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La formación de un pseudoaneurisma arterial en el contexto del post-operatorio de una cirugía pancreática es una de las complicaciones más temidas y graves con las que el médico tratante tiene que lidiar, alcanzando una mortalidad elevada. Clásicamente, el tratamiento durante mucho tiempo fue la cirugía, pero en la actualidad el abordaje endovascular se ha posicionado como el tratamiento de elección. Los stents recubiertos constituyen una efectiva herramienta para tratar esta grave complicación en forma mínimamente invasiva.

Previamente, la seropositividad para el virus de la inmuno- deficiencia humana (HIV) era una contraindicación absoluta del trasplante. Sin embargo, reportes de la época posterior al tratamiento antirretroviral altamente activo (HAART) demostraron que los resultados no se diferenciarían de la población HIV negativa. Objetivo. Evaluar la experiencia en Argentina con pacientes HIV positivos incluidos en lista para trasplante hepático. Pacientes y métodos. Se incluyeron 52 pacientes HIV positivos ingresados en lista del 12 de julio de 2005 al 31 de marzo de 2010. Los resultados se compararon con 462 pacientes HIV negativos incluidos en lista durante el mismo período. Los datos se obtuvieron del SINTRA y centros intervinientes. Resultados. La etiología de hepatopatía en el grupo HIV positivo fue: hepatitis C en 40 pacientes, hepatitis B en 3, hepatitis fulminante en 3, alcohol en 2, retrasplante en 2 y otras en 2. El MELD promedio del grupo HIV positivo al ingreso en la lista fue 16,15 (menor de 19 en 40 pacientes, mayor de 19 en 8 y emergencia en 3) y el del grupo HIV negativo fue 16,64 (NS). La evolución en lista de espera para los pacientes HIV positivos y negativos fue respectivamente: muerte en lista 14 pacientes (27%) vs 61 (18,7%) (P < 0,05), trasplante con donante cadavérico 10 (13%) vs 95 (29,4%) (P < 0,01), trasplante con donante vivo 0 (0%) vs 5 (1,1%) (NS), tiempo medio desde el ingreso en lista a la muerte 270,70±298,11 días vs 267,29±266,53 días (NS), tiempo medio en la lista hasta el trasplante 70,26±74,05 vs 261±187,6 días (P < 0,01), MELD medio al fallecimiento 12,54 (13 casos menor de 15, 1 mayor de 19) vs 19,6±9,7 (P < 0,05), y MELD medio al momento del trasplante 24,33 vs 24,1±7,6 (NS). Conclusión. Los resultados del trasplante en pacientes HIV positivos son buenos. Sin embargo, presentan muy alta mortalidad en lista de espera que no correlaciona con su gravedad medida por el score de MELD. Quienes acceden al trasplante lo hacen rápidamente en el contexto de una descompensación, por hepatitis fulminante o por retrasplante.

La hepatitis tóxica por el consumo de productos Herbalife ® es una afección poco documentada y con gran impacto en la población debido a su amplio consumo. Presentamos el caso de una mujer de 63 años con diagnóstico probable de hepatitis tóxica secundaria al consumo de suplementos dietarios Herbalife®. Los suplementos dietarios basados en ingredientes naturales son de consumo masivo en todo el mundo. Debido a que son reconocidos como inocuos y de venta libre, carecen de controles adecuados. Existen casos reportados de hepatotoxicidad y otros efectos adversos inducidos por estos productos, pero la evidencia no es suficiente como para generar una respuesta de los organismos de control. Nosotros reportamos un caso de hepatitis aguda potencialmente secundaria al consumo de Herbalife®.

In recent years, nanopore direct RNA sequencing (DRS) became a valuable tool for studying the epitranscriptome, owing to its ability to detect multiple modifications within the same full-length native RNA molecules. Although RNA modifications can be identified in the form of systematic basecalling "errors" in DRS data sets, N6 -methyladenosine (m 6 A) modifications produce relatively low "errors" compared with other RNA modifications, limiting the applicability of this approach to m 6 A sites that are modified at high stoichiometries. Here, we demonstrate that the use of alternative RNA basecalling models, trained with fully unmodified sequences, increases the "error" signal of m 6 A, leading to enhanced detection and improved sensitivity even at low stoichiometries. Moreover, we find that high-accuracy alternative RNA basecalling models can show up to 97% median basecalling accuracy, outperforming currently available RNA basecalling models, which show 91% median basecalling accuracy. Notably, the use of high-accuracy basecalling models is accompanied by a significant increase in the number of mapped reads-especially in shorter RNA fractions-and increased basecalling error signatures at pseudouridine (Ψ)- and N1 -methylpseudouridine (m 1 Ψ)-modified sites. Overall, our work demonstrates that alternative RNA basecalling models can be used to improve the detection of RNA modifications, read mappability, and basecalling accuracy in nanopore DRS data sets., (© 2024 Diensthuber et al.; Published by Cold Spring Harbor Laboratory Press.)

