bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tree species richness and evenness affect forest biomass differently across biogeographic regions
Authors: Ondei Stefania , Buettel Jessie C. , Aandahl R. Zach , Brook Barry W. , Alroy John , Yates Luke A. 
Published: December 2023

AbstractThe relationship between tree species diversity, measures of forest structure, and forest biomass has long been debated, with local- or continental-scale studies often finding contrasting results. Given the importance of forests as global carbon sinks, understanding the characteristics that underpin biomass accumulation is thus a critical component of mitigating climate change. Here we present a global analysis of 11,400 forest plots, sourced from scientific publications and forest inventories, to investigate the association of forest basal area (used as a proxy for biomass) with stem density and measures of tree species diversity (richness and evenness). We used generalised additive models to account for the confounding effects of climate and spatial signal and we modelled the density, climate, and diversity effects both globally and for each biogeographic region. Stem density showed a strong positive association with basal area across all biogeographic regions, while the effect of species richness varied. In the Palearctic, Nearctic, and Neotropical biogeographic regions, basal area was positively associated with species richness, although this was only detectable for lower values of basal area. In the Ethiopian and Oriental biogeographic regions there was no relationship between richness and basal area, while in the Australian biogeographic regions it was negative. The weak-to-no association between species evenness and basal area in all bioregions other than Australia suggests that the overall correlation emerges from processes operating at more local scales. Our results highlight the importance of accounting for biogeographic processes when evaluating strategies to mitigate climate change and support nature conservation.
Sc-TUSV-ext: Single-cell clonal lineage inference from single nucleotide variants (SNV), copy number alterations (CNA) and structural variants (SV)
Authors: Bristy Nishat Anjum , Fu Xuecong , Schwartz Russell 
Published: December 2023

AbstractClonal lineage inference (“tumor phylogenetics”) has become a crucial tool for making sense of somatic evolution processes that underlie cancer development and are increasingly recognized as part of normal tissue growth and aging. The inference of clonal lineage trees from single cell sequence data offers particular promise for revealing processes of somatic evolution in unprecedented detail. However, most such tools are based on fairly restrictive models of the types of mutation events observed in somatic evolution and of the processes by which they develop. The present work seeks to enhance the power and versatility of tools for single-cell lineage reconstruction by making more comprehensive use of the range of molecular variant types by which tumors evolve. We introduce Sc-TUSV-ext, an integer linear programming (ILP) based tumor phylogeny reconstruction method that, for the first time, integrates single nucleotide variants (SNV), copy number alterations (CNA) and structural variations (SV) into clonal lineage reconstruction from single-cell DNA sequencing data. We show on synthetic data that accounting for these variant types collectively leads to improved accuracy in clonal lineage reconstruction relative to prior methods that consider only subsets of the variant types. We further demonstrate the effectiveness on real data in resolving clonal evolution in the presence of multiple variant types, providing a path towards more comprehensive insight into how various forms of somatic mutability collectively shape tissue development.
Divergent Epigenetic and Transcriptomic Reprogramming of Monocyte Subpopulations in Systemic Lupus Erythematosus
Authors: Ferreté-Bonastre Anna Guiomar , Martínez-Gallo Mónica , Morante-Palacios Octavio , Calvillo Celia Lourdes , Calafell-Segura Josep , Rodríguez-Ubreva Javier , Esteller Manel , Cortés-Hernández Josefina , Ballestar Esteban 
Published: December 2023

AbstractSystemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by systemic inflammation involving various immune cell types. Monocytes, pivotal in promoting and regulating inflammation in SLE, differentiate from classical monocytes into intermediate monocytes and non-classical monocytes, assuming diverse roles. In this study, we investigated the epigenetic and transcriptomic profiles of these three monocyte subsets in an SLE cohort. In addition to common DNA methylation and transcriptomic alterations, we identified monocyte subset-specific alterations, especially in DNA methylation, which reflect an impact of SLE on the monocyte differentiation process. SLE classical monocytes exhibited a stronger proinflammatory profile, with an interferon signature and were primed for macrophage differentiation. SLE non-classical monocytes displayed a phenotype related to T cell differentiation regulation, and a Th17-promoting phenotype. Changes in monocyte proportions, DNA methylation and expression occurred in relation to disease activity and involved the STAT1 pathway. Integrating bulk datasets with single-cell RNA-seq data of SLE patients further supported the interferon signature in classical monocytes, associating intermediate and non-classical populations with exacerbated complement activation pathways. Our results indicate a subversion of the epigenome and transcriptome in monocyte differentiation toward non-classical subsets in SLE, impacting function, in relation to disease activity and progression.
The genomes of theMacadamiagenus
Authors: Sharma Priyanka , Masouleh Ardashir Kharabian , Constantin Lena , Topp Bruce , Furtado Agnelo , Henry Robert J. 
Published: December 2023

