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Viruses are the most abundant biological entities in the world's oceans, where they play important ecological and biogeochemical roles. Metagenomics is revealing new groups of eukaryotic viruses, although disconnected from known hosts. Among these are the recently described mirusviruses, which share some similarities with herpesviruses.1 50 years ago, "herpes-type" viral particles2 were found in a thraustochytrid member of the labyrinthulomycetes, a diverse group of abundant and ecologically important marine eukaryotes,3,4 but could not be further characterized by methods then available. Long-read sequencing has allowed us to connect the biology of mirusviruses and thraustochytrids. We sequenced the genome of the genetically tractable model thraustochytrid Aurantiochytrium limacinum ATCC MYA-1381 and found that its 26 linear chromosomes have an extraordinary configuration. Subtelomeric ribosomal DNAs (rDNAs) found at all chromosome ends are interspersed with long repeated sequence elements denoted as long repeated-telomere and rDNA spacers (LORE-TEARS). We identified two genomic elements that are related to mirusvirus genomes. The first is a ∼300-kbp episome (circular element 1 [CE1]) present at a high copy number. Strikingly, the second, distinct, mirusvirus-like element is integrated between two sets of rDNAs and LORE-TEARS at the left end of chromosome 15 (LE-Chr15). Similar to metagenomically derived mirusviruses, these putative A. limacinum mirusviruses have a virion module related to that of herpesviruses along with an informational module related to nucleocytoplasmic large DNA viruses (NCLDVs). CE1 and LE-Chr15 bear striking similarities to episomal and endogenous latent forms of herpesviruses, respectively, and open new avenues of research into marine virus-host interactions.

ObjectiveTo determine the influence of hair removal as part of the aseptic skin preparation of canine arthrocentesis sites and to characterize the bacterial flora remaining after aseptic skin preparation.Study designRandomized controlled trial.Study populationThirteen shorthaired beagle-cross dogs.MethodsA coin toss was used to randomly determine to have one carpus, elbow, tarsus, and stifle clipped. The contralateral side was left unclipped. Aseptic skin preparation was performed on all sites with 4% chlorhexidine followed by 70% isopropyl alcohol. The skin of each site was sampled for aerobic and anaerobic bacterial cultures before and after aseptic skin preparation. Bacterial cultures were submitted for laboratory testing to determine the colony-forming units (CFU) of bacteria and bacterial species isolated for each site.ResultsEach group (clipped and unclipped) included 52 sites. Aseptic skin preparation reduced bacterial CFU in both groups. There was no association between values for CFU per milliliter after skin preparation of dogs and side (P = .07), joint (P = .71), pre-aseptic skin preparation CFU (P = .94), or clipping (P = .42). Staphylococcus spp were the most common of the bacterial species cultured.ConclusionIn clean shorthaired dogs without visible evidence of dermatological disease, leaving arthrocentesis sites unclipped rather than performing traditional surgical clipping did not result in increased bacterial skin counts after aseptic skin preparation.Clinical significanceIn this study we did not find evidence to support that clipping of canine arthrocentesis sites is required for effective aseptic skin preparation. A prospective clinical trial is required to determine whether a change in practice would be associated with increased morbidity.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation.

The Liver Imaging Reporting and Data System (LI-RADS) standardizes performance of liver imaging in patients at risk for hepatocellular carcinoma (HCC) as well as interpretation and reporting of the results. Developed by experts in liver imaging and supported by the American College of Radiology, LI-RADS assigns to observations categories that reflect the relative probability of benignity, HCC, or other malignancy. While category assignment is based mainly on major imaging features, ancillary features may be applied to improve detection and characterization, increase confidence, or adjust LI-RADS categories. Ancillary features are classified as favoring malignancy in general, HCC in particular, or benignity. Those favoring malignancy in general or HCC in particular may be used to upgrade by a maximum of one category up to LR-4; those favoring benignity may be used to downgrade by a maximum of one category. If there are conflicting ancillary features (ie, one or more favoring malignancy and one or more favoring benignity), the category should not be adjusted. Ancillary features may be seen at diagnostic CT, MRI performed with extracellular agents, or MRI performed with hepatobiliary agents, with the exception of one ancillary feature assessed at US. This article focuses on LI-RADS version 2018 ancillary features seen at MRI. Specific topics include rules for ancillary feature application; definitions, rationale, and illustrations with clinical MRI examples; summary of evidence and diagnostic performance; pitfalls; and future directions. ©RSNA, 2018.

