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Mitochondria are essential organelles for maintaining intracellular homeostasis. Their dysfunction can directly or indirectly affect cell functioning and is linked to multiple diseases. Donation of exogenous mitochondria is potentially a viable therapeutic strategy. For this, selecting appropriate donors of exogenous mitochondria is critical. We previously demonstrated that ultra-purified bone marrow-derived mesenchymal stem cells (RECs) have better stem cell properties and homogeneity than conventionally cultured bone marrow-derived mesenchymal stem cells. Here, we explored the effect of contact and noncontact systems on three possible mitochondrial transfer mechanisms involving tunneling nanotubes, connexin 43 (Cx43)-mediated gap junction channels (GJCs), and extracellular vesicles (Evs). We show that Evs and Cx43-GJCs provide the main mechanism for mitochondrial transfer from RECs. Through these two critical mitochondrial transfer pathways, RECs could transfer a greater number of mitochondria into mitochondria-deficient (ρ0) cells and could significantly restore mitochondrial functional parameters. Furthermore, we analyzed the effect of exosomes (EXO) on the rate of mitochondrial transfer from RECs and recovery of mitochondrial function. REC-derived EXO appeared to promote mitochondrial transfer and slightly improve the recovery of mtDNA content and oxidative phosphorylation in ρ0 cells. Thus, ultrapure, homogenous, and safe stem cell RECs could provide a potential therapeutic tool for diseases associated with mitochondrial dysfunction.

For the first time a record of total solar irradiance covering 9300 years is presented, which covers almost the entire Holocene. This reconstruction is based on a recently observationally derived relationship between total solar irradiance and the open solar magnetic field. Here we show that the open solar magnetic field can be obtained from the cosmogenic radionuclide 10Be measured in ice cores. Thus, 10Be allows to reconstruct total solar irradiance much further back than the existing record of the sunspot number which is usually used to reconstruct total solar irradiance. The resulting increase in solar‐cycle averaged TSI from the Maunder Minimum to the present amounts to (0.9 ± 0.4) Wm−2. In combination with climate models, our reconstruction offers the possibility to test the claimed links between climate and TSI forcing.

The SOS response of bacteria is a global regulatory network targeted at addressing DNA damage. Governed by the products of the lexA and recA genes, it co-ordinates a comprehensive response against DNA lesions and its description in Escherichia coli has stood for years as a textbook paradigm of stress-response systems in bacteria. In this paper we review the current state of research on the SOS response outside E. coli. By retracing research on the identification of multiple diverging LexA-binding motifs across the Bacteria Domain, we show how this work has led to the description of a minimum regulon core, but also of a heterogeneous collection of SOS regulatory networks that challenges many tenets of the E. coli model. We also review recent attempts at reconstructing the evolutionary history of the SOS network that have cast new light on the SOS response. Exploiting the newly gained knowledge on LexA-binding motifs and the tight association of LexA with a recently described mutagenesis cassette, these works put forward likely evolutionary scenarios for the SOS response, and we discuss their relevance on the ultimate nature of this stress-response system and the evolutionary pressures driving its evolution.

Homologous recombination is essential for the accurate repair of double-stranded DNA breaks (DSBs) 1 . Initially, the RecBCD complex 2 resects the ends of the DSB into 3′ single-stranded DNA on which a RecA filament assembles 3 . Next, the filament locates the homologous repair template on the sister chromosome 4 . Here we directly visualize the repair of DSBs in single cells, using high-throughput microfluidics and fluorescence microscopy. We find that, in Escherichia coli , repair of DSBs between segregated sister loci is completed in 15 ± 5 min (mean ± s.d.) with minimal fitness loss. We further show that the search takes less than 9 ± 3 min (mean ± s.d) and is mediated by a thin, highly dynamic RecA filament that stretches throughout the cell. We propose that the architecture of the RecA filament effectively reduces search dimensionality. This model predicts a search time that is consistent with our measurement and is corroborated by the observation that the search time does not depend on the length of the cell or the amount of DNA. Given the abundance of RecA homologues 5 , we believe this model to be widely conserved across living organisms. Observations of rapid repair of double-stranded DNA breaks in sister choromosomes in Escherichia coli are consistent with a reduced-dimensionality-search model of RecA-mediated repair.

