bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex third-party effects in theDictyostelium–Paraburkholderiasymbiosis: prey bacteria that are eaten, carried or left behind
Authors: Scott Trey J. , Queller David C. , Strassmann Joan E.
Published: July 2024

Symbiotic interactions may change depending on third parties like predators or prey. Third-party interactions with prey bacteria are central to the symbiosis betweenDictyostelium discoideumsocial amoeba hosts andParaburkholderiabacterial symbionts. Symbiosis with inedibleParaburkholderiaallows hostD. discoideumto carry prey bacteria through the dispersal stage where hosts aggregate and develop into fruiting bodies that disperse spores. Carrying prey bacteria benefits hosts when prey are scarce but harms hosts when prey bacteria are plentiful, possibly because hosts leave some prey bacteria behind while carrying. Thus, understanding benefits and costs in this symbiosis requires measuring how many prey bacteria are eaten, carried and left behind by infected hosts. We found thatParaburkholderiainfection makes hosts leave behind both symbionts and prey bacteria. However, the number of prey bacteria left uneaten was too small to explain why infected hosts produced fewer spores than uninfected hosts. Turning to carried bacteria, we found that hosts carry prey bacteria more often after developing in prey-poor environments than in prey-rich ones. This suggests that carriage is actively modified to ensure hosts have prey in the harshest conditions. Our results show that multi-faceted interactions with third parties shape the evolution of symbioses in complex ways.
Towards a Yersinia pestis lipid A recreated in an Escherichia coli scaffold genome
Authors: McDonald Nathan D. , Antoshak Erin E.
Published: July 2024

Synthetic biology and genome engineering capabilities have facilitated the utilization of bacteria for a myriad of applications, ranging from medical treatments to biomanufacturing of complex molecules. The bacterial outer membrane, specifically the lipopolysaccharide (LPS), plays an integral role in the physiology, pathogenesis, and serves as a main target of existing detection assays for Gram-negative bacteria. Here we use CRISPR/Cas9 recombineering to insert Yersinia pestis lipid A biosynthesis genes into the genome of an Escherichia coli strain expressing the lipid IVa subunit. We successfully inserted three genes: kdsD, lpxM, and lpxP into the E. coli genome and demonstrated their expression via reverse transcription PCR (RT-PCR). Despite observing expression of these genes, analytical characterization of the engineered strain’s lipid A structure via MALDI-TOF mass spectrometry indicated that the Y. pestis lipid A was not recapitulated in the E. coli background. As synthetic biology and genome engineering technologies advance, novel applications and utilities for the detection and treatments of dangerous pathogens like Yersinia pestis will continue to be developed.
Molecular characteristics of CTX-M β-lactamase-producing and quinolone-resistant Escherichia coli among deer in a popular tourist spot in Japan
Authors: Ikushima Shiori , Sugiyama Michiyo , Asai Tetsuo
Published: July 2024

Introduction: Antimicrobial resistance (AMR) is a growing global concern. Clonal lineages of CTX-M β-lactamase-producing Escherichia coli (CTXE) and quinolone-resistant E. coli (QREC) were disseminated among deer population in a famous tourist destination (Nara Park; NP) in Japan.
Hypothesis or Gap statement: The molecular characteristics of CTXE or QREC isolates which could threat public health has not been elucidated.
Aim: This study aimed to characterize the genetic traits of CTXE and QREC isolates derived from NP deer and compare them with lineages prevalent worldwide.
Methodology: Sixteen CTXE and three QREC isolates recovered from NP deer feces between 2018 and 2020 were analyzed using whole-genome sequencing. For endemic lineages, phylogenetic trees were constructed using the core genome single nucleotide polymorphism scheme.
Results: Several pandemic lineages, such as ST38, ST58, and ST117, were included. The QREC lineages prevalent among deer were designated as extra-intestinal pathogenic E. coli or uropathogenic E. coli. Thirteen of the 24 ARG were considered high-risk ARG families. Chromosomal integration of blaCTX-M-15 was observed in all plasmid-negative isolates. Phylogenetic analysis showed relationship between ST3580 O8:H12 isolates obtained in NP and neighboring area.
Conclusion: Our study provides the evidence that multiple clinically important lineages of CTXE and QREC are endemic in NP deer and they could have public health impact. Further studies are required to investigate the relationship between chromosomal integration of plasmid-encoded genes and the stable propagation of AMR bacteria in wildlife and the environment.
Pedobacter faecalis sp. nov., isolated from the faeces of eland, Taurotragus oryx
Authors: Park Yerim , Min Jihyeon , Kim Bitnara , Park Woojun
Published: July 2024

