bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Molecular Characterization of Glioma Patients: miR-21 Expression as a Prognostic Biomarker in Tissue and Serum
Authors: Laghari Altaf Ali , Sufiyan Sufiyan , Amin Wajiha , Adnan Umer , Naeem Sana , Abidi Syed Hani , Ilyas Sahar , Uddin Siraj , Bajwa Mohammad Hamza , Enam Syed Ather , Mughal Nouman 
Published: November 2024

AbstractBackgroundGlioma remains challenging due to high recurrence rates and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often leads to significant patient attrition. Serum microRNA (miRNA) expression profiles, which have been shown to correlate with tissue expression profiles, are detectable in peripheral blood samples, providing a promising avenue for non-invasive and repeatable liquid biopsies. miR-21 shows promise in many populations; however, there is a dearth of data from our region.MethodologyWe collected 90 tumor tissues, 42 pre- and post-operative serum samples from glioma patients, and included 10 normal tissue adjacent to the tumor (NATs) along with serum samples from 8 healthy individuals and analyzed for miR-21 expression through RT-qPCR. Shapiro Wilk test was applied to calculate data distribution, ANOVA, Fisher’s exact, and Wilcox test, along with pairwise Student’s t-test, were applied to determine the differences in gene expression. The expression level of miR-21 was assessed for correlation with Kaplan-Meier survival curves and different molecular markers (IDH, Ki-67, ATRX and p53). The quantitative hazard ratio was determined using Cox regression analysis.ResultsmiR-21 expression in tissue increased with the mean log fold expression 0.101 (median fold = 2.35) in grade 2, 1.00 (median fold = 7.49) in grade 3 and 1.53 (median fold = 26.0) in grade 4 for glioma patients. The expression level showed significant difference between control tissue and grade 4 patients along with significant inter-comparison between grade 1 and grade 4, as well as grade 2 and grade 4.A significant elevated expression of miR-21 has been noticed in patients above 50 years of age. Similarly, in serum samples a significant decline in miR-21 expression was observed in post-operative samples as compared to pre-operative samples mean log fold in grade 2 is 1.30 (11.6-fold), grade 3 is 1.08 (15.3-fold) and grade 4 is 0.749 (13.2-fold). Furthermore, there was positive correlation of miR-21 expression with tumor volume. IDH-wildtype and high Ki-67 expression in gliomas showed significant upregulation of miR-21 compared to IDH-mutant and low Ki-67 respectively. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression. Quantitative hazard analysis indicates that patients in the high expression group have a 3.4 times higher risk of mortality (95% CI: 1.6-7.1), in comparison to patients in the low expression group with AUC of 0.742 (all p <0.05).ConclusionThis study demonstrates the potential of microRNA 21 as a serum biomarker for early, cost-effective diagnosis of glioma. Furthermore, it may inform the development of targeted treatment strategies for various glioma grades, particularly in our population.
Accelerated growth of the scleractinian coralOrbicella faveolataunder turbid and polluted water conditions
Authors: Lizcano-Sandoval Luis , Marulanda-Gómez Angela , López-Victoria Mateo , Rodriguez-Ramirez Alberto 
Published: November 2024

AbstractCartagena Bay, Colombia, experienced historical changes in water quality, mainly due to dredging and channelization of the Canal del Dique, which connects the bay with the Magdalena River. In 1981 the largest dredging events occurred in the Canal del Dique, which negatively affected the water quality in the bay. In this bay, the coral reef of Varadero depicts high coral diversity and large coral colonies, showing apparent signs of a healthy ecosystem, under highly turbid and polluted waters. Here, we evaluated the potential effects of historical water quality changes and environmental variables on the coral skeletal growth ofOrbicella faveolata. We obtained coral growth information from 65 years in the period 1951–2015. Coral skeletal density was 0.73 g cm-3, linear extension 1.02 cm yr-1, and calcification 0.74 g cm-2yr-1. After 1981, significant changes in coral growth and luminescence were found: skeletal density decreased (9.9%), linear extension increased (6.6%), and skeletal luminescence was less intense (1.6%). In overall, Atlantic Multidecadal Oscillation (AMO) data explained changes in skeletal density (8–10%) and linear extension (7–19%). Air temperature explained changes in skeletal luminescence (22–45%). Water flow of the Canal del Dique did not contribute significantly to any coral growth and luminescence variables. The growth ofO. faveolatain Varadero Reef was characterized by low density skeletons and an accelerated linear extension, apparently influenced by the dredging events of 1981. Further research is required to understand coral growth responses and resilience to the conditions of high turbidity, pollution, and low light in Cartagena Bay.
Neural correlates of kinematic features of passive finger movement revealed by univariate and multivariate fMRI analyses
Authors: Pamplona Gustavo S. P. , Sulzer James , Beldzik Ewa , Lambercy Olivier , Ionta Silvio , Gassert Roger , Lewis-Peacock Jarrod 
Published: November 2024

