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Surveillance of Rotavirus A (RVA) infections in North America swine populations are limited and not performed over a significant time period to properly assess the diversity of RVA strains in swine. The VP7 (G) and VP4 (P) genes of 32 Canadian RVA strains, circulating between 2009 and 2015 were sequenced, identifying the G3P[13], G5P[7], G9P[7], G9[13], and G9[19] genotype combinations. The Canadian RVA strains were compared to the RVA strains present in the swine ProSystems RCE rotavirus vaccine. The comparison revealed multiple amino acid differences in the G and P antigenic epitopes, regardless of the G and P genotypes but specifically in the Canadian G3, P[13] and P[19] genotypes. Our study further contributes to the characterization of RVA's evolution and disease mitigation among swine, which may optimize target vaccine design, thereby minimizing RVA disease in this economically important animal population. [ABSTRACT FROM AUTHOR]

Porcine deltacoronavirus (PDCoV) was identified in multiple states across the United States (US) in 2014. In this study, we investigate the presence of PDCoV in diagnostic samples, which were further categorized by case identification (ID), and the association between occurrence, age, specimen and location between March and September 2014. Approximately, 7% of the case IDs submitted from the US were positive for PDCoV. Specimens were categorized into eight groups, and the univariate analysis indicated that oral fluids had 1.89 times higher odds of detecting PDCoV compared to feces. While the 43–56 day age group had the highest percentage of PDCoV positives (8.4%), the univariate analysis indicated no significant differences between age groups. However, multivariable analysis for age adjusted by specimen indicated the >147 day age group had 59% lower odds than suckling pigs of being positive for PDCoV. The percentage of PDCoV in diagnostic samples decreased to <1% in September 2014. In addition, 19 complete PDCoV genomes were sequenced, and Bayesian analysis was conducted to estimate the emergence of the US clade. The evolutionary rate of the PDCoV genome is estimated to be 3.8 × 10 −4 substitutions/site/year (2.3 × 10 −4 –5.4 × 10 −4 , 95% HPD). Our results indicate that oral fluids continue to be a valuable specimen to monitor swineherd health, and PDCoV has been circulating in the US prior to 2014. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) has caused severe economic losses both recently in the United States (US) and historically throughout Europe and Asia. Traditionally, analysis of the spike gene has been used to determine phylogenetic relationships between PEDV strains. We determined the complete genomes of 93 PEDV field samples from US swine and analyzed the data in conjunction with complete genome sequences available from GenBank ( n = 126) to determine the most variable genomic areas. Our results indicate high levels of variation within the ORF1 and spike regions while the C-terminal domains of structural genes were highly conserved. Analysis of the Receptor Binding Domains in the spike gene revealed a limited number of amino acid substitutions in US strains compared to Asian strains. Phylogenetic analysis of the complete genome sequence data revealed high rates of recombination, resulting in differing evolutionary patterns in phylogenies inferred for the spike region versus whole genomes. These finding suggest that significant genetic events outside of the spike region have contributed to the evolution of PEDV. [ABSTRACT FROM AUTHOR]

Aims: Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer. A3B‐related mutations are identified through C‐to‐T/−G base substitutions in 5′‐TCA/T motifs. Herein, we present immunohistochemical and genomic data supportive of a role for A3B in head/neck MMs. Methods and results: A3B protein levels were assessed in oral (n = 13) and sinonasal (n = 13) melanomas, and oral melanocytic nevi (n = 13) by immunohistochemistry using a custom rabbit α‐A3B mAb (5210‐87‐13). Heterogeneous, selective‐to‐diffuse, nuclear only, A3B immunopositivity was observed in 12 of 13 (92.3%) oral melanomas (H‐score range = 9–72, median = 40) and 8 of 13 (62%) sinonasal melanomas (H‐score range = 1–110, median = 24). Two cases negative for A3B showed prominent cytoplasmic staining consistent with A3G. A3B protein levels were significantly higher in oral and sinonasal MMs than intraoral melanocytic nevi (P < 0.0001 and P = 0.0022, respectively), which were A3B‐negative (H‐score range = 1–8, median = 4). A3B levels, however, did not differ significantly between oral and sinonasal tumours (P > 0.99). NGS performed in 10 sinonasal MMs revealed missense NRAS mutations in 50% of the studied cases and one each KIT and HRAS mutations. Publicly available whole‐genome sequencing (WGS) data disclosed that the number of C‐to‐T mutations and APOBEC3 enrichment score were markedly elevated in head/neck MMs (n = 2). Conclusion: The above data strongly indicate a possible role for the mutagenic enzyme A3B in head/neck melanomagenesis, but not benign melanocytic neoplasms. [ABSTRACT FROM AUTHOR]