Strain ELA7T, a novel Gram-negative, non-motile bacterium with a white pigment and rod-shaped morphology, was isolated from the faeces of an eland at Seoul Grand Park, a zoo in the Republic of Korea. The novel bacterial strain grew optimally in R2A medium under the following conditions: 0 % (w/v) NaCl, pH 8.0, and 34 °C. Based on phylogenetic analyses using 16S rRNA gene sequencing, strain ELA7T was found to have the closest relatedness to Pedobacter ginsengisoli Gsoil 104T (97.8 %), P. frigoris RP-3-15T (97.2 %), P. humi THG S15-2T (97.0 %), P. seoulensis THG-G12T (97.0 %), and P. foliorum LMG 31463T (96.9 %). The genome size and genomic DNA G+C content of strain ELA7T were 3.63 Mbp and 46.5 %, respectively. A whole genome-level comparison of strain ELA7T with P. ginsengisoli Gsoil 104T, P. frigoris RP-3-15T, P. africanus DSM 12126T, and P. psychroterrae RP-1-14T revealed average nucleotide identity values of 72.0, 71.8, 71.9, and 71.6 %, respectively. The major fatty acids were summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c) and MK-7 was the predominant respiratory quinone. The major polar lipids of strain ELA7T were phosphatidylethanolamine, sphingolipid, unidentified aminolipid, unidentified phosphoglycolipid, unidentified glycolipid, and eight unidentified lipids. Considering our chemotaxonomic, genotypic, and phenotypic findings, strain ELA7T (=KACC 23137T=JCM 36003T) is identified as representing a novel species within the genus Pedobacter, for which the name Pedobacter faecalis sp. nov. is proposed.
Mobile genetic element-driven genomic changes in a community-associated methicillin-resistant Staphylococcus aureus clone during its transmission in a regional community outbreak in Japan
Authors: Katahira Katsuyuki , Gotoh Yasuhiro , Kasama Kentaro , Yoshimura Dai , Itoh Takehiko , Shimauchi Chieko , Tajiri Akihiko , Hayashi Tetsuya
Published: July 2024

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are now a public health concern in both community and healthcare settings worldwide. We previously identified a suspected case of a maternity clinic-centred outbreak of CA-MRSA skin infection in a regional community in Japan by PFGE-based analysis. In this study, we performed genome sequence-based analyses of 151 CA-MRSA isolates, which included not only outbreak-related isolates that we previously defined based on identical or similar PFGE patterns but also other isolates obtained during the same period in the same region. Our analysis accurately defined 133 isolates as outbreak-related isolates, collectively called the TDC clone. They belonged to a CA-MRSA lineage in clonal complex (CC) 30, known as the South West Pacific (SWP) clone. A high-resolution phylogenetic analysis of these isolates combined with their epidemiological data revealed that the TDC clone was already present and circulating in the region before the outbreak was recognized, and only the isolates belonging to two sublineages (named SL4 and SL5) were directly involved in the outbreak. Long persistence in patients/carriers and frequent intrahousehold transmission of the TDC clone were also revealed by this analysis. Moreover, by systematic analyses of the genome changes that occurred in this CA-MRSA clone during transmission in the community, we revealed that most variations were associated with mobile genetic elements (MGEs). Variant PFGE types were generated by alterations of prophages and genomic islands or insertion sequence (IS)-mediated insertion of a plasmid or a sequence of unknown origin. Dynamic changes in plasmid content, which were linked to changes in antimicrobial resistance profiles in specific isolates, were generated by frequent gain and loss of plasmids, most of which were self-transmissible or mobilizable. The introduction of IS256 by a plasmid (named pTDC02) into sublineage SL5 led to SL5-specific amplification of IS256, and amplified IS256 copies were involved in some of the structural changes of chromosomes and plasmids and generated variations in the repertoire of virulence-related genes in limited isolates. These data revealed how CA-MRSA genomes change during transmission in the community and how MGEs are involved in this process.
Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury
Authors: Martynyuk Tetyana , Ricard Jerome , Bracchi-Ricard Valerie , Price Samuel , McGrath Jenna , Dougherty Kimberly , Tom Veronica , Bethea John R.
Published: July 2024

Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual’s outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kB dependent in VGluT2+ INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.
Cryptic diversity shapes coral symbioses, physiology, and response to thermal challenge
Authors: Aichelman Hannah E. , Benson Brooke E. , Gomez-Campo Kelly , Martinez-Rugerio M. Isabel , Fifer James E. , Tsang Laura , Hughes Annabel M. , Bove Colleen B. , Nieves Olivia C. , Pereslete Alyssa M. , Stanizzi Darren , Kriefall Nicola G. , Baumann Justin H. , Rippe John P. , Gondola Plinio , Castillo Karl D. , Davies Sarah W.
Published: July 2024

Coral persistence in the Anthropocene is shaped by interactions among holobiont partners (coral animals, microbial symbionts) and their environment. Cryptic coral lineages–genetically distinct yet morphologically similar groups–are critically important as they often exhibit functional diversity relevant to thermal tolerance. Additionally, environmental parameters such as thermal variability may promote tolerance, but how variability interacts with holobiont partners to shape responses to thermal challenge remains unclear. Here, we identified three cryptic lineages ofSiderastrea sidereain Bocas del Toro, Panamá that differ in distributions across inshore and offshore reefs, microbial associations, holobiont phenomes, and skeleton morphologies. A thermal variability experiment failed to increase thermal tolerance, but subsequent thermal challenge and recovery revealed one lineage maintained elevated energetic reserves, photochemical efficiency, and growth. Lastly, coral cores highlighted that this lineage also exhibited faster growth historically. Functional variation among cryptic lineages highlights their importance in predicting coral reef responses to climate change.