Understanding the impacts of, and options for, controlling invasive species is crucial to their management. Wetlands are a widely invaded ecosystem, since dispersal of aquatic species is facilitated by seasonal flooding. This study evaluated the effects of the translocated pondweed Monochoria hastata on fish and rice production in two wetlands of Bangladesh over six years (2017-2022). Fish and rice production were compared between control (negligible M. hastata) and three treatments under different M. hastata management methods comprising manual-, herbicide- and mechanical-treatment. Density of M. hastata increased significantly in all treatment groups over time in both wet and dry seasons. However, M. hastata density was lower by 270% in the dry season than the wet season. For fishes, a negative relationship between M. hastata density and fish production was recorded for snakeheads and catfishes, the most saleable fishes, whereas a mixed pattern was recorded for barbs and minnows across treatments. A positive relationship occurred between the density of M. hastata and production of the most common fish, mud eel, and therefore, the overall fish production increased in all treatment groups. Compared to control plots, rice production was lower in M. hastata infested plot groups. Among the M. hastata infested plot groups, rice production in herbicide-and mechanical-treatment groups was similar but lower than the manual-treatment group. Although manual-treatment plots yielded greater rice production, the weed management cost was also higher. This study provides evidence that translocated M. hastata can be of an invasive nature and impact rice production, not only by reducing yield but also by increasing the production costs through additional management for M. hastata control. Its presence in wetlands in Bangladesh can increase overall fish production due to the overriding influence of increased mud eel yield which has little demand locally but can decrease the species of high demand (e.g. snakehead and catfish). None of the existing control measures are effective in controlling M. hastata. Further research is needed on better management approaches for both agricultural and fish production in areas invaded by M. hastata., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC ( Pdx1-Cre , LSL-Kras G12D/+ , LSL-Trp53 R172H/+ ) and poorly metastatic KP fl C ( Pdx1-Cre , LSL-Kras G12D/+ , Trp53 fl/+ ) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KP fl C, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

Transfer RNAs (tRNAs) play a central role in protein translation. Studying them has been difficult in part because a simple method to simultaneously quantify their abundance and chemical modifications is lacking. Here we introduce Nano-tRNAseq, a nanopore-based approach to sequence native tRNA populations that provides quantitative estimates of both tRNA abundances and modification dynamics in a single experiment. We show that default nanopore sequencing settings discard the vast majority of tRNA reads, leading to poor sequencing yields and biased representations of tRNA abundances based on their transcript length. Re-processing of raw nanopore current intensity signals leads to a 12-fold increase in the number of recovered tRNA reads and enables recapitulation of accurate tRNA abundances. We then apply Nano-tRNAseq to Saccharomyces cerevisiae tRNA populations, revealing crosstalks and interdependencies between different tRNA modification types within the same molecule and changes in tRNA populations in response to oxidative stress., (© 2023. The Author(s).)

Background: Bronchobiliary fistula is a rare and complex entity defined by an abnormal communication between the biliary and bronchial systems. The etiopathogenesis is not completely understood, but the most common factors implicated are hepatobiliary tumors, biliary obstruction, iatrogenic damage or trauma., Methods: Here we present a case of a 69-year-old man that developed a bronchobiliary fistula and a pulmonary abscess after migration of a bile duct stent placed as part of the treatment of an iatrogenic bile duct injury that occurred during elective cholecystectomy., Results: A conservative approach, that included broad-spectrum antibiotic, removal of the stent, and sphincterotomy, was enough for the closure of the fistula and resolution of the symptoms., Conclusion: We emphasize the importance of prompt recognition of this entity and a concerted therapeutic strategy to optimize the probability of success, avoiding the destructive consequences of the bile in the pulmonary parenchyma and septic complications.

The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma., (© 2023. The Author(s).)