Focuses on influence of information technology on postmodern culture of literature. Easy accessibility of signs, data and information by postmodern citizens; Examination of role of contemporary British poetry in postmodern pleasure principle; Examples of pleasure-seeking activities of British poets.

Discusses the role of cultural memory in the work of British poet Barry MacSweeney. Belief of the poet that postmodernism would mean that the contemporary artwork is no longer entirely contemporary; Description of the literary works of the poet as a postmodern historicity of archival fragment that remains to be an important element in the overall poetical texture.

Bark microrelief is of importance to the physiological ecology of forested ecosystems because it has been documented to influence the distribution of corticolous lichens, stemilow generation, and forest biogeochemical cycles. Hitherto no instrument existed to characterize the inherent variability of bark microrelief with high spatial resolution. Our newly designed prototype instrument consists of a hinged ring, laser rangefinder, and motor linked to a standard laptop. The prototype produces trunk cross sections at a 0.33° horizontal resolution and detects bark-ridge-to-furrow heights at < 1 mm resolution. The prototype was validated by comparing measurements of bark microrelief between the instrument and digital calipers. The mean absolute error of the prototype as a percentage of the measured average microrelief was 1.0%, with a mean absolute error of 0.83 mm. Our bark microrelief prototype instrument can supply critical requisite information of bark microstructure that can be used by researchers to interpret the distribution of lichens and bryophytes on tree surfaces, relate stemilow yield and chemistry to bark microrelief, and provide detailed measurements of the changes of bark microrelief with stem dehydration. In short, the prototype instrument can be used to gain a more holistic understanding of the physiological ecology of forest ecosystems. [ABSTRACT FROM AUTHOR]

A prominent source of mutation in cancer is single-stranded DNA cytosine deamination by cellular APOBEC3 enzymes, which results in signature C-to-T and C-to-G mutations in TCA and TCT motifs. Although multiple enzymes have been implicated, reports conflict and it is unclear which protein(s) are responsible. Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates—APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies of TK mutation and similar TC-biased cytosine mutation profiles in the selectable TK reporter gene. Whole genome sequences from independent clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs 70% of the time and APOBEC3B 50% of the time (Y = C/T; W = A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes contribute in a combinatorial manner to the overall mutation landscape. Although the vast majority of APOBEC3A- and APOBEC3B-induced single base substitution mutations occur outside of predicted chromosomal DNA hairpin structures, whole genome sequence analyses and supporting biochemical studies also indicate that both enzymes are capable of deaminating the single-stranded loop regions of DNA hairpins at elevated rates. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both APOBEC3A and APOBEC3B. Author summary: A large source of mutation in cancer is attributable to single-stranded DNA cytosine to uracil (C-to-U) deamination by APOBEC3 family enzymes. Chromosomal DNA U's directly template the insertion of adenine (A), which results in C/G-to-T/A mutations. Chromosomal U's also trigger error-prone DNA repair processes, which less directly result in C/G-to-T/A mutations, C/G-to-G/C mutations, and more complex events such as insertion/deletion mutations. We report a human cell line for cancer mutation studies, where mutations can be identified selectively or by genomic DNA sequencing. Only APOBEC3A and APOBEC3B proved capable of inflicting the aforementioned types of single base substitution mutations. Interestingly, 70% and 50% of the single base substitution mutations attributable to APOBEC3A and APOBEC3B, respectively, occurred in TCA and TCT trinucleotide motifs preceded by a pyrimidine (T or C). This is significant because most APOBEC3-positive breast tumors exhibit an intermediate percentage of signature mutations in these broader tetranucleotide motifs, which supports the idea that both APOBEC3A and APOBEC3B contribute in a combinatorial manner to the overall mutation landscape in these tumors. [ABSTRACT FROM AUTHOR]

