Search

Repetitive elements (REs) are integral to the composition, structure, and function of eukaryotic genomes, yet remain understudied in most taxonomic groups. We investigated REs across 601 insect species and report wide variation in RE dynamics across groups. Analysis of associations between REs and protein-coding genes revealed dynamic evolution at the interface between REs and coding regions across insects, including notably elevated RE-gene associations in lineages with abundant long interspersed nuclear elements (LINEs). We leveraged this large, empirical data set to quantify impacts of long-read technology on RE detection and investigate fundamental challenges to RE annotation in diverse groups. In long-read assemblies, we detected ∼36% more REs than short-read assemblies, with long terminal repeats (LTRs) showing 162% increased detection, whereas DNA transposons and LINEs showed less respective technology-related bias. In most insect lineages, 25%-85% of repetitive sequences were unclassified following automated annotation, compared with only ∼13% in Drosophila species. Although the diversity of available insect genomes has rapidly expanded, we show the rate of community contributions to RE databases has not kept pace, preventing efficient annotation and high-resolution study of REs in most groups. We highlight the tremendous opportunity and need for the biodiversity genomics field to embrace REs and suggest collective steps for making progress toward this goal.

A new species of the carabid beetle genus Bembidion Latreille is described from the Central Valley, Los Angeles Basin, and surrounding areas of California. Bembidionbrownorumsp. nov. is a distinctive species, a relatively large member of the subgenus Notaphus Dejean, and within Notaphus a member of the B.obtusangulum LeConte species group. It has faint spots on the elytra and a large, convex, rounded prothorax. Of the 22 specimens from 11 localities, all but one were collected more than 55 years ago. Although the collection of the holotype in 2021 at UV light suggest the species is still extant, the lack of other recent specimens suggests the species may have a more restricted distribution than in the past, and its populations may be in decline.

Key messageFunctional redundancy and subfunctionalization of β-hydroxylases in tetraploid wheat tissues open up opportunities for manipulation of carotenoid metabolism for trait improvement. The genetic diversity provided by subgenome homoeologs in allopolyploid wheat can be leveraged for developing improved wheat varieties with modified chemical traits, including profiles of carotenoids, which play critical roles in photosynthesis, photoprotection, and growth regulation. Carotenoid profiles are greatly influenced by hydroxylation catalyzed by β-hydroxylases (HYDs). To genetically dissect the contribution of HYDs to carotenoid metabolism and wheat growth and yield, we isolated loss-of-function mutants of the two homoeologs of HYD1 (HYD-A1 and HYD-B1) and HYD2 (HYD-A2 and HYD-B2) from the sequenced ethyl methanesulfonate mutant population of the tetraploid wheat cultivar Kronos, and generated various mutant combinations. Although functional redundancy between HYD1 and HYD2 paralogs was observed in leaves, HYD1 homoeologs contributed more than HYD2 homoeologs to carotenoid β-ring hydroxylation in this tissue. By contrast, the HYD2 homoeologs functioned toward production of lutein, the major carotenoid in mature grains, whereas HYD1 homoeologs had a limited role. These results collectively suggested subfunctionalization of HYD genes and homoeologs in different tissues of tetraploid wheat. Despite reduced photoprotective responses observed in the triple hyd-A1 hyd-B1 hyd-A2 and the quadruple hyd-A1 hyd-B1 hyd-A2 hyd-B2 combinatorial mutants, comprehensive plant phenotyping analysis revealed that all mutants analyzed were comparable to the control for growth, yield, and fertility, except for a slight delay in anthesis and senescence as well as accelerated germination in the quadruple mutant. Overall, this research takes steps toward untangling the functions of HYDs in wheat and has implications for improving performance and consumer traits of this economically important global crop.

The first insect genome assembly (Drosophila melanogaster) was published two decades ago. Today, nuclear genome assemblies are available for a staggering 601 insect species representing 20 orders. In this study, we analyzed the most-contiguous assembly for each species and provide a "state-of-the-field" perspective, emphasizing taxonomic representation, assembly quality, gene completeness, and sequencing technologies. Relative to species richness, genomic efforts have been biased toward four orders (Diptera, Hymenoptera, Collembola, and Phasmatodea), Coleoptera are underrepresented, and 11 orders still lack a publicly available genome assembly. The average insect genome assembly is 439.2 Mb in length with 87.5% of single-copy benchmarking genes intact. Most notable has been the impact of long-read sequencing; assemblies that incorporate long reads are ∼48× more contiguous than those that do not. We offer four recommendations as we collectively continue building insect genome resources: 1) seek better integration between independent research groups and consortia, 2) balance future sampling between filling taxonomic gaps and generating data for targeted questions, 3) take advantage of long-read sequencing technologies, and 4) expand and improve gene annotations.