Teaser

Cryptic host diversity drives coral phenotypes relevant to climate change.
Expansion of mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis
Authors: Jaquish Abigail , Phung Eleni , Gong Xutong , Baldominos-Flores Pilar , Galvan-Pena Silvia , Bursulaya Isabelle , Magill Ian ,   ImmgenT consortium, Bertrand Kerri , Chambers Christina , Agudo Judith , Mathis Diane , Benoist Christophe , Ramanan Deepshika
Published: July 2024

Pregnancy brings about profound changes to the mammary gland in preparation for lactation. Changes in immunocyte populations that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells through all parous stages, revealing a marked increase in CD4+ and CD8+ T effector cells in late pregnancy and lactation. T cell expansion was partly dependent on microbial signals and included an increase in TCRαβ+CD8αα+ cells with strong cytotoxic markers, located in the epithelium, that resemble intraepithelial lymphocytes of mucosal tissues. This relationship was substantiated by demonstrating T cell migration from gut to mammary gland in late pregnancy, by TCR clonotypes shared by intestine and mammary tissue in the same mouse, including intriguing gut TCR families. Putative counterparts of CD8αα+ IELs were found in human milk. Mammary T cells are thus poised to manage the transition from a non-mucosal tissue to a mucosal barrier during lactogenesis.
Sulfonylurea receptor coupled conductances alter the performace of two central pattern generating circuits inCancer borealis
Authors: Kedia Sonal , Awal Naziru M. , Seddon Jackie , Marder Eve
Published: July 2024

Neuronal activity and energy supply must maintain a fine balance for neuronal fitness. Various channels of communication between the two could impact network output in different ways. Sulfonylurea receptors (SURs) are a modification of ATP-binding cassette proteins (ABCs) that confer ATP-dependent gating on their associated ion channels. They are widely expressed and link metabolic states directly to neuronal activity. The role they play varies in different circuits, both enabling bursting and inhibiting activity in pathological conditions. The crab, Cancer borealis, has central patterns generators (CPGs) that fire in rhythmic bursts nearly constantly and it is unknown how energy availability influences these networks. The pyloric network of the stomatogastric ganglion (STG) and cardiac ganglion (GC) control rhythmic contractions of the foregut and heart respectively. Pharmacological manipulation of SURs results in opposite effects in the two CPGs. Neuronal firing completely stops in the STG when SUR-associated channels are open, and firing increases when the channels are closed. This results from a decrease in the excitability of pyloric dilator (PD) neurons, which are a part of the pacemaker kernel. The neurons of the CG, paradoxically, increase firing within bursts when SUR-associated channels are opened, and bursting slows when SUR-associated channels are closed. The channel permeability and sensitivities analyses present novel SUR-conductance biophysics, which nevertheless change activity in ways reminiscent of the predominantly studied mammalian receptor/channels. We suggest that SUR-associated conductances allow different neurons to respond to energy states in different ways through a common mechanism.
An updated DNA barcoding tool forAloe veraand related CITES-regulated species
Authors: Woudstra Yannick , Rees Paul , Rakotoarisoa Solofo E. , Rønsted Nina , Howard Caroline , Grace Olwen M.
Published: July 2024

DNA barcoding has revolutionised the identification of illegally traded material of endangered species as it overcomes the lack of resolution encountered with morphological identification. Nonetheless, in recently evolved and highly diverse clades, such as the relatives ofAloe vera, the lack of interspecific sequence variation in standardised markers compromises the barcoding efficacy. We present a new DNA barcoding tool using 189 nuclear markers, optimised for aloes (Asphodelaceae, Alooideae). We built a comprehensive sequence reference dataset from taxonomically verified sources for >300 species and validated its reliability for identification using phylogenomic inference. Seven anonymised samples from verified botanical collections and ten plants seized at London Heathrow Airport were correctly identified to species level, including a critically endangered species from Madagascar. Commercially purchased samples were confirmed to be the species as advertised. An accurate, reliable DNA barcoding method for aloe identification introduces new assurance to regulatory processes for endangered plants in trade.
DGTS overproduced in seed plants is excluded from plastid membranes and promotes endomembrane expansion
Authors: Salomon Sarah , Schilling Marion , Albrieux Catherine , Si Larbi Grégory , Jouneau Pierre-Henri , Roy Sylvaine , Falconet Denis , Michaud Morgane , Jouhet Juliette
Published: July 2024