Purpose: Successful voice therapy requires the patient to learn new vocal behaviors, but little is currently known regarding how vocal motor skills are improved and retained. To quantitatively characterize the motor learning process in a clinically meaningful context, a virtual task was developed based on the Vocal Function Exercises. In the virtual task, subjects control a computational model of a ball floating on a column of airflow via modifications to mean airflow (L/s) and intensity (dB-C) to keep the ball within a target range representing a normative ratio (dB x s/L). Method: One vocally healthy female and one female with nonphonotraumatic vocal hyperfunction practiced the task for 11 days and completed retention testing 1 and 6 months later. The mapping between the two execution variables (airflow and intensity) and one error measure (proximity to the normative ratio) was evaluated by quantifying distributional variability (tolerance cost and noise cost) and temporal variability (scaling index of detrended fluctuation analysis). Results: Both subjects reduced their error over practice and retained their performance 6 months later. Tolerance cost and noise cost were positively correlated with decreases in error during early practice and late practice, respectively. After extended practice, temporal variability was modulated to align with the task's solution manifold. Conclusions: These case studies illustrated, in a healthy control and a patient with nonphonotraumatic vocal hyperfunction, that the virtual floating ball task produces quantitative measures characterizing the learning process. Future work will further investigate the task's potential to enhance clinical assessment and treatments involving voice control. [ABSTRACT FROM AUTHOR]

Successful voice training (e.g., singing lessons) and vocal rehabilitation (e.g., therapy for a voice disorder) involve learning complex, vocal behaviors. However, there are no metrics describing how humans learn new vocal skills or predicting how long the improved behavior will persist post-therapy. To develop measures capable of describing and predicting vocal motor learning, a theory-based paradigm from limb motor control inspired the development of a virtual task where subjects throw projectiles at a target via modifications in vocal pitch and loudness. Ten subjects with healthy voices practiced this complex vocal task for five days. The many-to-one mapping between the execution variables pitch and loudness and resulting target error was evaluated using an analysis that quantified distributional properties of variability: Tolerance, noise, covariation costs (TNC costs). Lag-1 autocorrelation (AC1) and detrended-fluctuation-analysis scaling index (SCI) analyzed temporal aspects of variability. Vocal data replicated limb-based findings: TNC costs were positively correlated with error; AC1 and SCI were modulated in relation to the task’s solution manifold. The data suggests that vocal and limb motor learning are similar in how the learner navigates the solution space. Future work calls for investigating the game’s potential to improve voice disorder diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer diagnosis is shifting towards a minimally invasive approach, maintaining accuracy and efficacy while reducing morbidity. We aimed to assess if PSMA–Ga68 PET/CT can accurately grade and localise prostatic malignancy using objective methods, compared with pathology and MRI. Methods: Retrospective analysis on 114 consecutive patients undergoing staging PSMA PET/CT scans over 12 months was carried out. The SUVmax and site of highest PSMA activity within the prostate gland were recorded. Pathology/biopsy review assessed maximum Gleason score (and location). MRI analysis assessed the highest PIRADS score and location. The grade, location and size of malignant tissue on biopsy, and PSA, were correlated with the SUVmax and the PIRADS score. Results: SUVmax was significantly elevated in cases with PSA ≥10 (P = 0.003) and Gleason score ≥8 (P = 0.0002). SUVmax demonstrated equivalent sensitivity to MRI‐PIRADS in predicting Gleason ≥8 disease, with higher specificity when tested under a high‐specificity regime (SUVmax ≥10, PIRADS = 5, P = 0.002). Furthermore, the region of highest SUVmax was superior to MRI‐PIRADS for localising the highest grade tumour region, correctly identifying 71% of highest grade regions compared to 54% with MRI (P = 0.015). Conclusion: PSMA PET/CT is as effective as MRI in identifying high‐grade prostate malignancy. Our findings also support previous studies in showing a significant relationship between SUVmax and Gleason grade. These benefits, along with the known advantage in identifying distant metastases and the reduced cost, further support the argument that PSMA PET/CT should be offered as an initial investigation in the workup of prostate cancer. [ABSTRACT FROM AUTHOR]

