bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mod-minimizer: a simple and efficient sampling algorithm for longk-mers
Authors: Koerkamp Ragnar Groot , Pibiri Giulio Ermanno 
Published: June 2024

AbstractMotivationGiven a stringS, aminimizerscheme is an algorithm defined by a triple (k, w, 𝒪) that samples a subset ofk-mers (k-long substrings) from a stringS. Specifically, it samples the smallestk-mer according to the order 𝒪 from each window ofwconsecutivek-mers inS. Because consecutive windows can sample the samek-mer, the set of the sampledk-mers is typically much smaller thanS. More generally, we consider substring sampling algorithms that respect awindow guarantee: at least onek-mer must be sampled from every window ofwconsecutivek-mers. As a sampledk-mer is uniquely identified by its absolute position inS, we can define thedensityof a sampling algorithm as the fraction of distinct sampled positions. Good methods have low density which, by respecting the window guarantee, is lower bounded by 1/w. It is however difficult to design a sequence-agnostic algorithm with provably optimal density. In practice, the order 𝒪 is usually implemented using a pseudo-random hash function to obtain the so-calledrandomminimizer. This scheme is simple to implement, very fast to compute even in streaming fashion, and easy to analyze. However, its density is almost a factor of 2 away from the lower bound for large windows.MethodsIn this work we introducemod-sampling, a two-step sampling algorithm to obtain new minimizer schemes. Given a (small) parametert, the mod-sampling algorithm finds the positionpof the smallestt-mer in a window. It then samples thek-mer at positionpmodw. Thelr-minimizerusest=k − wand themod-minimizerusest ≡ k(modw).ResultsThese new schemes have provably lower density than random minimizers and other schemes whenkis large compared tow, while being as fast to compute. Importantly, the mod-minimizer achieves optimal density whenk → ∞. Although the mod-minimizer is not the first method to achieve optimal density for largek, its proof of optimality is simpler than previous work.We provide pseudocode for a number of other methods and compare to them. In practice, the mod-minimizer has considerably lower density than the random minimizer and other state-of-the-art methods, like closed syncmers and miniception, whenk > w. We plugged the mod-minimizer into SSHash, ak-mer dictionary based on minimizers. For default parameters (w, k) = (11, 21), space usage decreases by 15% when indexing the whole human genome (GRCh38), while maintaining its fast query time.2012 ACM Subject ClassificationTheory of computation → Sketching and sampling; Applied computing → BioinformaticsDigital Object Identifier10.4230/LIPIcs.WABI.2024.11Supplementary MaterialSoftware (C++): github.com/jermp/minimizersSoftware (Rust): github.com/RagnarGrootKoerkamp/minimizersFundingRagnar Groot Koerkamp: ETH Research Grant ETH-1721-1 to Gunnar Rätsch.Giulio Ermanno Pibiri: European Union’s Horizon Europe research and innovation programme (EFRA project, Grant Agreement Number 101093026). This work was also partially supported by DAIS – Ca’ Foscari University of Venice within the IRIDE program.
BakRep – A searchable large-scale web repository for bacterial genomes, characterizations and metadata
Authors: Fenske Linda , Jelonek Lukas , Goesmann Alexander , Schwengers Oliver 
Published: June 2024

AbstractBacteria are fascinating research objects in many disciplines for countless reasons, and whole-genome sequencing has become the paramount methodology to advance our microbiological understanding. Meanwhile, access to cost-effective sequencing platforms has accelerated bacterial whole-genome sequencing to unprecedented levels introducing new challenges in terms of data accessibility, computational demands, heterogeneity of analysis workflows, and thus, ultimately its scientific usability. To that end,Blackwell et al. released a uniformly processed set of 661,405 bacterial genome assemblies obtained from the European Nucleotide Archive as of November 2018. Building on these accomplishments, we conducted further genome-based analyses like taxonomic classification, MLST subtyping and annotation of all genomes. Here we present BakRep, a searchable large-scale web repository of these genomes enriched with consistent genome characterizations and original metadata. The platform provides a flexible search engine combining taxonomic, genomic and metadata information, as well as interactive elements to visualize genomic features. Furthermore, all results can be downloaded for offline analyses via an accompanying command line tool. The web repository is accessible viahttps://bakrep.computational.bio.
Evolutionary rescue of bacterial populations by heterozygosity on multicopy plasmids
Authors: Dewan Ian , Uecker Hildegard 
Published: June 2024