The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally diverse 'specialized ribosomes' is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralogue of RPL3 (uL3) that is exclusively expressed in skeletal muscle and heart tissues, by generating a viable homozygous Rpl3l knockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes up-regulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L modulates neither translational efficiency nor ribosome affinity towards a specific subset of transcripts. In contrast, we show that depletion of RPL3L leads to increased ribosome-mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of fine-tuning of mitochondrial activity. Our results demonstrate that the existence of tissue-specific RP paralogues does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

River catchments worldwide are heavily fragmented by anthropogenic barriers, reducing their longitudinal connectivity and contributing to the decline of migratory fish populations. Direct impacts of individual barriers on migratory fish are well-established, but barrier impacts on onward migration are poorly understood, despite their relevance to evidence-based, catchment-scale, management of threatened species. This study investigated the upstream spawning migration of 352 acoustic tagged river lamprey (Lampetra fluviatilis), translocated upstream of two key barriers (R2: n = 60 & 59; R3: n = 59 & 52) compared to a control group (R1: n = 61 & 59), across two contrasting (dry and wet, n = 180 and 172) years in the River Yorkshire Ouse, England, to reveal the impact of barriers on the onward migration of upstream migrating fish. Release further upstream increased the degree of catchment penetration, with median distance upstream of R1 56.1% and 68.6% greater for lamprey released at R2 and R3 respectively. Median delays at the two downstream-most main river barriers by the control group were 23.8 and 5.4 days (2018/19) and 9.3 and 11.4 days (2019/20). However, impacts of delay were only observed on the time to reach spawning habitat, time to reach final assumed spawning location and speed of movement in one upper catchment tributary during 2019/20 whilst they were only observed on time to reach spawning habitat during 2018/19 and on assumed spawning location distance during 2019/20 in the other. Ultimately, limited impacts of delay at barriers on onward fish migration post-passage were observed but median catchment penetration was increased with consecutive release upstream. This study demonstrated the importance of a true understanding of barrier impacts to inform catchment-wide planning, evidence vital for management worldwide. Although the findings of this study do support the use of trap and transport as a measure to remediate barrier impacts on migration, fish passage engineering improvements or barrier removal, at structures shown to be the most inhibiting to fish migration should be considered the best and most sustainable option to improve barrier passage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Achondroplasia is a rare disease affecting bone growth and is caused by a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. In the past few years, there were multiple experimental drugs entering into clinical trials for treating achondroplasia including vosoritide, the first precision medicine approved for this indication. This perspective presents the mechanism of action, benefit, and potential mechanistic limitation of the drugs currently being evaluated in clinical trials for achondroplasia. This article also discusses the potential impact of those drugs not only in increasing the growth of individuals living with achondroplasia but also in improving their quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Outbreaks of Lymantria dispar asiatica (the Asian spongy moth; Lepidoptera: Erebidae) occur sporadically, causing widespread damage to forest and fruit trees. Owing to the development of pesticide resistance and environmental contamination, biopesticides, including L. dispar multiple nucleopolyhedrovirus (LdMNPV) and Bacillus thuringiensis var. kurstaki (Btk), can significantly contribute to controlling overall larval stage of this species. Although both pathogens are highly effective at the larval stage, their effects on different instar stages have not been investigated. In this study, we analyzed the mortality and lethality in different L. dispar asiatica instars exposed to single or combined pathogen treatments. Treatments with low or medium LdMNPV concentrations induced lower mortality and had higher LT 50 values at the 4th and 5th instars compared with other instars, whereas high LdMNPV treatments induced high mortality in all instars, with higher LT 50 values at later instars. Treatment with Btk induced a rapid 100% mortality in all instars, with higher LT 50 values for the later instars. The combination of LdMNPV and Btk delayed the killing time compared with the effects of single treatments, with the effect being more pronounced in the 1st and 5th instar stage than at other stages at low Btk concentrations. Our findings indicate that the pathogenic effects of LdMNPV and Btk on L. dispar asiatica differ according to larval stage, thereby providing novel insights into enhancing the biological control efficacy of these agents against L. dispar asiatica in the field., (© 2023 Wiley Periodicals LLC.)

