bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for maintenance of key components of vocal learning in ageing budgerigars despite diminished affiliative social interaction
Authors: Moussaoui Bushra , Overcashier Samantha L. , Kohn Gregory M. , Araya-Salas Marcelo , Wright Timothy F.
Published: June 2023

In some species, the ability to acquire new vocalizations persists into adulthood and may be an important mediator of social interactions. While it is generally assumed that vocal learning persists undiminished throughout the lifespan of these open-ended learners, the stability of this trait remains largely unexplored. We hypothesize that vocal learning exhibits senescence, as is typical of complex cognitive traits, and that this decline relates to age-dependent changes in social behaviour. The budgerigar (
Melopsittacus undulatus
), an open-ended learner that develops new contact call types that are shared with social associates upon joining new flocks, provides a robust assay for measuring the effects of ageing on vocal learning ability. We formed captive flocks of 4 previously unfamiliar adult males of the same age class, either ‘young adults’ (6 mo−1 y) or ‘older adults’ (≥ 3 y), and concurrently tracked changes in contact call structure and social interactions over time. Older adults exhibited decreased vocal diversity, which may be related to sparser and weaker affiliative bonds observed in older adults. Older adults, however, displayed equivalent levels of vocal plasticity and vocal convergence compared to young adults, suggesting that many components of vocal learning are largely maintained into later adulthood in an open-ended learner.
Bee pollination services and the burden of biogeography
Authors: Tierney Simon M. , Bernauer Olivia M. , King Lachlan , Spooner-Hart Robert , Cook James M.
Published: June 2023

Native bees augment pollination services in the Northern Hemisphere, especially cultivated apple crops, yet Southern Hemisphere contexts are poorly known. We observed the foraging behaviour of 69 354 invertebrate flower visitors in Australian orchards (two regions, 3 years) to assess the efficacy of pollination service (Peff). Native stingless bees and introduced honey bees were the most abundant visitors and most efficacious pollinators (Tetragonula Peff= 6.16;Apis Peff= 13.02), withTetragonulabecoming important service providers above 22°C. However, visits by tree-nesting stingless bees decreased with distance from native forest (less than 200 m) and their tropical/subtropical distribution precludes pollination service in other major Australian apple-producing regions. More broadly distributed native allodapine and halictine bees transferred the most pollen per-visit, but their low abundances reduce efficacies (Exoneura Peff= 0.03;Lasioglossum Peff= 0.06), resulting in a general dependence on honey bees. This reliance is a burden of biogeography, since key Northern Hemisphere pollinators of apple (Andrena, Apis,Bombus,Osmia) do not naturally occur in Australasia—where there is only 15% generic overlap with Central Asian bees sympatric with wild apple distributions (cf. Palaearctic 66% and Nearctic 46% generic overlaps). The historical biogeography of bees therefore drives an extreme dependence on one introduced species for apple pollination in Australia.
Parasite diversity at isolated, disturbed hydrothermal vents
Authors: Dykman Lauren N. , Tepolt Carolyn K. , Kuris Armand M. , Solow Andrew R. , Mullineaux Lauren S.
Published: June 2023

Habitat isolation and disturbance are important regulators of biodiversity, yet it remains unclear how these environmental features drive differences in parasite diversity between ecosystems. We test whether the biological communities in an isolated, frequently disturbed marine ecosystem (deep-sea hydrothermal vents) have reduced parasite richness and relatively fewer parasite species with indirect life cycles (ILCs) compared to ecosystems that are less isolated and less disturbed. We surveyed the parasite fauna of the biological community at the 9°50′N hydrothermal vent field on the East Pacific Rise and compared it to similar datasets from a well-connected and moderately disturbed ecosystem (kelp forest) and an isolated and undisturbed ecosystem (atoll sandflat). Parasite richness within host species did not differ significantly between ecosystems, yet total parasite richness in the vent community was much lower due to the low number of predatory fish species. Contrary to expectation, the proportion of ILC parasite species was not lower at vents due to a high richness of trematodes, while other ILC parasite taxa were scarce (nematodes) or absent (cestodes). These results demonstrate the success of diverse parasite taxa in an extreme environment and reinforce the importance of host diversity and food web complexity in governing parasite diversity.
Genomic analysis of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli colonising adults in Blantyre, Malawi reveals previously undescribed diversity
Authors: Lewis Joseph M. , Mphasa Madalitso , Banda Rachel , Beale Mathew A. , Mallewa Jane , Anscome Catherine , Zuza Allan , Roberts Adam P. , Heinz Eva , Thomson Nicholas R. , Feasey Nicholas A.
Published: June 2023