AbstractBacterial plasmids and other extrachromosomal DNA elements frequently carry genes with important fitness effects for their hosts. Multicopy plasmids can additionally carry distinct alleles of host-fitness-relevant genes on different plasmid copies, allowing for heterozygosity not possible for loci on haploid chromosomes. Plasmid-mediated heterozygosity may increase the fitness of bacterial cells in circumstances where there is an advantage to having multiple distinct alleles (heterozyogote advantage); however, plasmid-mediated heterozygosity is also subject to constant loss due to random segregation of plasmid copies on cell division. We analyze a multitype branching process model to study the evolution and maintenance of plasmid-mediated heterozygosity under a heterozygote advantage. We focus on an evolutionary rescue scenario in which a novel mutant allele on a plasmid must be maintained together with the wild-type allele to allow population persistance (although our results apply more generally to the maintenance of heterozygosity due to heterozygote advantage). We determine the probability of rescue and derive an analytical expression for the threshold on the fitness of heterozygotes required to overcome segregation and make rescue possible; this threshold decreases with increasing plasmids copy number. We further show that the formation of cointegrates from the fusion of plasmid copies increases the probability of rescue. Overall, our results provide a rigorous quantitative assessment of the conditions under which bacterial populations can adapt to multiple stressors through plasmid-mediated heterozygosity. Many of the results are furthermore applicable to the related problem of the maintenance of incompatible plasmids in the same cell under selection for both.MSC Classification92D15, 60J85
Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew
Authors: Skiadas Petros , Vidal Sofía Riera , Dommisse Joris , Mendel Melanie N. , Elberse Joyce , Van den Ackerveken Guido , de Jonge Ronnie , Seidl Michael F. 
Published: June 2024

AbstractPlant pathogens adapt at speeds that challenge contemporary disease management strategies like the deployment of disease resistance genes. The strong evolutionary pressure to adapt, shapes pathogens’ genomes, and comparative genomics has been instrumental in characterizing this process. With the aim to capture genomic variation at high resolution and study the processes contributing to adaptation, we here leverage and expand on an innovative, multi-genome method to construct, annotate, and analyse the first pangenome graph of an oomycete plant pathogen. We generated telomere-to-telomere genome assemblies of six genetically diverse isolates of the oomycete pathogenPeronospora effusa, the economically most important disease in cultivated spinach worldwide. The pangenome graph demonstrates thatP. effusagenomes are highly conserved, both in chromosomal structure and gene content, and revealed the continued activity of transposable elements which are directly responsible for 80% of the observed variation between the isolates. While most genes are generally conserved, pathogenicity related genes are highly variable between the isolates. Most of the variation is found in large gene clusters resulting from extensive copy-number expansion. Pangenome graph-based discovery can thus be effectively used to capture genomic variation at exceptional resolution, thereby providing a framework to study the biology and evolution of plant pathogens.Author SummaryPlant pathogens are known to evolve rapidly and overcome disease resistance of newly introduced crop varieties. This swift adaptation is visible in the genomes of these pathogens, which can be highly variable. Such genomic variation cannot be captured with contemporary comparative genomic methods that rely on a single reference genome or focus solely on protein coding genes. To overcome these limitations and compare multiple genomes in a robust and scalable method, we constructed the first pangenome graph for an oomycete filamentous plant pathogen with six telomere-to-telomere genome assemblies ofPeronospora effusa. This high-resolution pangenomic framework enabled detailed comparisons of the genomes at any level, from the nucleotide to the chromosome, and for any subset of protein-coding genes or transposable elements, to discover novel biology and potential mechanisms for the rapid evolution of this devastating pathogen.
Raman mineral-to-matrix ratios correlate with weight percentage mineral-to-matrix ratio determined by in-SEM Raman imaging of bone tissue
Authors: Mabilleau Guillaume , Boorman Dale , Diniz Jorge 
Published: June 2024