River barriers reduce river connectivity and lead to fragmentation of fish habitats, which can result in decline or even extinction of aquatic biota, including fish populations. In the Mekong basin, previous studies have mainly focused on the impacts of large dams but ignored the impacts of small-scale barriers, or drew conclusions from incomplete barrier databases, potentially leading to research biases. To test the completeness of existing databases and to evaluate the catchment-scale fragmentation level, a detailed investigation of river barriers for the whole Upper Mekong (Lancang catchment) was performed, by conducting visual interpretation of high-resolution remotely sensed images. Then, a complete catchment-scale barrier database was created for the first time. By comparing our barrier database with existing databases, this study indicates that 93.7% of river barriers were absent from the existing database, including 75% of dams and 99.5% of small barriers. Barrier density and dendritic connectivity index (DCI D and DCI P ) were used to measure channel fragmentation within the catchment. Overall, 50.5% of sub-catchments contained river barriers. The Middle region is the most fragmented area within the Lancang catchment, with a median [quartiles] barrier density of 5.34 [0.70-9.67] per 100 km, DCI P value of 49.50 [21.50-90.00] and DCI D value of 38.50 [9.00-92.25]. Furthermore, since 2010, distribution ranges of two representative fish species Schizothorax lissolabiatus (a rheophilic cyprinid) and Bagarius yarrelli (a large catfish) have reduced by 19.2% and 32.8% respectively, probably due in part to the construction of river barriers. Our findings indicate that small-scale barriers, in particular weirs and also small dams are the main reason for habitat fragmentation in the Lancang and must be considered alongside large dams in water management and biodiversity conservation within the Mekong., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumourigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumours, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse., (© 2022. The Author(s).)

Over 170 post-transcriptional RNA modifications have been described and are common in all kingdoms of life. These modifications range from methylation to complex chemical structures, with methylation being the most abundant. RNA modifications play a key role in RNA folding and function and their dysregulation in humans has been linked to several diseases such as cancer, metabolic diseases or neurological disorder. Nowadays, liquid chromatography-tandem mass spectrometry is considered the gold standard method for the identification and quantification of these modifications due to its sensitivity and accuracy. However, the analysis of modified ribonucleosides by mass spectrometry is complex due to the presence of positional isomers. In this scenario, optimal separation of these compounds by highly sensitive liquid chromatography combined with the generation of high-information spectra is critical to unequivocally identify them, especially in high-complex mixtures. Here we present an analytical method that comprises a new type of mixed-mode nano-flow liquid chromatography column combined with high- and low-collision energy data-independent mass spectrometric acquisition for the identification and quantitation of modified ribonucleosides. The method produces content-rich spectra and combines targeted and screening capabilities thus enabling the identification of a variety of modified nucleosides in biological matrices by single-shot liquid chromatographic analysis coupled to mass spectrometry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

There is increasing evidence that personality traits may drive dispersal patterns of animals, including invasive species. We investigated, using the widespread signal crayfish Pacifastacus leniusculus as a model invasive species, whether effects of personality traits on dispersal were independent of, or affected by, other factors including population density, habitat, crayfish size, sex and limb loss, along an invasion gradient. Behavioural traits (boldness, activity, exploration, willingness to climb) of 310 individually marked signal crayfish were measured at fully-established, newly-established and invasion front sites of two upland streams. After a period at liberty, recaptured crayfish were reassessed for behavioural traits (newly-established, invasion front). Dispersal distance and direction of crayfish movement, local population density, fine-scale habitat characteristics and crayfish size, sex and limb loss were also measured. Individual crayfish exhibited consistency in behavioural traits over time which formed a behavioural syndrome. Dispersal was both positively and negatively affected by personality traits, positively by local population density and negatively by refuge availability. No effect of size, sex and limb loss was recorded. Personality played a role in promoting dispersal but population density and local habitat complexity were also important determinants. Predicting biological invasion in animals is likely to require better integration of these processes., (© 2022. The Author(s).)

