Mosaic Architecture Research Articles

Liver Imaging Reporting and Data System Category 5: MRI Predictors of Microvascular Invasion and Recurrence After Hepatectomy for Hepatocellular Carcinoma.

OBJECTIVE. We investigated in Liver Imaging Reporting and Data System category 5 (LR-5) observations whether imaging features, including LI-RADS imaging features, could predict microvascular invasion (MVI) and posthepatectomy recurrence in high-risk adult patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS. We retrospectively identified 149 high-risk patients who underwent 3-T MRI within 1 month before hepatectomy for HCC; 81 of 149 patients with no HCC recurrence were followed for more than 1 year. Tumors with clear surgical margins were confirmed in each hepatectomy specimen. MVI was evaluated histologically by a histopathologist. Tumor recurrence was determined by clinical and imaging follow-up. Two independent radiologists reviewed the prehepatectomy MR images and assessed LI-RADS v2018 imaging features as well as some non-LI-RADS features in all LR-5 observations in consensus. Alpha-fetoprotein level, tumor number, and imaging features were analyzed as potential predictors for MVI and posthepatectomy recurrence using multivariate logistic regression and Cox proportional hazards models. RESULTS. One hundred forty-nine patients with pathologically confirmed HCC were included; 64 of 149 (43.0%) patients had MVI, whereas 48 of 129 (37.2%) patients had tumor recurrence within 3 years after hepatectomy. Mosaic architecture (odds ratio, 3.420; p < 0.001) and nonsmooth tumor margin (odds ratio, 2.554; p = 0.011) were independent predictors of MVI. Multifocal tumors (hazard ratio, 2.101; p = 0.034), absence of fat in mass (hazard ratio, 2.109; p = 0.015), and nonsmooth tumor margin (hazard ratio, 2.415; p = 0.005) were independent predictors of posthepatectomy recurrence. CONCLUSION. In high-risk patients with LR-5 HCC, mosaic architecture and non-smooth tumor margin independently predicted MVI. Multifocal tumors, absence of fat in mass, and nonsmooth tumor margin independently predicted recurrence.

Staphylococci phages display vast genomic diversity and evolutionary relationships

BackgroundBacteriophages are the most abundant and diverse entities in the biosphere, and this diversity is driven by constant predator–prey evolutionary dynamics and horizontal gene transfer. Phage genome sequences are under-sampled and therefore present an untapped and uncharacterized source of genetic diversity, typically characterized by highly mosaic genomes and no universal genes. To better understand the diversity and relationships among phages infecting human pathogens, we have analysed the complete genome sequences of 205 phages of Staphylococcus sp.ResultsThese are predicted to encode 20,579 proteins, which can be sorted into 2139 phamilies (phams) of related sequences; 745 of these are orphams and possess only a single gene. Based on shared gene content, these phages were grouped into four clusters (A, B, C and D), 27 subclusters (A1-A2, B1-B17, C1-C6 and D1-D2) and one singleton. However, the genomes have mosaic architectures and individual genes with common ancestors are positioned in distinct genomic contexts in different clusters. The staphylococcal Cluster B siphoviridae are predicted to be temperate, and the integration cassettes are often closely-linked to genes implicated in bacterial virulence determinants. There are four unusual endolysin organization strategies found in Staphylococcus phage genomes, with endolysins predicted to be encoded as single genes, two genes spliced, two genes adjacent and as a single gene with inter-lytic-domain secondary translational start site. Comparison of the endolysins reveals multi-domain modularity, with conservation of the SH3 cell wall binding domain.ConclusionsThis study provides a high-resolution view of staphylococcal viral genetic diversity, and insights into their gene flux patterns within and across different phage groups (cluster and subclusters) providing insights into their evolution.

Advances in the Assembly Model of Bacterial Type IVB Secretion Systems

Bacterial type IV secretion systems (T4SSs) are related to not only secretion of effector proteins and virulence factors, but also to bacterial conjugation systems that promote bacterial horizontal gene transfer. The subgroup T4BSS, with a unique mosaic architecture system, consists of nearly 30 proteins that are similar to those from other secretory systems. Despite being intensively studied, the secretion mechanism of T4BSS remains unclear. This review systematically summarizes the protein composition, coding gene set, core complex, and protein interactions of T4BSS. The interactions of proteins in the core complex of the system and the operation mechanism between each element needs to be further studied.