Abstract DNA repair defects underlie many cancer syndromes. We tested whether de novo germline mutations (DNMs) are increased in families with germline defects in polymerase proofreading or base excision repair. A parent with a single germline POLE or POLD1 mutation, or biallelic MUTYH mutations, had 3-4 fold increased DNMs over sex-matched controls. POLE had the largest effect. The DNMs carried mutational signatures of the appropriate DNA repair deficiency. No DNM increase occurred in offspring of MUTYH heterozygous parents. Parental DNA repair defects caused about 20–150 DNMs per child, additional to the ~60 found in controls, but almost all extra DNMs occurred in non-coding regions. No increase in post-zygotic mutations was detected, excepting a child with bi-allelic MUTYH mutations who was excluded from the main analysis; she had received chemotherapy and may have undergone oligoclonal haematopoiesis. Inherited DNA repair defects associated with base pair-level mutations increase DNMs, but phenotypic consequences appear unlikely.

This study aims to prepare the energy sector for uncertainty using a foresight tool known as weak signals. Weak signals (subtle signs of emerging issues with significant impact potential) are often overlooked during strategic planning due to their inherent predictive uncertainty. However, the value does not lie in precise forecasting but in broadening the consideration of future possibilities. By proactively monitoring and addressing these otherwise neglected developments, stakeholders can gain early awareness of threats and opportunities and enhance their resilience, adaptability, and innovation.A panel of technology experts identified eight weak signals in this study: 1) growing mistrust and local grid security measures, 2) consumer reactions to overly prescriptive policies, 3) long-term forecasting errors for thin-margin projects, 4) emergence of variable power industries, and 5) establishment of intercontinental transmission precedence; including three potential ‘wild cards’ requiring proactive mitigation: 6) escalating electrical generation dependence on continued imports, 7) a new threat surpassing climate change, and 8) mass deployment of low-emissions technology triggering a runaway loss of social license.Political factors were the predominant source of uncertainty, as decisions can suddenly transform the energy landscape. Economic, technological, and social factors followed closely behind, generally through the emergence of new industries and behavioural responses. While environmental and legal factors were less frequent, stakeholders should still adopt a holistic approach, as the signals were found to be highly interconnected. Organisations should also assess their local context when applying these findings and continuously update and respond to their own list of weak signals.

High-throughput sequencing technology is central to our current understanding of the human methylome. The vast majority of studies use chemical conversion to analyse bulk-level patterns of DNA methylation across the genome from a population of cells. While this technology has been used to probe single-molecule methylation patterns, such analyses are limited to short reads of a few hundred basepairs. DNA methylation can also be directly detected using Nanopore sequencing which can generate reads measuring megabases in length. However, thus far these analyses have largely focused on bulk-level assessment of DNA methylation. Here, we analyse DNA methylation in single Nanopore reads from human lymphoblastoid cells, to show that bulk-level metrics underestimate large-scale heterogeneity in the methylome. We use the correlation in methylation state between neighbouring sites to quantify single-molecule heterogeneity and find that heterogeneity varies significantly across the human genome, with some regions having heterogeneous methylation patterns at the single-molecule level and others possessing more homogeneous methylation patterns. By comparing the genomic distribution of the correlation to epigenomic annotations, we find that the greatest heterogeneity in single-molecule patterns is observed within heterochromatic partially methylated domains (PMDs). In contrast, reads originating from euchromatic regions and gene bodies have more ordered DNA methylation patterns. By analysing the patterns of single molecules in more detail, we show the existence of a nucleosome-scale periodicity in DNA methylation that accounts for some of the heterogeneity we uncover in long single-molecule DNA methylation patterns. We find that this periodic structure is partially masked in bulk data and correlates with DNA accessibility as measured by nanoNOMe-seq, suggesting that it could be generated by nucleosomes. Our findings demonstrate the power of single-molecule analysis of long-read data to understand the structure of the human methylome.