Escherichia coli

is one of the most prevalent Gram-negative species associated with drug resistant infections. Strains that produce extended-spectrum beta-lactamases (ESBLs) or carbapenemases are both particularly problematic and disproportionately impact resource limited healthcare settings where last-line antimicrobials may not be available. A large number of

E. coli

genomes are now available and have allowed insights into pathogenesis and epidemiology of ESBL

E. coli

but genomes from sub-Saharan Africa (sSA) are significantly underrepresented. To reduce this gap, we investigated ESBL-producing

E. coli

colonising adults in Blantyre, Malawi to assess bacterial diversity and AMR determinants and to place these isolates in the context of the wider population structure. We performed short-read whole-genome sequencing of 473 colonising ESBL

E. coli

isolated from human stool and contextualised the genomes with a previously curated multi-country collection of 10 146

E. coli

genomes and sequence type (ST)-specific collections for our three most commonly identified STs. These were the globally successful ST131, ST410 and ST167, and the dominant ESBL genes were bla
CTX-M, mirroring global trends. However, 37 % of Malawian isolates did not cluster with any isolates in the curated multicountry collection and phylogenies were consistent with locally spreading monophyletic clades, including within the globally distributed, carbapenemase-associated B4/H24RxC ST410 lineage. A single ST2083 isolate in this collection harboured a carbapenemase gene. Long read sequencing demonstrated the presence of a globally distributed ST410-associated carbapenemase carrying plasmid in this isolate, which was absent from the ST410 strains in our collection. We conclude there is a risk that carbapenem resistance in

E. coli

could proliferate rapidly in Malawi under increasing selection pressure, and that both ongoing antimicrobial stewardship and genomic surveillance are critical as local carbapenem use increases.
Rigorous software pipeline for clinical somatic mutation analyses of solid tumors
Authors: Stoimenov Ivaylo , Rashyna Marina , Adlerteg Tom , Nunes Luís , Ekström Joakim , Ljungström Viktor , Mathot Lucy , Cheong Ian , Sjöblom Tobias
Published: June 2023

Mutational analyses of tumor DNA guide the use of targeted therapies and checkpoint inhibitors in management of solid tumors. Reducing false positive mutation calls without compromising sensitivity as gene panels increase in size, and whole exome and genome sequencing enters clinical use, remains a major challenge. Aiming for robust somatic mutation analyses in the clinical setting, we have developed VARify, an integrated, accurate and computationally efficient software for cancer genome analyses encompassing all steps from pre-processing of sequencing reads to mutation identification. Benchmarking to two state-of-the-art open-source somatic mutation analysis pipelines demonstrated accurate detection of clinically actionable point mutations, all while strongly reducing the number of false positive mutations reported, at comparable or faster speed. Further, the VARify output classified microsatellite unstable colorectal cancers by tumor mutation burden better than the other pipelines. In comparisons where the same tumors were subjected to different panel enrichment and sequencing technologies, VARify had the most consistent intersection of consensus mutations. False positive calls were produced when the same data was used as tumor and reference by the other pipelines, while VARify did not produce such calls. The calling uniformity across sequencing technologies of VARify and its tumor-only analysis derivative pipeline ALTOmate was also demonstrated. Taken together, these two novel pipelines can improve clinical mutation analysis to the benefit of cancer patients.
ACitrullusgenus super-pangenome reveals extensive variations in wild and cultivated watermelons and sheds light on watermelon evolution and domestication
Authors: Wu Shan , Sun Honghe , Gao Lei , Branham Sandra , McGregor Cecilia , Renner Susanne S. , Xu Yong , Kousik Chandrasekar , Wechter W. Patrick , Levi Amnon , Fei Zhangjun
Published: June 2023

Sweet watermelon (Citrullus lanatussubsp.vulgaris) is among the most important vegetable crops in the world. Wild relatives are important resources for watermelon breeding. Here we report high-quality reference genomes of three wild watermelons,C. mucosospermus, C. amarusandC. colocynthis, and the divergence and genome evolution of differentCitrullusspecies. Using genomic data from 547 watermelon accessions spanning fourCitrullusspecies, we construct a super-pangenome to represent theCitrullusgene repertoire and provide a catalogue of orthologous relationships among species. Gene presence/absence variation analysis uncovers many disease resistance genes that are missing in cultivated watermelons, as well as genes with significantly different occurrence frequencies between populations that might underlie watermelon evolution and domestication. We revisit watermelon domestication using the recently identified wild progenitor, Kordofan melon, which provides insights into the domestication of fruit bitterness, sweetness and flesh coloration. TheCitrullussuper-pangenome provides a valuable resource for breeding and biological discovery, and our comparative genomic analyses shed additional light on watermelon evolution and domestication.
Antibiotic that inhibitstrans-translation blocks binding of EF-Tu to tmRNA but not to tRNA
Authors: Marathe Neeraja , Nguyen Ha An , Alumasa John N. , Kuzmishin Nagy Alexandra B. , Vazquez Michael , Dunham Christine M. , Keiler Kenneth C.
Published: June 2023

