bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial analysis of Hofbauer cell transcriptome, distribution and morphology in placentas exposed toPlasmodium falciparum
Authors: Ataide Ricardo , Harding Rebecca , Dharmaratne Malindrie , Chen Yunshun , Fielding Katherine , Whitehead Lachlan , Rogers Kelly L. , Anttila Casey , Ling Ling , Hickey Peter , Amann-Zalcenstein Daniela , Moya Ernest , Mhango Gomezghani , Kamiza Steve , Randall Louise , Bennett Cavan , Mzembe Glory , Mwangi Martin N. , Braat Sabine , Phiri Kamija , Pasricha Sant-Rayn 
Published: November 2023

AbstractPlacental infection remains a significant health burden for mothers and their babies in low-income countries, especially in sub-Saharan Africa, where malaria transmission is intense. An increase in inflammatory biomarkers and poor vascularisation are characteristics of placentas infected with malaria. Hofbauer cells (HBCs) – placental villous macrophages of fetal origin – are one of the most abundant immune cells in the placenta. HBCs are thought to have roles in angiogenic processes and have been linked with the pathophysiology of several infections and inflammatory conditions during pregnancy, including malaria (caused byPlasmodium falciparum). However, there is limitedin situdata on the transcriptional, proteomic or morphologic profile of these cells either during or following clearance ofP. falciparuminfection. We leveraged placental samples prospectively collected at delivery from 610 Malawian women enduring a high burden of malaria and other infections and nutritional deficiencies. We profiled placentas through spatial transcriptomic and proteomic platforms to discernin situHBC features that could distinguish placentas with or without evidence of past malaria. In this cohort, past placental infection was common and was associated with lower birth weight babies (adjusted effect [95% confidence interval], −80.9 [−165.9, −3.7] g, P= 0.040). However, at term, HBC numbers, abundance, and transcriptional profiles from placentas with evidence of past infection were similar to those of placentas without malaria. HBCs may recover post-infection back to a basal state or may be replaced in the tissue over the course of pregnancy. Placentas with evidence of past malaria did show evidence of reduced fetal vessel development (mean area difference: −22.8% [−37.6, −7.9], P=0.003). Reduced vascular development following infection early in pregnancy may reflect disturbances to the normal vasculogenic and angiogenic processes, of which HBCs are an integral part.
Mechanical loading rescues mechanoresponsiveness in a human osteoarthritis explant model despite Wnt activation
Authors: Castro-Viñuelas R , Viudes-Sarrión N , Rojo-García AV , Monteagudo S , Lories RJ , Jonkers I 
Published: November 2023

AbstractObjectivesOptimizing rehabilitation strategies for osteoarthritis necessitates a comprehensive understanding of chondrocytes’ mechanoresponse in both health and disease, especially in the context of the interplay between loading and key pathways involved in osteoarthritis development, like canonical Wnt signaling. This study aims to elucidate the role of Wnt signaling in the mechanoresponsiveness of healthy and osteoarthritic human cartilage.MethodsWe used an ex-vivo model involving short-term physiological mechanical loading of human cartilage explants. First, the loading protocol for subsequent experiments was determined. Next, loading was applied to non-OA explants with or without Wnt activation with CHIR99021. Molecular read-outs of anabolic, pericellular matrix and matrix remodeling markers were used to assess the effect of Wnt on cartilage mechanoresponse. Finally, the same set-up was used to study the effect of loading in cartilage from patients with established OA.ResultsOur results confirm that physiological loading maintains expression of anabolic genes in non-OA cartilage, but indicate a deleterious effect of Wnt activation in the chondrogenic mechanoresponsiveness. This suggests that loading-induced regulation of cartilage markers occurs downstream of canonical Wnt signaling. Interestingly, our study highlighted contrasting mechanoresponsiveness in the model of Wnt activation and the established OA samples, with established OA cartilage maintaining its mechanoresponsiveness, and mechanical loading rescuing the chondrogenic phenotype.ConclusionThis study provides insights into the mechanoresponsiveness of human cartilage in both non-OA and OA conditions. These findings hold the potential to contribute to the development of strategies that optimize the effect of dynamic compression by correcting OA pathological cell signaling.
Tokenizing Foldable Protein Structures with Machine-Learned Artificial Amino-Acid Vocabulary
Authors: Lin Xiaohan , Chen Zhenyu , Li Yanheng , Ma Zicheng , Fan Chuanliu , Cao Ziqiang , Feng Shihao , Gao Yi Qin , Zhang Jun 
Published: November 2023

