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The bacterial tight adherence pilus system (TadPS) assembles surface pili essential for adhesion and colonisation in many human pathogens. Pilus dynamics are powered by the ATPase CpaF (TadA), which drives extension and retraction cycles in Caulobacter crescentus through an unknown mechanism. Here we use cryogenic electron microscopy and cell-based light microscopy to characterise CpaF mechanism. We show that CpaF assembles into a hexamer with C2 symmetry in different nucleotide states. Nucleotide cycling occurs through an intra-subunit clamp-like mechanism that promotes sequential conformational changes between subunits. Moreover, a comparison of the active sites with different nucleotides bound suggests a mechanism for bidirectional motion. Conserved CpaF residues, predicted to interact with platform proteins CpaG (TadB) and CpaH (TadC), are mutated in vivo to establish their role in pilus processing. Our findings provide a model for how CpaF drives TadPS pilus dynamics and have broad implications for how other ancient type 4 filament family members power pilus assembly. The ATPase CpaF from C. crescentus powers pilus dynamics in the bacterial Tad pilus system. Cryo-EM and light microscopy characterisation of CpaF uncovers a mechanism for how CpaF may drive both pilus extension and retraction. [ABSTRACT FROM AUTHOR]

Gene Transfer Agents (GTAs) are phage-like particles that cannot self-multiply and be infectious. Caulobacter crescentus, a bacterium best known as a model organism to study bacterial cell biology and cell cycle regulation, has recently been demonstrated to produce bona fide GTA particles (CcGTA). Since C. crescentus ultimately die to release GTA particles, the production of GTA particles must be tightly regulated and integrated with the host physiology to prevent a collapse in cell population. Two direct activators of the CcGTA biosynthetic gene cluster, GafY and GafZ, have been identified, however, it is unknown how GafYZ controls transcription or how they coordinate gene expression of the CcGTA gene cluster with other accessory genes elsewhere on the genome for complete CcGTA production. Here, we show that the CcGTA gene cluster is transcriptionally co-activated by GafY, integration host factor (IHF), and by GafZ-mediated transcription anti-termination. We present evidence that GafZ is a transcription anti-terminator that likely forms an anti-termination complex with RNA polymerase, NusA, NusG, and NusE to bypass transcription terminators within the 14 kb CcGTA cluster. Overall, we reveal a two-tier regulation that coordinates the synthesis of GTA particles in C. crescentus. This study reveals that in the alpha-proteobacterium, Caulobacter crescent, a two-tier regulation by transcriptional activation and anti-termination coordinates the synthesis of phage-like Gene Transfer Agents (GTA) particles. [ABSTRACT FROM AUTHOR]

DNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respond to such damage remain incompletely understood. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), which orchestrates a methylation-dependent adaptive response in Caulobacter. This response operates independently of the SOS response, governs the expression of genes crucial for direct repair, and is essential for surviving methylation-induced damage. Our molecular investigation of Cada2 reveals a cysteine methylation-dependent posttranslational modification (PTM) and mode of action distinct from its Escherichia coli counterpart, a trait conserved across all bacteria harboring a Cada2-like homolog instead. Extending across the bacterial kingdom, our findings support the notion of divergence and coevolution of adaptive response transcription factors and their corresponding sequence-specific DNA motifs. Despite this diversity, the ubiquitous prevalence of adaptive response regulators underscores the significance of a transcriptional switch, mediated by methylation PTM, in driving a specific and essential bacterial DNA damage response. [ABSTRACT FROM AUTHOR]

Bacterial cells require DNA segregation machinery to properly distribute a genome to both daughter cells upon division. The most common system involved in chromosome and plasmid segregation in bacteria is the ParABS system. A core protein of this system - partition protein B (ParB) - regulates chromosome organization and chromosome segregation during the bacterial cell cycle. Over the past decades, research has greatly advanced our knowledge of the ParABS system. However, many intricate details of the mechanism of ParB proteins were only recently uncovered using in vitro single-molecule techniques. These approaches allowed the exploration of ParB proteins in precisely controlled environments, free from the complexities of the cellular milieu. This review covers the early developments of this field but emphasizes recent advances in our knowledge of the mechanistic understanding of ParB proteins as revealed by in vitro single-molecule methods. Furthermore, we provide an outlook on future endeavors in investigating ParB, ParB-like proteins, and their interaction partners. [ABSTRACT FROM AUTHOR]

