Food insecurity is a public health issue for many regions globally, and especially Indigenous communities. We propose food budget ratio (FBR)-the ratio of food spending to after-tax income-as an ...affordability metric that better aligns with health equity over traditional price-focused metrics. Existing census and inflation monitoring programs render FBR an accessible tool for future affordability research.
Public census and food pricing datasets from 2011 to 2021 were analyzed to evaluate food affordability for a cohort of 121 remote Indigenous communities in Canada (n = 80,354 persons as of March 2021). Trends in population-weighted versus community-weighted averages, inflation-adjusted mean price of the Revised Northern Food Basket (RNFB), and distributions of FBR, per-capita price of food, and per-capita after-tax income were calculated and compared to Canada at large.
Population-weighted versus community-weighted mean price of the RNFB differed by < 5% for most points in time, peaking at 17%. Mean raw price of the RNFB was relatively stable, while mean inflation-adjusted price of the RNFB decreased 19%. Mean and standard deviation in FBR trended downwards from (0.40; 0.21) in 2011 to (0.25; 0.10) in 2021, while the mean for Canada held stable at 0.10 ± 0.01. Mean and standard deviation in inflation-adjusted per-capita price of food fell from ($5,621; $493) to ($4,510; $243), while the Canada-wide mean rose from $2,189 to $2,567; values for per-capita after-tax income increased from ($17,384; $7,816) to ($21,661; $9,707), while the Canada-wide mean remained between $24,443 and $26,006. Current Nutrition North Canada (NNC) subsidy rates correlate closely with distance to nearest transportation hub (σ
= 0.68 to 0.70) whereas food pricing, after-tax income, and FBR correlate poorly with distance (σ
= -0.22 to 0.03).
The FBR approach yields greater insights on food affordability compared to price-based results, while using readily available public datasets. Whereas 19% reductions in RNFB per-capita food price were observed, FBR decreased 63% yet remained 2.5 times the Canada-wide FBR. The reduction in FBR was driven both by the reduced price of food and a 25% increase in after-tax income. It is recommended that NNC consider FBR for performance measurement and setting subsidy rates.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long read sequencing is changing the landscape of genomic research, especially de novo assembly. Despite the high error rate inherent to long read technologies, increased read lengths dramatically ...improve the continuity and accuracy of genome assemblies. However, the cost and throughput of these technologies limits their application to complex genomes. One solution is to decrease the cost and time to assemble novel genomes by leveraging "hybrid" assemblies that use long reads for scaffolding and short reads for accuracy.
We describe a novel method leveraging a multi-string Burrows-Wheeler Transform with auxiliary FM-index to correct errors in long read sequences using a set of complementary short reads. We demonstrate that our method efficiently produces significantly more high quality corrected sequence than existing hybrid error-correction methods. We also show that our method produces more contiguous assemblies, in many cases, than existing state-of-the-art hybrid and long-read only de novo assembly methods.
Our method accurately corrects long read sequence data using complementary short reads. We demonstrate higher total throughput of corrected long reads and a corresponding increase in contiguity of the resulting de novo assemblies. Improved throughput and computational efficiency than existing methods will help better economically utilize emerging long read sequencing technologies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Retrotransposons play an important role in genome evolution but pose acute challenges to host genome integrity, particularly in early stage germ cells where epigenetic control is relaxed to permit ...genome-wide reprogramming. In most species, the inability to silence retrotransposons in the germline is usually associated with sterility. LINE1 is the most abundant retrotransposon type in the mammalian genome. Mammalian germ cells employ multiple mechanisms to suppress retrotransposon activity, including small non-coding piRNAs, DNA methylation, and repressive histone modifications. Novel factors contributing to the epigenetic silencing of retrotransposons in the germline continue to be identified. Recent studies have provided insight into how epigenetic changes associated with retrotransposon activation impact on fertility.