The use of new vehicle technologies such as fuel cell hybrid electric and fully electric powertrains for biomass feedstock supply is an unexplored solution to reducing biofuel production cost, greenhouse gas emissions, and health impacts. These technologies have found success in light-duty vehicle applications and are in development for heavy-duty trucks. This study presents the first detailed stochastic techno-economic analysis and life-cycle assessment of biomass feedstock supply systems with diesel, fuel cell hybrid electric, and fully electric trucks and determines their impacts on biofuel production considering butanol as a representative biofuel. This study finds that fuel cell hybrid electric and fully electric trucks consume less energy relative to the diesel-powered truck regardless of the evaluated circumstances, including payloads of truck (loaded and empty), pavement types (gravel and paved), road conditions (normal and damaged), and road networks (local and highways). The use of fuel cell hybrid and fully electric trucks powered by H2-fuel and renewable sources of electricity, respectively, results in a large reduction in cost and carbon footprint, specifically for a long-distance hauling, and minimize other economic and environmental impacts. While the economic advantage of fuel cell hybrid electric vehicle is dependent on the price of H2-fuel and road conditions, use reduces the GHG emissions of biobutanol per 100 km-trucking-distance by 0.98–10.9 gCO2e/MJ. Results show that converting to fully electric truck transport decreases the biobutanol production cost and GHG emissions per 100 km-trucking-distance by 0.4–7.3 cents/L and 0.78 to 9.1 gCO2e/MJ, respectively. This study establishes the foundation for future investigations that will guide the development of economically, socially, and environmentally sustainable biomass feedstock supply system for cellulosic biorefineries or other goods transportation systems.

A new species of the carabid beetle genus Bembidion Latreille is described from the Central Valley, Los Angeles Basin, and surrounding areas of California. Bembidion brownorum sp. nov. is a distinctive species, a relatively large member of the subgenus Notaphus Dejean, and within Notaphus a member of the B. obtusangulum LeConte species group. It has faint spots on the elytra and a large, convex, rounded prothorax. Of the 22 specimens from 11 localities, all but one were collected more than 55 years ago. Although the collection of the holotype in 2021 at UV light suggest the species is still extant, the lack of other recent specimens suggests the species may have a more restricted distribution than in the past, and its populations may be in decline.

The post-smolt phase is considered a critical period for Atlantic salmon (Salmo salar). Hence, identifying migration routes used by post-smolts is needed to protect the habitats they require to successfully complete their life cycle. We used a biophysical model coupled with output from a water circulation model (FVCOM) to simulate dispersal of Atlantic salmon post-smolts in a semi-enclosed bay: Passamaquoddy Bay, New Brunswick, Canada. The model was run with nine post-smolt behaviours and six swimming speeds, and then tested against acoustic telemetry data. While no modelled behaviour entirely captured observed salmon migration routes, we identified some behaviours that could allow salmon to successfully leave the bay and resulted in predictions that matched observations reasonably well (e.g., swimming southwest, negative, or tide-varying rheotaxis). We could also rule out several behaviours as unlikely to be used by Atlantic salmon post-smolts in this area (e.g., passive dispersal, orienting based on salinity or temperature, and positive rheotaxis). Hence, with suitable behaviours and models, this approach can provide estimates of the essential habitats and migration routes of wild post-smolts. Key words: acoustic telemetry, Atlantic salmon, dispersal model, migration route, post-smolt La phase post-saumoneau est consideree comme une periode critique pour le saumon atlantique (Salmo salar). Par consequent, l'identification des routes migratoires utilisees par les post-saumoneaux est necessaire pour proteger les habitats dont ils ont besoin pour completer leur cycle de vie. Nous avons utilise un modele biophysique couple a un modele oceanographique physique (FVCOM) pour simuler la dispersion des post-saumoneaux du saumon atlantique dans une baie semi-fermee: la baie de Passamaquoddy, Nouveau-Brunswick, Canada. Le modele a ete execute avec neuf comportements et six vitesses de nage, puis teste par rapport aux donnees de telemetrie acoustique. Bien qu'aucun comportement modelise ne capture entierement les voies de migration du saumon observees, nous avons identifie certains comportements qui pourraient permettre au saumon de quitter la baie avec succes et ont abouti a des predictions qui correspondent raisonnablement bien aux observations (p. ex., nage vers le sud-ouest, rheotaxie negative ou variable selon la maree). Nous avons egalement exclus plusieurs comportements comme peu susceptibles d'etre utilises par les post-saumoneaux du saumon atlantique dans cette zone (p. ex., dispersion passive, orientation en fonction de la salinite ou de la temperature, rheotaxie positive). Par consequent, avec des comportements appropries, ce modele peut fournir des estimations des habitats essentiels et des routes migratoires des post- saumoneaux sauvages. Mots-cles : telemetrie acoustique, saumon atlantique, modele de dispersion, voie de migration, post-saumoneau, Introduction Atlantic salmon (Salmo salar) maybe particularly vulnerable to anthropogenic stressors during their initial seaward outmigration from natal rivers, a period considered critical for salmon due to their small size [...]