Plants and algae must adapt to environmental changes, facing various stresses that negatively impact their growth and development. One common stress is phosphate (Pi) deficiency, which is often in limiting quantity in the environment. In response to Pi deficiency, these organisms increase Pi uptake and remobilize intracellular Pi. Phospholipids are degraded to provide Pi and replaced by non-phosphorous lipids, such as glycolipids or betaine lipids. During the evolution, seed plants lost their capacity to synthesize betaine lipid. By expressing BTA1 genes, involved in the synthesis of diacylglyceryl-N,N,N-trimethyl-homoserine (DGTS), from different species, our work shows that DGTS can be produced in seed plants. In Arabidopsis, expressing BTA1 under a phosphate starvation-inducible promoter resulted in limited DGTS production without having any impact on plant growth or lipid remodeling. In transient expression systems inNicotiana benthamiana, leaves were able to accumulate DGTS up to 20 % of their glycerolipid content at a slight expense of galactolipid and phospholipid production. At the subcellular level, we showed that DGTS is absent from plastid and seems to be enriched in endomembrane, driving an ER membrane proliferation. Finally, DGTS synthesis pathway seems to compete with PC synthesis via the Kennedy pathway but does not seem to be derived from PC diacylglycerol backbone and therefore does not interfere with the eukaryotic pathway involved in galactolipid synthesis.
Climate adaptation inP. trichocarpa: key adaptive loci identified for stomata and leaf traits
Authors: Klein Marie C , Meng Zi , Bailey-Bale Jack , Milner Suzanne , Shi Peicai , Muchero Wellington , Chen Jin-Gui , Tschaplinski Timothy J , Jacobson Daniel , Lagergren John , Lane Matthew , O’Brien Chris , Chhetri Hari , Shu Mengjun , Freer-Smith Peter , Buckley Thomas N. , Magney Troy , Monroe J Grey , Tuskan Gerald A. , Taylor Gail
Published: July 2024

Identifying the genetic basis of traits underlying climate adaptation remains a key goal for predicting species responses to climate change, enabling the elucidation of gene targets for future climate-resilient crops. Here, we measured 14 leaf and stomatal traits under control (well-watered) and drought conditions, subsampling a diversity collection of over 1,300Populus trichocarpagenotypes, a potential biofuel feedstock crop. Stomatal traits were correlated with the climate of origin for genotypes, such that those originating from environments subject to water deficit tended to have smaller stomata, but with higher density. Stomatal traits were also correlated with leaf morphology, with larger leaves having larger stomata and lower stomatal density mirrored in correlations to climate of origin. The direction of plastic responses - reduced stomatal size under drought - mirrors the correlations seen among genotypes with respect to the aridity of environmental origin. Genome-Wide Association Studies (GWAS) identified loci underlying trait diversity, including candidates contributing to stomatal size. We used climate of origin to predict stomatal size in genotypes with unknown trait values and found that these predicted phenotypes confirmed empirically measured allele effects. Finally, we found evidence that future climates may select for alleles contributing to decreased stomatal size, with the strength of selection depending on the availability of moisture. These findings reveal adaptive variation in stomatal and physiological traits along with underlying genetic loci, with implications for future selection and breeding - providing insights into the responses to future climate change.

Highlight

Research onPopulus trichocarpareveals adaptation of physiological and stomatal traits linked to drought tolerance, with genotypes from arid regions exhibiting smaller stomata, offering insights for climate change adaptation and sustainable biofuel production.
Nanopore-based native RNA sequencing of human transcriptomes reveals the complexity of mRNA modifications and crosstalk between RNA regulatory features
Authors: Kim Yerin , O’Neill Kieran , Garant Jean-Michel , Saville Luke , Haile Simon , Ghashghaei Maryam , Park Yongjin P. , Jones Steven J.M. , Vu Ly P
Published: July 2024

The identification and functional characterization of chemical modifications on an mRNA molecule, in particular N6-methyladenosine (m6A) modification, significantly broadened our understanding of RNA function and regulation. While interactions between RNA modifications and other RNA features have been proposed, direct evidence showing correlation is limited. Here, using Oxford Nanopore long-read direct RNA sequencing (dRNA-seq), we simultaneously interrogate the transcriptome and epitranscriptome of a human leukemia cell line to investigate the correlation between m6A modifications, mRNA abundance, polyA tail length and alternative splicing. We demonstrated that high quality dRNA-seq is critically important for unbiased and large-scale correlative analyses of these RNA features. The genome wide landscape of RNA methylation was captured with single nucleotide and individual isoform resolution. The length of polyA tails were ascribed to individual transcripts and genes, allowing for unprecedent measurement of polyA tail length distribution. Global analysis indicated negative association between polyA tail length and mRNA abundance while uncovering pathway-specific responses upon depletion of m6A forming enzyme METTL3. Overall, our study presented a rich dRNA-seq data resource which has been validated and can be further exploited to inquire into the complexity of RNA modifications and potential interplays between RNA regulatory elements.
Distinct structural and functional heterochromatin partitioning of lamin B1 and B2 revealed using genome-wide Nicking Enzyme Epitope targeted DNA sequencing.
Authors: Sen Sagnik , Esteve Pierre O. , Karthikeyan Raman , Beaulieu Julie , Chin Hang Gyeong , Feehary George , Vishnu Udayakumar S , Xu Shuang yong , Samuelson Jim , Pradhan Sriharsa
Published: July 2024

