcher Megan , Barba Estefania , Feinberg Andrew P , Rusyn Ivan , Chiu Weihsueh A , Threadgill David W 
Published: May 2023

Abstract
Blood lead (Pb) level (BLL) is a commonly used biomarker to evaluate associations with health effects. However, interventions to reduce the adverse effects of Pb require relating BLL to external exposure. Moreover, risk mitigation actions need to ensure protection of more susceptible individuals with a greater tendency to accumulate Pb. Because little data is available to quantify inter-individual variability in biokinetics of Pb, we investigated the influence of genetics and diet on BLL in the genetically diverse Collaborative Cross (CC) mouse population. Adult female mice from 49 CC strains received either a standard mouse chow or a chow mimicking the American diet while being provided water ad libitum with 1000 ppm Pb for 4 weeks. In both arms of the study, inter-strain variability was observed; however, in American diet-fed animals, the BLL was greater and more variable. Importantly, the degree of variation in BLL among strains on the American diet was greater (2.3) than the default variability estimate (1.6) used in setting the regulatory standards. Genetic analysis identified suggestive diet-associated haplotypes that were associated with variation in BLL, largely contributed by the PWK/PhJ strain. This study quantified the variation in BLL that is due to genetic background, diet, and their interactions, and observed that it may be greater than that assumed for current regulatory standards for Pb in drinking water. Moreover, this work highlights the need of characterizing inter-individual variation in BLL to ensure adequate public health interventions aimed at reducing human health risks from Pb.
Endoscopic-assisted Surgical Removal of Infected Interosseous Wires 40 Years After Mandibular Surgery
Authors: Sukegawa Shintaro , Miyazaki Ryo , Matsuki Yusuke , Iwata Masashi , Nakai Fumi , Nakai Yasuhiro , Miyake Minoru 
Published: May 2023

We demonstrate a highly reliable minimally invasive treatment for removal of residual wire from the mandible. The patient was a 55-year-old Japanese man who was referred to our department for a fistula in his submental area. The patient had undergone open reduction and fixation with wires for mandibular fractures (left parasymphysis, right angle fracture) more than 40 years prior and mandibular tooth extraction and drainage 6 months prior. Minimally invasive endoscopy-assisted wire removal surgery was performed under general anesthesia with good visualization in a narrow surgical field. Bone resection was minimized using an ultrasonic cutting instrument with a wide choice of tip shapes.
The use of endoscopy with ultrasonic cutting tools makes it possible to effectively utilize narrow surgical fields with a small skin incision and minimal bone cutting. The advantages and disadvantages of the newer endoscopic systems in oral and maxillofacial surgical units are discussed.
Assortative mating and parental genetic relatedness drive the pathogenicity of variably expressive variants
Authors: Smolen Corrine , Jensen Matthew , Dyer Lisa , Pizzo Lucilla , Tyryshkina Anastasia , Banerjee Deepro , Rohan Laura , Huber Emily , Khattabi Laila El , Prontera Paolo , Caberg Jean-Hubert , Van Dijck Anke , Schwartz Charles , Faivre Laurence , Callier Patrick , Mosca-Boidron Anne-Laure , Lefebvre Mathilde , Pope Kate , Snell Penny , Lockhart Paul J. , Castiglia Lucia , Galesi Ornella , Avola Emanuela , Mattina Teresa , Fichera Marco , Mandarà Giuseppa Maria Luana , Bruccheri Maria Grazia , Pichon Olivier , Le Caignec Cedric , Stoeva Radka , Cuinat Silvestre , Mercier Sandra , Bénéteau Claire , Blesson Sophie , Nordsletten Ashley , Martin-Coignard Dominique , Sistermans Erik , Kooy R. Frank , Amor David J. , Romano Corrado , Isidor Bertrand , Juusola Jane , Girirajan Santhosh 
Published: May 2023

