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Multiple studies have demonstrated that cancer cells with microsatellite instability (MSI) are intolerant to loss of the Werner syndrome helicase (WRN), whereas microsatellite-stable (MSS) cancer cells are not. Therefore, WRN represents a promising new synthetic lethal target for developing drugs to treat cancers with MSI. Given the uncertainty of how effective inhibitors of WRN activity will prov

Homologous recombination (HR) is an important route for repairing DNA double-strand breaks (DSBs). The early stages of HR are well understood, but later stages remain mysterious. In this issue of Genes & Development, Hustedt and colleagues (pp. 1397–1415) reveal HROB as a new player in HR required for recruitment of the MCM8–9 complex, which is paralogous to the MCM2–7 replicative helicase. HR

DNA sequence and epigenetic information embedded in chromatin must be faithfully duplicated and transmitted to daughter cells during cell division. However, how chromatin assembly and DNA replication are integrated remains unclear. We examined the contribution of the Tousled-like kinases 1 and 2 (TLK1/TLK2) to chromatin assembly and maintenance of replication fork integrity. We show that TLK activ

Transboundary crises often create a problem of fit, where existing institutional structures are inadequate to meet the demands of the situation, requiring strategic adaptations. This study examines how Italy, Sweden, and Norway, in different ways, addressed national-level leadership needs of decision-making, coordination, and information flow during the early onset of the COVID-19 pandemic, not on

While a naive algorithm for multiplying two 2 × 2 matrices requires eight multiplications and four additions, Strassen showed how to compute the same matrix product using seven multiplications and 18 additions. Winograd reduced the number of additions to 15, which was assumed to be optimal. However, by introducing a change of basis, Karstadt and Schwartz showed how to lower the number of additions

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and t

Genotoxic DNA double-strand breaks (DSBs) can be repaired by error-free homologous recombination (HR) or mutagenic non-homologous end-joining 1 . HR supresses tumorigenesis 1 , but is restricted to the S and G2 phases of the cell cycle when a sister chromatid is present 2 . Breast cancer type 1 susceptibility protein (BRCA1) promotes HR by antagonizing the anti-resection factor TP53-binding prote

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding

To evaluate the behaviour of a single timber-concrete composite (TCC) T-beam, a simplified 2D finite element (FE) model in Abaqus is developed and validated using experimental tests and the Gamma method given in Annex B of EN 1995–1-1. The shear connection used in the beam consist of perfobond connectors, which are adhesively bonded to the timber beam. In the developed model, beam and shell finite

In timber-concrete composites (TCC), more researchers are trying to find the “ultimate” shear connector, which combines multiple advantages. Bonded steel plates are one of the possible solutions. This paper provides an analytical and a numerical approach, calibrated with previously conducted experiments, to predict the load carrying capacity, and corresponding governing failure mode, of perfobond

With the need of renovation in the current timber structures, use of a cement based layer is a popular solution, which improves the structural integrity and increases the structural mass. In this paper, the use of a lightweight concrete with dowel type connections is investigated since such a combination can serve for both new and existing structures. Two types of dowel connections are experimenta

In this paper, perforated shear connectors (perfobond), used extensively in steel-concrete composite (SCC) beams, are implemented in timber-concrete composite beams (TCC) and experimentally investigated. In contrast to its original use, the perfobond connector is connected with an adhesive to the timber beam while welded in the SCC solution. On the concrete slab side, connection is achieved using

In this paper, the use of low strength lightweight concrete in combination with glue-laminated timber (TLCC) is studied. Six series of push-out tests were conducted to assess the mechanical performance of the screw shear connection between these materials with a perpendicular and inclined (shearcompression)configuration with various screw diameters and lengths. The tests show that though low stren

Produktion av dricksvatten är en fundamental del av vårt samhälles infrastruktur och ökad förståelse för de faktorer som avgör dricksvattenkvaliteten är därmed av stort värde. En av dessa faktorer är mikrobiomen, alltså vilka mikroorganismer som lever i vattnet. Dessa kommer huvudsakligen från så kallad biofilm, ett tunt slem-liknande skikt som formas på insidan av vattenrör. Skiktet skapas av ämnThe development of the water-borne microbiome in newly installed polyethylene pipes of a non-chlorinated drinking water distribution system was studied over a period of six months. Water samples were taken from two identical newly installed pipes (“NP1”, “NP2”), as well as from a reference point at equal distance (“DS1”). These water samples were filtered and had the DNA extracted using FastDNA SP

Invasive species can cause serious damage to ecosystems and built-up structures. “Japanese knotweed” is one of the most problematic invasive plant species in Scania. It has spread in a fast and uncontrollable manner throughout the years, and major efforts are being made to decrease its extension and further spread. Once established, it's difficult to exterminate without causing environmental h

After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of postreplicative chromatin, re

Användningen av artificiell intelligens ökar inom många områden i det samtida samhället, inklusive datorsynssystem som bygger på maskininlärning och artificiella neuronnätverk. Dessa system omformar handlingsmöjligheter och beskrivs ofta som ”svarta lådor” som utmanar etablerade former av vetenskaplig förståelse och teknisk kontroll. Det är därför viktigt att förstå de aktiviteter genom vilka sådaThe uses of artificial intelligence are increasing across many areas of contemporary society, including computer vision systems involving machine learning and artificial neural networks. These systems rearrange action possibilities and are often described as “black boxes” that challenge conventional modes of scientific understanding and engineering control. It is important to understand the activi

Small bodies exist in distinct populations within their planetary systems. These reservoir populations hold a range of compositions, which to first order are dependent on formation location relative to their star. We provide a general overview of the nature of the reservoirs that source exocomets, from the influence of the stellar environment through planetesimal formation to comparisons with Sola

Malaria remains a great public health concern, with an estimated 263 million cases and 597,000 estimated deaths in 2023. Artemisinin-based combination therapies (ACTs) are currently the first-line treatment for uncomplicated P. falciparum malaria in Sub-Saharan Africa (SSA), but the emergence of resistant parasites is threatening their efficacy. Single-nucleotide polymorphisms (SNPs) in the pfk13