A genome-wide chromatin profiling technology, named as Nicking Enzyme Epitope targeted DNA sequencing (NEED-seq) in which antibody-targeted controlled nicking by Nt.CviPII-pGL is used to study specific protein-DNA complexes. NEED-seq is performed in situ in formaldehyde fixed cells, allowing for both visual and genomic resolution of epitope bound chromatin. When applied to nuclei, NEED-seq yielded genome-wide chromatin associated proteins and histone post-translational modifications (PTMs). NEED-seq of lamin B1/B2 demonstrated their association with heterochromatin. Lamin B1 and B2 associated domains (LAD) segregated to three different states, and states with stronger LAD correlated with heterochromatic marks. Hi-C analysis displayed A and B compartment with equal lamin B1/B2 distribution, although methylated DNA remained high in B compartment. LAD clustering with Hi-C resulted in subcompartments, with lamin B1-B2 partitioning to facultative and constitutive heterochromatin respectively and were associated with neuronal development. Thus, lamin B1 and B2 have structural and functional partitioning in mammalian nucleus.
Localizedin vivogene editing of murine cancer-associated fibroblasts
Authors: Kuhn Nicholas F. , Zaleta-Linares Itzia , Nyberg William A. , Eyquem Justin , Krummel Matthew F.
Published: July 2024

Discovering the role of fibroblasts residing in the tumor microenvironment (TME) requires controlled, localized perturbations because fibroblasts play critical roles in regulating immunity and tumor biology at multiple sites. Systemic perturbations can lead to unintended, confounding secondary effects, and methods to locally genetically engineer fibroblasts are lacking. To specifically investigate murine stromal cell perturbations restricted to the TME, we developed an adeno-associated virus (AAV)-based method to target any gene-of-interest in fibroblasts at high efficiency (>80%). As proof of concept, we generated single (sKO) and double gene KOs (dKO) ofOsmr,Tgfbr2, andIl1r1in cancer-associated fibroblasts (CAFs) and investigated how their cell states and those of other cells of the TME subsequently change in mouse models of melanoma and pancreatic ductal adenocarcinoma (PDAC). Furthermore, we developed anin vivoknockin-knockout (KIKO) strategy to achieve long-term tracking of CAFs with target gene KO via knocked-in reporter gene expression. This validatedin vivogene editing toolbox is fast, affordable, and modular, and thus holds great potential for further exploration of gene function in stromal cells residing in tumors and beyond.

Graphical Abstract
Re2Pair: Increasing the Scalability of RePair by Decreasing Memory Usage
Authors: Kim Justin , Varki Rahul , Oliva Marco , Boucher Christina
Published: July 2024

The RePair compression algorithm produces a context-free grammar by iteratively substituting the most frequently occurring pair of consecutive symbols with a new symbol until all consecutive pairs of symbols appear only once in the compressed text. It is widely used in the settings of bioinformatics, machine learning, and information retrieval where random access to the original input text is needed. For example, in pangenomics, RePair is used for random access to a population of genomes. BigRePair improves the scalability of the original RePair algorithm by using Prefix-Free Parsing (PFP) to preprocess the text prior to building the RePair grammar. Despite the efficiency of PFP on repetitive text, there is a scalability issue with the size of the parse which causes a memory bottleneck in BigRePair. In this paper, we design and implement recursive RePair (denoted as Re2Pair), which builds the RePair grammar using recursive PFP. Our novel algorithm faces the challenge of constructing the RePair grammar without direct access to the parse of text, relying solely on the dictionary of the text and the parse and dictionary of the parse of the text. We compare Re2Pair to BigRePair using SARS-CoV-2 haplotypes and haplotypes from the 1000 Genomes Project. We show that our method Re2Pair achieves over a 40% peak memory reduction and a speed up ranging between 12% to 79% compared to BigRePair when compressing the largest input texts in all experiments. Re2Pair is made publicly available under the GNU public license here:https://github.com/jkim210/Recursive-RePair

2012 ACM Subject Classification

Theory of computation → Formal languages and automata theory
Filtering for highly variable genes and high quality spots improves phylogenetic analysis of cancer spatial transcriptomics Visium data
Authors: Gavryushkina Alexandra “Sasha” , Pinkney Holly R , Diermeier Sarah D , Gavryushkin Alex
Published: July 2024