Meiotic recombination permits exchange of genetic material between homologous chromosomes. The replication protein A (RPA) complex, the predominant ssDNA-binding complex, is required for nearly all ...aspects of DNA metabolism, but its role in mammalian meiotic recombination remains unknown due to the embryonic lethality of RPA mutant mice. RPA is a heterotrimer of RPA1, RPA2, and RPA3. We find that loss of RPA1, the largest subunit, leads to disappearance of RPA2 and RPA3, resulting in the absence of the RPA complex. Using an inducible germline-specific inactivation strategy, we find that loss of RPA completely abrogates loading of RAD51/DMC1 recombinases to programmed meiotic DNA double strand breaks, thus blocking strand invasion required for chromosome pairing and synapsis. Surprisingly, loading of MEIOB, SPATA22, and ATR to DNA double strand breaks is RPA-independent and does not promote RAD51/DMC1 recruitment in the absence of RPA. Finally, inactivation of RPA reduces crossover formation. Our results demonstrate that RPA plays two distinct roles in meiotic recombination: an essential role in recombinase recruitment at early stages and an important role in promoting crossover formation at later stages.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Traditional Riemann solvers fall into two broad categories: exact solvers, which require multiple iterations to achieve high accuracy, and approximate linearized solvers, which achieve fast runtime ...at the expense of reduced accuracy. Here we explore learning-based Riemann solvers, termed FluxNets, as a new approach that balances accuracy and computational efficiency especially for transcritical and supercritical flow problems involving non-ideal thermodynamics. Various designs and training strategies are applied to fully connected neural networks. By comparing data-driven versus physics-informed loss functions, as well as neural networks of varying size, the results show that order-of-magnitude reductions in error compared to the Roe solver can be achieved with compact architectures. Numerical validation on 1D and 2D test cases reveals that a physics-informed FluxNet promotes smoothness, numerical stability, and generalizability, and is capable of producing entropy-stable results free of non-physical expansion shocks as compared to the Roe solver. Parallelization can be leveraged to accelerate inference such that the gains in accuracy are achieved at one quarter the runtime of exact solvers. The trade-off in accuracy versus efficiency may be justified in the case of non-ideal flows where even minor errors can result in spurious oscillations and instabilities.
•Evaluate the merits and feasibility of learning-based Riemann solvers (termed FluxNets) for Godunov-type schemes.•Examine errors, convergence, and stability of training data-driven versus physics-informed FluxNets of varying size.•Demonstrate the importance of a physics-informed approach to ensuring that fluxes yield smooth, stable, generalizable, and physically consistent solutions.•Quantify the error and time complexity of a compact MLP FluxNet versus exact and Roe-type Riemann solvers in the context of transcritical flows.
Piwi-piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce retrotransposon silencing, a function critical for preserving the genome integrity of germ cells. The molecular functions of most ...of the factors that have been genetically implicated in primary piRNA biogenesis are still elusive. Here we show that MOV10L1 exhibits 5'-to-3' directional RNA-unwinding activity in vitro and that a point mutation that abolishes this activity causes a failure in primary piRNA biogenesis in vivo. We demonstrate that MOV10L1 selectively binds piRNA precursor transcripts and is essential for the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins. Multiple analyses suggest an intimate coupling of piRNA precursor processing with elements of local secondary structures such as G quadruplexes. Our results support a model in which MOV10L1 RNA helicase activity promotes unwinding and funneling of the single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing.