SummaryMacadamia, a genus native to Eastern Australia, comprises four species,Macadamia integrifolia, M. tetraphylla, M. ternifolia,andM. jansenii. Macadamia was recently domesticated largely from a limited gene pool of Hawaiian germplasm and has become a commercially significant nut crop. Disease susceptibility and climate adaptability challenges, highlight the need for use of a wider range of genetic resources for macadamia production. High quality haploid resolved genome assemblies were generated using HiFiasm to allow comparison of the genomes of the four species. Assembly sizes ranged from 735 Mb to 795 Mb and N50 from 53.7 Mb to 56 Mb, indicating high assembly continuity with most of the chromosomes covered telomere to telomere. Repeat analysis revealed that approximately 61% of the genomes were repetitive sequence. The BUSCO completeness scores ranged from 95.0% to 98.9%, confirming good coverage of the genomes. Gene prediction identified 37198 to 40534 genes. The ks distribution plot ofMacadamiaandTelopeasuggestsMacadamiahas undergone a whole genome duplication event prior to divergence of the four species and thatTelopeagenome was duplicated more recently. Synteny analysis revealed a high conservation and similarity of the genome structure in all four species. Differences in the content of genes of fatty acid and cyanogenic glycoside biosynthesis were found between the species. An antimicrobial gene with a conserved cysteine motif was found in all four species. The four genomes provide reference genomes for exploring genetic variation across the genus in wild and domesticated germplasm to support plant breeding.
Cortical signatures of sleep are altered following effective deep brain stimulation for depression
Authors: van Rheede Joram J. , Alagapan Sankaraleengam , Denison Timothy J. , Riva-Posse Patricio , Rozell Christopher J. , Mayberg Helen S. , Waters Allison C. , Sharott Andrew 
Published: December 2023

AbstractDeep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This is a crucial gap in knowledge, given the link between depression and sleep disturbances, and an emerging interest in the interaction between DBS, sleep, and circadian rhythms. We therefore sought to characterise changes in electrophysiological markers of sleep associated with DBS treatment for depression. We analysed key electrophysiological signatures of sleep – slow-wave activity (SWA, 0.5-4.5Hz) and sleep spindles – in LFPs recorded from the SCC of 9 patients who responded to DBS for TRD. This allowed us to compare the electrophysiological changes before and after 24 weeks of therapeutically effective SCC DBS.SWA power was highly correlated between hemispheres, consistent with a global sleep state. Furthermore, SWA occurred earlier in the night after chronic DBS and had a more prominent peak. While we found no evidence for changes to slow wave power or stability, we found an increase in the density of sleep spindles. Our results represent a first-of-its-kind report on long-term electrophysiological markers of sleep recorded from the SCC in patients with TRD, and provides evidence of earlier NREM sleep and increased sleep spindle activity following clinically effective DBS treatment. Future work is needed to establish the causal relationship between long-term DBS and the neural mechanisms underlying sleep.Conflict of interest statementJJvR has received honoraria from Medtronic. TD is a founder and director of Amber who own Bioinduction Ltd, has received honoraria from Medtronic, and is an advisor for Cortec Neuro and Synchron. PR-P receives consulting fees from Abbott Labs, LivaNova, and Janssen Pharmaceuticals. HM receives consulting and Intellectual Property licensing fees from Abbott Labs. SA, CR, ACW and AS have nothing to declare.
Reengineering of an artificial protein cage for efficient packaging of active enzymes
Authors: Azuma Yusuke , Gaweł Szymon , Pasternak Monika , Woźnicka Olga , Pyza Elżbieta , Heddle Jonathan G. 
Published: December 2023