Abstract Caspase-2 (Casp2) is a promising therapeutic target in several human diseases, including nonalcoholic steatohepatitis (NASH) and Alzheimer’s disease (AD). However, the design of an active-site-directed inhibitor selective to individual caspase family members is challenging because caspases have extremely similar active sites. Here we present new peptidomimetics derived from the VDVAD pentapeptide structure, harboring non-natural modifications at the P2 position and an irreversible warhead. Enzyme kinetics show that these new compounds, such as LJ2 or its specific isomers LJ2a, and LJ3a, strongly and irreversibly inhibit Casp2 with genuine selectivity. In agreement with the established role of Casp2 in cellular stress responses, LJ2 inhibits cell death induced by microtubule destabilization or hydroxamic acid-based deacetylase inhibition. The most potent peptidomimetic, LJ2a, inhibits human Casp2 with a remarkably high inactivation rate (k 3/K i ~5,500,000 M−1 s− 1), and the most selective inhibitor, LJ3a, has close to a 1000 times higher inactivation rate on Casp2 as compared to Casp3. Structural analysis of LJ3a shows that the spatial configuration of Cα at the P2 position determines inhibitor efficacy. In transfected human cell lines overexpressing site-1 protease (S1P), sterol regulatory element-binding protein 2 (SREBP2) and Casp2, LJ2a and LJ3a fully inhibit Casp2-mediated S1P cleavage and thus SREBP2 activation, suggesting a potential to prevent NASH development. Furthermore, in primary hippocampal neurons treated with β-amyloid oligomers, submicromolar concentrations of LJ2a and of LJ3a prevent synapse loss, indicating a potential for further investigations in AD treatment.

Abstract Background DNA methylation is an epigenetic mark associated with the repression of gene promoters. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Altered rates of aging inferred from these clocks are observed in human disease. However, the molecular mechanisms underpinning age-associated DNA methylation changes remain unknown. Local DNA sequence can program steady-state DNA methylation levels, but how it influences age-associated methylation changes is unknown. Results We analyze longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs. We show that changes in methylation with age occur at 182,760 loci largely independently of variation in cell type proportions. These changes are especially apparent at 8322 low CpG density loci. Using SNP data from the same individuals, we demonstrate that methylation trajectories are affected by local sequence polymorphisms at 1487 low CpG density loci. More generally, we find that low CpG density regions are particularly prone to change and do so variably between individuals in people aged over 65. This differs from the behavior of these regions in younger individuals where they predominantly lose methylation. Conclusions Our results, which we reproduce in two independent groups of individuals, demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.

Loss of excitatory synapses occur prior to the formation of amyloid plaques in Alzheimer’s disease. Here the authors show in an animal model that the loss of synapses induced by amyloid-beta oligomers requires over-activation of a stress-response pathway inducing structural remodelling of mitochondria in dendrites of cortical and hippocampal neurons.

Aquaculture farm cages have the ability to interact with local circulation due to the drag caused by the cages. We examined how the drag influences the residence time of particles within fish farms in the southwest Isles region of New Brunswick, Canada, in the Bay of Fundy using a high-resolution hydrodynamic model. To accomplish this, we parameterized the cage drag in the model and modeled flow structures at multiple spatial scales, ranging from several meters within the cages, to tens of kilometers in the adjacent open ocean. We used models with and without cage drag to demonstrate how residence time was influenced by the imposition of the cage infrastructure. Our examination indicated that the drag produced by cages is able to significantly change the residence time of particles. The magnitude of the change is strongly sensitive to the timing of tides, tidal speeds and specific locations of farms. Our results suggest that the flushing properties of the wastes from aquaculture activities—for example, feed and subsequently fecal material—are strongly related to flow properties and their interactions with cages. These results emphasize that the design of fish farms should explicitly account for the influence of physical infrastructure (i.e. cages) on depositional processes in order to try and minimize environmental effects.