ABSTRACTRaman imaging combined with scanning electron microscopy (SEM) is a powerful technique that allows for topographical, chemical and structural correlative multi-scale imaging. It provides the perfect tool to determine which of the Raman mineral-to-matrix ratios represent the best parameter to accurately measure the degree of mineralization of the bone matrix using quantitative backscattered electron imaging (qBEI) as the reference methodology. Indeed, previous studies evidenced that the v2PO4and v4PO4vibrational modes were less sensitive to laser polarization than the v1PO4. However, using the v2PO4or v4PO4requires a longer acquisition time or lower spectral resolution. In the present study, we evaluated the correlation between mineral-to-matrix ratios computed from v1PO4and v2PO4in a human bone sample retrieved from orthopaedic surgery during hip replacement and wt% mineral / wt% organic matrix obtained from qBEI using the inLux SEM Raman interface. We reported here that all mineral-to-matrix ratios were significantly linearly correlated with wt% mineral / wt% organic matrix and that v1PO4/CH2exhibited the strongest correlation coefficient (r=0.880). This study suggests that the v1PO4is still a valid Raman peak to estimate the mineral-to-matrix ratio in bone samples and can be used to diagnose bone fragility disorders.
Integrative epigenetics and transcriptomics identify aging genes in human blood
Authors: Moqri Mahdi , Poganik Jesse , Herzog Chiara , Ying Kejun , Chen Qingwen , Emamifar Mehrnoosh , Tyshkovskiy Alexander , Eames Alec , Mur Jure , Matei-Dediu Benyamin , Goeminne Ludger , Mitchell Wayne , Mccartney Daniel , Marioni Riccardo , Lasky-Su Jessica A. , Snyder Michael P. , Gladyshev Vadim N. 
Published: June 2024

AbstractRecent epigenome-wide studies have identified a large number of genomic regions that consistently exhibit changes in their methylation status with aging across diverse populations, but the functional consequences of these changes are largely unknown. On the other hand, transcriptomic changes are more easily interpreted than epigenetic alterations, but previously identified age-related gene expression changes have shown limited replicability across populations. Here, we develop an approach that leverages high-resolution multi-omic data for an integrative analysis of epigenetic and transcriptomic age-related changes and identify genomic regions associated with both epigenetic and transcriptomic age-dependent changes in blood. Our results show that these “multi-omic aging genes” in blood are enriched for adaptive immune functions, replicate more robustly across diverse populations and are more strongly associated with aging-related outcomes compared to the genes identified using epigenetic or transcriptomic data alone. These multi-omic aging genes may serve as targets for epigenetic editing to facilitate cellular rejuvenation.
Ultra-high dose oralω3 docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) block tumorigenesis in aMYCN-driven neuroblastoma model
Authors: Patel Vishwa , Li Yan Ning , Benhamou Lorraine-Rana E. , Park Hui Gyu , Raleigh Mariya , Brenna J. Thomas , Powers John T. 
Published: June 2024