The accurate distribution of genetic material is crucial for all organisms. In most bacteria, chromosome segregation is achieved by the ParABS system, in which the ParB-bound parS sequence is actively partitioned by ParA. While this system is highly conserved, its adaptation in organisms with unique lifestyles and its regulation between developmental stages remain largely unexplored. Bdellovibrio bacteriovorus is a predatory bacterium proliferating through polyploid replication and non-binary division inside other bacteria. Our study reveals the subcellular dynamics and multi-layered regulation of the ParABS system, coupled to the cell cycle of B. bacteriovorus. We found that ParA:ParB ratios fluctuate between predation stages, their balance being critical for cell cycle progression. Moreover, the parS chromosomal context in non-replicative cells, combined with ParB depletion at cell division, critically contribute to the unique cell cycle-dependent organization of the centromere in this bacterium, highlighting new levels of complexity in chromosome segregation and cell cycle control. Author summary: The precise distribution of genetic material to the progeny is essential for all living organisms, and the ParABS system is critical for this process in most bacteria. Our study provides novel insights into the regulation of this system in a predatory bacterium that exhibits a non-canonical cell cycle, in which the chromosome is copied and segregated multiple times during growth inside a prey bacterium. Our work reveals the subcellular dynamics and multi-level regulation of the ParABS system in this bacterium, which results in the unique cell-cycle dependent assembly of the segregation complex at the chromosomal centromere-like region. Our findings provide a deeper understanding of the adaptation of the ParABS system across bacterial species and developmental stages. [ABSTRACT FROM AUTHOR]

Nowadays, in a communicating society, fashion is an integral part of a human life, and it is more comfortable and confident when people dress well. Outfit compatibility is not only a combination of different items but also regarding various aspects, such as style, user preferences, and specific occasions. Most of the existing works lead to address the outfit compatibility concerning only style or user preferences, and have no regard for occasions. In this paper, we propose an efficient method for both outfit compatibility and the fill-in-the-blank tasks according to specific occasions. To this end, we utilized an auxiliary classification branch to learn the significantly important features regarding specific occasions. Besides, a sequence to sequence approach is also applied to learn the relationship of different items along with a visual semantic space, which is able to learn the connection between visual features and their semantic presentation. To demonstrate the effectiveness of the proposed method, we conduct experiments on our newly collected Shoplook-Occasion dataset. The experimental results indicate that our proposed method improved the AUC metric from 0.02 to 0.15% and from 0.5 to 4% on accuracy, compared with other approaches for outfit compatibility problem conditioning on specific occasions. [ABSTRACT FROM AUTHOR]

Gene transfer agents (GTAs) are prophage-like entities found in many bacterial genomes that cannot propagate themselves and instead package approximately 5 to 15 kbp fragments of the host genome that can then be transferred to related recipient cells. Although suggested to facilitate horizontal gene transfer (HGT) in the wild, no clear physiological role for GTAs has been elucidated. Here, we demonstrate that the α-proteobacterium Caulobacter crescentus produces bona fide GTAs. The production of Caulobacter GTAs is tightly regulated by a newly identified transcription factor, RogA, that represses gafYZ, the direct activators of GTA synthesis. Cells lacking rogA or expressing gafYZ produce GTAs harboring approximately 8.3 kbp fragment of the genome that can, after cell lysis, be transferred into recipient cells. Notably, we find that GTAs promote the survival of Caulobacter in stationary phase and following DNA damage by providing recipient cells a template for homologous recombination-based repair. This function may be broadly conserved in other GTA-producing organisms and explain the prevalence of this unusual HGT mechanism. The model organism Caulobacter crescentus is found to produce a prophage-like gene transfer agent that mediates survival to stationary phase and DNA damaging conditions by providing genomic DNA from donor cells for recombination-based repair in recipient cells. [ABSTRACT FROM AUTHOR]

Kinetic Monte Carlo simulations of a model of thin film heteroepitaxy are performed to investigate the effects of the deposition temperature in the initial growth stages. Broad ranges of the rates of surface processes are used to model materials with several activation energies and several temperature changes, in conditions of larger diffusivity on the substrate in comparison with other film layers. When films with the same coverage are compared, the roughness increases with the deposition temperature in the regimes of island growth, coalescence, and initial formation of the continuous films. Concomitantly, the position of the minimum of the autocorrelation function is displaced to larger sizes. These apparently universal trends are consequences of the formation of wider and taller islands, and are observed with or without Ehrlich-Schwöebel barriers for adatom diffusion at step edges. The roughness increase with temperature qualitatively matches the observations of recent works on the deposition of inorganic and organic materials. In thicker films, simulations with some parameter sets show the decrease of roughness with temperature. In these cases, a re-entrance of roughness may be observed in the initial formation of the continuous films. [ABSTRACT FROM AUTHOR]