During meiosis, homologous recombination (HR) is essential to repair programmed DNA double-strand breaks (DSBs), and a dedicated protein machinery ensures that the homologous chromosome is favored over the nearby sister chromatid as a repair template. The homologous-pairing protein2/meiotic nuclear division protein1 (HOP2/MND1) protein complex has been identified as a crucial factor of meiotic HR in Arabidopsis thaliana, since loss of either MND1 or HOP2 results in failure of DNA repair. We isolated two mutant alleles of HOP2 (hop2-2 and hop2-3) that retained the capacity to repair meiotic DSBs via the sister chromatid but failed to use the homologous chromosome. We show that in these alleles, the recombinases radiation sensitive51 (RAD51) and disrupted meiotic cDNA1 (DMC1) are loaded, but only the intersister DNA repair pathway is activated. The hop2-2 phenotype is correlated with a decrease in HOP2/MND1 complex abundance. In hop2-3, a truncated HOP2 protein is produced that retains its ability to bind to DMC1 and DNA but forms less stable complexes with MND1 and fails to efficiently stimulate DMC1-driven D-loop formation. Genetic analyses demonstrated that in the absence of DMC1, HOP2/MND1 is dispensable for RAD51-mediated intersister DNA repair, while in the presence of DMC1, a minimal amount of functional HOP2/MND1 is essential to drive intersister DNA repair.

The bacterial SOS response plays a key role in adaptation to DNA damage, including genomic stress caused by antibiotics. SOS induction begins when activated RecA*, an oligomeric nucleoprotein filament that forms on single-stranded DNA, binds to and stimulates autoproteolysis of the repressor LexA. Here, we present the structure of the complete Escherichia coli SOS signal complex, constituting full-length LexA bound to RecA*. We uncover an extensive interface unexpectedly including the LexA DNA-binding domain, providing a new molecular rationale for ordered SOS gene induction. We further find that the interface involves three RecA subunits, with a single residue in the central engaged subunit acting as a molecular key, inserting into an allosteric binding pocket to induce LexA cleavage. Given the pro-mutagenic nature of SOS activation, our structural and mechanistic insights provide a foundation for developing new therapeutics to slow the evolution of antibiotic resistance. Here, using cryo-EM, the authors reveal the mechanism by which RecA filamented on single-stranded DNA binds to and induces LexA cleavage, the key signal governing the bacterial DNA damage response pathway implicated in antibiotic resistance.

Heliangelus regalis Fitzpatrick, Willard & Terborgh, 1979 is known to occur in northeastern Peru and southeastern Ecuador. We report the first record of a single female at Jungle Dave’s Farm in the Ecuadorian Andes, 59 km northwest of its previously known range. The hummingbird was observed actively feeding on Satyria leucostoma (a species of Ericaceae) in a patch of scrubland within a cattle pasture for 58 days and displayed nonaggressive behavior towards other birds. This find provides new information on ecological flexibility of H. regalis in a human‑modified landscape and provides novel insights into the behavior and natural history of this species.

The Internet of Things (IoT) is transforming various domains, including smart energy management, by enabling the integration of complex digital and physical components in distributed cyber-physical systems (DCPSs). The design of DCPSs has so far been focused on performance-related, non-functional requirements. However, with the growing power consumption and computation expenses, sustainability is becoming an important aspect to consider. This has led to the concept of energy-aware DCPSs, which integrate conventional non-functional requirements with additional attributes for sustainability, such as energy consumption. This research activity aimed to investigate and develop energy-aware architectural models and edge/cloud computing technologies to design next-generation, AI-enabled (and, specifically, deep-learning-enhanced), self-conscious IoT-extended DCPSs. Our key contributions include energy-aware edge-to-cloud architectural models and technologies, the orchestration of a (possibly federated) edge-to-cloud infrastructure, abstractions and unified models for distributed heterogeneous virtualized resources, innovative machine learning algorithms for the dynamic reallocation and reconfiguration of energy resources, and the management of energy communities. The proposed solution was validated through case studies on optimizing renewable energy communities (RECs), or energy-aware DCPSs, which are particularly challenging due to their unique requirements and constraints; in more detail, in this work, we aim to define the optimal implementation of an energy-aware DCPS. Moreover, smart grids play a crucial role in developing energy-aware DCPSs, providing a flexible and efficient power system integrating renewable energy sources, microgrids, and other distributed energy resources. The proposed energy-aware DCPSs contribute to the development of smart grids by providing a sustainable, self-consistent, and efficient way to manage energy distribution and consumption. The performance demonstrates our approach’s effectiveness for consumption and production (based on RMSE and MAE metrics). Our research supports the transition towards a more sustainable future, where communities adopting REC principles become key players in the energy landscape.

