bluuebunny/crossref_metadata_2025_split huggingface dataset:
StripePy: fast and robust characterization of architectural stripes
Authors: Raffo Andrea , Rossini Roberto , Paulsen Jonas 
Published: December 2024

AbstractArchitectural stripes in Hi-C and related data are crucial for gene regulation, development, and DNA repair. Despite their importance, few tools exist for automatic stripe detection. We introduce StripePy, which leverages computational geometry methods to identify and analyze architectural stripes in contact maps from Chromosome Conformation Capture experiments like Hi-C and Micro-C. StripePy outperforms existing tools, as shown through tests on various datasets and a newly developed simulated benchmark, StripeBench, providing a valuable resource for the community.
Putative EGF ligand and receptor ofEchinococcus multilocularisthat are critical for parasite development
Authors: Koike Akito , Cailliau Katia , Vicogne Jérôme , Becker Frank , Dissous Colette , Hannus Stefan , Brehm Klaus 
Published: December 2024

AbstractThe neglected zoonosis alveolar echinococcosis (AE) is caused by infiltrative growth of the metacestode larval stage of the cestodeEchinococcus multiloculariswithin host organs. We previously demonstrated that metacestode growth depends on the mitotic activity of a population of parasite stem cells, called germinative cells, but it is not yet clear which molecular mechanisms governEchinococcusstem cell dynamics such as cell-cycle progression, self-renewal and differentiation. Based on previous reports showing that epidermal growth factor (EGF) signalling contributes toEchinococcusstem cell regulation, we herein characterized three EGF receptors of the parasite and demonstrated by RNAi and inhibitor assays that one of these, EmER1, is crucial for the development of metacestode vesicles from parasite stem cells. We also showed that EmER1 serves as a target for afatinib, an EGF receptor inhibitor with profound anti-parasitic activitiesin vitroandin vivo. By bioinformatic analyses and membrane-bound yeast two-hybrid assays, we identified a parasite-derived, neuregulin-like cognate ligand for EmER1, EmNRG, the expression of which is strongly upregulated in metacestode vesicles during clonal expansion of germinative cells. Furthermore, we demonstrate that RNAi knockdown of the EmNRG encoding gene drastically affects the ability of germinative cells to produce metacestode vesicles. We propose that EmNRG and EmER1 form a cognate ligand-receptor system utilized byE. multilocularisto regulate asymmetric versus symmetric division decisions of stem cells. These data are relevant for further studies intoEchinococcusstem cell dynamics and for the development of EGF signalling-based anti-infectives against echinococcosis.
A modulatory attentional gate promotes recent memory expression in Drosophila
Authors: Kapoor Ishaan , Waddell Scott 
Published: December 2024

AbstractUsing short-term memory (STM) requires that animals can distinguish memories of recent experience from those learned previously. InDrosophilathe neuromodulator octopamine (OA) specifically affects STM through adrenergic-like receptors within neurons in the Mushroom Body (MB) network. However, why OA preferentially impacts STM remains unclear. A fly brain connectome reveals that two OA-VPM3 neurons provide most OA input to the MB network. Artificial OA-VPM3 activation during olfactory learning enhances STM and can divert odor salience. α-adrenergic-like receptor knock-down in MB β and γ lobe MB Output Neurons (MBONs) generally impaired STM, while β-adrenergic-like receptor loss from α lobe MBONs enhanced memory. The identity and connectivity of the relevant MBONs suggests OA modulates an interaction between sites of STM and long-term memory (LTM) storage. Indeed, synthetic, odor, and learning-driven, OA-VPM3 activation temporarily blocks LTM expression. Therefore, OA reconfigures the MBON network so the fly prioritizes expression of recent over remote memories.
Autofluorescence of the parathyroid glands during total thyroidectomy. Review of systematic reviews
Authors: Pardal-Refoyo José Luis , Pardal-Pelaéz Beatriz 
Published: December 2024