Monitoring Viable Cells of the Biological Control Agent Lactobacillus plantarum PM411 in Aerial Plant Surfaces by Means of a Strain-Specific Viability Quantitative PCR Method

ABSTRACTA viability quantitative PCR (v-qPCR) assay was developed for the unambiguous detection and quantification of Lactobacillus plantarum PM411 viable cells in aerial plant surfaces. A 972-bp region of a PM411 predicted prophage with mosaic architecture enabled the identification of a PM411 strain-specific molecular marker. Three primer sets with different amplicon lengths (92, 188, and 317 bp) and one TaqMan probe were designed. All the qPCR assays showed good linearity over a 4-log range and good efficiencies but differed in sensitivity. The nucleic acid-binding dye PEMAX was used to selectively detect and enumerate viable bacteria by v-qPCR. The primer set amplifying a 188-bp DNA fragment was selected as the most suitable for v-qPCR. The performance of the method was assessed on apple blossoms, pear, strawberry, and kiwifruit leaves in potted plants under controlled environmental conditions, as well as pear and apple blossoms under field conditions, by comparing v-qPCR population estimations to those obtained by qPCR and specific plate counting on de Man-Rogosa-Sharpe (MRS)-rifampin. The population estimation did not differ significantly between methods when conditions were conducive to bacterial survival. However, under stressful conditions, differences between methods were observed due to cell death or viable-but-nonculturable state induction. While qPCR overestimated the population level, plate counting underestimated this value in comparison to v-qPCR. PM411 attained stable population levels of viable cells on the flower environment under high relative humidity. However, the unfavorable conditions on the leaf surface and the relatively dryness in the field caused an important decrease in the viable population.IMPORTANCE The v-qPCR method in combination with plate counting and qPCR is a powerful tool for studies of colonization and survival under field conditions, to improve formulations and delivery strategies of PM411, and to optimize the dose and timing of spray schedules. It is expected that PEMAX v-qPCR could also be developed for monitoring other strains on plant surfaces not only as biological control agents but also beneficial bacteria useful in the sustainable management of crop production.

LI-RADS for MR Imaging Diagnosis of Hepatocellular Carcinoma: Performance of Major and Ancillary Features.

Purpose To evaluate the performance of major features, ancillary features, and categories of Liver Imaging Reporting and Data System (LI-RADS) version 2014 at magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC). Materials and Methods This retrospective institutional review board-approved study included patients with liver MR imaging and at least one pathologically proved lesion. Between 2004 and 2016, 102 patients (275 observations including 113 HCCs) met inclusion criteria. Two radiologists independently assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS category. Per-lesion estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed by using generalized estimating equation models. Results Major features (arterial phase hyperenhancement, washout, capsule, and threshold growth) had a sensitivity of 88.5%, 60.6%, 32.9%, and 41.6%, and a specificity of 18.6%, 84.8%, 98.8%, and 83.2% for HCC, respectively. Ancillary features (mild-moderate T2 hyperintensity, restricted diffusion, mosaic architecture, intralesional fat, lesional fat sparing, blood products, and subthreshold growth) had a sensitivity of 62.2%, 54.8%, 9.9%, 30.9%, 23.1%, 2.8%, and 48.3%, and a specificity of 79.4%, 90.6%, 99.4%, 94.2%, 83.1%, 99.3%, and 91.4% for HCC, respectively. The LR-5 or LR-5 V categories had a per-lesion sensitivity of 50.8% and a specificity of 95.8% for HCC, respectively. The LR-4, LR-5, or LR-5 V categories (determined by using major features only vs combination of major and ancillary features) had a per-lesion sensitivity of 75.9% and 87.9% and a per-lesion specificity of 87.5% and 86.2%, respectively. Conclusion The use of ancillary features in combination with major features increases the sensitivity while preserving a high specificity for the diagnosis of HCC.