APOBEC3B (A3B)-catalyzed DNA cytosine deamination contributes to the overall mutational landscape in breast cancer. Molecular mechanisms responsible for A3B upregulation in cancer are poorly understood. Here we show that a single E2F cis-element mediates repression in normal cells and that expression is activated by its mutational disruption in a reporter construct or the endogenous A3B gene. The same E2F site is required for A3B induction by polyomavirus T antigen indicating a shared molecular mechanism. Proteomic and biochemical experiments demonstrate the binding of wildtype but not mutant E2F promoters by repressive PRC1.6/E2F6 and DREAM/E2F4 complexes. Knockdown and overexpression studies confirm the involvement of these repressive complexes in regulating A3B expression. Altogether, these studies demonstrate that A3B expression is suppressed in normal cells by repressive E2F complexes and that viral or mutational disruption of this regulatory network triggers overexpression in breast cancer and provides fuel for tumor evolution. [ABSTRACT FROM AUTHOR]

An integral part of the antiviral innate immune response is the APOBEC3 family of single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and -independent activities. Viruses have evolved mechanisms to counteract these enzymes, such as HIV-1 Vif-mediated formation of a ubiquitin ligase to degrade virus-restrictive APOBEC3 enzymes. A new example is Epstein-Barr virus (EBV) ribonucleotide reductase (RNR)-mediated inhibition of cellular APOBEC3B (A3B). The large subunit of the viral RNR, BORF2, causes A3B relocalization from the nucleus to cytoplasmic bodies and thereby protects viral DNA during lytic replication. Here, we use coimmunoprecipitation and immunofluorescence microscopy approaches to ask whether this mechanism is shared with the closely related gammaherpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV) and the more distantly related alphaherpesvirus herpes simplex virus 1 (HSV-1). The large RNR subunit of KSHV, open reading frame 61 (ORF61), coprecipitated multiple APOBEC3s, including A3B and APOBEC3A (A3A). KSHV ORF61 also caused relocalization of these two enzymes to perinuclear bodies (A3B) and to oblong cytoplasmic structures (A3A). The large RNR subunit of HSV-1, ICP6, also coprecipitated A3B and A3A and was sufficient to promote the relocalization of these enzymes from nuclear to cytoplasmic compartments. HSV-1 infection caused similar relocalization phenotypes that required ICP6. However, unlike the infectivity defects previously reported for BORF2-null EBV, ICP6 mutant HSV-1 showed normal growth rates and plaque phenotypes. Combined, these results indicate that both gamma- and alphaherpesviruses use a conserved RNR-dependent mechanism to relocalize A3B and A3A and furthermore suggest that HSV-1 possesses at least one additional mechanism to neutralize these antiviral enzymes. IMPORTANCE The APOBEC3 family of DNA cytosine deaminases constitutes a vital innate immune defense against a range of different viruses. A novel counterrestriction mechanism has recently been uncovered for the gammaherpesvirus EBV, in which a subunit of the viral protein known to produce DNA building blocks (ribonucleotide reductase) causes A3B to relocalize from the nucleus to the cytosol. Here, we extend these observations with A3B to include a closely related gammaherpesvirus, KSHV, and a more distantly related alphaherpesvirus, HSV-1. These different viral ribonucleotide reductases also caused relocalization of A3A, which is 92% identical to A3B. These studies are important because they suggest a conserved mechanism of APOBEC3 evasion by large double-stranded DNA herpesviruses. Strategies to block this host-pathogen interaction may be effective for treating infections caused by these herpesviruses. [ABSTRACT FROM AUTHOR]