SummaryIntroduction and ObjectiveThis study reviews the use of near-infrared autofluorescence (NIRAF) for identifying parathyroid glands during total thyroidectomy. The main goal is to evaluate whether using NIRAF reduces the incidence of postoperative hypocalcemia, a common complication of thyroid surgery. The study analyzes previously published meta-analyses to assess the effectiveness of NIRAF compared to traditional visual identification methods. The preservation of parathyroid glands during thyroid surgery is essential to prevent hypoparathyroidism and consequent hypocalcemia.MethodsThe research involved a review of systematic reviews and meta-analyses found in PubMed, WoS, and the Cochrane Library databases. Three meta-analyses that included studies on total thyroidectomy with and without NIRAF were selected. These meta-analyses evaluated transient and permanent postoperative hypocalcemia. The data from 15 studies included in the meta-analyses were extracted and statistically reanalyzed (meta-meta-analysis). The statistical analysis was performed using the ESCI statistical package of the JAMOVI program and METAFOR by JASP. The PRISMA guidelines were followed.ResultsThe use of NIRAF during total thyroidectomy was associated with a significantly lower incidence of both global and transient hypocalcemia. The prevalence of permanent hypocalcemia was also lower in the NIRAF group, but the difference was not statistically significant. The meta-meta-analysis showed a statistically significant association between the use of NIRAF and a reduction in hypocalcemia. There was moderate to high heterogeneity in errors and possible asymmetry in the data for global and transient hypocalcemia, but not for permanent hypocalcemia.ConclusionsNIRAF is a useful tool for identifying and preserving parathyroid glands during total thyroidectomy, and its use is associated with a reduced risk of postoperative hypocalcemia. The current evidence supports the use of NIRAF, although the strength of the recommendation is weak because of heterogeneity, risk of bias, and inconsistent results among the studies. More well-designed studies are needed to confirm these findings and establish NIRAF as a standard.
Language Profile of Posterior Cortical Atrophy: A Comparative Study with Alzheimer’s Disease Variants
Authors: Wang Linshan , St-Georges Marie-Anne , Lavoie Monica , Migliaccio Raffaella , Montembeault Maxime 
Published: December 2024

AbstractObjectiveThis study investigates language impairments in early-stage posterior cortical atrophy (PCA) patients, examining five language subdomains to resolve existing controversies and gaps in the literature.MethodsParticipants diagnosed with posterior cortical atrophy (PCA; n=105), typical Alzheimer’s disease (tAD; n=105), logopenic variant primary progressive aphasia (lvPPA; n=116) and healthy controls (HC; n=165) were selected from the National Alzheimer’s Coordinating Center (NACC) database. We utilized language tests from the Uniform Data Set and Frontotemporal Lobar Degeneration Module to assess different aspects of linguistic ability, including verbal fluency, reading, naming, semantics and repetition.ResultOur findings revealed a global decline in visual and non-visual language functions among PCA patients compared to HC, with no spared domains. Furthermore, we investigated specific language errors in reading and sentence repetition, and we found that PCA patients committed a mix of phonological, semantic and word omission errors. They were more impaired on irregular vs. regular word reading and more impaired on verb vs noun naming. Overall PCA patients showed less severe language deficits than lvPPA, except in single word comprehension and verb naming, where the opposite pattern was found. They also showed more impaired visual language impairments and similar non-visual language impairments in comparison to tAD.DiscussionThese findings highlight that language impairments in PCA extend beyond visual deficits, playing a key role in its clinical presentation. Recognizing these language issues is essential for differentiating PCA from tAD and lvPPA, where distinct patterns of impairment help refine diagnosis.
Three-Dimensional ECG: A Novel Methodology for Detecting Acute Myocardial Ischemia
Authors: Bermejo Valdés Alejandro Jesús 
Published: December 2024