AbstractUnderstanding functions of proteins and designing proteins committed to specific functionsin silicoare highly valuable for science, industry and therapeutics. However, there is a long-standing divergence in how to present function-related protein structures to the machine learning models: Although the 1-dimensional (1D) representation of proteins via Anfinsen’s tokens (i.e., amino acids) is sufficient in principle and more machine-friendly, it is less successful in structure-oriented protein design compared to symmetry-constrained 3D representation (i.e., atom coordinates). Aiming to bridge the gap between 1D and 3D protein representations and harvest the advantages of the two, we developprobabilistic tokenization theoryfor metastable protein structures. We present an unsupervised learning strategy, which conjugates inverse folding with structure prediction, to encode protein structures into artificial amino-acid tokens (ProTokens) and decode them back to atom coordinates. We show that tokenizing protein structuresvariationallycan lead to compact and informative representations. Compared to amino acids — the Anfinsen’s tokens — ProTokens are easier to detokenize and more descriptive of finer conformational ensembles. Therefore, protein structures can be efficiently compressed, stored, aligned and compared in the form of ProTokens. By unifying the discrete and continuous representations of protein structures, ProTokens also enable all-atom protein structure design via various generative models without the concern of symmetry or modality mismatch, and allows scalable foundation models to perceive, process and explore the microscopic structures of biomolecules effectively.
Phosphoproteomics identifies targets of Mos-MAPK regulating translation and spindle organization in oocyte meiosis
Authors: Avilov Ivan , Horokhovskyi Yehor , Cai Mingfang , Orzechowski Aleksander , Welp Luisa , Urlaub Henning , Liepe Juliane , Lenart Peter 
Published: November 2023

AbstractThe Mos kinase is a constitutive activator of the ERK/MAPK pathway exclusively expressed during oocyte meiosis, mediating key meiotic functions across animal species. While a few of its downstream effectors have been studied in some detail, molecular targets under the control of Mos-MAPK have not yet been identified systematically. Here, we combined live-cell microscopy of starfish oocytes to characterize the cellular phenotypes caused by Mos-MAPK inhibition with phosphoproteomic analysis of synchronous oocyte populations at key transitions. This revealed a large set of proteins involved in regulation of translation through the CPE-element binding protein CPEB to be controlled by Mos-MAPK. Our data indicate that cyclin B is the main target of this regulation to drive the second meiotic division. A second large group of phospho-proteins we found to be controlled by Mos-MAPK are regulators of the actin and microtubule cytoskeleton, in particular regulators of centrosomal microtubule nucleation. Indeed, we show that Mos-MAPK inhibition increases the size of microtubule asters and promotes separation of spindle poles in meiotic anaphase, i.e turning meiotic spindles mitotic-like. Together, here we identified core molecular modules controlled by Mos-MAPK driving key meiotic functions, haploidization and the asymmetric polar body divisions. These molecular modules are highly conserved and are thus likely to be involved in reproductive processes across species including humans. In addition, our work may help understand disease mechanisms when Mos is expressed erroneously, acting as an oncogene.
Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins
Authors: Halwachs Bettina , Moesslacher Christina S. , Kohlmayr Johanna M. , Fasching Sandra , Masser Sarah , Choteau Sébastien A. , Zanzoni Andreas , Kunowska Natalia , Stelzl Ulrich 
Published: November 2023