The Liver Imaging Reporting and Data System (LI-RADS) standardizes performance of liver imaging in patients at risk for hepatocellular carcinoma (HCC) as well as interpretation and reporting of the results. Developed by experts in liver imaging and supported by the American College of Radiology, LI-RADS assigns to observations categories that reflect the relative probability of benignity, HCC, or other malignancy. While category assignment is based mainly on major imaging features, ancillary features may be applied to improve detection and characterization, increase confidence, or adjust LI-RADS categories. Ancillary features are classified as favoring malignancy in general, HCC in particular, or benignity. Those favoring malignancy in general or HCC in particular may be used to upgrade by a maximum of one category up to LR-4; those favoring benignity may be used to downgrade by a maximum of one category. If there are conflicting ancillary features (ie, one or more favoring malignancy and one or more favoring benignity), the category should not be adjusted. Ancillary features may be seen at diagnostic CT, MRI performed with extracellular agents, or MRI performed with hepatobiliary agents, with the exception of one ancillary feature assessed at US. This article focuses on LI-RADS version 2018 ancillary features seen at MRI. Specific topics include rules for ancillary feature application; definitions, rationale, and illustrations with clinical MRI examples; summary of evidence and diagnostic performance; pitfalls; and future directions. ©RSNA, 2018.

Oil and gas percolate profusely through the sediments of the Gulf of Mexico, leading to numerous seeps at the seafloor, where complex microbial, and sometimes animal communities flourish. Sediments from three areas (two cold seeps with contrasting hydrocarbon composition and a site outside any area of active seepage) of the Gulf of Mexico were investigated and compared. Consistent with the existence of a seep microbiome, a distinct microbial community was observed in seep areas compared to sediment from outside areas of active seepage. The microbial community from sediments without any influence from hydrocarbon seepage was characterized by Planctomycetes and the metabolic potential was consistent with detrital marine snow degradation. By contrast, in seep samples with methane as the principal hydrocarbon, methane oxidation by abundant members of ANME-1 was likely the predominant process. Seep samples characterized by fluids containing both methane and complex hydrocarbons, were characterized by abundant Chloroflexi (Anaerolinaceae) and deltaproteobacterial lineages and exhibited potential for complex hydrocarbon degradation. These different metabolic capacities suggested that microorganisms in cold seeps can potentially rely on other processes beyond methane oxidation and that the hydrocarbon composition of the seep fluids may be a critical factor structuring the seafloor microbial community composition and function.

Oil and gas percolate profusely through the sediments of the Gulf of Mexico, leading to numerous seeps at the seafloor, where complex microbial, and sometimes animal communities flourish. Sediments from three areas (two cold seeps with contrasting hydrocarbon composition and a site outside any area of active seepage) of the Gulf of Mexico were investigated and compared. Consistent with the existence of a seep microbiome, a distinct microbial community was observed in seep areas compared to sediment from outside areas of active seepage. The microbial community from sediments without any influence from hydrocarbon seepage was characterized by Planctomycetes and the metabolic potential was consistent with detrital marine snow degradation. By contrast, in seep samples with methane as the principal hydrocarbon, methane oxidation by abundant members of ANME-1 was likely the predominant process. Seep samples characterized by fluids containing both methane and complex hydrocarbons, were characterized by abundant Chloroflexi (Anaerolinaceae) and deltaproteobacterial lineages and exhibited potential for complex hydrocarbon degradation. These different metabolic capacities suggested that microorganisms in cold seeps can potentially rely on other processes beyond methane oxidation and that the hydrocarbon composition of the seep fluids may be a critical factor structuring the seafloor microbial community composition and function.

Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (∆F508 CFTR) is the major cause of cystic fibrosis, one of the most common inherited childhood diseases. The mutated CFTR anion channel is not fully glycosylated and shows minimal activity in bronchial epithelial cells of patients with cystic fibrosis. Low temperature or inhibition of histone deacetylases can partly rescue ∆F508 CFTR cellular processing defects and function. A favourable change of ∆F508 CFTR protein-protein interactions was proposed as a mechanism of rescue; however, CFTR interactome dynamics during temperature shift and inhibition of histone deacetylases are unknown. Here we report the first comprehensive analysis of the CFTR and ∆F508 CFTR interactome and its dynamics during temperature shift and inhibition of histone deacetylases. By using a novel deep proteomic analysis method, we identify 638 individual high-confidence CFTR interactors and discover a ∆F508 deletion-specific interactome, which is extensively remodelled upon rescue. Detailed analysis of the interactome remodelling identifies key novel interactors, whose loss promote ∆F508 CFTR channel function in primary cystic fibrosis epithelia or which are critical for CFTR biogenesis. Our results demonstrate that global remodelling of ∆F508 CFTR interactions is crucial for rescue, and provide comprehensive insight into the molecular disease mechanisms of cystic fibrosis caused by deletion of F508.

Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (∆F508 CFTR) is the major cause of cystic fibrosis, one of the most common inherited childhood diseases. The mutated CFTR anion channel is not fully glycosylated and shows minimal activity in bronchial epithelial cells of patients with cystic fibrosis. Low temperature or inhibition of histone deacetylases can partly rescue ∆F508 CFTR cellular processing defects and function. A favourable change of ∆F508 CFTR protein-protein interactions was proposed as a mechanism of rescue; however, CFTR interactome dynamics during temperature shift and inhibition of histone deacetylases are unknown. Here we report the first comprehensive analysis of the CFTR and ∆F508 CFTR interactome and its dynamics during temperature shift and inhibition of histone deacetylases. By using a novel deep proteomic analysis method, we identify 638 individual high-confidence CFTR interactors and discover a ∆F508 deletion-specific interactome, which is extensively remodelled upon rescue. Detailed analysis of the interactome remodelling identifies key novel interactors, whose loss promote ∆F508 CFTR channel function in primary cystic fibrosis epithelia or which are critical for CFTR biogenesis. Our results demonstrate that global remodelling of ∆F508 CFTR interactions is crucial for rescue, and provide comprehensive insight into the molecular disease mechanisms of cystic fibrosis caused by deletion of F508.

Dietary flaxseed has cardioprotective effects that may be achieved through its rich content of the omega-3 fatty acid, alpha linolenic acid (ALA). Because ALA can be stored in adipose tissue, it is possible that some of its beneficial actions may be due to effects it has on the adipose tissue. We investigated the effects of dietary flaxseed both with and without an atherogenic cholesterol-enriched diet to determine the effects of dietary flaxseed on the expression of the adipose cytokines leptin and adiponectin. Rabbits were fed one of four diets: a regular (RG) diet, or a regular diet with added 0.5% cholesterol (CH), or 10% ground flaxseed (FX), or both (CF) for 8 weeks. Levels of leptin and adiponectin expression were assessed by RT-PCR in visceral adipose tissue. Consumption of flaxseed significantly increased plasma and adipose levels of ALA. Leptin protein and mRNA expression were lower in CH animals and were elevated in CF animals. Changes in leptin expression were strongly and positively correlated with adipose ALA levels and inversely correlated with levels of en face atherosclerosis. Adiponectin expression was not significantly affected by any of the dietary interventions. Our data demonstrate that the type of fat in the diet as well as its caloric content can specifically influence leptin expression. The findings support the hypothesis that the beneficial cardiovascular effects associated with flaxseed consumption may be related to a change in leptin expression.