AbstractBackground/ObjectivesNeuroblastoma is a genetically diverse, highly metastatic pediatric cancer accounting for 15% of childhood cancer deaths despite only having ~8% of childhood cancer incidence. The current standard of care for high-risk disease is highly genotoxic. This, combined with less than 50% survival in high-risk disease and an abysmal 5% survival in relapsed cases, makes discovering novel, effective, and less toxic treatments essential.MethodsA prophylactic syngeneic mouse model was used to test high-dose lipid-mediator highly unsaturated fatty acids on tumorigenesis. Wild-type mice were gavaged with 12.3-14.6 g/d (adult human equivalent) omega-3 EPA, DHA, or oxidation-resistant bis allylic deuterated DHA (D-DHA) and 4.6-6.0 g/d arachidonic acid (ARA). At seven days,MYCN-expressing murine neuro-2a cells syngeneic to the gavaged mice were injected subcutaneously. Oral gavage continued for 10-20 d post-injection when tumors and tissues were harvested.ResultsFifty percent of control (not gavaged) animals form tumors (4/8) at about 10 d. High-dose DHA, D-DHA, and EPA block tumor formation completely in n=8 or 10 animals. In contrast, ω6 arachidonic acid (4.6-6.0 g/d) enhances tumor formation (6/10 tumors) and reduces latency (5.5 to 10 days)compared to control. Co-delivery of ARA and EPA results in a reduced tumor burden analogous to the control group, suggesting that EPA directly opposes the mechanism of ARA-mediated tumor formation. DHA acts through a non-oxidative mechanism.ConclusionsSustained high dose ω3 (weeks/months) is safe and well tolerated in humans. These results suggest that ω3 DHA and EPA delivery at ultra-high doses may represent a viable low-toxicity therapy for neuroblastoma.Simple SummaryPediatric Neuroblastoma has an overall mortality rate above 50%, and the current standard of care consists of highly genotoxic compounds. The biological actions of omega-6 (ω6) and omega-3 (ω3) highly unsaturated fatty acids (HUFA) generally oppose one another with the ω6 HUFA signaling for inflammation and angiogenesis (new blood vessel formation). Prolonged use of ultrahigh dose (15-20 g/d) ω3 HUFA has shown efficacy in catastrophic human traumatic brain injury and is well tolerated. Tumors form in about 50% of mice in our pediatric neuro-blastoma model. We show that 12-14 g/d adult human equivalent doses of ω3 EPA or DHA, as well as an oxidation-resistant form of DHA (D-DHA), completely block tumor formation, whereas a dose of about 5 g/d of ω6 ARA enhances tumorigenesis. Our data suggest that ultra-high dose ω3 therapy should be carefully investigated as a low-toxicity approach to neuroblastoma intervention.
Plio-Pleistocene decline of mesic forest underpins diversification in a clade of AustralianPanesthiacockroaches
Authors: Adams Maxim W.D. , Walker James A. , Rose Harley A. , Jones Braxton R. , Zwick Andreas , Yang Huiming , Nicholls James , Hartley Diana , Bent Stephen , Carlile Nicholas , Hutton Ian , Ho Simon Y.W. , Lo Nathan 
Published: June 2024

AbstractThe progressive aridification of the Australian continent, and coincident decline of mesic forest, has been a powerful driver of allopatric and environmental speciation in native species. The relictual mesic forests of the eastern seaboard now harbor a diverse group of endemic fauna, including the wood-feeding cockroaches of the genusPanesthia, which reached the continent via two separate invasions from Melanesia. The more recent of these colonization events gave rise to a group of five recognized species, occurring in mainland woodlands, sclerophylls and rainforests, as well as the forests and grasslands of the Lord Howe Island Group. Due to limited sampling in molecular studies and doubt regarding the standing taxonomy, there is little certainty about relationships among the species and poor understanding of the effects of ancient climatic changes upon their evolution. We undertook a comprehensive phylogenetic analysis of the clade, using complete mitogenomes and nuclear ribosomal markers from nearly all known morphospecies and populations. Our time-calibrated phylogenetic analyses reveal six unrecognized, highly divergent lineages, and suggest that these have arisen primarily through vicariance as rainforests fragmented during Plio-Pleistocene glacial cycles (2–5 million years ago). Ancestral niche reconstructions also evidence a tropical rainforest origin for the group, followed by at least three niche transitions into drier forest, including one associated with the singular colonization of the Lord Howe Island Group. Finally, we find evidence of frequent, parallel wing reduction, in potential association with the contraction of forest habitats into small refugia. Our results reiterate the far-reaching role of ancient aridification in driving speciation, niche expansion and morphological evolution in Australian fauna.
Parental smoking and respiratory outcomes in young childhood cancer survivors
Authors: Žarković Maša , Sommer Grit , Nigg Carina , Sláma Tomáš , Schneider Christine , Ansari Marc , von der Weid Nicolas , Schindera Christina , Kuehni Claudia E 
Published: June 2024