AbstractThe dysregulation of cellular signaling upon SARS-CoV-2 infection is mediated via direct protein interactions, with the human protein kinases constituting the major impact nodes in the signaling networks. Here, we employed a targeted yeast two-hybrid matrix approach to identify direct SARS-CoV-2 protein interactions with an extensive set of human kinases. We discovered 51 interactions involving 14 SARS-CoV-2 proteins and 29 human kinases, including many of the CAMK and CMGC kinase family members, as well as non-receptor tyrosine kinases. By integrating the interactions identified in our screen with transcriptomics and phospho-proteomics data, we revealed connections between SARS-CoV-2 protein interactions, kinase activity changes, and the cellular phospho-response to infection and identified altered activity patterns in infected cells for AURKB, CDK2, CDK4, CDK7, ABL2, PIM2, PLK1, NEK2, TRIB3, RIPK2, MAPK13, and MAPK14. Finally, we demonstrated direct inhibition of the FER human tyrosine kinase by the SARS-CoV-2 auxiliary protein ORF6, hinting at pressures underlying ORF6 changes observed in recent SARS-CoV-2 strains. Our study expands the SARS-CoV-2 – host interaction knowledge, illuminating the critical role of dysregulated kinase signaling during SARS-CoV-2 infection.
Can changes in ploidy drive the evolution to allogamy in a selfing species complex?
Authors: García-Muñoz Ana , Ferrón Camilo , Vaca-Benito Celia , Martínez-Gómez María Nazaret , Castro Sílvia , Castro Mariana , Loureiro João , Muñoz-Pajares A. Jesús , Abdelaziz Mohamed 
Published: November 2023

SummaryThe evolution of mating systems in plants is central for understanding the rise of their diversity on Earth. The transition towards self-fertilization is a well-known example of convergent evolution although the opposite direction is expected to be forbidden according to evolutionary theories. We suggest that the ploidy level could promote changes in the reproductive strategies through its effect on traits related to pollination.We performed controlled crosses on several populations from the polyploidErysimum incanumspecies complex, described as predominantly selfing, to evaluate the inbreeding depression. Additionally, we measured mating traits such as floral size, herkogamy, anther exertion, the relative investment in male and female components (P:O ratio) and genetic diversity.We described three ploidy levels in the complex – hexaploids were unknown until now. We found significant differences in the self-pollination success among ploidies and even among populations within the same ploidy. Inbreeding depression was present in higher ploidies, accompanied by bigger flowers with higher anther exposure, increased herkogamy and P:O and genetic diversity.These findings suggest that ploidy could be promoting alternative reproductive strategies to selfing, driving mating system diversification within a selfing species, which has not been previously described in the wild.
Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed inCandida albicansandPorphyromonas gingivalis
Authors: Amer Lubna , Retout Maurice , Jokerst Jesse V. 
Published: November 2023

ABSTRACTWe report the controlled release of an antimicrobial peptide using enzyme-activatable prodrugs to treat and detectCandida albicansandPorphyromonas gingivalis. Our motivation lies in the prevalence of these microorganisms in the subgingival area where the frequency of fungal colonization increases with periodontal disease. This work is based on an antimicrobial peptide that is both therapeutic and induces a color change in a nanoparticle reporter. This antimicrobial peptide was then built into a zwitterionic prodrug that quenches its activity until activation by a protease inherent to these pathogens of interest: SAP9 or RgpB forC. albicansandP. gingivalis, respectively. We first confirmed that the intact zwitterionic prodrug has negligible toxicity to fungal, bacterial, and mammalian cells absent a protease trigger. Next, the therapeutic impact was assessed via disk diffusion and viability assays and showed a minimum inhibitory concentration of 3.1 – 16 µg/mL, which is comparable to the antimicrobial peptide alone (absent integration into prodrug). Finally, the zwitterionic design was exploited for colorimetric detection ofC. albicansandP. gingivalisproteases. When the prodrugs were cleaved, the plasmonic nanoparticles aggregated causing a color change with a limit of detection of 10 nM with gold nanoparticles and 3 nM with silver nanoparticles. This approach has value as a convenient and selective protease sensing and protease-induced treatment mechanism based on bioinspired antimicrobial peptides.Abstract Figure
Olfactory system structure and function in newly hatched and adult locusts
Authors: Sun Kui , Ray Subhasis , Gupta Nitin , Aldworth Zane , Stopfer Mark 
Published: November 2023