Trans-Translation is conserved throughout bacteria and is essential in many species. High-throughput screening identified a tetrazole-basedtrans-translation inhibitor, KKL-55, that has broad-spectrum antibiotic activity. A biotinylated version of KKL-55 pulled down Elongation Factor Thermo-unstable (EF-Tu) from bacterial lysates. Purified EF-Tu bound KKL-55in vitrowith aKd= 2 µM, confirming a high-affinity interaction. An X-ray crystal structure showed KKL-55 binds in domain 3 of EF-Tu, and mutation of residues in the binding pocket abolished KKL-55 binding. RNA binding assaysin vitroshowed that KKL-55 inhibits binding between EF-Tu and tmRNA, but not between EF-Tu and tRNA. These data demonstrate a new mechanism for inhibition of EF-Tu function and suggest that this specific inhibition of EF-Tu•tmRNA binding is a viable target for antibiotic development.

IMPORTANCE

EF-Tu is a universally conserved translation factor that mediates productive interactions between tRNAs and the ribosome. In bacteria, EF-Tu also delivers tmRNA-SmpB to the ribosome duringtrans-translation. We report the first small molecule, KKL-55, that specifically inhibits EF-Tu activity intrans-translation without affecting its activity in normal translation. KKL-55 has broad-spectrum antibiotic activity, suggesting that compounds targeted to the tmRNA-binding interface of EF-Tu could be developed into new antibiotics to treat drug-resistant infections.
TB-annotator: a scalable web application that allowsin-depthanalysis of very large sets of publicly availableMycobacterium tuberculosiscomplex genomes
Authors: Senelle Gaetan , Guyeux Christophe , Refrégier Guislaine , Sola Christophe
Published: June 2023

Tuberculosis continues to be one of the most threatening bacterial diseases in the world. However, we currently have more than 160,000 Short Read Archives (SRAs) ofMycobacterium tuberculosiscomplex. Such a large amount of data should help to the understanding and the fight against this bacterium. To accomplish this, it would be necessary to thoroughly and comprehensively examine this significant mass of data. This is what TB-Annotator proposes to do, combining a database containing all the diversity of these 160,000 SRAs (at least, SRAs with a reasonable read size and quality), and a fully featured analysis platform to explore and query such a large amount of data. The objective of this article is to present this platform centered on the key notion of exclusivity, to show its numerous capacities (detection of single nucleotide variants, insertion sequences, deletion regions, spoligotyping, etc.) and its general functioning. We will compare TB-Annotator to existing tools for the study of tuberculosis, and show that its objectives are original and have no equivalent at present. The database on which it is based will be presented, with the numerous advanced search queries and screening capacities it offers, and the interest and originality of its phylogenetic tree navigation interface will be detailed. We will end this article with examples of the achievements made possible by the TB-Annotator, followed by avenues for future improvement.
The dynamics of phage predation on a microcolony
Authors: Eriksen Rasmus Skytte , Larsen Frej , Svenningsen Sine Lo , Sneppen Kim , Mitarai Namiko
Published: June 2023

Phage predation is an important factor for controlling the bacterial biomass. At face value, dense microbial habitats are expected to be vulnerable to phage epidemics due to the abundance of fresh hosts immediately next to any infected bacteria. Despite this, the bacterial microcolony is a common habitat for bacteria in nature. Here we experimentally quantify the fate of microcolonies ofEscherichia coliexposed to virulent phageT4. It has been proposed that the outer bacterial layers of the colony will shield the inner layers from the phage invasion and thereby constrain the phage to the colony’s surface. We develop a dynamical model that incorporates this shielding mechanism and fits the results with experimental measurements to extract important phage-bacteria interaction parameters. The analysis suggests that, while the shielding mechanism delays phage attack,T4phage are able to diffuse so deep into the dense bacterial environment that colony level survival of the bacterial community is challenged.

Significance

The shielding mechanism of bacterial microcolonies against phage invasion has been experimentally quantified, and the result was analyzed by using a mathematical model. The analysis suggests that while forming a dense colony delays phage attack by limiting the infection closer to the colony surface,T4phage can diffuse so deep into the dense bacterial environment that colony-level survival of the bacterial community is challenged. This finding highlights the importance of the interplay between the phage infection dynamics and the physical structure of bacterial colonies in controlling the microbial population.
Rewiring of the epigenome and chromatin architecture by retinoic acid signaling during zebrafish embryonic development
Authors: Moreno-Oñate Marta , Gallardo-Fuentes Lourdes , Martínez-García Pedro M. , Naranjo Silvia , Jiménez-Gancedo Sandra , Gómez-Skarmeta José L. , Tena Juan J. , Santos-Pereira José M.
Published: June 2023

Background

Retinoic acid (RA) functions as a ligand for the nuclear RA receptors (RARs), which regulate the expression of target genes by binding to RA response elements. RA signaling is required for multiple processes during chordate embryonic development, such as body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling duringin vivoembryonic development.