Srs2 dismantles presynaptic Rad51 filaments and prevents its re-formation as an anti-recombinase. However, the molecular mechanism by which Srs2 accomplishes these tasks remains unclear. Here we report a single-molecule fluorescence study of the dynamics of Rad51 filament formation and its disruption by Srs2. Rad51 forms filaments on single-stranded DNA by sequential binding of primarily monomers and dimers in a 5′–3′ direction. One Rad51 molecule binds to three nucleotides, and six monomers are required to achieve a stable nucleation cluster. Srs2 exhibits ATP-dependent repetitive motion on single-stranded DNA and this activity prevents re-formation of the Rad51 filament. The same activity of Srs2 cannot prevent RecA filament formation, indicating its specificity for Rad51. Srs2’s DNA-unwinding activity is greatly suppressed when Rad51 filaments form on duplex DNA. Taken together, our results reveal an exquisite and highly specific mechanism by which Srs2 regulates the Rad51 filament formation. Srs2 is a DNA helicase and single-stranded DNA translocase that prevents homologous recombination by dismantling Rad51 filaments. Qiu et al. use single-molecule techniques to describe Rad51 filament formation and show that Srs2 displays repetitive activity on single-stranded DNA, which prevents re-formation of Rad51 filaments after dismantling.

RecA bundles are shown to be important for the pairing of homologous loci that have segregated to opposite ends of the cell during DNA double-strand break repair in vivo in Escherichia coli . RecA active in bundle form Although bacterial RecA protein functions as a filament during DNA strand exchange, early studies of RecA also noted that, in vivo , it formed bundles. These bundles were inactive in vitro , so were thought to be a way of storing RecA until it was needed. David Sherratt and colleagues now show that RecA bundles do have an important function in vivo . Super-resolution microscopy imaging shows that bundles are excluded from the bulk of the nucleoid and locate to the cell periphery where they facilitate the pairing of homologous loci that have segregated to opposite ends of the cell. After sister locus pairing, RecA bundles disassemble. DNA double-strand break (DSB) repair by homologous recombination has evolved to maintain genetic integrity in all organisms 1 . Although many reactions that occur during homologous recombination are known 1 , 2 , 3 , it is unclear where, when and how they occur in cells. Here, by using conventional and super-resolution microscopy, we describe the progression of DSB repair in live Escherichia coli . Specifically, we investigate whether homologous recombination can occur efficiently between distant sister loci that have segregated to opposite halves of an E. coli cell. We show that a site-specific DSB in one sister can be repaired efficiently using distant sister homology. After RecBCD processing of the DSB, RecA is recruited to the cut locus, where it nucleates into a bundle that contains many more RecA molecules than can associate with the two single-stranded DNA regions that form at the DSB. Mature bundles extend along the long axis of the cell, in the space between the bulk nucleoid and the inner membrane. Bundle formation is followed by pairing, in which the two ends of the cut locus relocate at the periphery of the nucleoid and together move rapidly towards the homology of the uncut sister. After sister locus pairing, RecA bundles disassemble and proteins that act late in homologous recombination are recruited to give viable recombinants 1–2-generation-time equivalents after formation of the initial DSB. Mutated RecA proteins that do not form bundles are defective in sister pairing and in DSB-induced repair. This work reveals an unanticipated role of RecA bundles in channelling the movement of the DNA DSB ends, thereby facilitating the long-range homology search that occurs before the strand invasion and transfer reactions.