AbstractProtein cages that readily encapsulate active enzymes of interest present useful nanotools for delivery and catalysis, wherein those with programmable disassembly characteristics serve as particularly attractive platforms. Here we establish a general guest packaging system based on an artificial protein cage, TRAP-cage, the disassembly of which can be induced by the addition of reducing agents. In this system, TRAP-cage with SpyCatcher moieties in the lumen was prepared using genetic modification of the protein building block and assembled into a cage structure with either monovalent gold ions or molecular crosslinkers. The resulting protein cage can efficiently capture guest proteins equipped with a SpyTag by simply mixing them in aqueous solution. This post-assembly loading system which circumvents the exposure of guests to thiol-reactive crosslinkers, enables packaging of enzymes possessing a catalytic cysteine or a metal cofactor while retaining their catalytic activity.
Synchrotron-source micro-x-ray computed tomography for examining butterfly eyes
Authors: Paukner Dawn , Wildenberg Gregg A. , Badalamente Griffin S. , Littlewood Peter B. , Kronforst Marcus R. , Palmer Stephanie E. , Kasthuri Narayanan 
Published: December 2023

Abstract1. Comparative anatomy is an important tool for investigating evolutionary relationships amongst species, but the lack of scalable imaging tools and stains for rapidly mapping the microscale anatomies of related species poses a major impediment to using comparative anatomy approaches for identifying evolutionary adaptations.2. We describe a method using synchrotron source micro-x-ray computed tomography (syn-µXCT) combined with machine learning algorithms for high-throughput imaging of Lepidoptera (i.e.,butterfly and moth) eyes. Our pipeline allows for imaging at rates of ∼ 15 min/mm3at 600 nm3resolution. Image contrast is generated using standard electron microscopy labeling approaches (e.g., osmium tetroxide) that unbiasedly labels all cellular membranes in a species independent manner thus removing any barrier to imaging any species of interest.3. To demonstrate the power of the method, we analyzed the 3D morphologies of butterfly crystalline cones, a part of the visual system associated with acuity and sensitivity and found significant variation within six butterfly individuals. Despite this variation, a classic measure of optimization, the ratio of interommatidial angle to resolving power of ommatidia, largely agrees with early work on eye geometry across species.4. We show that this method can successfully be used to determine compound eye organization and crystalline cone morphology. Our novel pipeline provides for fast, scalable visualization and analysis of eye anatomies that can be applied to any arthropod species, enabling new questions about evolutionary adaptations of compound eyes and beyond.
A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development inTrypanosoma congolense
Authors: Silvester Eleanor , Szoor Balazs , Ivens Alasdair , Awuah-Mensah Georgina , Gadelha Caterina , Wickstead Bill , Matthews Keith R. 
Published: December 2023

