Helicobacter Pylori Hydrogenase Accessory Protein HypA and Urease Accessory Protein UreG Compete with Each Other for UreE Recognition

Background: The gastric pathogen Helicobacter pylori relies on nickel-containing urease and hydrogenase enzymes in order to colonize the host. Incorporation of Ni2+ into urease is essential for the function of the enzyme and requires the action of several accessory proteins, including the hydrogenase accessory proteins HypA and HypB and the urease accessory proteins UreE, UreF, UreG and UreH. Methods: Optical biosensing methods (biolayer interferometry and plasmon surface resonance) were used to screen for interactions between HypA, HypB, UreE and UreG. Results: Using both methods, affinity constants were found to be 5nM and 13nM for HypA–UreE and 8μM and 14μM for UreG-UreE. Neither Zn2+ nor Ni2+ had an effect on the kinetics or stability of the HypA–UreE complex. By contrast, addition of Zn2+, but not Ni2+, altered the kinetics and greatly increased the stability of the UreE–UreG complex, likely due in part to Zn2+-mediated oligomerization of UreE. Finally our results unambiguously show that HypA, UreE and UreG cannot form a heterotrimeric protein complex in vitro; instead, HypA and UreG compete with each other for UreE recognition. General significance: Factors influencing the pathogen\u27\u27s nickel budget are important to understand pathogenesis and for future drug design

The Synthesis and Evaluation of Flavone and Isoflavone Chimeras of Novobiocin and Derrubone

The natural products novobiocin and derrubone have both demonstrated Hsp90 inhibition and structure–activity relationships have been established for each scaffold. Given these compounds share several key structural features, we hypothesized that incorporation of elements from each could provide insight to structural features important for Hsp90 inhibition. Thus, chimeric analogues of novobiocin and derrubone were constructed and evaluated. These studies confirmed that the functionality present at the 3-position of the isoflavone plays a critical role in determining Hsp90 inhibition and suggests that the bicyclic ring system present in both novobiocin and derrubone do not share similar modes of binding

Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy:a narrative review

Introduction: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in patients with ischemic stroke, but the impact of EVT on clinical outcomes in patients with ischemic stroke with and without atrial fibrillation (AF), and the effect of adjunctive pharmacological therapies with EVT, remains unclear. Areas covered: The goal of this narrative review is to provide an overview of studies which have examined: 1) associations between EVT and outcomes for patients following ischemic stroke, 2) associations between EVT and outcomes for patients following ischemic stroke with and without AF, including function, reperfusion, hemorrhage, and mortality, 3) the effect of adjunctive pharmacological therapies peri- and post-thrombectomy, and 4) integration of prehospital care on endovascular treatment outcomes. Expert opinion: There is little evidence from randomized controlled trials on the effect of AF on stroke outcomes following EVT and the safety and efficacy of AF treatment in the peri-EVT such as tirofiban or Intravenous thrombolysis with Non-vitamin K Antagonist Oral Anticoagulant. The available evidence from observational studies on AF and EVT outcomes is inconsistent, but factors such as procedural EVT devices, the center volume, clinician experience, stroke recognition, and inclusion criteria of studies have all been associated with poorer clinical outcomes. Enhancing the clinical network among prehospital and hospitals will facilitate direct transfer to EVT centers, reducing stroke onset to EVT time and optimizing stroke outcomes.</p

Patterns of Sexual Arousal in Young, Heterosexual Men Who Experience Condom-Associated Erection Problems (CAEP)

Introduction Condom-associated erection problems (CAEP) are reported by a substantial number of young men and are associated with inconsistent and/or incomplete condom use. The underlying mechanisms of CAEP are not well understood and research examining the possibility that men who report CAEP differ from other men in their sexual responsivity is lacking. Aim This study used psychophysiological methods to examine whether men who report CAEP have a higher threshold for sexual arousal, a stronger need for tactile stimulation, and/or more easily lose their sexual arousal due to neutral distractors or performance-related demands. Methods A total of 142 young, heterosexual men (53% reporting CAEP) were presented with four 3-minute erotic film clips. Three film clips were combined with one of the following manipulations: 1) distraction, 2) performance demand, or 3) vibrotactile stimulation. One erotic film clip was presented with no further instructions or manipulations. Main Outcome Measures Average penile circumference changes during the first, second, and third minute (Time) of the erotic film stimuli (Condition) were submitted to a mixed-model ANOVA with Condition and Time as within-subjects factors and Group (CAEP/No-CAEP) as between-subjects factor. Results Significant main effects of Condition and Time and a significant interaction of Group×Time were found. No significant interactions involving Condition were found. Men who reported CAEP had smaller erectile responses during the first minute, regardless of film condition, than men who reported no CAEP (F(1,141)=8.64, p<.005). Conclusion The findings suggest that men with and without CAEP differ in the ease with which they become sexually aroused. Men reporting CAEP needed more time and/or more intense stimulation to become aroused. To our knowledge, this study is the first to use psychophysiological methods to assess sexual responsivity in men who report CAEP

An Integrated Framework to Assess Greenwashing

In this paper we examine definitions of ‘greenwashing’ and its different forms, developing a tool for assessing diverse ‘green’ claims made by various actors. Research shows that significant deception and misleading claims exist both in the regulated commercial sphere, as well as in the unregulated non-commercial sphere (e.g., governments, NGO partnerships, international pledges, etc.). Recently, serious concerns have been raised over rampant greenwashing, in particular with regard to rapidly emerging net zero commitments. The proposed framework we developed is the first actionable tool for analysing the quality and truthfulness of such claims. The framework has widespread and unique potential for highlighting efforts that seek to delay or distract real solutions that are urgently needed today to tackle multiple climate and environmental crises. In addition, we note how the framework may also assist in the development of practices and communication strategies that ultimately avoid greenwashing

An Integrated Framework to Assess Greenwashing

Funding: This research was funded by the Department of Political Science at University of Vienna, Austria and the Institute at Brown for Environment and Society, USA, in association with Climate Social Science Network.Peer reviewedPublisher PD

World Atlas of Desertification - Introductory Brochure

The brochure introduces the concept of the World Atlas of Desertification which relies on converging evidence of combined human-environment processes pointing out that land degradation cannot be modeled satisfactorily at global scales.The introductory brochure provides a short overview of the main land degradation issues, through illustration of a number key global datasets and some case study examples that reflect the global patterns and pathways to solutions. The brochure start with highlighting the human dominance that drives global environmental changes. The consequences of feeding a growing population include agriculture expansion and intensification, illustrated by maps and data on irrigation and nutrient use. Aridity and drought are important phenomena aggravating the already present human pressures on the environment. Other pressure patterns playing at global scale are illustrated with examples from China, India, S. America and the Sahel, along with a forward view on solutions.JRC.H.5-Land Resources Managemen