AbstractFinger movements are associated with a relatively large neural representation. Passive finger movement – which involves refraining from actively performing or resisting movement – is a robust approach to investigate the neural representation of kinesthesia and proprioception in the brain. While some studies have characterized the neural correlates of passive finger movement, they have relied solely on mass univariate analysis, potentially affecting result sensitivity. Additionally, limited consideration has been given to stimulus duration, a factor closely tied to some kinematic features (amplitude and velocity), which recently proposed modeling approaches now take into account. Here, we reanalyzed previously published data using univariate and multivariate analysis to understand how kinesthesia is neurally encoded in neurotypical subjects in two separate experiments. Systematic passive stimulation of the fingers was provided using an MR-compatible robot while functional magnetic resonance imaging data was recorded. Our analyses consisted of univariate and multivariate approaches, conducted separately for each kinematic feature and adjusted for stimulus duration, regardless of whether brain activation scales with it. We provide a detailed mapping of brain areas related to amplitude, velocity, and direction of passive finger movement, including sensorimotor, subcortical, and cerebellar areas. In general, multivariate pattern analysis was more sensitive than the univariate approach in identifying brain regions associated with passive finger movement. Our univariate analysis demonstrated that activity in sensorimotor and subcortical areas was higher for larger amplitudes and slower velocities, which opposes to the original study’s results, likely due to our treatment of stimulus duration as a confounder specified as a parametric modulator. A novel result, we also demonstrated that brain activity in sensorimotor areas was higher for extension compared to flexion of passive finger movement. In terms of kinematic features, a larger neural representation was found for amplitude and direction compared to velocity of passive finger movement. This indicates that kinesthesia and proprioception may be more reliant on displacement than kinematic aspects of passive finger movement. While univariate analyses are limited in addressing spatial heterogeneity and subject-level variability, our multivariate analyses showed increased sensitivity in identifying brain regions encoding passive movement. Our findings may extend the knowledge of how the brain encodes physical movements and may help design neurorehabilitation strategies.
Major changes in gene expression between strains of diapausing and non-diapause spruce budworm despite little evidence of genetic divergence
Authors: van der Burg Karin R. L. , Gauthier Jeff , Roe Amanda D. , Cusson Michel , Boyle Brian , Levesque Roger C. , Marshall Katie E. 
Published: November 2024