AbstractTrypanosomatid parasites undergo developmental regulation to adapt to the different environments encountered during their life cycle. InTrypanosoma brucei, a genome wide selectional screen previously identified a regulator of the protein family ESAG9, which is highly expressed in stumpy forms, a morphologically distinct bloodstream stage adapted for tsetse transmission. This regulator, TbREG9.1, has an orthologue inTrypanosoma congolense, despite the absence of a stumpy morphotype in that parasite species, which is an important cause of livestock trypanosomosis. RNAi mediated gene silencing of TcREG9.1 inTrypanosoma congolensecaused a loss of attachment of the parasites to a surface substrate in vitro, a key feature of the biology of these parasites that is distinct fromT. brucei. This detachment was phenocopied by treatment of the parasites with a phosphodiesterase inhibitor, which also promotes detachment in the insect trypanosomatidCrithidia fasciculata. RNAseq analysis revealed that TcREG9.1 silencing caused the upregulation of mRNAs for several classes of surface molecules, including transferrin receptor-like molecules, immunodominant proteins, and molecules related to those associated with stumpy development inT. brucei. Depletion of TcREG9.1 in vivo also generated an enhanced level of parasites in the blood circulation consistent with reduced parasite attachment to the microvasculature. The morphological progression to insect forms of the parasite was also perturbed. We propose a model whereby TcREG9.1 acts as a regulator of attachment and development, with detached parasites being adapted for transmission.Author summaryTrypanosoma congolenseis a major cause of livestock trypanosomosis in sub-Saharan Africa where it contributes to lost economic productivity and poverty. These parasites differ in two key respects from the better-studied African trypanosomes,Trypanosoma brucei. Firstly,T. congolenseadheres to surfaces in vitro and in the vaculature in vivo. Secondly, they lack a morphologically distinct transmission stage equivalent to the stumpy form ofT. brucei. In the current work we identify aT congolenseorthologue of a key developmental regulator inT. brucei, REG9.1, previously identified by a genome-wide RNAi screen. By RNA interference in transgenicT. congolensewe demonstrate that TcREG9.1 functions both in parasite adherence in vitro and in vivo, and also in parasite development. The work provides a first insight into the unusual adherence and developmental biology ofT. congolenseand also suggests a possible model for how these characteristics interact to promote disease spread.
Characterisation of protective vaccine antigens from the thiol-containing components of excretory/secretory material ofOstertagia ostertagi
Authors: Price Daniel R. G. , Steele Philip , Frew David , McLean Kevin , Androscuk Dorota , Geldhof Peter , Borloo Jimmy , Albaladejo Javier Palarea , Nisbet Alasdair J. , McNeilly Tom N. 
Published: December 2023

AbstractPrevious vaccination trials have demonstrated that thiol proteins affinity purified fromOstertagia ostertagiexcretory-secretory products (O. ostertagiES-thiol) are protective against homologous challenge. Here we have shown that protection induced by this vaccine was consistent across four independent vaccine-challenge experiments. Protection is associated with reduced cumulative faecal egg counts across the duration of the trials, relative to control animals. To better understand the diversity of antigens inO. ostertagiES-thiol we used high-resolution shotgun proteomics to identify 490 unique proteins in the vaccine preparation. The most numerous ES-thiol proteins, with 91 proteins identified, belong to the sperm-coating protein/Tpx/antigen 5/pathogenesis-related protein 1 (SCP/TAPS) family. This family includes previously identifiedO. ostertagivaccine antigensO. ostertagiASP-1 and ASP-2. The ES-thiol fraction also has numerous proteinases, representing three distinct classes, including: metallo-; aspartyl– and cysteine proteinases. In terms of number of family members, the M12 astacin-like metalloproteinases, with 33 proteins, are the most abundant family inO. ostertagiES-thiol. TheO. ostertagiES-thiol proteome provides a comprehensive database of proteins present in this vaccine preparation and will guide future vaccine antigen discovery projects.
Tuft cell-derived acetylcholine is an effector of type 2 immunity and directly targets helminth parasites in the gut lumen
Authors: Ndjim Marième , Herbert Fabien , Gasmi Imène , Joséphine Charlène , Henri Sylvain , Turtoi Evgenia , Thirard Steeve , Giordano Alicia , Ciancia Claire , Britton Collette , Devaney Eileen , McNeilly Tom N. , Berrard Sylvie , Turtoi Andrei , Maizels Rick M. , Gerbe François , Jay Philippe 
Published: December 2023

SUMMARYUpon parasitic helminth infection, activated intestinal tuft cells secrete IL-25, which initiates a type 2 immune response during whichlamina propriaILC2s produce IL-13. This causes epithelial remodelling, including tuft cell hyperplasia with an unknown function. We describe a novel cholinergic effector function of tuft cells, which we show are the only epithelial cells expressing Choline Acetyltransferase (ChAT). During parasite infections, mice with epithelial-specific deletion of ChAT have increased worm burden and faecal egg counts although they are able to mount a comparable type 2 immune response. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. We demonstrate a direct effect of ACh on worms, reducing their viability and fecundity via helminth muscarinic ACh receptors, with effects promoted by inhibition of acetylcholinesterase, an helminth-secreted enzyme. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infections serves an additional type 2 immune response effector function.
Investigating the ability of deep learning-based structure prediction to extrapolate and/or enrich the set of antibody CDR canonical forms
Authors: Greenshields-Watson Alexander , Abanades Brennan , Deane Charlotte M 
Published: December 2023