Piwi-interacting RNAs (piRNAs) play critical roles in protecting germline genome integrity and promoting normal spermiogenic differentiation. In mammals, there are two populations of piRNAs: ...pre-pachytene and pachytene. Transposon-rich pre-pachytene piRNAs are expressed in fetal and perinatal germ cells and are required for retrotransposon silencing, whereas transposon-poor pachytene piRNAs are expressed in spermatocytes and round spermatids and regulate mRNA transcript levels. MOV10L1, a germ cell-specific RNA helicase, is essential for the production of both populations of piRNAs. Although the requirement of the RNA helicase domain located in the MOV10L1 C-terminal region for piRNA biogenesis is well known, its large N-terminal region remains mysterious. Here we report a novel Mov10l1 mutation, named yama, in the Mov10l1 N-terminal region. The yama mutation results in a single amino acid substitution V229E. The yama mutation causes meiotic arrest, de-repression of transposable elements, and male sterility because of defects in pre-pachytene piRNA biogenesis. Moreover, restricting the Mov10l1 mutation effects to later stages in germ cell development by combining with a postnatal conditional deletion of a complementing wild-type allele causes absence of pachytene piRNAs, accumulation of piRNA precursors, polar conglomeration of piRNA pathway proteins in spermatocytes, and spermiogenic arrest. Mechanistically, the V229E substitution in MOV10L1 reduces its interaction with PLD6, an endonuclease that generates the 5' ends of piRNA intermediates. Our results uncover an important role for the MOV10L1-PLD6 interaction in piRNA biogenesis throughout male germ cell development.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The wave structure of approximate Riemann solvers has a significant impact on the accuracy and computational requirements of finite volume codes. We propose a class of structurally complete ...approximate Riemann solvers (StARS) and provide an efficient means for analytically restoring the expansion wave to pre-existing three-wave solvers. The method analytically restores the expansion, is valid for arbitrary thermodynamics, and has comparable complexity to the popular Harten-Hyman entropy fix. The StARS modification is applied to a Roe scheme, resulting in Roe-StARS with noticeable improvements in unsteady transcritical and supercritical conditions with large flow gradients. A novel scaling analysis is performed on the flow conditions that cause rarefaction fluxes and the magnitude of errors if the rarefaction is omitted. Four test cases are examined: a transcritical shock tube, a shock tube with periodic bounds resulting in interfering shocks and rarefactions, a two-dimensional Riemann problem, and a “gradient” Riemann problem—a variant on the traditional Riemann problem featuring an initial gradient of varying slope rather than an initial step function. The results highlight the complex causes and effects of entropy violations, and encourage further study of StARS-type solvers for modern flow problems in which high flow speeds, large gradients, and non-ideal thermodynamics are increasingly common.
•Quantify the error in Riemann solvers by omitting the expansion wave under trans- and supercritical conditions.•Highlight the strong coupling between the magnitude and prevalence of entropy violations with respect to the thermodynamic state and gradients of the flow.•Propose a Structurally complete Approximate Riemann Solver (StARS) that restores the expansion wave for a non-ideal equation of state using an analytical expression.•Show the linear convergence of the error, using a low-order numerical scheme, by restoring the expansion wave under transonic conditions.•Quantify the computational cost of the StARS modification to classical Riemann solvers and compare with other entropy fixes.
Piwi-interacting RNAs are a diverse class of small non-coding RNAs implicated in the silencing of transposable elements and the safeguarding of genome integrity. In mammals, male germ cells express ...two genetically and developmentally distinct populations of piRNAs at the pre-pachytene and pachytene stages of meiosis, respectively. Pre-pachytene piRNAs are mostly derived from retrotransposons and required for their silencing. In contrast, pachytene piRNAs originate from ~3,000 genomic clusters, and their biogenesis and function remain enigmatic. Here, we report that conditional inactivation of the putative RNA helicase MOV10L1 in mouse spermatocytes produces a specific loss of pachytene piRNAs, significant accumulation of pachytene piRNA precursor transcripts, and unusual polar conglomeration of Piwi proteins with mitochondria. Pachytene piRNA-deficient spermatocytes progress through meiosis without derepression of LINE1 retrotransposons, but become arrested at the post-meiotic round spermatid stage with massive DNA damage. Our results demonstrate that MOV10L1 acts upstream of Piwi proteins in the primary processing of pachytene piRNAs and suggest that, distinct from pre-pachytene piRNAs, pachytene piRNAs fulfill a unique function in maintaining post-meiotic genome integrity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Here we provide a genome-wide, high-resolution map of the phylogenetic origin of the genome of most extant laboratory mouse inbred strains. Our analysis is based on the genotypes of wild-caught mice ...from three subspecies of Mus musculus. We show that classical laboratory strains are derived from a few fancy mice with limited haplotype diversity. Their genomes are overwhelmingly Mus musculus domesticus in origin, and the remainder is mostly of Japanese origin. We generated genome-wide haplotype maps based on identity by descent from fancy mice and show that classical inbred strains have limited and non-randomly distributed genetic diversity. In contrast, wild-derived laboratory strains represent a broad sampling of diversity within M. musculus. Intersubspecific introgression is pervasive in these strains, and contamination by laboratory stocks has played a role in this process. The subspecific origin, haplotype diversity and identity by descent maps can be visualized using the Mouse Phylogeny Viewer (see URLs).
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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