AbstractTo survive harsh winter conditions, many insects enter a state of dormancy called diapause which allows them to withstand extreme temperatures and lack of food. When diapause is induced, insects enter a state of arrested development and low metabolic rate. Because diapause and environmental conditions are closely linked, variation within and between species in diapause induction, depth, and duration is extremely common. Studies investigating the genetic underpinnings of diapause tend to focus on either different populations and/or environmental variation, which runs the risk of confounding the genetic signal either due to isolation-by-distance or variation in environmental conditions. We use the eastern spruce budworm (Choristoneura fumiferana) to circumvent these issues and investigate within-population variation in diapause.C. fumiferanausually diapauses as second instar larvae, but a small subset of individuals does not diapause and instead continues through development. This non-diapause phenotype can be selected to create a non-diapause strain. Here, we present a chromosome-level assembly of such a non-diapause strain, and compare it to an earlier published genome assembly of the diapause strain. We did not find evidence of major chromosome rearrangements, indicating that the genetic variation between strains is likely small and multi-genic. Gene expression comparisons between the strains indicate major gene expression changes, where genes associated with glycolysis and environmental signaling processing increase in expression in the diapause strain. Lastly, we found that gene expression diverges halfway through the first instar, and not before, indicating that the signal to induce diapause happens early in the first instar.Significance statementThe ability to enter diapause is a crucial adaptation for many insects to survive cold winters. The genetic underpinnings of the diapause phenotype has been the target of many investigations. However, many of these studies focus on variation in diapause on between geographic regions or changes in environmental conditions, which can lead to confounding factors. Here, we focus on within-population variation in diapause in the eastern spruce budworm, with two strains established from the same source population that vary in their ability to induce diapause. We present a chromosome level assembly of the non-diapause strain, and report that genetic changes between the diapause and the non-diapause line are likely small and involve multiple loci. Gene expression differences were extensive, and mostly associated with mechanisms to avoid freezing. This work sets the stage to further investigate how minimal genetic changes can lead to large-scale phenotypic changes as impactful as diapause.
The Effect of Human Presence and Activity Type on Innovative Problem-Solving of Urban Eurasian Red Squirrels
Authors: Chow Pizza Ka Yee , Loukola Olli J , Solvi Cwyn 
Published: November 2024

AbstractHumans impact wildlife positively and negatively, and increasing evidence shows that humans potentially play a major role in shaping cognition in wild animals. Recent evidence suggests, in particular, that the ability to innovate (an important cognitive ability for urban wildlife) can be affected by humans. However, the specific anthropogenic factors associated with shaping animal cognitive performance remain unclear.Here, across 15 urban areas in Oulu, Finland, we recorded 64 wild Eurasian red squirrels’ interactions with a novel puzzle box (innovative problem-solving) to obtain a highly preferred food, hazelnuts.We then examined how different levels of human presence nearby, types of activity (walking, dog walking, cycling, and playground activities), and distance to the nearest footpaths influenced squirrels’ innovative problem-solving ability – measured as solving success at the population level and solving latency at the individual level.At the population level, higher mean human presence nearby significantly decreased the proportion of squirrels that successfully solved the novel food-extraction problem (“innovators”), and greater human presence nearby decreased first-visit solving latency at individual level. Except for cycling, all types of human activities (walking, dog walking, and playground activity) significantly decreased first-visit success rate. Dog walking and playground activity had a greater negative impact on success rate at the population level than walking. Dog walking was the only outstanding factor affecting first-success latency. We also detected interaction effects between the types of human activities and nearest footpath on overall success rate of all innovators.These results provide evidence for the negative effect of specific human-related factors on squirrels’ innovative problem-solving abilities. These factors may also exert selective pressure, potentially shaping the evolution of wildlife cognition.
De novo identification of protein domains in cryo-electron tomography maps from AlphaFold2 models
Authors: Lu Yi , Chen Guanglin , Sun Fei , Zhu Yun , Zhang Zhiyong 
Published: November 2024

AbstractIn recent years, in situ cryo-electron tomography (cryo-ET) has emerged as a powerful method for visualizing structures of protein complexes within their native cellular environment. However, the resolution of in situ cryo-ET remains lower than that of in vitro cryo-electron microscopy single particle analysis (cryo-EM/SPA). Identifying proteins in a cryo-ET density map is particularly challenging owing to the limited visibility of side chains. To address this issue, we developed DomainSeeker, a tool designed for de novo identification of protein domains in cryo-ET maps of protein complexes. DomainSeeker integrates AlphaFold2-predicted models to partition proteins into domains using predicted aligned errors and a clique-based graph cluttering algorithm, and subsequently fits these domains into segmented density maps. Finally, it uses a two-dimensional scoring metric to identify the most probable domain of each density map. On a test set containing 26 model-based densities segmented from a sperm microtubule doublet map, DomainSeeker efficiently identified nearly all of these domains at both 6.5 Å and 10 Å. On another test set of 20 auto-segmented densities, 17 out of them were also determined. Furthermore, we successfully identified a new protein within an unmodeled region of this map.
A compendium ofbona fidereference markers for genuine plant-derived extracellular vesicles and their degree of phylogenetic conservation
Authors: Rodríguez de Lope Miriam M. , Sánchez-Pajares Ibone R. , Herranz Estela , López-Vázquez Cristina M. , González-Moro Ainara , Rivera-Tenorio Alan , Carlos González-Sanz , Sacristán Soledad , Chicano-Gálvez Eduardo , de la Cuesta Fernando 
Published: November 2024