Dietary flaxseed has cardioprotective effects that may be achieved through its rich content of the omega-3 fatty acid, alpha linolenic acid (ALA). Because ALA can be stored in adipose tissue, it is possible that some of its beneficial actions may be due to effects it has on the adipose tissue. We investigated the effects of dietary flaxseed both with and without an atherogenic cholesterol-enriched diet to determine the effects of dietary flaxseed on the expression of the adipose cytokines leptin and adiponectin. Rabbits were fed one of four diets: a regular (RG) diet, or a regular diet with added 0.5% cholesterol (CH), or 10% ground flaxseed (FX), or both (CF) for 8 weeks. Levels of leptin and adiponectin expression were assessed by RT-PCR in visceral adipose tissue. Consumption of flaxseed significantly increased plasma and adipose levels of ALA. Leptin protein and mRNA expression were lower in CH animals and were elevated in CF animals. Changes in leptin expression were strongly and positively correlated with adipose ALA levels and inversely correlated with levels of en face atherosclerosis. Adiponectin expression was not significantly affected by any of the dietary interventions. Our data demonstrate that the type of fat in the diet as well as its caloric content can specifically influence leptin expression. The findings support the hypothesis that the beneficial cardiovascular effects associated with flaxseed consumption may be related to a change in leptin expression.

We investigate the emergent dynamics when the nonlinear Dieterich-Ruina rate and state friction law is attached to a Burridge-Knopoff spring-block model. We derive both the discrete equations and the continuum formulation governing the system in this framework. The discrete system (ODEs) exhibits both periodic and chaotic motion, where the system’s transition to chaos is size-dependent, i.e. how many blocks are considered. From the discrete model we derive the nonlinear elastic wave equation by taking the continuum limit. This results in a nonlinear partial differential equation (PDE) and we find that both temporal and spatial chaos ensues when the same parameter is increased. This critical parameter value needed for the onset of chaos in the continuous model is much smaller than the value needed in the case of a single block and we discuss the implications this has on dynamic modeling of earthquake rupture with this specific friction law. Most importantly, these results suggest that the friction law is scale-dependent, thus caution should be taken when attaching a friction law derived at laboratory scales to full-scale earthquake rupture models. Furthermore, we find solutions where the initial slip pulse propagates like a traveling wave, or remains localized in space, suggesting the presence of soliton and breather solutions. We discuss the significance of these pulse-like solutions and how they can be understood as a proxy for the propagation of the rupture front across the fault surface during an earthquake. We compute analytically the conditions for soliton solutions and by exploring the resulting parameter space, we introduce a possible method for determining a range of suitable parameter values to be used in future dynamic earthquake modeling.

Conditions under which a single oscillator model coupled with Dieterich-Ruina's rate and state dependent friction exhibits chaotic dynamics is studied. Properties of spring-block models are discussed. The parameter values of the system are explored and the corresponding numerical solutions presented. Bifurcation analysis is performed to determine the bifurcations and stability of stationary solutions and we find that the system undergoes a Hopf bifurcation to a periodic orbit. This periodic orbit then undergoes a period doubling cascade into a strange attractor, recognized as broadband noise in the power spectrum. The implications for earthquakes are discussed.

We show that both the slip distribution and the peak ground acceleration (PGA) for the 1999 Chi Chi earthquake can be described by Levy laws. Furthermore, we found that the tails of the probability density functions (PDF) characterizing the slip and the PGA are governed by a parameter, the Levy index, with almost the same values as predicted by the Central Limit theorem. The PDF tail controls the frequency at which extreme large events can occur. These events are the large stress drops-asperities distributed over the fault surface and the large PGA observed in the ground motion. Our results suggest that the frequency of these events is coupled; the PDF of the PGA is a direct consequence of the PDF of the asperities. The physical rationale responsible for the coupling is the principle of superposition of wave signals characterized by random properties that are governed by the Central Limit theorem.

Climatic variability can be characterized by invariant quantities arising from the analysis of scaling properties of paleoclimatic records. In this paper we discuss a stochastic model that reproduces the variability and the long-range correlation observed in dendrochronological time series. We have found that non-Gaussian distributions are better suited to describe the climatic variability embedded in these data. Our results indicate that Gaussian distribution fails to capture the large fluctuation -extreme events-that characterized climatic variability in these time series. This might have applications on the study of extreme weather events on future climate scenarios.