Formation of a Unique Cluster of G-Quadruplex Structures in the HIV-1 nef Coding Region: Implications for Antiviral Activity

G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis in vitro and in vivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment. © 2013 Perrone et al

Microbial carbon limitation : the need for integrating microorganisms into our understanding of ecosystem carbon cycling

Numerous studies have demonstrated that fertilization with nutrients such as nitrogen, phosphorus, and potassium increases plant productivity in both natural and managed ecosystems, demonstrating that primary productivity is nutrient limited in most terrestrial ecosystems. In contrast, it has been demonstrated that heterotrophic microbial communities in soil are primarily limited by organic carbon or energy. While this concept of contrasting limitations, that is, microbial carbon and plant nutrient limitation, is based on strong evidence that we review in this paper, it is often ignored in discussions of ecosystem response to global environment changes. The plant-centric perspective has equated plant nutrient limitations with those of whole ecosystems, thereby ignoring the important role of the heterotrophs responsible for soil decomposition in driving ecosystem carbon storage. To truly integrate carbon and nutrient cycles in ecosystem science, we must account for the fact that while plant productivity may be nutrient limited, the secondary productivity by heterotrophic communities is inherently carbon limited. Ecosystem carbon cycling integrates the independent physiological responses of its individual components, as well as tightly coupled exchanges between autotrophs and heterotrophs. To the extent that the interacting autotrophic and heterotrophic processes are controlled by organisms that are limited by nutrient versus carbon accessibility, respectively, we propose that ecosystems by definition cannot be 'limited' by nutrients or carbon alone. Here, we outline how models aimed at predicting non-steady state ecosystem responses over time can benefit from dissecting ecosystems into the organismal components and their inherent limitations to better represent plant-microbe interactions in coupled carbon and nutrient models

Hot-spot consensus of fluoroquinolone-mediated DNA cleavage by Gram-negative and Gram-positive type II DNA topoisomerases

Bacterial DNA gyrase and topoisomerase IV are selective targets of fluoroquinolones. Topoisomerase IV versus gyrase and Gram-positive versus Gram-negative behavior was studied based on the different recognition of DNA sequences by topoisomerase–quinolone complexes. A careful statistical analysis of preferred bases was performed on a large number (>400) of cleavage sites. We found discrete preferred sequences that were similar when using different enzymes (i.e. gyrase and topoisomerase IV) from the same bacterial source, but in part diverse when employing enzymes from different origins (i.e. Escherichia coli and Streptococcus pneumoniae). Subsequent analysis on the wild-type and mutated consensus sequences showed that: (i) Gn/Cn-rich sequences at and around the cleavage site are hot spots for quinolone-mediated strand breaks, especially for E. coli topoisomerases: we elucidated positions required for quinolone and enzyme recognition; (ii) for S. pneumoniae enzymes only, A and T at positions −2 and +6 are discriminating cleavage determinants; (iii) symmetry of the target sequence is a key trait to promote cleavage and (iv) the consensus sequence adopts a heteronomous A/B conformation, which may trigger DNA processing by the enzyme–drug complex

Negative erosion and negative emissions : Combining multiple land-based carbon dioxide removal techniques to rebuild fertile topsoils and enhance food production

Funding Information: This research was supported by the Research Foundation—Flanders (FWO) and by the European Commissions (H2020 FET-open project Super Bio-Accelerated Mineral weathering: A new climate risk hedging reactor technology—“BAM”). JS was supported by Spanish Government Project PID2020115770RB-I. Publisher Copyright: Copyright © 2022 Janssens, Roobroeck, Sardans, Obersteiner, Peñuelas, Richter, Smith, Verbruggen and Vicca.Peer reviewedPublisher PD

Coupled carbon and nitrogen losses in response to seven years of chronic warming in subarctic soils

Increasing temperatures may alter the stoichiometric demands of soil microbes and impair their capacity to stabilize carbon (C) and retain nitrogen (N), with critical consequences for the soil C and N storage at high latitude soils. Geothermally active areas in Iceland provided wide, continuous and stable gradients of soil temperatures to test this hypothesis. In order to characterize the stoichiometric demands of microbes from these subarctic soils, we incubated soils from ambient temperatures after the factorial addition of C, N and P substrates separately and in combination. In a second experiment, soils that had been exposed to different in situ warming intensities (+0, +0.5, +1.8, +3.4, +8.7, +15.9 °C above ambient) for seven years were incubated after the combined addition of C, N and P to evaluate the capacity of soil microbes to store and immobilize C and N at the different warming scenarios. The seven years of chronic soil warming triggered large and proportional soil C and N losses (4.1 ± 0.5% °C−1 of the stocks in unwarmed soils) from the upper 10 cm of soil, with a predominant depletion of the physically accessible organic substrates that were weakly sorbed in soil minerals up to 8.7 °C warming. Soil microbes met the increasing respiratory demands under conditions of low C accessibility at the expenses of a reduction of the standing biomass in warmer soils. This together with the strict microbial C:N stoichiometric demands also constrained their capacity of N retention, and increased the vulnerability of soil to N losses. Our findings suggest a strong control of microbial physiology and C:N stoichiometric needs on the retention of soil N and on the resilience of soil C stocks from high-latitudes to warming, particularly during periods of vegetation dormancy and low C inputs

Responses of soil hexapod communities to warming are mediated by microbial carbon and nitrogen in a subarctic grassland

Altres ajuts: acords transformatius de la UABWarming in subarctic ecosystems will be two-fold higher compared to lower latitudes under current climate change projections. While the effects of warming in northern ecosystems on plants and microorganisms have been extensively studied, the responses of soil fauna have received much less attention, despite their important role in regulating key soil processes. We analyzed the response of soil hexapod communities in a subarctic grassland exposed to a natural geothermal gradient in Iceland with increases of +3 and + 6 °C above ambient temperature. We characterized hexapod communities using environmental DNA (eDNA) metabarcoding. We analyzed the amounts of microbial carbon (Cmic), microbial N (Nmic), dissolved organic C (DOC) and dissolved organic N (DON) and then assessed whether these variables could help to account for the compositional dissimilarity of ground hexapod communities across temperatures. The increases in soil temperature did lead to changes in the composition of hexapod communities. The compositional differences caused by +6 °C plots were correlated with a decrease in Cmic and Nmic, soil DOC and DON. Our results highlight the response of soil hexapods to warming, and their interaction with microbial biomass ultimately correlated with changes in the availabilities of soil C and N

The Grizzly, March 7, 1986

Meyer to Undergo Surgery • Teachers Always Looking to the Future: NASA Finalists Speak to Some U.C. Students • Garbage: It\u27s Expensive Stuff • Letters: CAB Responds to Only at Ursinus Comments; Student Offended by Walkman Listener at Haydn Concert • Bomberger Concerts Deserve Crowd, Too • Tie for First in Air Band • How to get that \u27A\u27 • It\u27s All in Good Fun Guys • What are You Doing Next Week? • Nuclear War as a Just War • Women\u27s Studies Offered in Fall • Mer Chicks a Success at MAC\u27s • U.C. Boys Bearing Down • Women\u27s Lacrosse Preview • Coach Brown Named Ass\u27t Athletic Director • Townshend Strikes Gold With White City LP • Tolkien Collection On Display in Myrin • Faculty Views of Pledginghttps://digitalcommons.ursinus.edu/grizzlynews/1160/thumbnail.jp

The prevalence of probable depression and probable anxiety, and associations with adverse childhood experiences and socio-demographics: a national survey in South Africa

Objective and methods: Mental health problems among adults are a growing public health concern, and middle-income countries such as South Africa are disproportionally affected. Using a large scale nationally representative weighted survey, we assessed the prevalence of probable depression, probable anxiety, and adverse childhood experiences (ACEs), and explored associations between probable depression, probable anxiety, ACEs, socio-economic status, and demographic characteristics. Results: Nationally, 25.7, 17.8, and 23.6% of respondents, respectively, reported scores of ≥10 on the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), indicating probable depression or probable anxiety, and an ACE score of ≥4 (high exposure). Overall probable depression prevalence across South Africa varied from 14.7 to 38.8%. Both probable depression and probable anxiety were more frequently reported among adults who were: retired and older (>65 years of age), and widowed, divorced, or separated; living in metropolitan areas; and only had primary school education. In a multivariable adjusted logistic regression, the likelihood of reporting probable depression or probable anxiety was also found to increase with each standard deviation increase in the ACE score (p < 0.001), independent of other socio-demographic determinants. Conclusion: The prevalence of probable depression among respondents in South Africa varies significantly across the nine provinces. Furthermore, higher ACE score and several socio-demographic determinants were associated with a higher likelihood of probable depression and probable anxiety. Adult mental health services are urgently needed to identify groups of the population vulnerable to mental health problems for better targeting of interventions. Given the range of probable depression prevalence across the country, provincial level plans and resources should also reflect the burden of mental health problems in that province

Motivations and Barriers for the Use of Face Coverings during the COVID-19 Pandemic: Messaging Insights from Focus Groups

Widespread use of face coverings is a key public health strategy to prevent the spread of COVID-19. However, few studies have examined why Americans use or do not use face coverings, and little is known about the most effective messaging strategies. This study explored perceptions of face coverings, including motivations and barriers for use, and examined reactions to messaging promoting the use of face coverings. Six virtual focus groups were conducted with 34 North Carolina residents in July 2020. Participants reported high compliance with face covering recommendations but often did not wear them around family, friends, and colleagues. The most prevalent motivation for the use of face coverings was to protect or respect other people, including high-risk populations and individuals. Other motivators were self-protection, responsibility, desire for control, requirements, and expert advice. Barriers included physical and social discomfort, confusion or misinformation, low perceived susceptibility to COVID-19, and perceptions of identity and autonomy. Even among individuals who frequently wear face coverings, there are opportunities to improve compliance. Messaging should highlight how face coverings protect the wearer and others around them, normalize the use of face coverings in social settings, and emphasize requirements. Positive messages that focus on unity, personal experiences and the rationale for face coverings are recommended

The Lantern Vol. 51, No. 1, Fall 1984

• Sky Eyes • Flowerwait • Haiku • Sunwatch • Epitaph of A Tale • How Do You Tell A Child • Vineyard Wind • By The Sea • The Wanderer • In Back of the Real Supermarket in Collegeville • Mitosis • Smoke Dreams • On Humankind Today - A Message • Dragon • The Lull • Finale • The Sun • Three Steps in Life • Seaside • To Mark • To Father • Yesterday - Today • The Stars • The Journey • Our Shared Experience, Miles Away • Coming Home • Blossom • Life is the Teacher • Midnight Stroll in February • Eyes (Karen\u27s Poem) • Your Love • Same Welcome as Odysseus • Europa • Sinn Fein • Idle Dreams • I Can Take A Hint • In Retrospect • Rest • China and Porcelain are One in the Same • Momenthttps://digitalcommons.ursinus.edu/lantern/1125/thumbnail.jp