Barrier removal and fish pass construction are increasingly used as tools to restore river connectivity and improve habitat quality, but the effectiveness of subcatchment-scale connectivity restoration on recovery of fish communities is poorly understood. We used a before-after-downstream-upstream methodology to determine the effects of subcatchment-scale connectivity restoration on fishes in a fragmented tributary of the River Wear, Northeast England, between 2013 and 2019. Following restoration (three barriers removed, five barriers fitted with fish passes, two barriers unaltered), riffle habitat increased, fine sediment decreased, and most fish species benefitted. Total fish abundance, comprising seven native species, increased 3 years after the restoration and remained elevated to the end of the study. Mean brown trout (Salmo trutta) density increased from 20.9 ± 6.3 to 33.8 ± 16.8 per 100m 2 from 2013 to 2019, with Young-of-Year trout increasing from 10.6 ± 4.6 to 19.8 ± 11.8 per 100m 2 . Connectivity restoration reduced the mean age of trout, suggesting a change to an increased migratory component of the population. Density of bullhead (Cottus perifretum), a species with poor dispersal ability, increased from 4.6 ± 2.7 to 32.6 ± 17.9 per 100m 2 over 2013 to 2019. Stone loach (Barbatula barbatula), also a less mobile species but tolerant to fine sediment, decreased in abundance where barriers were removed. Atlantic salmon (Salmo salar) were absent over the study timescale, despite being common in the Wear, and despite suitable habitat and water quality in the restored subcatchment, suggesting a hysteresis effect. Our findings indicate that, where good water quality exists, restoring river connectivity and hydromorphology at a subcatchment scale is beneficial for most native resident and migratory fishes. However, the ecological benefits of connectivity restoration, especially in rivers with many barriers, may take several years to develop. We encourage well-controlled long-term studies reporting the outcomes of large-scale connectivity restoration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic, chemoresistant malignancy and is characterized by a dense, desmoplastic stroma that modulates PDAC progression. Here, we visualized transient manipulation of focal adhesion kinase (FAK), which integrates bidirectional cell-environment signaling, using intravital fluorescence lifetime imaging microscopy of the FAK-based Förster resonance energy transfer biosensor in mouse and patient-derived PDAC models. Parallel real-time quantification of the FUCCI cell cycle reporter guided us to improve PDAC response to standard-of-care chemotherapy at primary and secondary sites. Critically, micropatterned pillar plates and stiffness-tunable matrices were used to pinpoint the contribution of environmental cues to chemosensitization, while fluid flow–induced shear stress assessment, patient-derived matrices, and personalized in vivo models allowed us to deconstruct how FAK inhibition can reduce PDAC spread. Last, stratification of PDAC patient samples via Merlin status revealed a patient subset with poor prognosis that are likely to respond to FAK priming before chemotherapy.

Nanopore RNA sequencing shows promise as a method for discriminating and identifying different RNA modifications in native RNA. Expanding on the ability of nanopore sequencing to detect N 6 -methyladenosine, we show that other modifications, in particular pseudouridine (Ψ) and 2'-O-methylation (Nm), also result in characteristic base-calling 'error' signatures in the nanopore data. Focusing on Ψ modification sites, we detected known and uncovered previously unreported Ψ sites in mRNAs, non-coding RNAs and rRNAs, including a Pus4-dependent Ψ modification in yeast mitochondrial rRNA. To explore the dynamics of pseudouridylation, we treated yeast cells with oxidative, cold and heat stresses and detected heat-sensitive Ψ-modified sites in small nuclear RNAs, small nucleolar RNAs and mRNAs. Finally, we developed a software, nanoRMS, that estimates per-site modification stoichiometries by identifying single-molecule reads with altered current intensity and trace profiles. This work demonstrates that Nm and Ψ RNA modifications can be detected in cellular RNAs and that their modification stoichiometry can be quantified by nanopore sequencing of native RNA., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Variations in behavioral traits are widely recognized to drive animal behaviors exhibited within a population. However, information on how behavior traits influence behavior in anthropogenically modified habitats is lacking. Many habitats have become highly fragmented as a result of human processes. To mitigate this and improve habitat connectivity, wildlife passes are increasingly employed, with the aim of enabling animals to move freely between habitats. However, wildlife passes (e.g., fishways) are not always effective in achieving passage and it remains uncertain what factors play a role in an individual's likelihood of passing successfully. This study measured three behavioral traits (boldness, exploration, and activity) in juvenile brown trout ( Salmo trutta ; n  = 78) under field conditions within a river and tested whether these behavior traits influenced both the passage success and the behaviors exhibited during upstream fishway passage attempts. Although behavioral traits were found and collapsed into two behavioral trait dimensions, behavioral traits had low repeatability and so did not contribute to a personality spectrum. Boldness was found to negatively influence the number of passage attempts carried out by an individual and to positively influence passage success, with bolder individuals carrying out fewer attempts and having an increased probability of passage success. No behavioral traits were found to be related to other passage metrics (passage success, Time until First Attempt, and Passage Duration) during the first passage. But all three behavioral traits were significantly negatively related to the changes in passage behaviors at consecutive, successful passage attempts, with bolder, more exploratory and more active individuals passing through a fishway quicker on the second passage than on the first. This study suggests that bolder and more active individuals may perform better during fishway passage attempts, particularly within rivers where multiple barriers to movement exist., Competing Interests: The authors declare no competing interests., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors.