Comparative study of protein-protein interaction observed in PolyGalacturonase-Inhibiting Proteins from Phaseolus vulgaris and Glycine max and PolyGalacturonase from Fusarium moniliforme

<p>Abstract</p> <p>Background</p> <p>The PolyGalacturonase-Inhibiting Proteins (PGIP) of plant cell wall limit the invasion of phytopathogenic organisms by interacting with the enzyme PolyGalacturonase (PG) they secrete to degrade pectin present in the cell walls. PGIPs from different or same plant differ in their inhibitory activity towards the same PG. PGIP2 from <it>Phaseolus vulgaris </it>(<it>Pv</it>) inhibits the PG from <it>Fusarium moniliforme </it>(<it>Fm</it>) although PGIP1, another member of the multigene family from the same plant sharing 99% sequence similarity, cannot. Interestingly, PGIP3 from <it>Glycine max </it>(<it>Gm</it>) which is a homologue of PGIP2 is capable of inhibiting the same PG although the extent of similarity is lower and is 88%. It therefore appears that subtle changes in the sequence of plant PGIPs give rise to different specificity for inhibiting pathogenic PGs and there exists no direct dependence of function on the extent of sequence similarity.</p> <p>Results</p> <p>Structural information for any PGIP-PG complex being absent, we resorted to molecular modelling to gain insight into the mechanism of recognition and discrimination of PGs by PGIPs. We have built homology models of <it>Pv</it>PGIP1 and <it>Gm</it>PGIP3 using the crystal structure of <it>Pv</it>PGIP2 (<ext-link ext-link-id="1OGQ" ext-link-type="pdb">1OGQ</ext-link>) as template. These PGIPs were then docked individually to <it>Fm</it>PG to elucidate the characteristics of their interactions. The mode of binding for <it>Pv</it>PGIP1 to <it>Fm</it>PG considerably differs from the mode observed for <it>Pv</it>PGIP2-<it>Fm</it>PG complex, regardless of the high sequence similarity the two PGIPs share. Both <it>Pv</it>PGIP2 and <it>Gm</it>PGIP3 despite being relatively less similar, interact with residues of <it>Fm</it>PG that are known from mutational studies to constitute the active site of the enzyme. <it>Pv</it>PGIP1 tends to interact with residues not located at the active site of <it>Fm</it>PG. Looking into the electrostatic potential surface for individual PGIPs, it was evident that a portion of the interacting surface for <it>Pv</it>PGIP1 differs from the corresponding region of <it>Pv</it>PGIP2 or <it>Gm</it>PGIP3.</p> <p>Conclusion</p> <p>van der Waals and eletrostatic interactions play an active role in PGIPs for proper recognition and discrimination of PGs. Docking studies reveal that <it>Pv</it>PGIP2 and <it>Gm</it>PGIP3 interact with the residues constituting the active site of <it>Fm</it>PG with implications that the proteins bind/block <it>Fm</it>PG at its active site and thereby inhibit the enzyme.</p

Kardar-Parisi-Zhang universality in a two-component driven diffusive model

We elucidate the universal spatio-temporal scaling properties of the time-dependent correlation functions in a two-component one-dimensional (1D) driven diffusive system that consists of two coupled asymmetric exclusion process. By using a perturbative renormalization group framework, we show that the relevant scaling exponents have values same as those for the 1D Kardar-Parisi-Zhang (KPZ) equation. We thus establish that the model belongs to the 1D KPZ universality class.Comment: 13 pages, 2 figure

Statistical Shape Analysis of Shape Graphs with Applications to Retinal Blood-Vessel Networks

This paper provides theoretical and computational developments in statistical shape analysis of shape graphs, and demonstrates them using analysis of complex data from retinal blood-vessel (RBV) networks. The shape graphs are represented by a set of nodes and edges (planar articulated curves) connecting some of these nodes. The goals are to utilize shapes of edges and connectivities and locations of nodes to: (1) characterize full shapes, (2) quantify shape differences, and (3) model statistical variability. We develop a mathematical representation, elastic Riemannian shape metrics, and associated tools for such statistical analysis. Specifically, we derive tools for shape graph registration, geodesics, summaries, and shape modeling. Geodesics are convenient for visualizing optimal deformations, and PCA helps in dimension reduction and statistical modeling. One key challenge here is comparisons of shape graphs with vastly different complexities (in number of nodes and edges). This paper introduces a novel multi-scale representation of shape graphs to handle this challenge. Using the notions of (1) ``effective resistance" to cluster nodes and (2) elastic shape averaging of edge curves, one can reduce shape graph complexity while maintaining overall structures. This way, we can compare shape graphs by bringing them to similar complexity. We demonstrate these ideas on Retinal Blood Vessel (RBV) networks taken from the STARE and DRIVE databases

Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n = 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth

Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n = 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth

The uptake study: a cross-sectional survey examining the insights and beliefs of the UK population on COVID-19 vaccine uptake and hesitancy

© 2021 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/bmjopen-2021-048856Objective: A key challenge towards a successful COVID-19 vaccine uptake is vaccine hesitancy. We examine and provide novel insights on the key drivers and barriers towards COVID-19 vaccine uptake. Design: This study involved an anonymous cross-sectional online survey circulated across the UK in September 2020. The survey was designed to include several sections to collect demographic data and responses on: i) extent of agreement regarding various statements about COVID-19 and vaccinations; ii) previous vaccination habits (e.g. if they had previously declined vaccination); and iii) interest in participation in vaccine trials. Multi-nominal logistic models examined demographic factors that may impact vaccine uptake. We used principle component analysis and text mining to explore perception related to vaccine uptake. Setting: The survey was circulated through various media, including: posts on social media networks (Facebook, Twitter, LinkedIn and Instagram), national radio, news articles, Clinical Research Network (CRN) website and newsletter, and through 150 West Midlands general practices via a text messaging service. Participants: There was a total of 4884 respondents of which 9.44% were BAME (Black Asian Minority Ethnic) group. The majority were females (n=3416, 69·9%) and of White ethnicity (n=4127, 84·5%). Results: Regarding respondents, overall 3873 (79·3%) were interested in taking approved COVID-19 vaccines while 677 (13·9%) were unsure, and 334 (6·8%) would not take a vaccine. Participants aged over 70 years (Odds Ratio (OR)=4·63) and the BAME community (OR=5·48) were more likely to take an approved vaccine. Smokers (OR=0·45) and respondents with no known illness (OR=0·70) were less likely to accept approved vaccines. The study identified 16 key reasons for not accepting approved vaccines, the most common (60%) being the possibility of the COVID-19 vaccine having side effects. Conclusions: This study provides an insight into focusing on specific populations to reduce vaccine hesitancy. This proves crucial in managing the COVID-19 pandemic

The UPTAKE study: implications for the future of COVID-19 vaccination trial recruitment in UK and beyond

© 2021 The Authors. Published by BMC (Springer Nature). This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s13063-021-05250-4Background Developing a safe and effective vaccine will be the principal way of controlling the COVID-19 pandemic. However, current COVID-19 vaccination trials are not adequately representing a diverse participant population in terms of age, ethnicity and comorbidities. Achieving the representative recruitment targets that are adequately powered to the study remains one of the greatest challenges in clinical trial management. To ensure accuracy and generalisability of the safety and efficacy conclusions generated by clinical trials, it is crucial to recruit patient cohorts as representative as possible of the future target population. Missing these targets can lead to reduced validity of the study results and can often slow down drug development leading to costly delays. Objective This study explores the key factors related to perceptions and participation in vaccination trials. Methods This study involved an anonymous cross-sectional online survey circulated across the UK. Statistical analysis was done in six phases. Multi-nominal logistic models examined demographic and geographic factors that may impact vaccine uptake. Results The survey had 4884 participants of which 9.44% were Black Asian Minority Ethnic (BAME). Overall, 2020 (41.4%) respondents were interested in participating in vaccine trials; 27.6% of the respondents were not interested and 31.1% were unsure. The most interested groups were male (OR = 1.29), graduates (OR = 1.28), the 40–49 and 50–59 age groups (OR = 1.88 and OR = 1.46 respectively) and those with no health issues (OR = 1.06). The least interested groups were BAME (OR = 0.43), those from villages and small towns (OR = 0.66 and 0.54 respectively) and those aged 70 and above (OR = 1.11). Conclusions In order to have a vaccination that is generalisable to the entire population, greater work needs to be done in engaging a diverse cohort of participants. Public health campaigns need to be targeted in improving trial recruitment rates for the elderly, BAME community and the less educated rural population.Published onlin