Phylogenetic relationship of cells within tumours can help us to understand how cancer develops in space and time, iden-tify driver mutations and other evolutionary events that enable can-cer growth and spread. Numerous studies have reconstructed phylo-genies from single-cell DNA-seq data. Here we are looking into the problem of phylogenetic analysis of spatially resolved near single-cell RNA-seq data, which is a cost-efficient alternative (or complemen-tary) data source that integrates multiple sources of evolutionary information including point mutations, copy-number changes, and epimutations. Recent attempts to use such data, although promis-ing, raised many methodological challenges. Here, we explored data-preprocessing and modelling approaches for evolutionary analyses of Visium spatial transcriptomics data. We conclude that using only highly variable genes and accounting for heterogeneous RNA capture across tissue-covered spots improves the reconstructed topological relationships and influences estimated branch lengths.
Unbounding fish: Assessing vulnerability to overexploitation for transboundary fish populations
Authors: Gangal Mayuresh , Arthur Rohan , Suri Venkatachalam , Pandit Awadhesh , Tyagi Abhinav , Prakash Praveen , Sule Mihir , Majgaonkar Iravatee , Krishnaswamy Jagadish , Ramakrishnan Uma
Published: July 2024

Tropical fish populations often traverse management boundaries, making it difficult to evaluate species vulnerabilities and optimise sustainable fishing goals. Most vulnerability assessments rely on life histories and gear susceptibility, but ignore transboundary differences in management, which can strongly affect vulnerability. We propose a novel vulnerability matrix, the Biology – Transboundary Management (BTM) index for individual fish populations based on 1) Species specific vulnerability 2) distribution of genetically-distinct populations with respect to jurisdictional boundaries and 3) sustainability of management practices across jurisdictions. Combining single-nucleotide polymorphism (SNP) analyses and policy assessments, we evaluate relative vulnerabilities of nine commercially relevant fish populations over a 3400km stretch of India’s west coast, across multiple jurisdictions. The BTM matrix indicates that transboundary differences in management strongly influences biological vulnerability. The matrix is sensitive to population-level differences and policy changes. Our analyses emphasise the need for population-level assessments and transboundary cooperation in achieving sustainable multi species fisheries.
The state-of-the-art machine learning model for Plasma Protein Binding Prediction: computational modeling with OCHEM and experimental validation
Authors: Han Zunsheng , Xia Zhonghua , Xia Jie , Tetko Igor V. , Wu Song
Published: July 2024

Plasma protein binding (PPB) is closely related to pharmacokinetics, pharmacodynamics and drug toxicity. Prediction of PPB is an alternative to experimental approaches that are known to be time-consuming and costly. Although there are various models and web servers for PPB prediction already available, they suffer from low prediction accuracy and poor interpretability, in particular for molecules with high values, and are most often not properly validated in prospective studies. Here, we carried out strict data curation, and applied consensus modeling to obtain a model with a coefficient of determination of 0.90 and 0.91 on the training set and the test set, respectively. This model was further validated in a prospective study to predict 63 poly-fluorinated and another 25 highly diverse compounds, and its performance for both these sets was superior to that of other previously reported models. To identify structural features related to PPB, we analyzed a model based on Morgan2 fingerprints and identified that features such as aromatic rings, halogen atoms, heterocyclic rings can discriminate high- and low-PPB molecules. In conclusion, we have established a PPB prediction model that showed state-of-the-art performance in prospective screening, which we have made publicly available in the OCHEM platform (https://ochem.eu/article/29).

Graphic Abstract
Influence of predation mortality on past and future dynamics of Pacific Herring: implications for stock status and future biomass
Authors: Doherty Beau , Johnson Samuel D. N. , Benson Ashleen J. , Cox Sean P. , Cleary Jaclyn S. , Lane Jim
Published: July 2024

The recovery of marine mammals from historical over-exploitation in the 1970s represents one of the largest changes in trophic structure in the northeast Pacific Ocean over the last century, for which the impacts on key forage species such as Pacific Herring (Clupea pallasii) are poorly understood. This has prompted hypotheses that increasing marine mammal populations are the primary cause for productivity declines for some fish stocks and their lack of recovery to historical abundance levels. In this study, we evaluate such a hypothesis for Pacific Herring by quantifying historical predation rates by key predators including cetaceans (Pacific Humpbacks, Grey Whales), pinnipeds (Stellar Sea Lions, Harbour Seals), and piscivorous fish (Pacific Hake). Predation mortality is quantified via a novel approach that integrates a single-species catch-at-age model with estimates of predator consumption derived from bioenergetic models. We found that predator consumption, largely driven by Humpback Whales, explained increasing Pacific Herring natural mortality rates in recent years and could be used to forecast future mortality. Incorporating higher future natural mortality rates produced higher estimates of current stock status (1.09-1.2B0) based on lower estimates of equilibrium unfished biomass (17.5-20.3 kt). Conversely, models that assumed mortality was more like the historical average had lower stock status (0.63B0) and higher estimates of unfished biomass (32.4 kt). We demonstrate a practical approach for ecosystem modelling that can be used to develop operating model scenarios for management strategy evaluation, improving scientific defensibility by removing an element of analyst choice for future mortality scenarios. We discuss how simpler modifications to single-species model assumptions can be more pragmatic for providing fisheries management advice, while more complex multi-species or ecosystem models might provide more nuanced insights for exploring research questions related to multi-species ecosystems and fisheries interactions.
Drug-repurposing screen identifies thiostrepton as a novel regulator of the tumor suppressor DAB2IP
Authors: De Florian Fania Rossella , Maiocchi Serena , Klima Raffaella , Pellegrini Valeria , Ghetti Sabrina , Selvestrel Davide , Fava Luca L , Braga Luca , Collavin Licio
Published: July 2024