Results

Here we stimulate the RA pathway during development by treating zebrafish embryos with all-trans-RA (atRA), the most abundant form of RA, and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which RA signaling control target gene expression. We find that RA signaling is involved in anterior/posterior patterning and development of the central nervous system, participating in the transition from pluripotency to differentiation. atRA treatment also induces alterations in chromatin accessibility during early development and promotes chromatin binding of RARαa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions that are consistent with target gene expression. This is illustrated by the specific induction of anterior HoxB genes by RARs, among other examples.

Conclusions

Altogether, our findings identify genome-wide targets of RA signaling during embryonic development and provide a molecular mechanism by which developmental signaling pathways regulate the expression of target genes by altering chromatin topology.
Mechanical loading of the Achilles tendon during different rehabilitation exercises: A cross sectional observational study
Authors: New Paul , Wood Lianne
Published: June 2023

Background

Achilles tendon injuries are common in active populations and heel raising exercises are commonly used in tendon rehabilitation programmes. This study compared characteristics of force occurring within the healthy Achilles tendon during two different types of exercise conditions that can be used in Achilles tendon rehabilitation.

Method

A cross-sectional, observational study was conducted to compare force fluctuations occurring within the Achilles tendon during two different types of heel raising exercise. All subjects performed firstly, a set of traditional eccentric heel drops (HD) and secondly an adapted walking drill (WD), and results were compared. 13 Healthy subjects were recruited from staff and post graduate students as a sample of convenience from the biomechanics department at the University of Bath. Tendon forces were calculated using a combination of data collected from force plate, motion analysis and real time ultrasound.

Results

Fluctuations in force were seen in all subjects in both exercise conditions. The HD condition produced a statistically significant increase in force fluctuations compared to the WD condition (p<0.001).

Conclusion

This study shows that force fluctuations can be stimulated at different levels during functional movement patterns and exercise conditions. Therefore, exercise routines can be tailored to meet individual needs and the stage of the pathology. These findings may have implications for exercise progressions in the rehabilitation of Achilles tendon disorders. Future research is needed determine if differences in tendon force fluctuations correlate with pathology.

Summary Statement

This study is of interest to clinicians, exercise professionals and researchers with an interest in the study of Achilles tendon biomechanics and the management of tendon injuries.
Targeting staphylococcal cell-wall biosynthesis protein FemX through steered molecular dynamics and drug-repurposing approach
Authors: Rahman Shakilur , Nath Subham , Mohan Utpal , Das Amit Kumar
Published: June 2023

Staphylococcus aureus-mediated infection is a serious threat in this antimicrobial-resistant world.S. aureushas become a ‘superbug’ by challenging conventional as well as modern treatment strategies. Nowadays, drug repurposing has become a new trend for the discovery of new drug molecules. This study focuses on evaluating FDA-approved drugs that can be repurposed againstS. aureusinfection. Steered molecular dynamics (SMD) has been performed for Lumacaftor and Olaparib against staphylococcal FemX to understand their binding to the active site. A time-dependent external force or rupture has been applied to the ligands to calculate the force required to dislocate the ligand from the binding pocket. SMD analysis indicates that Lumacaftor has a high affinity for the substrate binding pocket in comparison to Olaparib. Umbrella sampling exhibits that Lumacaftor possesses a higher free energy barrier to displace it from the ligand-binding site. The bactericidal activity of Lumacaftor and Olaparib has been tested, and it shows that Lumacaftor has shown moderate activity along with biofilm inhibition potential (MIC value with conc. 128 μg/mL). Pharmacokinetic and toxicology evaluations indicate that Lumacaftor has higher pharmacokinetic potential with lower toxicity. This is the first experimental report where staphylococcal FemX has been targeted for the discovery of new drugs. It is suggested that Lumacaftor may be a potential lead molecule againstS. aureus.
Long noncoding RNAs emerge from transposon-derived antisense sequences and may contribute to infection stage-specific transposon regulation in a fungal phytopathogen
Authors: Qian Jiangzhao , Ibrahim Heba M. M. , Erz Myriam , Kümmel Florian , Panstruga Ralph , Kusch Stefan
Published: June 2023