Bacteria of the genus Streptomyces have a linear chromosome, with a core region and two 'arms'. During their complex life cycle, these bacteria develop multi-genomic hyphae that differentiate into chains of exospores that carry a single copy of the genome. Sporulation-associated cell division requires chromosome segregation and compaction. Here, we show that the arms of Streptomyces venezuelae chromosomes are spatially separated at entry to sporulation, but during sporogenic cell division they are closely aligned with the core region. Arm proximity is imposed by segregation protein ParB and condensin SMC. Moreover, the chromosomal terminal regions are organized into distinct domains by the Streptomyces-specific HU-family protein HupS. Thus, as seen in eukaryotes, there is substantial chromosomal remodelling during the Streptomyces life cycle, with the chromosome undergoing rearrangements from an 'open' to a 'closed' conformation. Streptomyces bacteria have a linear chromosome and a complex life cycle, including development of multi-genomic hyphae that differentiate into mono-genomic exospores. Here, Szafran et al. show that the chromosome of Streptomyces venezuelae undergoes substantial remodelling during sporulation, from an 'open' to a 'closed' conformation. [ABSTRACT FROM AUTHOR]

Bacteria of the genus Streptomyces have a linear chromosome, with a core region and two 'arms'. During their complex life cycle, these bacteria develop multi-genomic hyphae that differentiate into chains of exospores that carry a single copy of the genome. Sporulation-associated cell division requires chromosome segregation and compaction. Here, we show that the arms of Streptomyces venezuelae chromosomes are spatially separated at entry to sporulation, but during sporogenic cell division they are closely aligned with the core region. Arm proximity is imposed by segregation protein ParB and condensin SMC. Moreover, the chromosomal terminal regions are organized into distinct domains by the Streptomyces-specific HU-family protein HupS. Thus, as seen in eukaryotes, there is substantial chromosomal remodelling during the Streptomyces life cycle, with the chromosome undergoing rearrangements from an 'open' to a 'closed' conformation. Streptomyces bacteria have a linear chromosome and a complex life cycle, including development of multi-genomic hyphae that differentiate into mono-genomic exospores. Here, Szafran et al. show that the chromosome of Streptomyces venezuelae undergoes substantial remodelling during sporulation, from an 'open' to a 'closed' conformation. [ABSTRACT FROM AUTHOR]

There is a growing interest in using new technology to create high-quality 3D recordings of heritage sites at potential risk of damage from conflict or natural disaster. Project Anqa is a multi-partner initiative to digitally document and present seven such at-risk heritage sites, all of which are located in Damascus, Syria. Through a training program, we enabled Syrian locals to collect a variety of data from all seven sites. With this data - a combination of photographs, laser-scan data and audio interviews - we present a web-application that provides researchers and the public a visually rich experience that showcases these at-risk sites. We term this approach "digitally-assisted storytelling." Our goal is to raise awareness of the need to document and preserve at-risk heritage in the Middle East while providing local professionals in the region with the skills to carry out these tasks. Furthermore, Project Anqa aims to be an educational resource for both researchers and the public. By allowing all collected data to be downloaded at no charge through an open access platform, we encourage the transfer of knowledge and information while preserving the digital longevity of this endeavour. [ABSTRACT FROM AUTHOR]

Abstract: The technical efficiency of randomly sampled pangasius farms in the Mekong Delta of Vietnam was estimated using data envelopment analysis, and factors affecting technical and scale efficiency were examined with bootstrap truncated regression. The mean technical efficiency score assuming variable returns to scale was 0.84. The technical efficiency of downstream farmers was higher due to lower energy costs and stocking once a year. Most of the up‐ and midstream farms needed to pump water and stocked at least three times in 2 yr. Regression analysis showed a positive effect on technical efficiency of the farmers' education level and having experienced climate change impact through flooding or salinity intrusion in the past. Farms affected by salinity intrusion had a lower scale efficiency as they reduce stocking frequency and rate. In general, reducing fish mortality and the cost of inputs, increasing scale of operation, and being trained, using appropriate methods, in management strategies may improve technical efficiency. [ABSTRACT FROM AUTHOR]

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair–the attenuation of DNA-end processing and the initiation of homology search by RecA–thereby helping to ensure that genomic integrity is maintained during DSB repair. [ABSTRACT FROM AUTHOR]

The search for a simple meta-system with negative refractive index has attracted a lot of attention recently. In this paper, we study a negative refractive transmission operating at 300 GHz by using "single-atom" metamaterials which were initially designed for achieving negative permeability. The nature of the negativity is discussed extensively by the effective medium analysis and confirmed by the dispersion diagram. [ABSTRACT FROM AUTHOR]