ABSTRACTWe examined more than 38,000 spouse pairs from four neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents associated with neurodevelopmental disease risk in children. We identified correlations between six phenotypes in parents and children, including correlations of clinical diagnoses such as obsessive-compulsive disorder (R=0.31-0.49, p<0.001), and two measures of sub-clinical autism features in parents affecting several autism severity measures in children, such as bi-parental mean Social Responsiveness Scale (SRS) scores affecting proband SRS scores (regression coefficient=0.11, p=0.003). We further describe patterns of phenotypic and genetic similarity between spouses, where spouses show both within- and cross-disorder correlations for seven neurological and psychiatric phenotypes, including a within-disorder correlation for depression (R=0.25-0.72, p<0.001) and a cross-disorder correlation between schizophrenia and personality disorder (R=0.20-0.57, p<0.001). Further, these spouses with similar phenotypes were significantly correlated for rare variant burden (R=0.07-0.57, p<0.0001). We propose that assortative mating on these features may drive the increases in genetic risk over generations and the appearance of “genetic anticipation” associated with many variably expressive variants. We further identified parental relatedness as a risk factor for neurodevelopmental disorders through its inverse correlations with burden and pathogenicity of rare variants and propose that parental relatedness drives disease risk by increasing genome-wide homozygosity in children (R=0.09-0.30, p<0.001). Our results highlight the utility of assessing parent phenotypes and genotypes in predicting features in children carrying variably expressive variants and counseling families carrying these variants.
The implementation and effectiveness of multi-tasked, paid community health workers on maternal and child health: A cluster-randomized pragmatic trial and qualitative process evaluation in Tanzania
Authors: Baynes Colin , Kanté Almamy Malick , Exavery Amon , Kassimu Tani , Sikustahili Gloria , Mushi Hildegalda , Baraka Jitihada , Ramsey Kate , Sherr Kenneth , Weiner Bryan , Phillips James F. 
Published: May 2023

AbstractCommunity health worker programs have proliferated worldwide based on evidence that they help prevent mortality, particularly among children. However, there is limited evidence from randomized studies on the processes and effectiveness of implementing community health worker programs through public health systems. This paper describes the results of a cluster-randomized pragmatic implementation trial (registration numberISRCTN96819844) and qualitative process evaluation of a community health worker program in Tanzania that was implemented from 2011-2015. Program effects on maternal, newborn and child health service utilization, childhood morbidity and sick childcare seeking were evaluated using difference-in-difference regression analysis with outcomes measured through pre and post-intervention household surveys in intervention and comparison trial arms. A qualitative process evaluation was conducted between 2012 and 2014 and comprised of in-depth interviews and focus group discussions with community health workers, community members, facility-based health workers and staff of district health management teams. The community health worker program reduced incidence of childhood illness and improved access to timely and appropriate sick childcare; however, there was no effect on maternal, newborn and child health service utilization. The positive outcomes occurred because of high levels of acceptability of community health workers within communities, as well as the durability of community health workers’ motivation and confidence. Implementation factors that generated these effects were the engagement of communities in program startup; the training, remuneration and supervision of the community health workers from the local health system and community. The lack of program effects on maternal, newborn and child health service utilization were attributed to lapses in the availability of needed care at facilities and of working materials among community health workers. Strategies that strengthen and align communities’ and health systems core capacities, and their ability to learn, adapt and integrate evidence-based interventions, are needed to maximize the health impact of community health workers.
Mining multi-omics data for molecular subtyping in gliomas facilitates precise clinical treatment
Authors: Feng Peng , Pan Yawen 
Published: May 2023

