Influenza virus (IV) causes several outbreaks of the flu each year resulting in an economic burden to the healthcare system in the billions of dollars. Several influenza pandemics have occurred ...during the last century and estimated to have caused 100 million deaths. There are four genera of IV, A (IVA), B (IVB), C (IVC), and D (IVD), with IVA being the most virulent to the human population. Hemagglutinin (HA) is an IVA surface protein that allows the virus to attach to host cell receptors and enter the cell. Here we have characterised the high-resolution structures of seven IVA HAs, with one in complex with the anti-influenza head-binding antibody C05. Our analysis revealed conserved receptor binding residues in all structures, as seen in previously characterised IV HAs. Amino acid conservation is more prevalent on the stalk than the receptor binding domain (RBD; also called the head domain), allowing the virus to escape from antibodies targeting the RBD. The equivalent site of C05 antibody binding to A/Denver/57 HA appears hypervariable in the other H1N1 IV HAs. Modifications within this region appear to disrupt binding of the C05 antibody, as these HAs no longer bind the C05 antibody by analytical SEC. Our study brings new insights into the structural and functional recognition of IV HA proteins and can contribute to further development of anti-influenza vaccines.
Summary
Understanding the anatomical basis of plant water transport in forest ecosystems is crucial for contextualizing community‐level adaptations to drought, especially in life‐form‐rich tropical ...forests. To provide this context, we explored wood functional anatomy traits related to plant hydraulic architecture across different plant functional groups in a lowland tropical rain forest.
We measured wood traits in 90 species from six functional groups (mature‐phase, understorey and pioneer trees; understorey and pioneer shrubs; vines) and related these traits to intrinsic water‐use efficiency (WUEi) as a measure of physiological performance. We also examined vessel size distribution patterns across groups to determine trade‐offs in theoretical hydraulic safety vs. efficiency.
Some plant functional groups exhibited significant differences in vessel parameters and WUEi. Vessel diameters in vines and pioneer trees were two‐ to threefold greater on average than in understorey trees and shrubs. Contrastingly, vessels in understorey trees and shrubs fell within the smaller size classes, suggesting greater safety mechanisms. In addition to these trends, large vessel dimensions were important predictors of WUEi among the functional groups.
We conclude that wood functional anatomy profiles varied across plant functional groups in a tropical rain forest. These groups can therefore serve as a framework for further investigations on structure–function relationships and a sound basis for modelling species responses to drought.
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Lay Summary
Objective
To establish the effectiveness of a brief intervention to prevent falls in older patients presenting to the ED post‐discharge.
Methods
The present study is a prospective single‐centre, ...quasi‐randomised controlled clinical trial of a brief targeted educational intervention to prevent falls. The intervention group received brief scripted education and were advised of their percentage probability of falling in the next 6 months. The key message was to reinforce the importance of falls prevention strategies and the seriousness of falls.
Results
A total of 412 over 65 years old were recruited; 63 (32.1%) patients in the intervention group and 67 (36.8%) in the control group reported falls in the 6 month follow up period (OR 0.81, 95% confidence interval CI 0.53–1.25, P = 0.34). No significant differences were noted for mortalities (P = 0.54), ED representations (P = 0.15) and medication changes (P = 0.17). Patients receiving intervention had less hospital admissions (P = 0.002) after adjustment for confounding variables. Intervention patients who presented with a fall had significant (P = 0.007) improvement in function at 6 months, whereas those not presenting with a fall experienced functional decline.
Conclusion
A brief intervention was associated with maintenance of function in fallers and reduced hospital admissions, without preventing falls post‐discharge.
Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co‐infections. Increasing resistance of Ng to ...currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng‐Ct co‐infections. Development of a safe, effective, and inexpensive dual therapy for Ng‐Ct co‐infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X‐ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high‐throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.
To compare the Falls Risk for Older Persons-Community Setting Screening Tool (FROP Com Screen) with the Two-Item Screening Tool in older adults presenting to the ED.
A prospective cohort study, ...comparing the efficacy of the two falls risk assessment tools by applying them simultaneously in a sample of hospital ED presentations.
Two hundred and one patients over 65 years old were recruited. Thirty-six per cent reported falls in the 6-month follow-up period. The area under the receiver operating characteristic curve was 0.57 (95% CI 0.48 to 0.66) for the FROP Com Screen and 0.54 (95% CI 0.45 to 0.63) for the Two-Item Screening Tool. FROP Com Screen had a sensitivity of 39% (95% CI 0.27 to 0.51) and a specificity of 70% (95% CI 0.61 to 0.78), while the Two-Item Screening Tool had a sensitivity of 48% (95% CI 0.36 to 0.60) and a specificity of 57% (95% CI 0.47 to 0.66).
Both tools have limited predictive ability in the ED setting.
This qualitative study examined how and why research experiences for teachers (RETs) influenced middle and high school science teachers' beliefs, attitudes, and values about teaching science as ...inquiry. Changes teachers reported after participating in the RET ranged from modifying a few lessons (belief change) to a comprehensive revision of what and how they taught to better reflect inquiry (attitude change). Some teachers who described comprehensively changing their instruction also described implementing actions meant to change science education within their respective schools, not just their own classrooms (value change). We present how and why teachers went about changes in their practices in relation to the researcher-created teacher inquiry beliefs system spectrum (TIBSS). The TIBSS conceptualizes the range of changes observed in participating teachers. We also describe the features of the RET and external factors, such as personal experiences and school contexts, that teachers cited as influential to these changes.
The work of the Committee on Enslaved and Disenfranchised Population in Rutgers History. Visit the project's website at http://scarletandblack.rutgers.edu
Aim: To determine whether a multifactorial intervention can decrease the frequency of secondary falls in older patients presenting to an emergency department with a fall. Methods: A randomized ...control design comparing multifactorial follow-up intervention to standard care. Risk assessments included Falls Risk for Older Persons-Community Setting Screening Tool (FROP Com Screen) and the Two Item Screening Tool, which were compared for sensitivity. Results: Eight patients (14%) in the control group and 11 patients (20.8%) in the intervention group experienced falls (p = 0.373). The proportion of those identified as high risk that fell was similar between the FROP Com Screen (17%) and the Two Item Screening Tool (17%). Patients on average waited 35 days in the control group and 40 days in the intervention group for an outpatient appointment. Conclusions: There was no significant benefit of the intervention. Our findings support interdisciplinary collaboration, multifactorial intervention, and risk management for falls prevention.
A comprehensive and authoritative overview of current research, major theoretical perspectives, and new research directions in the study of science, technology, and society.
The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor ...in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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