Human cells express up to 9 active DNA cytosine deaminases with functions in adaptive and innate immunity. Many cancers manifest an APOBEC mutation signature and APOBEC3B (A3B) is likely the main enzyme responsible. Although significant numbers of APOBEC signature mutations accumulate in tumor genomes, the majority of APOBEC-catalyzed uracil lesions are probably counteracted in an error-free manner by the uracil base excision repair pathway. Here, we show that A3B-expressing cells can be selectively killed by inhibiting uracil DNA glycosylase 2 (UNG) and that this synthetic lethal phenotype requires functional mismatch repair (MMR) proteins and p53. UNG knockout human 293 and MCF10A cells elicit an A3B-dependent death. This synthetic lethal phenotype is dependent on A3B catalytic activity and reversible by UNG complementation. A3B expression in UNG-null cells causes a buildup of genomic uracil, and the ensuing lethality requires processing of uracil lesions (likely U/G mispairs) by MSH2 and MLH1 (likely noncanonical MMR). Cancer cells expressing high levels of endogenous A3B and functional p53 can also be killed by expressing an UNG inhibitor. Taken together, UNG-initiated base excision repair is a major mechanism counteracting genomic mutagenesis by A3B, and blocking UNG is a potential strategy for inducing the selective death of tumors. [ABSTRACT FROM AUTHOR]

Rotavirus C (RVC) causes enteric disease in multiple species, including humans, swine, bovines, and canines. To date, the evolutionary relationships of RVC populations circulating in different host species are poorly understood, owing to the low availability of genetic sequence data. To address this gap, we sequenced 45 RVC complete genomes from swine samples collected in the United States and Mexico. A phylogenetic analysis of each genome segment indicates that RVC populations have been evolving independently in human, swine, canine, and bovine hosts for at least the last century, with inter‐species transmission events occurring deep in the phylogenetic tree, and none in the last 100 years. Bovine and canine RVC populations clustered together nine of the 11 gene segments, indicating a shared common ancestor centuries ago. The evolutionary relationships of RVC in humans and swine were more complex, due to the extensive genetic diversity and multiple RVC clades identified in pigs, which were not structured geographically. Topological differences between trees inferred for different genome segments occurred frequently, including at nodes deep in the tree, indicating that RVC's evolutionary history includes multiple reassortment events that occurred a long time ago. Overall, we find that RVC is evolving within host‐defined lineages, but the evolutionary history of RVC is more complex than previously recognized due to the high genetic diversity of RVC in swine, with a common ancestor dating back centuries. Pigs may act as a reservoir host for RVC, and a source of the lineages identified in other species, including humans, but additional sequencing is needed to understand the full diversity of this understudied pathogen across multiple host species. [ABSTRACT FROM AUTHOR]

No known research has examined the concentration and flux of dissolved organic carbon (DOC) for stemflow across temporal scales from within single storm events to seasonal and annual scales or employed UV-Vis spectral metrics to examine the chemical character of dissolved organic matter (DOM) of stemflow drainage. Thus, our study examined stemflow DOC concentration and flux and DOM character from American beech ( Fagus grandifolia Ehrh.) and yellow poplar ( Liriodendron tulipifera L.) to address this data gap. Intrastorm stemflow DOC concentrations and fluxes diminished by an order of magnitude over time for American beech but remained relatively constant for yellow poplar. Stemflow DOM aromaticity, however, generally increased and E2: E3 ratios generally decreased as events progressed, suggesting transport of different compounds at different moments. Although less enriched in DOC than yellow poplar, American beech stemflow DOC fluxes were double per annum. Differential interspecific stemflow DOM characteristics are ascribed to ( i) significant differences in SUVA254 values (aromaticity) for the leafless season and annually and ( ii) significantly higher E2: E3 and SR ratios for yellow poplar stemflow than for American beech annually and across leafed and leafless seasons. Our results suggest that stemflow significantly affects the amount and chemical character of carbon flux to the forest floor that may engender hot spots around tree boles. [ABSTRACT FROM AUTHOR]