Expression and evolutionary patterns of mycobacteriophage D29 and its temperate close relatives

BackgroundMycobacteriophages are viruses that infect Mycobacterium hosts. A large collection of phages known to infect the same bacterial host strain – Mycobacterium smegmatis mc2155 – exhibit substantial diversity and characteristically mosaic architectures. The well-studied lytic mycobacteriophage D29 appears to be a deletion derivative of a putative temperate parent, although its parent has yet to be identified.ResultsHere we describe three newly-isolated temperate phages – Kerberos, Pomar16 and StarStuff – that are related to D29, and are predicted to be very close relatives of its putative temperate parent, revealing the repressor and additional genes that are lost in D29. Transcriptional profiles show the patterns of both lysogenic and lytic gene expression and identify highly-expressed, abundant, stable, small non-coding transcripts made from the Pleft early lytic promoter, and which are toxic to M. smegmatis.ConclusionsComparative genomics of phages D29, Kerberos, Pomar16 and StarStuff provide insights into bacteriophage evolution, and comparative transcriptomics identifies the pattern of lysogenic and lytic expression with unusual features including highly expressed, small, non-coding RNAs.

Mosaic architecture of hepatocellular carcinoma.

Mosaic architecture of hepatocellular carcinoma.

Benign nodules in post-Fontan livers can show imaging features considered diagnostic for hepatocellular carcinoma.

To describe the imaging appearance of hyperenhancing nodules arising in post-Fontan patients and to identify specific features best correlated with malignancy. Hyperenhancing hepatic nodules visible on CT and/or MRI in post-Fontan patients were identified retrospectively and reviewed by subspecialty radiologists. Nodules with characteristic imaging findings of focal nodular hyperplasia (FNH) were defined as typical, the remainder were defined as atypical, described in detail according to LIRADS criteria, andlength of stability over time was recorded. Clinical data, alpha fetoprotein levels (AFP), central venous pressures (CVP), and histopathology were recorded. 245 hyperenhancing nodules (215 typical, 30 atypical) were evaluated in 30 patients. Twenty-nine atypical nodules showed washout (portal phase in 6, delayed phase in 29), 0 showed pseudocapsule, 1 showed threshold growth, 1 showed tumor in vein, and 5 showed ancillary features favoring malignancy. Pathology confirmed hepatocellular carcinoma (HCC) in 3 atypical nodules and FNH-like histology in 3 atypical and 4 typical nodules. 2 atypical nodules were present in a patient with clinical diagnosis of HCC. 20 nodules (7 typical, 13 atypical due to washout) were studied with hepatobiliary contrast agent and all showed homogenous hepatobiliary phase retention. Atypical nodules were significantly more likely to be HCC than biopsy-proven FNH-like or stable≥24months when showing portal phase washout (P<0.001), mosaic architecture (P=0.020) or in the presence of cirrhosis (P=0.004) or elevated AFP (P=0.004). Atypical nodules that were HCC had higher median CVP than those that were FNH-like (19, range 16-27 vs. 13, range 12-16mmHg, P=0.0003), there was not a significant difference based on median patient age (HCC 30, range 10-41 vs. FNH-like 40range 10-41, P=0.244). Benign hyperenhancing masses in Fontan patients may demonstrate washout and be mistaken for HCC by imaging criteria. Portal phase washout, mosaic architecture, elevated AFP and higher CVP were associated with HCC in the atypical nodules found in this population.

The complete nucleotide sequence of an IncP-2 megaplasmid unveils a mosaic architecture comprising a putative novel blaVIM-2-harbouring transposon in Pseudomonas aeruginosa.

In Pseudomonas aeruginosa , bla VIM-2 has been mostly associated with a chromosomal location and rarely with a plasmid backbone. Until now, only three complete bla VIM-2 -carrying plasmid sequences have been described in this species. Here we explore the modular structure of pJB37, the first bla VIM-2 -carrying megaplasmid described in P. aeruginosa . The complete nucleotide sequence of plasmid pJB37 was determined with an Illumina HiSeq, with de novo assembly by SPAdes, annotation by RAST and searching for antimicrobial resistance genes and virulence factors. Conjugation assays were conducted. Megaplasmid pJB37 (464 804 bp long and GC content of 57.2%) comprised: an IncP-2 repA-oriV-parAB region; a conjugative transfer region ( traF , traG , virD2 and trbBCDEJLFGI genes); Tn 6356 , a new putative bla VIM-2 -carrying transposon; heavy metal (mercury and tellurite) resistance operons; and an arsenal of virulence genes. Plasmid pJB37 was transferable by conjugation to a spontaneous rifampicin-resistant mutant of P. aeruginosa PAO1. Here, a bla VIM-2 -harbouring In58 integron was associated with a new complex transposable structure, herein named Tn 6356 , suggesting that In58 was most likely acquired by insertion of this element. The mosaic arrangement exhibited by the pJB37 IncP-2 megaplasmid, which highlights the vast assembly potential of distinct genetic elements in a Pseudomonas widespread plasmid platform, gives new insights into bacterial adaptation and evolution.