AbstractWe present a novel methodology that generates a three-dimensional (3D) electrocardiogram (ECG) directly derived from standard two-dimensional (2D) recordings using conventional cardiac electrode configurations. Through spherical-to-Cartesian coordinate transformations, we generate 3D representations that form loops over the standard deflections used in routine medical practice, while geometrically integratingtimewithvoltagewithin the coordinates themselves. To validate our approach from a clinical perspective, we analyzed datasets focused on acute myocardial ischemia. We evaluated the diagnostic value by comparing 2D and 3D ECG metrics, specifically perimeter and curvature, across different ischemic states. Additionally, we propose a novel mathematical formulation, analogous to curvature, designed to more accurately detect variations in the progression of ischemia. This formulation, referred to as “almost-curvature”, achieves maximum efficiency when integrated with our 3D representation method. Our results highlighted significant geometric differences in the 3D metrics, demonstrating their potential to detect ischemic alterations with greater effectiveness than traditional methods. These findings support the potential of 3D ECG as a transformative tool in cardiac diagnostics and underscore the need for continued research to expand its clinical applicability.
Protein aggregation capture assisted profiling of the thiol redox proteome
Authors: Martinez-Val Ana , Lozano-Juárez Samuel , Lumbreras Jorge , Rodríguez Irene , Couselo-Seijas Marinela , Simón-Chica Ana , Galán-Arriola Carlos , Fernández Rodrigo , Núñez Estefanía , Jorge Inmaculada , Filgueiras-Rama David , Ibáñez Borja , Vázquez Jesús 
Published: December 2024

AbstractOxidative damage is critical in various diseases, including cardiovascular and neurological conditions. Thiol redox reactions, acting as oxidative stress sensors, influence protein structure and function. Redox proteomics based on differential alkylation of reduced and oxidized Cys forms using mass spectrometry enables comprehensive analysis of thiol redox status in cells and tissues.We introduce PACREDOX, an innovative redox proteomics approach based on the Protein Aggregation Capture (PAC) protocol and we demonstrate its compatibility with library free data-independent acquisition (DIA). PACREDOX reduces preparation time and costs compared to traditional methods, such as FASILOX, while maintaining thiol and proteome coverage. To enable library-free DIA, we corrected in silico spectral libraries in DIA-NN using experimental retention time data from beta-methylthiol-modified peptides. PACREDOX with DIA quantified 4,000 protein groups and ∼45,000 modified peptides in myocardial tissue from a porcine model of atrial fibrillation, including over 8,000 cysteine-containing peptides, 30% of which were reversibly oxidized.Benchmarking PACREDOX and DIA against FASILOX in a myocardial infarction model reflects the potential and efficiency of this methodology to study oxidative damage. Overall, PACREDOX offers a high-throughput, cost-effective strategy for thiol redox proteome analysis, compatible with label-free quantitative workflows.
Impact of mitochondrial fission and fusion on neuronal health and incidence of dementia
Authors: Holt Alan G , Davies Adrian M 
Published: December 2024

AbstractMitochondria are highly dynamic structures that undergo constant remodeling by the process of fission and fusion. Using simulation methods we study the effects of neuron loss in humans due to the proliferation of deletion mutations. We implement two models of an organelle, namely, closed cristae (CC) and open mitochondrion (OM). With CC, mtDNA are confined to a cristae unlessmixedby the process of fission and fusion. Conversely, mtDNA can diffuse freely throughout the organelle in the OM model. We also implement selective mitophagy in the CC model.Higher rates of mixing mtDNA increase the rate of neuron loss which, in turn, increases the prevalence of dementia. Selective mitophagy mitigates against the effect of high rate mixing. However, this mitigation is all or nothing. Even at nominal rates compared to mixing, neuron loss is almost completely eliminated resulting in minimal cognitive decline. These results do not fit the observations of normal aging and dementia prevalence in the elderly human population.This study brings into question the role that fission and fusion is believed play in the removal of defective mtDNA.
Uptake and survival ofLeishmania amazonensisinAcanthamoeba castellanii: An infection organism model?
Authors: Geres Leonardo Fernandes , Gallo Francisco Pedro Henrique , Machado Diullia de Andrade , Teófilo Francisco Breno S. , Brocchi Marcelo , Giorgio Selma 
Published: December 2024