AbstractAn important question in neuroscience is how sensory systems change as animals grow and interact with the environment. Exploring sensory systems in animals as they develop can reveal how networks of neurons process information as the neurons themselves grow and the needs of the animal change. Here we compared the structure and function of peripheral parts of the olfactory pathway in newly hatched and adult locusts. We found that populations of olfactory sensory neurons (OSNs) in hatchlings and adults responded with similar tunings to a panel of odors. The morphologies of local neurons (LNs) and projection neurons (PNs) in the antennal lobes (ALs) were very similar in both age groups, though they were smaller in hatchlings, they were proportional to overall brain size. The odor evoked responses of LNs and PNs were also very similar in both age groups, characterized by complex patterns of activity including oscillatory synchronization. Notably, in hatchlings, spontaneous and odor-evoked firing rates of PNs were lower, and LFP oscillations were lower in frequency, than in the adult. Hatchlings have smaller antennae with fewer OSNs; removing antennal segments from adults also reduced LFP oscillation frequency. Thus, consistent with earlier computational models, the developmental increase in frequency is due to increasing intensity of input to the oscillation circuitry. Overall, our results show that locusts hatch with a fully formed olfactory system that structurally and functionally matches that of the adult, despite its small size and lack of prior experience with olfactory stimuli.
Aggressive mimicry lure polymorphisms in the parasitic musselLampsilis fasciolamodel fish or leech host prey and differ in morphology and pigmentation, but not in display behavior
Authors: Hewitt Trevor L. , Johnson Paul , Buntin Michael , Moore Talia , Foighil Diarmaid Ó 
Published: November 2023

ABSTRACTUnionoid freshwater mussels (Bivalvia: Unionidae) are free-living apart from a brief, obligately parasitic, larval stage that infects fish hosts and gravid female mussels have evolved a spectrum of strategies to infect fish hosts with their larvae. In many North American species, this involves displaying a mantle lure: a pigmented fleshy extension that acts as an aggressive mimic of a host fish prey, thereby eliciting a feeding response that results in host infection. The mantle lure ofLampsilis fasciolais of particular interest because it is apparently polymorphic, with two distinct primary lure phenotypes. One, described as “darter-like”, has “eyespots”, a mottled body coloration, prominent marginal extensions, and a distinct “tail”. The other, described as “worm-like”, lacks those features and has an orange and black coloration. We investigated this phenomenon to 1) confirm that it is a true polymorphism; 2) investigate its ecological persistence; 3) identify the range of putative model species targeted by this mimicry system within a river drainage; 4) determine whether the mantle lure polymorphism includes a behavioral component. Detection of within-brood lure variation and within-population phylogenomic (ddRAD-seq) analyses of individuals bearing different lures confirmed that this phenomenon is a true polymorphism. It appears stable over ecological timeframes: the ratio of the two lure phenotypes in a River Raisin (MI) population in 2017 was consistent with that of museum samples collected at the same site 6 decades earlier. Within the River Raisin, four main “darter-like” lure motifs visually approximated four co-occurring darter species (Etheostoma blennioides, E. exile, E. microperca,andPercina maculata) and the “worm-like” lure resembled a widespread common leech,Macrobdella decora. Darters and leeches are typical prey ofMicropterus dolomieui(smallmouth bass), the primary fish host ofL. fasciola.In situfield recordings were made of theL. fasciola“darter” and “leech” lure display behaviors, in addition to the non-polymorphic lure display of co-occurringL. cardium. Despite having putative models in distinct phyla, bothL. fasciolalure morphs have similar display behaviors that differ significantly from that of sympatricL. cardiumindividuals. We conclude that theL. fasciolamantle lure polymorphism does not include a behavioral component. Discovery of discrete within-brood inheritance of the lure polymorphism implies potential control by a single genetic locus and identifiesL. fasciolaas a promising study system to identify regulatory genes controlling a key adaptive trait of freshwater mussels.
Applying Super-Resolution and Tomography Concepts to Identify Receptive Field Subunits in the Retina
Authors: Krüppel Steffen , Khani Mohammad H. , Schreyer Helene M. , Sridhar Shashwat , Ramakrishna Varsha , Zapp Sören J. , Mietsch Matthias , Karamanlis Dimokratis , Gollisch Tim 
Published: November 2023