AbstractAlthough the field of plant-derived EVs (PDEVs) is experimenting an exponential growth, rigorous characterization complying with MISEV guidelines has not been yet implemented due to the lack ofbona fidereference markers. In this work, we have paved the way for the standardization of PDEV markers, providing the most profound proteomic data so far from apoplastic washing fluid-derived EVs, a sample enriched in genuine extracellular vesicles from plant tissue, as opposed to methods involving tissue disruption; of two reference plant species:Arabidopsis thaliana(Arath-EVs) andBrassica oleracea(Braol-EVs). Additionally, we have conducted an exhaustive analysis of the proteomic data available so far from genuine EVs from any plant species, evaluating current potential markers, together with those found in our proteomic analyses. Our results provide evidence supporting the potential use of the following families as PDEV markers: fasciclin-like arabinogalactan proteins (FLAs), patellins, germin-like proteins, aquaporins, heat shock 70 proteins, 14-3-3 like proteins, Rab proteins, and vacuolar-type ATPase complex subunits. Next, we analyzed the presence of orthologues and their degree of conservation throughout plant taxa, as well as in 2 reference species from the animal kingdom: human and mouse. Their degree of conservation was compared with that of current EV markers used in animal-derived EVs: CD63, CD81 and CD9. Among the protein families with potential to be used as PDEV markers, 3 were found to be plant-specific: FLAs, patellins and germin-like proteins. Among these, fasciclin-like arabinogalactan (FLA) proteins, in particular FLA1, FLA2 and FLA8, were recurrently identified in EVs from different plant sources showing great abundance and thus arise as a novel family of plant-specific GPI-anchored PDEV markers. Furthermore, FLAs hold promise as ideal PDEV markers since they have orthologues across the different plant subdivisions and display a similar phylogenetic distribution in plants to that of currently used markers in animals.
From high protection to lethal effect: diverse outcomes of immunization against invasive candidiasis with differentCandida albicansextracellular vesicles
Authors: Martínez-López Raquel , Molero Gloria , Parra-Giraldo Claudia , Cabeza Matías , Castejón Guillermo , García-Duran Carmen , Clemente Felipe , Hernáez María Luisa , Gil Concha , Monteoliva Lucía 
Published: November 2024

AbstractExtracellular vesicles (EVs) fromCandida albicanscan elicit immune responses, positioning them as promising acellular vaccine candidates. We characterized EVs from an avirulentC. albicanscell wall mutant (ecm33Δ) and evaluated their protective potential against invasive candidiasis. EVs from the yeast (YEVs) and hyphal (HEVs) forms of the SC5314 wild-type strain were also tested, yielding high survival rates with SC5314 YEVs (91%) andecm33YEVs immunization (64%). Surprisingly, HEV immunization showed a dual effect, resulting in 36% protection but also causing premature death in some mice. Proteomic analyses revealed distinct profiles among the top 100 proteins in the different EVs which may explain these effects: a shared core of 50 immunogenic proteins such as Pgk1, Cdc19, and Fba1; unique, relevant immunogenic proteins in SC5314 YEVs, and proteins linked to pathogenesis, like Ece1 in SC5314 HEVs. Sera from SC5314 YEVs-immunized mice showed the highest IgG2a titers and moderate IL-17, IFN-γ, and TNF-α levels, indicating the importance of both humoral and cellular responses for protection. These findings highlight the distinct immunogenic properties ofC. albicansEVs, suggesting their potential in acellular vaccine development while emphasizing the need to carefully evaluate pathogenic risks associated with certain EVs.
Glutamic acid-lysine (EK) rich motif of RabD2 self-associates and regulates pathogenesis through multivesicular bodies pathway inE. histolytica
Authors: Navyaka P , Verma Kuldeep 
Published: November 2024