The tumor suppressor DAB2IP, a RasGAP and cytoplasmic adaptor protein, modulates signal transduction in response to several extracellular stimuli, negatively regulating multiple oncogenic pathways. Accordingly, the loss of DAB2IP in tumor cells fosters metastasis and enhances chemo- and radio-resistance. DAB2IP is rarely mutated in cancer but is frequently downregulated or inactivated by multiple mechanisms. Solid experimental evidence show that DAB2IP reactivation can reduce cancer aggressiveness in tumors driven by multiple different oncogenic mutations, making this protein an interesting target for anti-cancer therapy. Based on these premises, we screened a library of FDA-approved drugs to search for molecules that can increase DAB2IP protein levels. We exploited CRISPR/Cas9 gene editing to generate two prostate cancer cell models in which endogenous DAB2IP is fused to HiBiT, a peptide tag that enables luminescence-based detection of protein levels in a sensitive and quantitative manner. Using this approach, we identified drugs able to increase DAB2IP levels. We focus our attention on thiostrepton, a natural cyclic oligopeptide antibiotic that has been reported to inhibit survival of various cancer cell lines. Functional experiments revealed that the cancer inhibitory effect of thiostrepton is reduced in the absence of DAB2IP, suggesting that the observed upregulation contributes to its action. These findings encourage the further development of thiostrepton for the treatment of solid cancers, and unveil a novel molecular mechanism underlying its anti-tumoral action.
7 Tesla MRS estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex
Authors: Paparella Ilenia , Cardone Paolo , Zanichelli Benedetta , Lamalle Laurent , Collette Fabienne , Sherif Siya , Zubkov Mikhail , Clarke William T , Stagg Charlotte J , Maquet Pierre , Vandewalle Gilles
Published: July 2024

GABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high field 7 Tesla MRS and Transcranial Magnetic Stimulation coupled with high-density Electroencephalography (TMS-hdEEG) from the motor cortex of twenty healthy participants (age 23.95±6.4), while they were at rest. We first applied a Neural Mass Model to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of Parametric Empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS and will contribute to the concretization of MRS-GABA promises to improve our understanding of human behaviour, brain physiology and pathophysiology.

Key points

GABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke.

Quantification of GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated.

By using a biophysical Neural Mass Model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex.
Assembling a true ‘Olympic Gel’ from >16,000 combinatorial DNA rings
Authors: Speed Sarah , Atabay Azra , Peng Yu-Hsuan , Gupta Krishna , Müller Toni , Fischer Carolin , Sommer Jens-Uwe , Lang Michael , Krieg Elisha
Published: July 2024

Olympic gels are an elusive form of soft matter, comprising a three-dimensional network of mechanically interlocked cyclic molecules. In the absence of defined network junctions, the high conformational freedom of the molecules was previously theorized to confer unique mechanical properties to Olympic gels, such as non-linear elasticity and unconventional swelling characteristics. However, the synthesis of an Olympic gel exhibiting these intriguing features is challenging, since unintended crosslinking and polymerization processes are often favored over cyclization. Here, we report the successful assembly of a true Olympic gel from a library of DNA rings comprising more than 16,000 distinct molecules. Each of these rings contains a unique sequence domain that can be enzymatically activated to produce reactive termini that favor intramolecular cyclization. We characterized the material’s genetic, mechanical, and structural characteristics by next-generation sequencing, oscillatory rheology, large-scale computational simulations, atomic force microscopy, and cryogenic electron microscopy. Our results confirm the formation of a stable Olympic gel, which exhibits unique swelling behavior and an elastic response that is exclusively determined by entanglements, yet persists on long time scales. By combining concepts from polymer physics, synthetic biology, and DNA nanotechnology, this new material class provides a flexible experimental platform for future studies into the effects of network topology on macroscopic material properties and its function as a carrier of genetic information in biological and biomimetic systems. This work moreover demonstrates that exotic material properties can emerge in systems with a high compositional complexity that is more reminiscent of biological than synthetic matter.