The mosaic architecture of Aeromonas salmonicida subsp. salmonicida pAsa4 plasmid and its consequences on antibiotic resistance.

Aeromonas salmonicida subsp. salmonicida, the causative agent of furunculosis in salmonids, is an issue especially because many isolates of this bacterium display antibiotic resistances, which limit treatments against the disease. Recent results suggested the possible existence of alternative forms of pAsa4, a large plasmid found in A. salmonicida subsp. salmonicida and bearing multiple antibiotic resistance genes. The present study reveals the existence of two newly detected pAsa4 variants, pAsa4b and pAsa4c. We present the extensive characterization of the genomic architecture, the mobile genetic elements and the antimicrobial resistance genes of these plasmids in addition to the reference pAsa4 from the strain A449. The analysis showed differences between the three architectures with consequences on the content of resistance genes. The genomic plasticity of the three pAsa4 variants could be partially explained by the action of mobile genetic elements like insertion sequences. Eight additional isolates from Canada and Europe that bore similar antibiotic resistance patterns as pAsa4-bearing strains were genotyped and specific pAsa4 variants could be attributed to phenotypic profiles. pAsa4 and pAsa4c were found in Europe, while pAsa4b was found in Canada. In accordance with their content in conjugative transfer genes, only pAsa4b and pAsa4c can be transferred by conjugation in Escherichia coli. The plasticity of pAsa4 variants related to the acquisition of antibiotic resistance indicates that these plasmids may pose a threat in terms of the dissemination of antimicrobial-resistant A. salmonicida subsp. salmonicida bacteria.

Characterization of prophages containing "evolved" Dit/Tal modules in the genome of Lactobacillus casei BL23.

Lactic acid bacteria (LAB) have many applications in food and industrial fermentations. Prophage induction and generation of new virulent phages is a risk for the dairy industry. We identified three complete prophages (PLE1, PLE2, and PLE3) in the genome of the well-studied probiotic strain Lactobacillus casei BL23. All of them have mosaic architectures with homologous sequences to Streptococcus, Lactococcus, Lactobacillus, and Listeria phages or strains. Using a combination of quantitative real-time PCR, genomics, and proteomics, we showed that PLE2 and PLE3 can be induced-but with different kinetics-in the presence of mitomycin C, although PLE1 remains as a prophage. A structural analysis of the distal tail (Dit) and tail associated lysin (Tal) baseplate proteins of these prophages and other L. casei/paracasei phages and prophages provides evidence that carbohydrate-binding modules (CBM) located within these "evolved" proteins may replace receptor binding proteins (RBPs) present in other well-studied LAB phages. The detailed study of prophage induction in this prototype strain in combination with characterization of the proteins involved in host recognition will facilitate the design of new strategies for avoiding phage propagation in the dairy industry.

Snapshot colored compressive spectral imager.

Traditional spectral imaging approaches require sensing all the voxels of a scene. Colored mosaic FPA detector-based architectures can acquire sets of the scene's spectral components, but the number of spectral planes depends directly on the number of available filters used on the FPA, which leads to reduced spatiospectral resolutions. Instead of sensing all the voxels of the scene, compressive spectral imaging (CSI) captures coded and dispersed projections of the spatiospectral source. This approach mitigates the resolution issues by exploiting optical phenomena in lenses and other elements, which, in turn, compromise the portability of the devices. This paper presents a compact snapshot colored compressive spectral imager (SCCSI) that exploits the benefits of the colored mosaic FPA detectors and the compression capabilities of CSI sensing techniques. The proposed optical architecture has no moving parts and can capture the spatiospectral information of a scene in a single snapshot by using a dispersive element and a color-patterned detector. The optical and the mathematical models of SCCSI are presented along with a testbed implementation of the system. Simulations and real experiments show the accuracy of SCCSI and compare the reconstructions with those of similar CSI optical architectures, such as the CASSI and SSCSI systems, resulting in improvements of up to 6 dB and 1 dB of PSNR, respectively.

