Different essential viral proteins are translated via programmed stop codon readthrough. Pea enation mosaic virus 1 (PEMV1) and potato leafroll virus (PLRV) are related positive-sense RNA plant ...viruses in the family Solemoviridae, and are type members of the Enamovirus and Polerovirus genera, respectively. Both use translational readthrough to express a C-terminally extended minor capsid protein (CP), termed CP-readthrough domain (CP-RTD), from a viral subgenomic mRNA that is transcribed during infections. Limited incorporation of CP-RTD subunits into virus particles is essential for aphid transmission, however the functional readthrough structures that mediate CP-RTD translation have not yet been defined. Through RNA solution structure probing, RNA secondary structure modeling, site-directed mutagenesis, and functional in vitro and in vivo analyses, we have investigated in detail the readthrough elements and complex structure involved in expression of CP-RTD in PEMV1, and assessed and deduced a comparatively simpler readthrough structure for PLRV. Collectively, this study has (i) generated the first higher-order RNA structural models for readthrough elements in an enamovirus and a polerovirus, (ii) revealed a stark contrast in the complexity of readthrough structures in these two related viruses, (iii) provided compelling experimental evidence for the strict requirement for long-distance RNA-RNA interactions in generating the active readthrough signals, (iv) uncovered what could be considered the most complex readthrough structure reported to date, that for PEMV1, and (v) proposed plausible assembly pathways for the formation of the elaborate PEMV1 and simple PLRV readthrough structures. These findings notably advance our understanding of this essential mode of gene expression in these agriculturally important plant viruses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A groundbreaking look at how group expectations unify Black Americans in their support of the Democratic party Black Americans are by far the most unified racial group in American electoral politics, ...with 80 to 90 percent identifying as Democrats—a surprising figure given that nearly a third now also identify as ideologically conservative, up from less than 10 percent in the 1970s. Why has ideological change failed to push more Black Americans into the Republican Party? Steadfast Democrats answers this question with a pathbreaking new theory that foregrounds the specificity of the Black American experience and illuminates social pressure as the key element of Black Americans' unwavering support for the Democratic Party.Ismail White and Chryl Laird argue that the roots of Black political unity were established through the adversities of slavery and segregation, when Black Americans forged uniquely strong social bonds for survival and resistance. White and Laird explain how these tight communities have continued to produce and enforce political norms—including Democratic Party identification in the post–Civil Rights era. The social experience of race for Black Americans is thus fundamental to their political choices. Black voters are uniquely influenced by the social expectations of other Black Americans to prioritize the group's ongoing struggle for freedom and equality. When navigating the choice of supporting a political party, this social expectation translates into affiliation with the Democratic Party. Through fresh analysis of survey data and original experiments, White and Laird explore where and how Black political norms are enforced, what this means for the future of Black politics, and how this framework can be used to understand the electoral behavior of other communities.An innovative explanation for why Black Americans continue in political lockstep, Steadfast Democrats sheds light on the motivations consolidating an influential portion of the American electoral population.
Abstract
Many eukaryotic RNA viruses transcribe subgenomic (sg) mRNAs during infections to control expression of a subset of viral genes. Such transcriptional events are commonly regulated by local ...or long-range intragenomic interactions that form higher-order RNA structures within these viral genomes. In contrast, here we report that an umbravirus activates sg mRNA transcription via base pair-mediated dimerization of its plus-strand RNA genome. Compelling in vivo and in vitro evidence demonstrate that this viral genome dimerizes via a kissing-loop interaction involving an RNA stem-loop structure located just upstream from its transcriptional initiation site. Both specific and non-specific features of the palindromic kissing-loop complex were found to contribute to transcriptional activation. Structural and mechanistic aspects of the process in umbraviruses are discussed and compared with genome dimerization events in other RNA viruses. Notably, probable dimer-promoting RNA stem-loop structures were also identified in a diverse group of umbra-like viruses, suggesting broader utilization of this unconventional transcriptional strategy.
Graphical Abstract
Graphical Abstract
Plus-strand RNA viruses can accumulate viral RNA degradation products during infections. Some of these decay intermediates are generated by the cytosolic 5'-to-3' exoribonuclease Xrn1 (mammals and ...yeast) or Xrn4 (plants) and are formed when the enzyme stalls on substrate RNAs upon encountering inhibitory RNA structures. Many Xrn-generated RNAs correspond to 3'-terminal segments within the 3'-UTR of viral genomes and perform important functions during infections. Here we have investigated a 3'-terminal small viral RNA (svRNA) generated by Xrn during infections with Tobacco necrosis virus-D (family Tombusviridae). Our results indicate that (i) unlike known stalling RNA structures that are compact and modular, the TNV-D structure encompasses the entire 212 nt of the svRNA and is not functionally transposable, (ii) at least two tertiary interactions within the RNA structure are required for effective Xrn blocking and (iii) most of the svRNA generated in infections is derived from viral polymerase-generated subgenomic mRNA1. In vitro and in vivo analyses allowed for inferences on roles for the svRNA. Our findings provide a new and distinct addition to the growing list of Xrn-resistant viral RNAs and stalling structures found associated with different plant and animal RNA viruses.
Skeletal abnormalities are an early and prominent feature of most mucopolysaccharide (MPS) disorders, with the degree of skeletal involvement varying between and within MPS subtypes. Most patients ...exhibit a constellation of radiographic abnormalities known as dysostosis multiplex, consisting of abnormally shaped vertebrae and ribs, enlarged skull, spatulate ribs, hypoplastic epiphyses, thickened diaphyses and bullet-shaped metacarpals. Thoracolumbar kyphosis or the gibbus deformity is often a key diagnostic clue. Also common are hip dysplasia, genu valgum and, later in the course of the disease, spinal cord compression, which can be life-threatening. Short stature is ubiquitous. Treatment of skeletal manifestations usually involves surgical intervention. All patients with MPS should be considered at high risk for surgical intervention requiring anaesthesia because of airway and cardiac disease manifestations. Regular imaging of the cervical, thoracic and lumbar spine, the hips and the lower extremities is recommended for patients with MPS.
Objective
To characterise the bladder microbiota of continent adult women.
Design
Cross‐sectional study of adult women who contributed catheterised urine samples, completed validated symptom ...questionnaires, and provided demographic data.
Setting
US academic medical centre.
Population
Well‐characterised continent adult women.
Methods
Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing.
Main outcome measures
Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen).
Results
The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively.
Conclusions
For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged.
Tweetable
In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice.
Tweetable
In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice.
Proteins display the capacity for adaptation to new functions, a property critical for evolvability. But what structural principles underlie the capacity for adaptation? Here, we show that adaptation ...to a physiologically distinct class of ligand specificity in a PSD95, DLG1, ZO-1 (PDZ) domain preferentially occurs through class-bridging intermediate mutations located distant from the ligand-binding site. These mutations provide a functional link between ligand classes and demonstrate the principle of “conditional neutrality” in mediating evolutionary adaptation. Structures show that class-bridging mutations work allosterically to open up conformational plasticity at the active site, permitting novel functions while retaining existing function. More generally, the class-bridging phenotype arises from mutations in an evolutionarily conserved network of coevolving amino acids in the PDZ family (the sector) that connects the active site to distant surface sites. These findings introduce the concept that allostery in proteins could have its origins not in protein function but in the capacity to adapt.
Display omitted
•Adaptation in a PDZ domain involves intermediate mutations that bridge ligand classes•A simple model shows that class-bridging mutations are evolutionarily preferred•Class-bridging mutations act allosterically•The origin of allostery in proteins could be in the capacity to adapt
Mutations that are neutral but that potentiate functional protein adaptation by a subsequent mutation result in enhanced conformational plasticity at the distal “business end” of the protein. The data suggest a model in which the origin of allostery lies in the capacity for adaptation.
Ketamine: a ‘One Health’ issue for us all White, K.
British journal of anaesthesia : BJA,
August 2016, 20160800, 2016-08-00, 20160801, Letnik:
117, Številka:
2
Journal Article
COVID-19 pandemic is a global calamity posing an unprecedented opportunity to study resilience. We developed a brief resilience survey probing self-reliance, emotion-regulation, ...interpersonal-relationship patterns and neighborhood-environment, and applied it online during the acute COVID-19 outbreak (April 6-15, 2020), on a crowdsourcing research website ( www.covid19resilience.org ) advertised through social media. We evaluated level of stress (worries) regarding COVID-19: (1) contracting, (2) dying from, (3) currently having, (4) family member contracting, (5) unknowingly infecting others with (6) experiencing significant financial burden following. Anxiety (GAD7) and depression (PHQ2) were measured. Totally, 3042 participants (n = 1964 females, age range 18-79, mean age = 39) completed the resilience and COVID-19-related stress survey and 1350 of them (mean age = 41, SD = 13; n = 997 females) completed GAD7 and PHQ2. Participants significantly endorsed more distress about family contracting COVID-19 (48.5%) and unknowingly infecting others (36%), than getting COVID-19 themselves (19.9%), p < 0.0005 covarying for demographics and proxy COVID-19 exposures like getting tested and knowing infected individuals. Patterns of COVID-19 related worries, rates of anxiety (GAD7 > 10, 22.2%) and depression (PHQ2 > 2, 16.1%) did not differ between healthcare providers and non-healthcare providers. Higher resilience scores were associated with lower COVID-19 related worries (main effect F
= 134.9; p < 0.00001, covarying for confounders). Increase in 1 SD on resilience score was associated with reduced rate of anxiety (65%) and depression (69%), across healthcare and non-healthcare professionals. Findings provide empirical evidence on mental health associated with COVID-19 outbreak in a large convenience sample, setting a stage for longitudinal studies evaluating mental health trajectories following COVID-19 pandemic.
In light of many recent critiques of Western modernity and its conceptual foundations, the problem of adequately justifying our most basic moral and political values looms large. Without recourse to ...traditional ontological or metaphysical foundations, how can one affirm--or sustain--a commitment to fundamentals? The answer, according to Stephen White, lies in a turn to "weak" ontology, an approach that allows for ultimate commitments but at the same time acknowledges their historical, contestable character. This turn, White suggests, is already underway. His book traces its emergence in a variety of quarters in political thought today and offers a clear and compelling account of what this might mean for our late modern self-understanding.As he elaborates the idea of weak ontology and the broad criteria behind it, White shows how these are already at work in the thought of contemporary writers of seemingly very different perspectives: George Kateb, Judith Butler, Charles Taylor, and William Connolly. Among these thinkers, often thought to be at odds, he exposes the commonalities that emerge around the idea of weak ontology. In its identification of a critical turn in political theory, and its nuanced explanation of that turn, his book both demonstrates and underscores the strengths of weak ontology.
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