Abstract Figure
CELLNET technology: Spatially organized, functional 3D networks at single cell resolution
Authors: Poudel Arun , Kunwar Puskal , Aryal Ujjwal , Merife Anna-Blessing , Soman Pranav
Published: July 2024

Cells possess the remarkable ability to generate tissue-specific 3D interconnected networks and respond to a wide range of stimuli. Understanding the link between the spatial arrangement of individual cells and their networks’ emergent properties is necessary for the discovery of both fundamental biology as well as applied therapeutics. However, current methods spanning from lithography to 3D photo-patterning to acoustofluidic devices are unable to generate interconnected and organized single cell 3D networks within native extracellular matrix (ECM). To address this challenge, we report a novel technology coined as CELLNET. This involves the generation of crosslinked collagen within multi-chambered microfluidic devices followed by femtosecond laser ablation of 3D microchannel networks and cell seeding. Using model cells, we show that cell migrate within ablated networks within hours, self-organize and form viable, interconnected, 3D networks in custom architectures such as square grid, concentric circle, parallel lines, and spiral patterns. Heterotypic CELLNETs can also be generated by seeding multiple cell types in side-chambers of the devices. The functionality of cell networks can be studied by monitoring the real-time calcium signaling response of individual cells and signal propagation within CELLNETs when subjected to flow stimulus alone or a sequential combination of flow and biochemical stimuli. Furthermore, user-defined disrupted CELLNETs can be generated by lethally injuring target cells within the 3D network and analyzing the changes in their signaling dynamics. As compared to the current self-assembly based methods that exhibit high variability and poor reproducibility, CELLNETs can generate organized 3D single-cell networks and their real-time signaling responses to a range of stimuli can be accurately captured using simple cell seeding and easy-to-handle microfluidic devices. CELLNET, a new technology agnostic of cell types, ECM formulations, 3D cell-connectivity designs, or location and timing of network disruptions, could pave the way to address a range of fundamental and applied bioscience applications.

Teaser

New technology to generate 3D single cell interconnected and disrupted networks within natural extracellular matrix in custom configurations.
Follicle stimulating hormone receptor expression in human pancreas and effects on insulin secretion: A translational study
Authors: Aydin Banu Kucukemre , Incedal Nilsson Ceren , Chowdhury Azazul , Wen Quan , Cerenius Sara Y. , Stenlid Rasmus , Mörwald Katharina , Ciba Iris , Manell Hannes , Weghuber Daniel , Forslund Anders , Idevall-Hagren Olof , Bergsten Peter
Published: July 2024

Follicle-stimulating hormone (FSH) is traditionally known for its role in reproduction, but recent studies suggest it may also influence metabolic processes. This study aimed to examine FSH receptor (FSHR) expression in human pancreatic islets and the direct effects of FSH on insulin secretion, as well as explore FSH’s metabolic role during puberty, focusing on enhanced insulin secretion during this critical period. FSHR gene and protein expression were detected in isolated human pancreatic islets and co-localized with insulin-producing beta-cells. Additionally, FSH at prepubertal (0.1 IU/L) and pubertal concentrations (10 IU/L) significantly enhanced glucose-stimulated insulin secretion (GSIS) and increased intracellular cAMP concentrations in intact human pancreatic islets. In children with obesity from the Beta-JUDO cohort (n=608), plasma FSH levels were positively associated with several insulin secretion indices, particularly in pubertal children. These findings suggest that FSH has significant metabolic roles beyond reproduction, involving insulin secretion and potentially contributing to puberty-related hyperinsulinemia and insulin resistance.
Nitrogen sharing strategies in six clonal species
Authors: Duchoslavová Jana
Published: July 2024

Nitrogen is often a limiting factor for plant growth, and its availability is a major determinant of level of competition. In clonal plants, patterns of nitrogen translocation between ramets may be part of plant nitrogen economics, and, as such, may also be related to the typical availability of nitrogen. In nutrient-poor habitats, extensive nutrient sharing balancing resource availability may be important, whereas nutrient sharing between established ramets may not be beneficial in productive habitats.

I tested the proposed nutrient sharing strategies on nitrogen translocation in six stoloniferous species that occur in habitats of varying productivity. Mother and daughter ramets of each species were grown either in a homogeneous nutrient-poor treatment or in a “nutrient-poor to nutrient-rich” treatment. I traced the translocation of nitrogen in both directions using stable isotope labelling when the daughter ramets were one month old.

Surprisingly, I found no effect of nutrient treatment on nitrogen translocation. Instead, each species translocated nitrogen either acropetally, basipetally, or equally in both directions. There was no relationship between the direction of translocation and the productivity of the species’ habitats. However, net translocation seemed to be related to the relative size of daughters across species, and withinVeronica officinalis.

The results suggest that the relative size of plant parts is an important determinant of the strength of the sink for nitrogen they form, and that the growth habit of a species can affect its nitrogen translocation. Under certain conditions, such internally induced source-sink relationships may dominate over external nitrogen heterogeneity. I speculate that growth habit, together with nitrogen translocation patterns, may be part of adaptive growth strategies.