SummaryGlioma is the most common malignancy in the skull, accounting for approximately 2% of adult systemic tumors. It is characterized by a high recurrence rate, high disability rate, and poor sensitivity to chemotherapy. Different subtypes of glioma exhibit varying prognosis and chemotherapy sensitivities. Currently, researchers extensively study the molecular classification of glioma based on transcriptomic features, facilitating the evaluation of prognosis. However, identification of tumor subtypes based on the single-layer-omics data have several limitations. In this regard, the present study aimed to identify new subtypes of glioma using three omics datasets for prognosis prediction. As a result, cluster A subtype was identified to be associated with lower activation of cell proliferation and better prognosis, while cluster B subtype exhibited higher infiltration of M2-type macrophages and higher activation of the epithelial-mesenchymal transition (EMT) pathway, potentially leading to a poorer prognosis. Furthermore, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm and limma R package to identify driver genes for clusters A and B. Consequently, nine genes were identified as gene signatures for cluster A. Based on this finding, we quantified the two subtypes using the single-sample gene set enrichment analysis (ssGSEA) algorithm, where a higher score were linked to elevated tumor mutation burden (TMD) and signaling pathways related to cell proliferation. Low scores indicated enrichment of tumorigenesis-related pathways and poor prognosis. In silico drug screening suggested that AGI-6780 could be an effective compound for high cluster subtypes, based on brain tumor cell lines. Consequently, our study determined that the score can serve as an effective index to predict the prognosis of glioma.
Electrostatically regulated active site assembly governs reactivity in non-heme iron halogenases
Authors: Smithwick Elizabeth R. , Wilson R. Hunter , Chatterjee Sourav , Pu Yu , Dalluge Joseph J. , Damodaran Anoop Rama , Bhagi-Damodaran Ambika 
Published: May 2023

ABSTRACTNon-heme iron halogenases (NHFe-Hals) catalyze the direct insertion of a chloride/bromide ion at an unactivated carbon position using a high-valent haloferryl intermediate. Despite more than a decade of structural and mechanistic characterization, how NHFe-Hals preferentially bind specific anions and substrates for C-H functionalization remains unknown. Herein, using lysine halogenating BesD and HalB enzymes as model systems, we demonstrate strong positive cooperativity between anion and substrate binding to the catalytic pocket. Detailed computational investigations indicate that a negatively charged glutamate hydrogen-bonded to iron’s equatorial-aqua ligand acts as an electrostatic lock preventing both lysine and anion binding in the absence of the other. Using a combination of UV-Vis spectroscopy, binding affinity studies, stopped-flow kinetics investigations, and biochemical assays, we explore the implication of such active site assembly towards chlorination, bromination, and azidation reactivities. Overall, our work highlights previously unknown features regarding how anion-substrate pair binding govern reactivity of iron halogenases that are crucial for engineering next-generation C-H functionalization biocatalysts.
In vitroreconstitution of SARS CoV-2 Nsp1-induced mRNA cleavage reveals the key roles of the N-terminal domain of Nsp1 and the RRM domain of eIF3g
Authors: Abaeva Irina S. , Arhab Yani , Miścicka Anna , Hellen Christopher U. T. , Pestova Tatyana V. 
Published: May 2023

ABSTRACTSARS CoV-2 nonstructural protein 1 (Nsp1) is the major pathogenesis factor that inhibits host translation using a dual strategy of impairing initiation and inducing endonucleolytic cleavage of cellular mRNAs. To investigate the mechanism of cleavage, we reconstituted itin vitroon β-globin, EMCV IRES and CrPV IRES mRNAs that use unrelated initiation mechanisms. In all instances, cleavage required Nsp1 and only canonical translational components (40S subunits and initiation factors), arguing against involvement of a putative cellular RNA endonuclease. Requirements for initiation factors differed for these mRNAs, reflecting their requirements for ribosomal attachment. Cleavage of CrPV IRES mRNA was supported by a minimal set of components consisting of 40S subunits and eIF3g’s RRM domain. The cleavage site was located in the coding region 18 nucleotides downstream from the mRNA entrance indicating that cleavage occurs on the solvent side of the 40S subunit. Mutational analysis identified a positively charged surface on Nsp1’s N-terminal domain (NTD) and a surface above the mRNA-binding channel on eIF3g’s RRM domain that contain residues essential for cleavage. These residues were required for cleavage on all three mRNAs, highlighting general roles of Nsp1-NTD and eIF3g’s RRM domain in cleavageper se, irrespective of the mode of ribosomal attachment.