Escherichia Coli RecG Functionally Suppresses Human Bloom Syndrome Phenotypes

Defects in the human BLM gene cause Bloom syndrome, notable for early development of tumors in a broad variety of tissues. On the basis of sequence similarity, BLM has been identified as one of the five human homologs of RecQ from Escherichia coli. Nevertheless, biochemical characterization of the BLM protein indicates far greater functional similarity to the E. coli RecG protein and there is no known RecG homolog in human cells. To explore the possibility that the shared biochemistries of BLM and RecG may represent an example of convergent evolution of cellular function where in humans BLM has evolved to fulfill the genomic stabilization role of RecG, we determined whether expression of RecG in human BLM-deficient cells could suppress established functional cellular Bloom syndrome phenotypes. We found that RecG can indeed largely suppress both the definitive elevated sister chromatid exchange phenotype and the more recently demonstrated gene cluster instability phenotype of BLM-deficient cells. In contrast, expression of RecG has no impact on either of these phenotypes in human cells with functional BLM protein. These results suggest that the combination of biochemical activities shared by RecG and BLM fill the same evolutionary niche in preserving genomic integrity without requiring exactly identical molecular mechanisms

The pUL37 tegument protein guides alphaherpesvirus retrograde axonal transport to promote neuroinvasion

A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector. Mutation of this region rendered herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV) incapable of spreading by retrograde axonal transport to peripheral ganglia both in culture and animals. By monitoring the axonal transport of individual viral particles by time-lapse fluorescence microscopy, the mutant viruses were determined to lack the characteristic sustained intracellular capsid motion along microtubules that normally traffics capsids to the neural soma. Consistent with the axonal transport deficit, the mutant viruses did not reach sites of latency in peripheral ganglia, and were avirulent. Despite this, viral propagation in peripheral tissues and in cultured epithelial cell lines remained robust. Selective elimination of retrograde delivery to the nervous system has long been sought after as a means to develop vaccines against these ubiquitous, and sometimes devastating viruses. In support of this potential, we find that HSV-1 and PRV mutated in the effector region of pUL37 evoked effective vaccination against subsequent nervous system challenges and encephalitic disease. These findings demonstrate that retrograde axonal transport of the herpesviruses occurs by a virus-directed mechanism that operates by coordinating opposing microtubule motors to favor sustained retrograde delivery of the virus to the peripheral ganglia. The ability to selectively eliminate the retrograde axonal transport mechanism from these viruses will be useful in trans-synaptic mapping studies of the mammalian nervous system, and affords a new vaccination paradigm for human and veterinary neurotropic herpesviruses

Four modalities of periodontal treatment compared over five years

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65517/1/j.1600-0765.1987.tb01573.x.pd

Qualitative and quantitative evidence of motivation states for physical activity, exercise and being sedentary from university student focus groups

Motivation for physical activity and sedentary behaviors (e.g., desires, urges, wants, cravings) varies from moment to moment. According to the WANT model, these motivation states may be affectively-charged (e.g., felt as tension), particularly after periods of maximal exercise or extended rest. The purpose of this study was to examine postulates of the WANT model utilizing a mixed-methods approach. We hypothesized that: (1) qualitative evidence would emerge from interviews to support this model, and (2) motivation states would quantitatively change over the course of an interview period. Seventeen undergraduate students (mean age = 18.6y, 13 women) engaged in focus groups where 12 structured questions were presented. Participants completed the “right now” version of the CRAVE scale before and after interviews. Qualitative data were analyzed with content analysis. A total of 410 unique lower-order themes were classified and grouped into 43 higher order themes (HOTs). From HOTs, six super higher order themes (SHOTs) were designated: (1) wants and aversions, (2) change and stability, (3) autonomy and automaticity, (4) objectives and impulses, (5) restraining and propelling forces, and (6) stress and boredom. Participants stated that they experienced desires to move and rest, including during the interview, but these states changed rapidly and varied both randomly as well as systematically across periods of minutes to months. Some also described a total absence of desire or even aversion to move and rest. Of note, strong urges and cravings for movement, typically from conditions of deprivation (e.g., sudden withdrawal from exercise training) were associated with physical and mental manifestations, such as fidgeting and feeling restless. Urges were often consummated with behavior (e.g., exercise sessions, naps), which commonly resulted in satiation and subsequent drop in desire. Importantly, stress was frequently described as both an inhibitor and instigator of motivation states. CRAVE-Move increased pre-to-post interviews (p < .01). CRAVE-Rest demonstrated a trend to decline (p = .057). Overall, qualitative and quantitative data largely corroborated postulates of the WANT model, demonstrating that people experience wants and cravings to move and rest, and that these states appear to fluctuate significantly, especially in the context of stress, boredom, satiety, and deprivation

Evaluating Knowledge to Support Climate Action: A Framework for Sustained Assessment. Report of an Independent Advisory Committee on Applied Climate Assessment

As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal "climate assessment consortium" to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit-cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.New York State Energy Research and Development Authority [123416]; Columbia University's Earth Institute; American Meteorological Society; Kresge Foundation6 month embargo; published online: 21 May 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Are local climate adaptation policies credible? A conceptual and operational assessment framework

After the Paris Agreement that put stronger emphasis on the development of climate change adaptation policies and on the definition of financing mechanisms, there is a patent need to track whether actual planning efforts are proving sufficient. This entails the development of assessment methods and metrics as plans are drafted and actions implemented. To this end, this paper explores the concept of credibility as a critical issue in climate policy and develops an Adaptation Policy Credibility (APC) conceptual and operational assessment framework for helping to allocate public funding and private investments, and for implementing and catalysing climate policy. Through a pilot testing in four early-adopting cities (Copenhagen, Durban, Quito and Vancouver), a clear potential for large-n tracking and assessment exercises of local climate adaptation plans is envisaged. The APC approach might also be useful to guide individual cities that aim to improve their adaptation planning and policy-making processes

Urges to Move and Other Motivation States for Physical Activity in Clinical and Healthy Populations: A Scoping Review Protocol

[EN] Motivation for bodily movement, physical activity and exercise varies from moment to moment. These motivation states may be “affectively-charged,” ranging from instances of lower tension (e.g., desires, wants) to higher tension (e.g., cravings and urges). Currently, it is not known how often these states have been investigated in clinical populations (e.g., eating disorders, exercise dependence/addiction, Restless Legs Syndrome, diabetes, obesity) vs. healthy populations (e.g., in studies of motor control; groove in music psychology). The objective of this scoping review protocol is to quantify the literature on motivation states, to determine what topical areas are represented in investigations of clinical and healthy populations, and to discover pertinent details, such as instrumentation, terminology, theories, and conceptual models, correlates and mechanisms of action. Iterative searches of scholarly databases will take place to determine which combination of search terms (e.g., “motivation states” and “physical activity”; “desire to be physically active,” etc.) captures the greatest number of relevant results. Studies will be included if motivation states for movement (e.g., desires, urges) are specifically measured or addressed. Studies will be excluded if referring to motivation as a trait. A charting data form was developed to scan all relevant documents for later data extraction. The primary outcome is simply the extent of the literature on the topic. Results will be stratified by population/condition. This scoping review will unify a diverse literature, which may result in the creation of unique models or paradigms that can be utilized to better understand motivation for bodily movement and exercise.GA was supported by a fellowship from the Office of Academic Affiliations at the United States Veterans Health Administration, a Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award, Bank of America, N.A., Trustee, and American Heart Association Grant #852679 (GA, 2021–2024).We would like to thank Melissa Eden, Ph.D. (Hanover College, IN) for her valuable assistance in refining aspects of the search strategy. Khristdman Cavalcanti helped with technical aspects of the study. Sunao Akashi Slayton, PharmD BCOP (Smilow Cancer Hospital, Yale – New Haven Hospital, CT) evaluated clinical information and provided nomenclatur

Conservative Fragments in Bacterial 16S rRNA Genes and Primer Design for 16S Ribosomal DNA Amplicons in Metagenomic Studies

Bacterial 16S ribosomal DNA (rDNA) amplicons have been widely used in the classification of uncultured bacteria inhabiting environmental niches. Primers targeting conservative regions of the rDNAs are used to generate amplicons of variant regions that are informative in taxonomic assignment. One problem is that the percentage coverage and application scope of the primers used in previous studies are largely unknown. In this study, conservative fragments of available rDNA sequences were first mined and then used to search for candidate primers within the fragments by measuring the coverage rate defined as the percentage of bacterial sequences containing the target. Thirty predicted primers with a high coverage rate (>90%) were identified, which were basically located in the same conservative regions as known primers in previous reports, whereas 30% of the known primers were associated with a coverage rate of <90%. The application scope of the primers was also examined by calculating the percentages of failed detections in bacterial phyla. Primers A519–539, E969–983, E1063–1081, U515 and E517, are highly recommended because of their high coverage in almost all phyla. As expected, the three predominant phyla, Firmicutes, Gemmatimonadetes and Proteobacteria, are best covered by the predicted primers. The primers recommended in this report shall facilitate a comprehensive and reliable survey of bacterial diversity in metagenomic studies

The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis

Background:To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role in cancer.Methods:Four snoRNAs, commonly used for normalisation, RNU44, RNU48, RNU43 and RNU6B, and miRNA known to be associated with pathological factors, were measured by real-time polymerase chain reaction in two patient series: 219 breast cancer and 46 head and neck squamous cell carcinoma (HNSCC). SnoRNA and miRNA were then correlated with clinicopathological features and prognosis.Results:Small-nucleolar RNA expression was as variable as miRNA expression (miR-21, miR-210, miR-10b). Normalising miRNA PCR expression data to these recommended snoRNAs introduced bias in associations between miRNA and pathology or outcome. Low snoRNA expression correlated with markers of aggressive pathology. Low levels of RNU44 were associated with a poor prognosis. RNU44 is an intronic gene in a cluster of highly conserved snoRNAs in the growth arrest specific 5 (GAS5) transcript, which is normally upregulated to arrest cell growth under stress. Low-tumour GAS5 expression was associated with a poor prognosis. RNU48 and RNU43 were also identified as intronic snoRNAs within genes that are dysregulated in cancer.Conclusion:Small-nucleolar RNAs are important in cancer prognosis, and their use as reference genes can introduce bias when determining miRNA expression. © 2011 Cancer Research UK All rights reserved