The genome of the obligate biotrophic phytopathogenic barley powdery mildew fungusBlumeria hordeiis inflated due to highly abundant and possibly active transposable elements (TEs). In the absence of the otherwise common repeat-induced point mutation transposon defense mechanism, noncoding RNAs could be key for regulating the activity of TEs and coding genes during the pathogenic life cycle. We performed time-course whole-transcriptome shotgun sequencing (RNA-seq) of total RNA derived from infected barley leaf epidermis at various stages of fungal pathogenesis and observed significant transcript accumulation and time point-dependent regulation of TEs inB. hordei. Using a manually curated consensus database of 344 TEs, we discovered phased small RNAs mapping to 104 consensus transposons, suggesting that RNA interference contributes significantly to their regulation. Further, we identified 5,127 long noncoding RNAs (lncRNAs) genome-wide inB. hordei, of which 823 originated from the antisense strand of a TE. Co-expression network analysis of lncRNAs, TEs, and coding genes throughout the asexual life cycle ofB. hordeipoints at extensive positive and negative co-regulation of lncRNAs, subsets of TEs and coding genes. Our work suggests that similar to mammals and plants, fungal lncRNAs support the dynamic modulation of transcript levels, including TEs, during pivotal stages of host infection. The lncRNAs may support transcriptional diversity and plasticity amid loss of coding genes in powdery mildew fungi and may give rise to novel regulatory elements and virulence peptides, thus representing key drivers of rapid evolutionary adaptation to promote pathogenicity and overcome host defense.
Charophytic Green Algae encode ancestral Pol IV/Pol V subunits and a CLSY/DRD1 homolog
Authors: Chakraborty Tania , Trujillo Joshua T. , Kendall Timmy , Mosher Rebecca A.
Published: June 2023

In flowering plants, euchromatic transposons are transcriptionally silenced by RNA-directed DNA methylation (RdDM), a small RNA-guidedde novomethylation pathway. RdDM requires the activity of the RNA Polymerase (Pol) IV and V, which produce small RNA precursors and non-coding targets of small RNAs, respectively. These polymerases are distinguished from Pol II by multiple plant-specific paralogous subunits. Most RdDM components are present in all land plants, and some have been found in the Charophytic green algae (CGA), a paraphyletic group that is sister to land plants. However, the evolutionary origin of key RdDM components, including the two largest subunits of Pol IV and Pol V, remains unclear. Here we show that multiple lineages of CGA encode a single-copy precursor of the largest subunits of Pol IV and Pol V, resolving the two presumed duplications in this gene family. We further demonstrate the presence of a Pol V-like C-terminal domain, suggesting that the earliest form of RdDM utilized a single Pol V-like polymerase. Finally, we reveal that CGAs encode a single CLSY/DRD1-type chromatin remodeling protein, further supporting the presence of a single specialized polymerase in CGA RdDM.
SARS-CoV-2 Envelope protein alters calcium signaling via SERCA interactions
Authors: Berta Blanka , Tordai Hedvig , Lukács Gergely L. , Papp Béla , Enyedi Ágnes , Padányi Rita , Hegedűs Tamás
Published: June 2023

The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor, however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca2+homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirmed that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca2+reload. Structural modeling and molecular dynamics of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.
Reduced mammillary body volume in individuals with a schizophrenia diagnosis: an analysis of the COBRE data set
Authors: Milczarek Michal M. , Gilani Syed I. A. , Lequin Maarten H. , Vann Seralynne D.
Published: June 2023

While the frontal cortices and medial temporal lobe are well-associated with schizophrenia, the involvement of wider limbic areas is less clear. The mammillary bodies are important for both complex memory formation and anxiety and are implicated in several neurological disorders that present with memory impairments. However, little is known about their role in schizophrenia. Post-mortem studies have reported both a loss of neurons in the mammillary bodies but also reports of increased mammillary body volume. The findings fromin vivoMRI studies have also been mixed, but studies have typically only involved small sample sizes. To address this, we acquired mammillary body volumes from the open-source COBRE dataset, where we were able to manually measure the mammillary bodies in 72 individuals with a schizophrenia diagnosis and 74 controls. Participant age ranged from 18-65. We found the mammillary bodies to be smaller in the patient group, across both hemispheres, after accounting for the effects of total brain volume and gender. Hippocampal volumes, but not subiculum or total grey matter volumes, were also significantly lower in patients. Given the importance of the mammillary bodies for both memory and anxiety, this atrophy could contribute to the symptomology in schizophrenia.
An adapted MS2-MCP system to visualize endogenous cytoplasmic mRNA with live imaging inCaenorhabditis elegans
Authors: Tocchini Cristina , Mango Susan E.
Published: June 2023