Because most antibiotics are potentially lethal to the producing organism, there must be mechanisms to ensure that the machinery responsible for export of the mature antibiotic is in place at the time of biosynthesis. Simocyclinone D8 is a potent DNA gyrase inhibitor produced by Streptomyces antibioticus Tü 6040. Within the simocyclinone biosynthetic cluster are two divergently transcribed genes, simR and simX, encoding proteins that resemble the TetR/TetA repressor–efflux pump pair that cause widespread resistance to clinically important tetracyclines. Engineered expression of simX from a strong, heterologous promoter conferred high level simocyclinone D8 resistance on Streptomyces lividans, showing that simX encodes a simocyclinone efflux pump. Transcription of simX is controlled by SimR, which directly represses the simX and simR promoters by binding to two operator sites in the simX–simR intergenic region. Simocyclinone D8 abolishes DNA binding by SimR, providing a mechanism that couples the biosynthesis of simocyclinone to its export. In addition, an intermediate in the biosynthetic pathway, simocyclinone C4, which is essentially inactive as a DNA gyrase inhibitor, also induces simX expression in vivo and relieves simX repression by SimR in vitro. [ABSTRACT FROM AUTHOR]

Background: Patients with ulcerative colitis and primary sclerosing cholangitis are at high risk for colonic dysplasia and cancer. This risk approaches 50% after 25 years of colitis. Ursodiol has been shown to protect against development of colorectal neoplasia in animal models.Objective: To assess the relationship between ursodiol use and colonic dysplasia, the precursor to colon cancer, in patients with ulcerative colitis and primary sclerosing cholangitis.Design: Cross-sectional study.Setting: University medical center.Patients: 59 patients with ulcerative colitis and primary sclerosing cholangitis who were undergoing colonoscopic surveillance for colonic dysplasia.Measurements: Use of ursodiol was assessed in all patients. The presence or absence of colonic dysplasia was evaluated by colonoscopic surveillance. Other variables assessed were age at onset and duration of ulcerative colitis; duration of primary sclerosing cholangitis; Child-Pugh classification; and use of sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, cyclosporine, azathioprine, and methotrexate.Results: Ursodiol use was strongly associated with decreased prevalence of colonic dysplasia (odds ratio, 0.18 [95% CI, 0.05 to 0.61]; P = 0.005). The association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, severity of liver disease, and sulfasalazine use (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P = 0.01). Younger age at onset of colitis was associated with an increased risk for dysplasia.Conclusions: Ursodiol use appears to be associated with a lower frequency of colonic dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis. A randomized trial investigating the chemoprotective effect of ursodiol in patients with ulcerative colitis may be warranted. [ABSTRACT FROM AUTHOR]

This has now been corrected in both the PDF and HTML versions of the Article. The original article can be found online at https://doi.org/10.1038/s41467-021-25461-2. The original version of this Article omitted the following from the Acknowledgements: "and BBSRC (BBS/E/J/000PR9791) for funding". [Extracted from the article]

We have analysed a new gene, CEM1, from Saccharomyces cerevisiae. Inactivation of this gene leads to a respiratory-deficient phenotype. The deduced protein sequence shows strong similarities with β-keto-acyl synthases or condensing enzymes. Typically, enzymes of this class are involved in the synthesis of fatty acids or similar molecules. An analysis of the mitochondrial lipids and fatty acids shows no major difference between the wild type and deleted strains, implying that the CEM1 gene product is not involved in the synthesis of the bulk fatty acids. Thus it is possible that the CEM1 protein is involved in the synthesis of a specialized molecule, probably related to a fatty acid, which is essential for mitochondrial respiration. [ABSTRACT FROM AUTHOR]

Crystals of SimR were grown by vapour diffusion. The protein crystallized with trigonal symmetry and X-ray data were recorded to a resolution of 2.3 Å from a single crystal at the synchrotron. SimR belongs to the TetR family of bacterial transcriptional regulators. In the absence of the antibiotic simocyclinone, SimR represses the transcription of a divergently transcribed gene encoding the simocyclinone efflux pump SimX in Streptomyces antibioticus by binding to operators in the simR- simX intergenic region. Simocyclinone binding causes SimR to dissociate from its operators, leading to expression of the SimX efflux pump. Thus, SimR represents an intimate link between the biosynthesis of simocyclinone and its export, which may also provide the mechanism of self-resistance to the antibiotic in the producer strain. [ABSTRACT FROM AUTHOR]

The article reflects on the results of the Early Treatment for Retinopathy of Prematurity Clinical Trial. Subgroup results have been presented, and the author comments that results have strengthened the confidence in the use of the clinical trial and help to shape individual clinical judgement in the application of clinical trials.