Adding pieces to the puzzle: New insights into bacteriophage diversity from integrated research-education programs.

Bacteriophages are the dark matter of the biological universe: the population is vast and replete with novel genes whose function is unknown. The genomic insights such as the mosaic architecture gleaned from perhaps 2,000 currently sequenced bacteriophage genomes is far from representative of the total number phage particles in the biosphere - about 10ˆ31. The recent comparative analysis of 627 mycobacteriophages isolated on Mycobacterium smegmatis mc2 155 is the most extensive examination yet in pursuit of this question.

Dark Matter of the Biosphere: the Amazing World of Bacteriophage Diversity.

Bacteriophages are the most abundant biological entities in the biosphere, and this dynamic and old population is, not surprisingly, highly diverse genetically. Relative to bacterial genomics, phage genomics has advanced slowly, and a higher-resolution picture of the phagosphere is only just emerging. This view reveals substantial diversity even among phages known to infect a common host strain, but the relationships are complex, with mosaic genomic architectures generated by illegitimate recombination over a long period of evolutionary history.

Nutrients drive transcriptional changes that maintain metabolic homeostasis but alter genome architecture in Microcystis.

The cyanobacterium Microcystis aeruginosa is a globally distributed bloom-forming organism that degrades freshwater systems around the world. Factors that drive its dispersion, diversification and success remain, however, poorly understood. To develop insight into cellular-level responses to nutrient drivers of eutrophication, RNA sequencing was coupled to a comprehensive metabolomics survey of M. aeruginosa sp. NIES 843 grown in various nutrient-reduced conditions. Transcriptomes were generated for cultures grown in nutrient-replete (with nitrate as the nitrogen (N) source), nitrogen-reduced (with nitrate, urea or ammonium acting as the N sources) and phosphate-reduced conditions. Extensive expression differences (up to 696 genes for urea-grown cells) relative to the control treatment were observed, demonstrating that the chemical variant of nitrogen available to cells affected transcriptional activity. Of particular note, a high number of transposase genes (up to 81) were significantly and reproducibly up-regulated relative to the control when grown on urea. Conversely, phosphorus (P) reduction resulted in a significant cessation in transcription of transposase genes, indicating that variation in nutrient chemistry may influence transcription of transposases and may impact the highly mosaic genomic architecture of M. aeruginosa. Corresponding metabolomes showed comparably few differences between treatments, suggesting broad changes to gene transcription are required to maintain metabolic homeostasis under nutrient reduction. The combined observations provide novel and extensive insight into the complex cellular interactions that take place in this important bloom-forming organism during variable nutrient conditions and highlight a potential unknown molecular mechanism that may drive Microcystis blooms and evolution.

PARAVERTEBRAL MASSES IN BLUE-TAILED MONITOR,VARANUS DORIANUS,INDICATIVE OF SOFT-TISSUE INFECTION WITH ASSOCIATED OSTEOMYELITIS

Paravertebral osseous masses in reptiles have been attributed to Paget's disease on the basis of histology. Histologically recognized mosaic architecture and cement lines, however, lack specificity. A Varanus dorianus with this condition was subjected to standard and computerized tomography. Because the masses were extraskeletal in nature, Paget's disease could be excluded. Although interpretation of the computed tomography suggested the process to be entirely extraskeletal, standard radiographs revealed disorganized vertebral architecture characteristic of osteomyelitis, crossing intervertebral spaces. Posttraumatic myositis ossificans and calcified hematoma were confidently excluded as diagnoses. The etiology of paraspinal masses in this V. dorianus appears attributable to infection, with infection of a puncture wound hypothesized as the underlying process. If one extrapolates the findings in this one animal, it seems reasonable to suggest that consideration be given to investigating the possibility of an infectious origin when similar masses are recognized in other reptiles.