AbstractBackgroundPassive exposure to cigarette smoke has negative effects on respiratory health. Childhood cancer survivors (CCS) are at an increased risk for respiratory disease due to treatment regimens that may harm the respiratory system. The objective of this study was to assess the prevalence of parental smoking among CCS and investigate its association with respiratory outcomes.ProcedureAs part of the Swiss Childhood Cancer Survivor Study, between 2007 and 2022 we sent questionnaires to parents of children aged ≤16 years who had survived ≥ 5 years after cancer diagnosis. Parents reported on their children’s respiratory outcomes including recurrent upper respiratory tract infections (otitis media and sinusitis), asthma, and lower respiratory symptoms (chronic cough persisting > 3 months, current and exercise wheeze), and on parental smoking. We used multivariable logistic regression to investigate associations between parental smoking and respiratory outcomes.ResultsOur study included 1037 CCS (response rate 66%). Median age at study was 12 years (interquartile range [IQR] 10–14). Eighteen percent of mothers and 23% of fathers reported current smoking. CCS exposed to smoking mothers were more likely to have recurrent upper respiratory tract infections (OR 2.1; 95% CI 1.1–3.7) and lower respiratory symptoms (OR 2.0; 95%CI 1.1-3.7). We found no association with paternal smoking.ConclusionsA substantial proportion of CCS in Switzerland have parents who smoke. Exposure to maternal smoking was associated with higher prevalence of upper and lower respiratory problems. Physicians should advise and assist families of CCS in their endeavors to quit smoking.
Complete spatiotemporal quantification of cardiac motion in mice through enhanced acquisition and super-resolution reconstruction
Authors: Mukherjee Tanmay , Keshavarzian Maziyar , Fugate Elizabeth M. , Naeini Vahid , Darwish Amr , Ohayon Jacques , Myers Kyle J. , Shah Dipan J. , Lindquist Diana , Sadayappan Sakthivel , Pettigrew Roderic I. , Avazmohammadi Reza 
Published: June 2024

ABSTRACTThe quantification of cardiac motion using cardiac magnetic resonance imaging (CMR) has shown promise as an early-stage marker for cardiovascular diseases. Despite the growing popularity of CMR-based myocardial strain calculations, measures of complete spatiotemporal strains (i.e., three-dimensional strains over the cardiac cycle) remain elusive. Complete spatiotemporal strain calculations are primarily hampered by poor spatial resolution, with the rapid motion of the cardiac wall also challenging the reproducibility of such strains. We hypothesize that a super-resolution reconstruction (SRR) framework that leverages combined image acquisitions at multiple orientations will enhance the reproducibility of complete spatiotemporal strain estimation. Two sets of CMR acquisitions were obtained for five wild-type mice, combining short-axis scans with radial and orthogonal long-axis scans. Super-resolution reconstruction, integrated with tissue classification, was performed to generate full four-dimensional (4D) images. The resulting enhanced and full 4D images enabled complete quantification of the motion in terms of 4D myocardial strains. Additionally, the effects of SRR in improving accurate strain measurements were evaluated using an in-silico heart phantom. The SRR framework revealed near isotropic spatial resolution, high structural similarity, and minimal loss of contrast, which led to overall improvements in strain accuracy. In essence, a comprehensive methodology was generated to quantify complete and reproducible myocardial deformation, aiding in the much-needed standardization of complete spatiotemporal strain calculations.
Deficiency of the hemoglobin-haptoglobin receptor, CD163, worsens insulin sensitivity in obese male mice
Authors: Schleh Michael W. , Ameka Magdalene , Rodriguez Alec , Hasty Alyssa H. 
Published: June 2024

AbstractExcessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles including managing inflammatory tone and regulating parachymal iron homeostasis; thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages, and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes(Tfr1, Cisd1, Slc40a1)in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Further, CD163 deficiency mediated a pro-inflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophagesin vivo, which culminated in iron spillover into adipocytes and CD45+CD11B-non-myeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting.Article HighlightsLoss of CD163 mediates a phenotypic switch in M2-like macrophages towards a pro-inflammatory state.CD163 is involved in free hemoglobin uptake and catabolism as well as oxidative metabolism, specifically in M2-like macrophages.In inguinal white adipose tissue (iWAT) of CD163 defficient mice, macrophage iron is reduced; while concomitantly, adipocyte and other immune cell iron content is increased.Loss of CD163 provokes glucose intolerance and insulin resistance in obese male mice.