AbstractEntamoeba histolytica, an enteric pathogen, causes disease by adhering to and destroying the host tissues. The interactions between the parasite and host tissue enable rewiring of the gene expression and global membrane trafficking in the parasite. A fine balance between cargoes/receptors endocytosis and exocytosis is required to establish infection in the host. Multivesicular bodies (MVBs) act as sorting platforms, delivering cargoes/receptors to lysosomes for degradation or secreting their content through plasma membrane fusion. Some of the small GTPases are known to control MVB biogenesis in various organisms. However, the functional contribution of Rab GTPases in MVB biogenesis is poorly studied inE. histolytica. Here, we identified a novel atypical protein RabD2, with an N-terminal glutamic acid-lysine rich motif and a C-terminal conserved Rab domain. Our biochemical and cell biological assays provide evidence that RabD2 self-associates, and this interaction is controlled by the N-terminal EK-rich motif and the GTPase activity mutants (in a nucleotide-specific manner). RabD2 localizes on the surface of MVBs and controls their biogenesis. In line with these findings, overexpression of RabD2 upregulates global ubiquitination, directing the down regulation of the heavy chain of GalNAc lectin, ultimately leading to decreased adherence ofE. histolyticatrophozoites to host cells. Thus, amoebic RabD2 is a new class of Rab protein that forms high-ordered self-association variants and regulates the pathogenicity ofE. histolyticathrough the biogenesis of MVBs.Author SummaryAmoebiasis is an enteral infection caused byEntamoeba histolyticathat primarily remains asymptomatic but can eventually result in systemic complications like amoebic dysentery, liver abscess, and pulmonary effusions. Recent studies showed thatEntamoebaubiquitin is a robust antigen and linked with the invasive amoebiasis patient samples. Here, we identified a novel RabD2 that self-associates via its glutamic acid-lysine rich motif that causes high ubiquitination levels and biogenesis of multivesicular bodies. We uncovered for the first time that RabD2-mediated ubiquitin-dependent pathway is involved in the down regulation of the notable antigenic marker heavy chain of galactose-N-acetylgalactosamine lectin and thereby controls the parasite adherence to host cells. Further studies on crosstalk between parasite ubiquitination and antigenic receptors downregulation provide insights into how parasites use these strategies to establish the infection in the host intestine.
Expansion of a single Helitron subfamily inHydractinia symbiolongicarpussuggests a shared mechanism of cnidarian chromosomal extension
Authors: Kon Tetsuo , Kon-Nanjo Koto , Simakov Oleg 
Published: November 2024

AbstractHelitrons are rolling-circle transposons that amplify through rolling-circle replication mechanism. Since Helitrons were relatively recently identified, their impact on genome evolution is still not fully understood. Here, we describe that a single Helitron subfamily specifically accumulates in the subtelomeric regions ofHydractinia symbiolongicarpus, a colonial hydrozoan cnidarian. Based on the sequence divergence, it is suggested that the Helitron subfamily underwent a burst of activity in the species’ recent history. Additionally, there is a IS3EU DNA element accumulation at the putative centromeric regions, as well as minisatellite sequences of approximately 200 bp in length extending from the telomere-side end of the Helitron towards the telomere. Phylogenetic analysis of Helitrons in theH. symbiolongicarpusgenome suggests that the Helitrons underwent local propagation at the subtelomeric regions. The single Helitron subfamily, along with the consecutive minisatellite, accounts for 26.1% of the genome coverage (126 Mb of the 483 Mb genome), which collectively contribute to the genome size increase observed inH. symbiolongicarpuscompared with other cnidarians. Homologous sequences of Helitron inH. symbiolongicarpuswere identified in the genomes of other cnidarians, suggesting that Helitrons in hydractinia were present in at least the common ancestor of Cnidaria. Furthermore, inNematostella vectensis, an anthozoan cnidarian, Helitrons were also accumulated at the subtelomeric regions. All these findings suggest that Helitrons constitute a common cnidarian mechanism of chromosomal extension through local amplification in subtelomeric regions, driving diverse genome expansions within the clade.