Progress challenges and opportunities for the re-engineering of trans-AT polyketide synthases

Polyketides are a structurally and functionally diverse family of bioactive natural products that are used extensively as pharmaceuticals and agrochemicals. In bacteria these molecules are biosynthesized by giant, multi-functional enzymatic complexes, termed modular polyketide synthases (PKSs), that function in assembly-line like fashion to fuse and tailor simple carboxylic acid monomers into a vast array of elaborate chemical scaffolds. Modifying PKSs through targeted synthase re-engineering is a promising approach for accessing functionally-optimized polyketides. Due to their highly mosaic architectures the recently identified trans-AT family of modular synthases appear inherently more amenable to re-engineering than their well studied cis-AT counterparts. Here, we review recent progress in the re-engineering of trans-AT PKSs, summarize opportunities for harnessing the biosynthetic potential of these systems, and highlight challenges that such re-engineering approaches present.

The Adherens Junction: A Mosaic of Cadherin and Nectin Clusters Bundled by Actin Filaments

SummaryCadherin and nectin are distinct transmembrane proteins of adherens junctions. Their ectodomains mediate adhesion while their cytosolic regions couple the adhesive contact to the cytoskeleton. Both these proteins are essential for adherens junction formation and maintenance. However, some basic aspects of these proteins, such as their organization in adherence junctions, have remained open. Therefore, using super-resolution microscopy and live-imaging, we focused on the subjunctional distribution of these proteins. We showed that cadherin and nectin in the junctions of A431 cells and human keratinocytes are located in separate clusters. The size of each cluster is independent of that of the adjacent clusters and can significantly fluctuate over time. Several nectin and cadherin clusters that constitute an individual adherens junction are united by the same actin filament bundle. Surprisingly, interactions between each cluster and F-actin are not uniform since neither vinculin nor LIM domain actin-binding proteins match the boundaries of cadherin or nectin clusters. Thus, the adherens junction is not a uniform structure but a mosaic of different adhesive units with very diverse modes of interaction with the cytoskeleton. We propose that such a mosaic architecture of adherence junctions is important for the fast regulation of their dynamics.

Gene networks: Dissecting pathways in retinal development and disease

During retinal neurogenesis, diverse cellular subtypes originate from multipotent neural progenitors in a spatiotemporal order leading to a highly specialized laminar structure combined with a distinct mosaic architecture. This is driven by the combinatorial action of transcription factors and signaling molecules which specify cell fate and differentiation. The emerging approach of gene network analysis has allowed a better understanding of the functional relationships between genes expressed in the developing retina. For instance, these gene networks have identified transcriptional hubs that have revealed potential targets and pathways for the development of therapeutic options for retinal diseases. Much of the current knowledge has been informed by targeted gene deletion experiments and gain-of-functional analysis. In this review we will provide an update on retinal development gene networks and address the wider implications for future disease therapeutics.

Massive gene acquisitions in Mycobacterium indicus pranii provide a perspective on mycobacterial evolution

Understanding the evolutionary and genomic mechanisms responsible for turning the soil-derived saprophytic mycobacteria into lethal intracellular pathogens is a critical step towards the development of strategies for the control of mycobacterial diseases. In this context, Mycobacterium indicus pranii (MIP) is of specific interest because of its unique immunological and evolutionary significance. Evolutionarily, it is the progenitor of opportunistic pathogens belonging to M. avium complex and is endowed with features that place it between saprophytic and pathogenic species. Herein, we have sequenced the complete MIP genome to understand its unique life style, basis of immunomodulation and habitat diversification in mycobacteria. As a case of massive gene acquisitions, 50.5% of MIP open reading frames (ORFs) are laterally acquired. We show, for the first time for Mycobacterium, that MIP genome has mosaic architecture. These gene acquisitions have led to the enrichment of selected gene families critical to MIP physiology. Comparative genomic analysis indicates a higher antigenic potential of MIP imparting it a unique ability for immunomodulation. Besides, it also suggests an important role of genomic fluidity in habitat diversification within mycobacteria and provides a unique view of evolutionary divergence and putative bottlenecks that might have eventually led to intracellular survival and pathogenic attributes in mycobacteria.