Technological developments allow students to access visual information from digital devices as small as phones or as large as whiteboards. Education technology research and policy typically address the software product, yet little research has focused on optimal viewing parameters or the impact it has on student users. Students with light sensitivity (migraine, concussion) potentially face a barrier with e-learning activities in the classroom. This review aimed to identify points of convergence and inconsistency across various literature sources containing guidelines for digital media use by students in schools. Inconsistencies were found between academic, manufacturer and school guidelines. Six parameters were identified for modification on behalf of students with light sensitivity relating to image colour, image flash frequency, duration of viewing, luminance and environmental lighting -- both natural and artificial. The findings highlight the need for revision of school policies regarding digital learning environments and awareness raising to support inclusive access and use by students with light sensitivity.

Abstract T-cell engagers (TCEs) are a growing class of biotherapeutics being investigated in the clinic for treatment of a variety of hematological and solid tumor indications. However, preclinical evaluation of TCEs in vivo has been mostly limited to xenograft tumor models in human T-cell reconstituted immunodeficient mice, which have a number of limitations. To explore the efficacy of human TCEs in fully immunocompetent hosts, we developed a knock-in mouse model (hCD3E-epi) in which a 5-residue N-terminal fragment of murine CD3-epsilon was replaced with an 11-residue stretch from the human sequence that encodes for a common epitope recognized by anti-human CD3E antibodies in the clinic. T cells from hCD3E-epi mice underwent normal thymic development and could be efficiently activated upon crosslinking of the T-cell receptor with anti-human CD3E antibodies in vitro. Furthermore, a TCE targeting human CD3E and murine CD20 induced robust T-cell redirected killing of murine CD20-positive B cells in ex vivo hCD3E-epi splenocyte cultures, and also depleted nearly 100% of peripheral B cells for up to 7 days following in vivo administration. These results highlight the utility of this novel mouse model for exploring the efficacy of human TCEs in vivo, and suggest a useful tool for evaluating TCEs in combination with immuno-oncology/non-immuno-oncology agents against heme and solid tumor targets in hosts with a fully intact immune system.

Background: Education of nurses from a diploma to a degree is a global phenomenon. However, bridging is often seen as a "backdoor" route to becoming a Registered Nurse and very little evaluation data exists to challenge this notion. Objectives: This research project was undertaken to explore student characteristics, academic performance, outcomes, and experiences in an RPN-to-BScN Bridging Program. Design: A mixed method design was employed. Student admission and registrarial data were examined in relation to student characteristics and academic performance. Secondary data analysis was conducted on focus group interviews with 110 students that explored their perceptions of the impact of the program on their lives. Setting: Data was collected through University databases and face to face focus groups. Participants: Admission and registrarial data for all students admitted to a nursing bridging program in Ontario, Canada, from 2005-2011 were analyzed. Participants in the qualitative focus group interviews included 110 students across all years of the program. Methods: Descriptive and analytical statistics provide insight into student performance and characteristics. Qualitative data analysis was conducted using NVivo 9 with multi-member teams. Results: Data analysis reveals important insights into student academic performance, including exploration of relevant variables such as ongoing and cumulative GPA, entrance GPA, and program completion. Qualitative analysis provides insight into how studying in the program affects students' lives. Conclusions: RPN-to-BScN education is not a "back door" to a nursing degree. Rather, it is a front door, as rigorous and as personally and professionally transformative as we expect a 4-year BScN Degree to be.

BackgroundActivating transcription factor 5 (ATF5) is a transcription factor that is highly expressed in undifferentiated neural progenitor/stem cells as well as a variety of human cancers including gliomas.AimsIn this study, we examined the expression and localization of ATF5 protein in canine gliomas, and targeting of ATF5 function in canine glioma cell lines.Materials and methodsParaffin-embedded canine brain glioma tissue sections and western blots of tumours and glioma cells were immunoassayed with anti-ATF5 antibody. Viability of glioma cells was tested with a synthetic cell-penetrating ATF5 peptide (CP-d/n ATF5) ATF5 antagonist.ResultsATF5 protein expression was in the nucleus and cytoplasm and was present in normal adult brain and tumour samples, with significantly higher expression in tumours as shown by western immunoblotting. CP-d/n ATF5 was found to decrease cell viability in canine glioma cell lines in vitro in a dose-dependent manner.ConclusionSimilarities in expression of ATF5 in rodent, dog and human tumours, and cross species efficacy of the CP-d/n ATF5 peptide support the development of this ATF5-targeting approach as a novel and translational therapy in dog gliomas.