Live imaging of RNA molecules constitutes an invaluable means to track the dynamics of mRNAs, but live imaging inCaenorhabditis eleganshas been difficult to achieve. Endogenous transcripts have been observed in nuclei, but endogenous mRNAs have not been detected in the cytoplasm, and functional mRNAs have not been generated. Here, we have adapted live imaging methods to visualize mRNA in embryonic epithelial cells. We have tagged endogenous transcripts with MS2 hairpins in the 3’ Untranslated Region (UTR) and visualized them after adjusting MS2 Coat Protein (MCP) expression. A reduced number of these transcripts accumulate in the cytoplasm, leading to loss-of-function phenotypes. In addition, mRNAs fordlg-1fail to associate with the adherens junction, as observed for the endogenous mRNA. These defects are reversed by inactivating the nonsense-mediated decay pathway. RNA accumulates in the cytoplasm,dlg-1associates with the adherens junction, and mutant phenotypes are rescued. These data suggest that MS2 repeats can induce the degradation of endogenous targets and alter the cytoplasmic distribution. Although our focus is RNAs expressed in epithelial cells during morphogenesis, this method can likely be applied to other cell types and stages.

Summary statement

An adapted MS2-MCP method to tag endogenous transcripts inC. elegansembryos for live imaging without affecting mRNA stability.
Neural Mechanisms of Creative Problem Solving - From Representational Change to Memory Formation
Authors: Becker Maxi , Sommer Tobias , Cabeza Roberto
Published: June 2023

Despite the need for innovative solutions to contemporary challenges, the neural mechanisms driving creative problem-solving, including representational change and its relation to memory, still remain largely unknown. We focused on the powerful creative process of insight, wherein rapid knowledge reorganisation and integration—termed representational change—yield solutions that evoke suddenness, certainty, positive emotion, and enduring memory. We posit that this process manifests as stronger shifts in activation patterns within brain regions housing solution-relevant information, including the visual cortex for visual problems, alongside regions linked to feelings of emotion, suddenness and subsequent memory. Our findings substantiate these hypotheses, revealing stronger representational changes in visual cortex, conjoined with activations in the amygdala and hippocampus—forming an interconnected network. Importantly, the representational change and hippocampal effects serve as predictive markers of subsequent memory. This study provides evidence of an integrated insight mechanism influencing memory. Implications extend to education, emphasising the significance of discovery-based learning approaches for boosting knowledge retention.
Mitogenome sequences of domestic cats demonstrate lineage expansions and dynamic mutation processes in a mitochondrial minisatellite
Authors: Patterson Emily , Lall Gurdeep Matharu , Neumann Rita , Ottolini Barbara , Batini Chiara , Sacchini Federico , Foster Aiden P. , Wetton Jon H. , Jobling Mark A.
Published: June 2023

As a population genetic tool, mitochondrial DNA is commonly divided into the ∼1-kb control region (CR), in which single nucleotide variant (SNV) diversity is relatively high, and the coding region, in which selective constraint is greater and diversity lower, but which provides an informative phylogeny. In some species, the CR contains variable tandemly repeated sequences that are understudied due to heteroplasmy. Domestic cats (Felis catus) have a recent origin and therefore traditional CR-based analysis of populations yields only a small number of haplotypes. To increase resolution we used Nanopore sequencing to analyse 119 cat mitogenomes via a long-amplicon approach. This greatly improves discrimination (from 15 to 87 distinct haplotypes) and defines a phylogeny showing similar starlike topologies within all cat haplogroups, likely reflecting post-domestication expansion. We sequenced RS2, a CR tandem array of 80-bp repeat units, placing RS2 array structures within the phylogeny and increasing overall haplotype diversity. Repeat number varies between 3 and 12 (median: 4) with over 30 different repeat unit types differing largely by SNVs. Five SNVs show evidence of independent recurrence within the phylogeny, and seven are involved in at least 11 instances of rapid spread along repeat arrays within haplogroups. In defining mitogenome variation our study provides key information for the forensic genetic analysis of cat hair evidence, and for the first time a phylogenetically informed picture of tandem repeat variation that reveals remarkably dynamic mutation processes at work in the mitochondrion.
Evaluating key evidence and formulating regulatory alternatives regarding the UK’s Hunting Trophies (Import Prohibition) Bill
Authors: Challender Dan , ’t Sas-Rolfes Michael , Dickman Amy , Hare Darragh , Hart Adam , Hoffmann Michael , Mallon David , Mandisodza-Chikerema Roseline , Roe Dilys
Published: June 2023

Public policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UK’s role in international hunting trophy trade by analyzing CITES trade data for 2000-2021 and 2015-2021. For CITES-listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature Red List of Threatened Species to determine whether hunting designated as “trophy hunting” is i) likely a major threat contributing to species being of elevated conservation concern, ii) likely or possibly causing localized declines, or iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Government’s impact assessment of the bill. In 2000-2021 an estimated 3494 hunting trophies from 73 CITES-listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), i.e. individual animals. Imports involved 158.86 ± 66.53 (mean ± SD) trophies/year (115.83 ± 32.27 WOEs/year). In 2015-2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of nine species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options.
Dissection and Integration of Bursty Transcriptional Dynamics for Complex Systems
Authors: Gao Cheng Frank , Vaikuntanathan Suriyanarayanan , Riesenfeld Samantha J.
Published: June 2023

RNA velocity estimation is a potentially powerful tool to reveal the directionality of transcriptional changes in single-cell RNA-seq data, but it lacks accuracy, absent advanced metabolic labeling techniques. We developed a novel approach,TopicVelo, that disentangles simultaneous, yet distinct, dynamics by using a probabilistic topic model, a highly interpretable form of latent space factorization, to infer cells and genes associated with individual processes, thereby capturing cellular pluripotency or multifaceted functionality. Focusing on process- associated cells and genes enables accurate estimation of process-specific velocities via a master equation for a transcriptional burst model accounting for intrinsic stochasticity. The method obtains a global transition matrix by leveraging cell topic weights to integrate process- specific signals. In challenging systems, this method accurately recovers complex transitions and terminal states, while our novel use of first-passage time analysis provides insights into transient transitions. These results expand the limits of RNA velocity, empowering future studies of cell fate and functional responses.
EnhancingEscherichia coliAbiotic Stress Resistance through Ornithine Lipid Formation
Authors: Bedoya-Pérez Leidy Patricia , Aguilar-Vera Alejandro , Sánchez-Pérez Mishael , Utrilla José , Sohlenkamp Christian
Published: June 2023

Escherichia coliis a common host for biotechnology and synthetic biology applications. During growth and fermentation, the microbes are often exposed to stress conditions, such as variations in pH or solvent concentrations. Bacterial membranes play a key role in response to abiotic stresses. Ornithine lipids (OLs) are a group of membrane lipids whose presence and synthesis have been related to stress resistance in bacteria. We wondered if this stress resistance could be transferred to bacteria not encoding the capacity to form OLs in their genome, such asE. coli. In this study, we engineered differentE. colistrains to produce unmodified OLs and hydroxylated OLs by expressing the synthetic operonolsFC. Our results showed that OL formation improved pH resistance and increased biomass under phosphate limitation. Transcriptome analysis revealed that OL-forming strains differentially expressed stress- and membrane-related genes. OL-producing strains also showed better growth in the presence of the ionophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP), suggesting reduced proton leakiness in OL-producing strains. Furthermore, our engineered strains showed improved heterologous violacein production at phosphate limitation and also at low pH. Overall, this study demonstrates the potential of engineering theE. colimembrane composition for constructing robust hosts with an increased abiotic stress resistance for biotechnology and synthetic biology applications.

Keypoints

TheE. colimembrane composition was engineered by producing ornithine lipids

Ornithine lipid production increase biomass yield under phosphate limitation

Engineered strains show enhanced production phenotype under low pH stress

Transcriptome analysis and CCCP experiments revealed reduced proton leakage

Graphical abstract
Distinct endocannabinoids specifically signal to astrocytes and neurons
Authors: Noriega-Prieto Jose Antonio , Falcón-Moya Rafael , Eraso-Pichot Abel , Fundazuri Unai B , Guttipatti Pavan , Belisle Lindsey , Rodríguez-Moreno Antonio , van der Stelt Mario , Cheer Joseph , Marsicano Giovanni , Kofuji Paulo , Araque Alfonso
Published: June 2023

The endocannabinoid system is an essential intercellular signaling mechanism with a decisive role in many physiological functions of the brain. Endocannabinoids (eCBs), directly acting on presynaptic neuronal CB1 receptors (CB1Rs), can inhibit neurotransmitter release. In addition, they can potentiate adjacent synapses, inducing lateral regulation of synaptic transmission through astrocyte CB1Rs. In contrast to most, if not all, neurotransmitter systems, the eCB system involves two distinct ligands, Anandamide and 2-Arachidonoylglycerol (AEA and 2AG), and a single receptor (CB1R). The physiological meaning of this particularity remains unknown. Here we show that different eCBs are signaling both astrocytes and neurons, inducing distinct and contrasting synaptic regulation. Combining two-photon with a pharmacological and optogenetic approaches and transgenic mice for the synthesis enzyme of both eCBs, we have found that the absence of 2-AG synthesis abolished the inhibitory effect, which was mediated exclusively by neuronal mechanisms. However, the absence of AEA synthesis prevents the lateral potentiation mediated by astrocyte calcium mobilization. Together this indicates that 2-AG signals to neurons, decreasing neurotransmitter release, while AEA signals to astrocytes and induces lateral potentiation. Additionally, AEA synthesis is required for the synaptic potentiation induced by spike-timing-dependent plasticity, as well as astrocyte CB1R, indicating that distinct eCBs-signaling influences neuronal plasticity. We conclude that 2-AG and AEA induce distinct and contrasting synaptic regulation through CB1R in different cell types.
Different gametogenesis states uniquely impact longevity inCaenorhabditis elegans
Authors: Chaturbedi Amaresh , Lee Siu Sylvia
Published: June 2023

Curtailed reproduction affects lifespan and fat metabolism in diverse organisms, suggesting a regulatory axis between these processes. InCaenorhabditis elegans, ablation of germline stem cells (GSCs) leads to extended lifespan and increased fat accumulation, suggesting GSCs emit signals that modulate systemic physiology. Previous studies mainly focused on the germline-lessglp-1(e2141)mutant, however, the hermaphroditic germline ofC. elegansprovides an excellent opportunity to study the impact of different types of germline anomalies on longevity and fat metabolism. In this study, we compared the metabolomic, transcriptomic, and genetic pathway differences in three sterile mutants: germline-lessglp-1, feminizedfem-3, and masculinizedmog-3. We found that although the three sterile mutants all accumulate excess fat and share expression changes in stress response and metabolism genes, the germline-lessglp-1mutant exhibits the most robust lifespan increase, whereas the feminizedfem-3mutant only lives longer at specific temperatures, and the masculinizedmog-3mutant lives drastically shorter. We demonstrated that overlapping but distinct genetic pathways are required for the longevity of the three different sterile mutants. Our data showed that disruptions of different germ cell populations result in unique and complex physiological and longevity consequences, highlighting exciting avenues for future investigations.
Implementing midwifery twinning partnerships: challenges and facilitators. A rapid evidence summary
Authors: Edwards Deborah , Csontos Judit , Thomas Grace
Published: June 2023

Twinning is a partnership method that focuses on mutual transfer of knowledge and skills between two parties, including organisations, clinical practices, universities, or individual health professionals. In midwifery, twinning is a particularly important tool that can help countries with high maternal and infant morbidity and mortality rates to make connections with countries where sickness and death rates related to birth are lower and the role of midwives is better developed. The aim of this rapid evidence summary is to explore the literature for midwifery twinning initiatives and the facilitators and challenges of twinning partnerships.

Sixteen research reports and textual evidence were identified.

Facilitators of successful implementation of twinning initiatives include having a clear vision and mission statement along with investing time and promoting a co-creational approach. Reciprocity along with the building of personal relationships. Strong leadership, commitment, values, mutual respect and personal rapport between the projects. Clear communication plans, workshops, peer exchange visits alongside regular virtual contact. Building on existing relationships, previous experience of international and cross-cultural work and being prepared to overcome cultural differences. Having a local project team and careful; matching and selection of twins and having an adaptable personality. Having funding available.

Challenges include communication issues, cultural differences in communication, technological issues and economic considerations. Additionally misplaced expectations, such as difference in social expectations, or one twin partner expecting opportunities that are not agreed upon by the other poses challenges to the successful implementation of twinning initiatives.
Spatial differences in elemental stoichiometry and essential fatty acid content of food sources and consumers in a stream food web
Authors: Torres-Ruiz Monica , Wehr John D. , Perrone Alissa A.
Published: June 2023

Our study characterizes spatial differences in food webs of two reaches of a New York 3rd-order stream differing in light availability. Food web components were analyzed using marker fatty acids (FAs). Food source nutritional quality for consumers and predators (insect larvae) was measured through stoichiometry of C, N and P and essential FAs. There were strong imbalances between detrital food sources (low N, P and essential FAs) and insects in both shaded and open reaches, and food sources and invertebrate consumers were differentially affected by light with respect to their elemental stoichiometry and essential FA content. Biochemical patterns indicated that invertebrates fed selectively on higher-quality sources (algae, bryophytes, epiphytic bacteria, transported matter) and less on lower-quality periphyton and benthic matter. In addition to confirming the importance of autochthonous food sources for stream invertebrates, this study has highlighted that local ecological processes driven by changes in light availability and canopy-derived nutrient-rich matter can alter the micro- and macronutrient content of primary producers and detrital matter. These changes tracked differently within each consumer and varied with types of nutrient. Invertebrates exhibited a greater degree of homeostasis with respect to N and P than their essential FAs, and across trophic levels.