AbstractSpatially nonlinear stimulus integration by retinal ganglion cells lies at the heart of various computations performed by the retina. It arises from the nonlinear transmission of signals that ganglion cells receive from bipolar cells, which thereby constitute functional subunits within a ganglion cell’s receptive field. Inferring these subunits from recorded ganglion cell activity promises a new avenue for studying the functional architecture of the retina. This calls for efficient methods, which leave sufficient experimental time to leverage the acquired knowledge. Here, we combine concepts from super-resolution microscopy and computed tomography and introduce super-resolved tomographic reconstruction (STR) as a technique to efficiently stimulate and locate receptive field subunits. Simulations demonstrate that this approach can reliably identify subunits across a wide range of model variations, and application in recordings of primate parasol ganglion cells validates the experimental feasibility. STR can potentially reveal comprehensive subunit layouts within less than an hour of recording time, making it ideal for online analysis and closed-loop investigations of receptive field substructure in retina recordings.
The epigenetics effects of transposable elements are context dependent and not restricted to gene silencing
Authors: Coronado-Zamora Marta , González Josefa 
Published: November 2023

ABSTRACTTransposable elements (TEs) represent a threat to genome integrity due to their proliferation capacity. Eukaryotic cells silence TEs through different epigenetic mechanisms, including the deposition of repressive histone marks. Previous studies have shown that repressive marks can spread to neighboring sequences. However, evidence for this spreading affecting nearby gene expression remains limited. Similarly, whether TEs induce changes in the enrichment of active histone marks genome-wide, and its potential impact on gene expression have not been widely studied. In this work, we performed a comprehensive study of the epigenetic effects of 2,235 TEs and their potential effects on nearby gene expression onD. melanogasterhead, gut and ovary. While most of the TEs (816) induce the enrichment of the H3K9me3 repressive mark, with stronger epigenetic effects in the ovary, a substantial number (345 TEs) induce the enrichment of the H3K27ac active mark, particularly in the gut. We found that 70% of the H3K9me3 enriched TEs induced gene down-regulation, and 50% of the H3K27ac enriched TEs induced gene up-regulation. These changes in expression affect specific regulatory networks in head and gut while in ovary, genes were not enriched for any biological functions. Furthermore, TE epigenetic effects on gene expression are genomic context dependent. Finally, we found that TEs also affect gene expression by disrupting regions enriched for histone marks. Overall, our results show that TEs do generate regulatory novelty through epigenetic changes, with these epigenetic effects not restricted to gene silencing and being context dependent.Significance statementTransposable elements (TEs) are repetitive DNA sequences found in nearly all studied organisms that have the capacity to move within the genome. To prevent their proliferation, eukaryotic cells target TEs with repressive histone marks, an epigenetic signal that blocks their expression. While these repressive marks can spread to neighboring genes, the evidence of how this impacts gene expression is limited. Similarly, whether TEs also influence the enrichment and depletion of active histone marks and their genome-wide impact is not understood. In this work, we studied the histone mark enrichment of 2,235 polymorphic TEs across three body parts ofD. melanogaster. Our results provide evidence for the genome-wide role of TEs in the generation of regulatory novelty through epigenetic changes.
Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes
Authors: Dereli Ihsan , Telychko Vladyslav , Papanikos Frantzeskos , Raveendran Kavya , Xu Jiaqi , Boekhout Michiel , Stanzione Marcello , Neuditschko Benjamin , Imjeti Naga Sailaja , Selezneva Elizaveta , Erbasi Hasibe Tuncay , Demir Sevgican , Giannattasio Teresa , Gentzel Marc , Bondarieva Anastasiia , Stevense Michelle , Barchi Marco , Schnittger Arp , Weir John R. , Herzog Franz , Keeney Scott , Tóth Attila 
Published: November 2023

SummaryProgrammed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We discovered in mice that efficient biogenesis of DSB-machinery clusters requires seeding by axial IHO1 platforms, which are based on a DBF4-dependent kinase (DDK)–modulated interaction between IHO1 and the chromosomal axis component HORMAD1. IHO1-HORMAD1-mediated seeding of the DSB-machinery on axes ensures sufficiency of DSBs for efficient pairing of homologous chromosomes. Without IHO1-HORMAD1 interaction, residual DSBs depend on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, recombination initiation is ensured by complementary pathways that differentially support seeding and growth of DSB-machinery clusters, thereby synergistically enabling DSB-machinery condensation on chromosomal axes.