ABSTRACTLeishmaniasis is a neglected tropical disease. Parasite strategies and the evaluation of drugs and vaccines are inferred from studies carried out using mouse models and macrophages. The development of model organisms with no ethical restrictions will contribute to our knowledge of leishmaniasis.Acanthamoeba castellanii, a free-living protozoan, is known to interact with various microorganisms. In this study, the interaction between the amoebaA. castellaniiand the trypanosomatidLeishmania amazonensiswas investigated by combining quantitative kinetics analysis, optical, fluorescence, electronic, confocal, and live video microcopy. We sought to standardize protocols for the co-culture; the optimal experimental conditions were: RPMI medium + 10% SFB at 26°C. L. amazonensisinvadesA. castellaniithrough its acanthopods, and the promastigotes interact with the trophozoites via their flagellum, which also occurs when parasites infect mammalian macrophages. The forms ofL. amazonensisinside the amoeba become rounded and lose their flagellum; they are similar to amastigotes. These round forms were isolated from trophozoites after 3 h of co-culture and differentiated into promastigotes, demonstrating their viability inside amoeba. The percentage of amoebas withL. amazonensiswas reduced overtime. Thus, considering thatA. castellaniican clearLeishmania, this interaction could serve as an effective model of cellular leishmanicidal mechanisms.
Banded mongooses discriminate relatedness and MHC diversity in unfamiliar conspecifics
Authors: Schubert Nadine , Stober Carolin , Born Maibrit , Mwanguhya Francis , Businge Robert , Kyambulima Solomon , Mwesige Kenneth , Cant Michael A. , Nichols Hazel J. , Winternitz Jamie C. 
Published: December 2024

ABSTRACTOlfactory cues are critical in mammalian social communication, conveying fitness-relevant information such as relatedness, genetic quality, and compatibility. Recognizing kin through scent can help avoid inbreeding depression and guide nepotistic behaviors, enhancing both direct and indirect fitness. While many species use familiarity to identify relatives, others rely on phenotype matching, where animals assess genetic similarity by comparing their own genetically determined odor with that of others. In banded mongooses, synchronized breeding disrupts familiarity cues, increasing reliance on alternative mechanisms for kin discrimination and mate selection. We tested whether banded mongooses use odors to assess genetic diversity and relatedness based on (1) major histocompatibility complex (MHC) genotypes and (2) neutral microsatellite loci that reflect genetic diversity and relatedness. We found that individuals respond differently to odors from unfamiliar individuals based on MHC diversity and genetic relatedness. Specifically, individuals show more interest in less MHC diverse and less related unfamiliar conspecifics, suggesting odor cues are used to evaluate threat level of intruders or competitors. Genetic diversity had no impact on responses to odors and was not significantly associated with MHC diversity, implying that responses to MHC diversity did not result from an underlying correlation with over-all genetic diversity. We also found no effect of MHC similarity, which might be caused by the limited sample size for this analysis. Our findings show that MHC diversity might signal the genetic quality of individuals, but regions of the genome other than MHC may be used to assess relatedness. These findings provide the basis for future research on the involvement of the MHC and other genes in social communication in species where phenotype matching is likely to be advantageous.
Cortical projection neurons with distinct axonal connectivity employ ribosomal complexes with distinct protein compositions
Authors: Tran Tien Phuoc , Budnik Bogdan , Froberg John E. , Macklis Jeffrey D. 
Published: December 2024

AbstractDiverse subtypes of cortical projection neurons (PN) form long-range axonal projections that are responsible for distinct sensory, motor, cognitive, and behavioral functions. Translational control has been identified at multiple stages of PN development, but how translational regulation contributes to formation of distinct, subtype-specific long-range circuits is poorly understood. Ribosomal complexes (RCs) exhibit variations of their component proteins, with an increasing set of examples that confer specialized translational control. Here, we directly compare the protein compositions of RCsin vivofrom two closely related cortical neuron subtypes–cortical output “subcerebral PN” (SCPN) and interhemispheric “callosal PN” (CPN)– during establishment of their distinct axonal connectivity. Using retrograde labeling of subtype-specific somata, purification by fluorescence-activated cell sorting, ribosome immunoprecipitation, and ultra-low-input mass spectrometry, we identify distinct protein compositions of RCs from these two subtypes. Strikingly, we identify 16 associated proteins reliably and exclusively detected only in RCs of SCPN. 10 of these proteins have known interaction with components of ribosomes; we further validated ribosome interaction with protein kinase C epsilon (PRKCE), a candidate with roles in synaptogenesis. PRKCE and a subset of SCPN-specific candidate ribosome-associated proteins also exhibit enriched gene expression by SCPN. Together, these results indicate that ribosomal complexes exhibit subtype-specific protein composition in distinct subtypes of cortical projection neurons during development, and identify potential candidates for further investigation of function in translational regulation involved in subtype-specific circuit formation.
An A-T Hoogsteen base pair in a naked DNA hairpin motif: A Protein-Recognized Conformation
Authors: Guseva Serafima , Szekely Or , Geng Ainan , Smith Kai , Pratihar Supriya , Gu Stephanie , Al-Hashimi Hashim M. 
Published: December 2024