AbstractDeep learning models have been shown to accurately predict protein structure from sequence, allowing researchers to explore protein space from the structural viewpoint. In this paper we explore whether “novel” features, such as distinct loop conformations can arise from these predictions despite not being present in the training data.Here we have used ABodyBuilder2, a deep learning antibody structure predictor, to predict the structures of ∼1.5M paired antibody sequences. We examined the predicted structures of the canonical CDR loops and found that most of these predictions fall into the already described CDR canonical form structural space. We also found a small number of “new” canonical clusters composed of heterogeneous sequences united by a common sequence motif and loop conformation. Analysis of these novel clusters showed their origins to be either shapes seen in the training data at very low frequency or shapes seen at high frequency but at a shorter sequence length.To evaluate explicitly the ability of ABodyBuilder2 to extrapolate, we retrained several models whilst with-holding all antibody structures of a specific CDR loop length or canonical form. These “starved” models showed evidence of generalisation across CDRs of different lengths, but they did not extrapolate to loop conformations which were highly distinct from those present in the training data. However, the models were able to accurately predict a canonical form even if only a very small number of examples of that shape were in the training data.Our results suggest that deep learning protein structure prediction methods are unable to make completely out-of-domain predictions for CDR loops. However, in our analysis we also found that even minimal amounts of data of a structural shape allow the method to recover its original predictive abilities. We have made the ∼1.5 M predicted structures used in this study available to download athttps://doi.org/10.5281/zenodo.10280181.
Diverse Genetic Contexts of HicA Toxin Domains Propose a Role in Anti-Phage Defense
Authors: Gerdes Kenn 
Published: December 2023

AbstractToxin – antitoxin (TA) modules are prevalent in prokaryotic genomes, often in substantial numbers. For instance, theMycobacterium tuberculosisgenome alone harbors close to 100 TA modules, half of which belong to a singular type. Traditionally ascribed multiple biological roles, recent insights challenge these notions and instead indicate a predominant function in phage defense. TAs are often located within Defense Islands, genomic regions that encode various defense systems. The analysis of genes within Defense Islands have unveiled a wide array of systems, including TAs that serve in anti-phage defence. Prokaryotic cells are equipped with anti-phage Viperins that, analogous to their mammalian counterparts, inhibit viral RNA transcription. Additionally, bacterial Structural Maintenance of Chromosome (SMC) proteins combat plasmid intrusion by recognizing foreign DNA signatures. This study undertakes a comprehensive bioinformatics analysis of genetic elements encoding the HicA double-stranded RNA-binding domain, complemented by protein structure modeling. The HicA toxin domains are found in at least 14 distinct contexts and thus exhibit a remarkable genetic diversity. Traditional bicistronic TA operons represent eight of these contexts, while four are characterized by monocistronic operons encoding fused HicA domains. Two contexts involvehicAadjacent to genes that encode bacterial Viperins. Notably, genes encoding RelE toxins are also adjacent to Viperin genes in some instances. This configuration hints at a synergistic enhancement of Viperin-mediated anti-phage action by HicA and RelE toxins. The discovery of a HicA domain merged with an SMC domain is compelling, prompting further investigation into its potential roles.ImportanceProkaryotic organisms harbor a multitude of Toxin – Antitoxin (TA) systems, which have long puzzled scientists as “genes in search for a function”. Recent scientific advancement have shed light on a primary role of TAs as anti-phage defense mechanisms. To gain an overview of TAs it is important to analyze their genetic contexts that can give hints on function and guide future experimental inquiries. This manuscript describes a thorough bioinformatics examination of genes encoding the HicA toxin domain, revealing its presence in no fewer than 14 unique genetic arrangements. Some configurations notably align with anti-phage activities, underscoring potential roles in microbial immunity. These insights robustly reinforce the hypothesis that HicA toxins are integral components of the prokaryotic anti-phage defense repertoire. The elucidation of these genetic contexts not only advances our understanding of TAs but also contributes to a paradigm shift in how we perceive their functionality within the microbial world.