AbstractIn duplex DNA, A-T and G-C form Watson-Crick base pairs, and Hoogsteen pairing only dominates upon protein binding or DNA damage. Using NMR, we show that an A-T Hoogsteen base pair previously observed in crystal structures of transposon DNA hairpins bound to TnpA protein forms in solution even in the absence of TnpA. This Hoogsteen base pair, located adjacent to a dinucleotide apical loop, exists in dynamic equilibrium with a minor Watson-Crick conformation (population ∼11% and lifetime ∼55 µs). Extending the apical loop to three residues inverted the equilibrium, making Watson-Crick the dominant state and the Hoogsteen conformation recognized by TnpA a minor state (population ∼14% and lifetime ∼28 µs). The propensity for Hoogsteen pairing depended on apical loop residues, which form contacts directly or indirectly stabilizing the Hoogsteen conformation. A structure survey did not reveal Hoogsteen pairing near RNA apical loops making them unique to DNA. Our results demonstrate that Hoogsteen can be the dominant state even in naked unmodified duplex DNA and identify 5’-CTT(T/C)AG-3’ as a DNA-specific apical loop motif stabilized by Hoogsteen pairing. Hoogsteen base pairs may be prevalent in DNA hairpins forming during replication and transcription, with broad implications for the genomic landscape.
The dominance of non-native plants over native plants increases with the number of global change factors
Authors: Shi Xiong , Chen Duo , van Kleunen Mark 
Published: December 2024

AbstractGlobal environmental change and plant invasion are both recognized as key indicators of the Anthropocene, with the former potentially accelerating the latter. Still, whether multiple co-acting global change factors (GCFs) influence plant invasions even stronger remains untested despite the fact that in nature GCFs usually act together rather than alone. Here, four non-native and four native species were cultivated jointly as communities in mesocosm pots, and we tested their responses to increasing GCF numbers (0, 1, 2, 3, 4, 5). We found that GCF number had no influence on community productivity but increased the biomass proportion of non-native plants. GCF number increased biomass but had no influence on height for non-native plants, whereas both biomass and height of native plants decreased with increasing GCF number. Consequently, our findings indicate that dominance may increases when habitats experience multiple global change factors, and thus that invasion risk of non-native plants could potentially be underestimated from studies on single GCFs.Open Research statementThe data supporting the results will be made available upon acceptance.
A Comprehensive Assessment of Methylation-Based Age Prediction Methods
Authors: Wang Han , Qu Jing , Zong Xizeng , Cai Ruirui , Li Yunkai , Zhao Shunlin , Hai Boquan , Tian Ruoting , Kuang Zhejun , Zhang Li , Zhao Jian , Liu Guixia , Zhang Chao 
Published: December 2024

AbstractDNA methylation (DNAm) clock is widely used to measure biological age, helping to identify key biomarkers associated with aging, infer the progression of aging, and have promise for elucidating, delaying, or even reversing aging. During the past decade, a large number of epigenetic clocks have been developed. However, they are decentralized, with applicable scopes overlapping. We benchmark 15 of these methods on 142 Illumina DNAm array datasets in five criteria and analyze the biological significance of CPGs about aging and overlapping. There are many exciting commons in models’ performance. We found the optimal model closely related to the numbers and characteristics of the training data. We provided a comprehensive assessment process to guide DNAm clock research at (https://dnamclock.com), the corresponding data and evaluation pipeline are freely available (https://github.comyNENUBioCompute/MethylationEvaluation), this study will aid in the development of improved tools designed to analyze increasingly large DNAm datasets.