Exploring Factors Associated with Citizens’ Perception of Their Political Environment: Evidence from Palestine

This study explores factors associated with citizens’ perception of their political environment in Palestine (N = 1270). Understanding these factors in this context has potential to enhance knowledge in relation to features that may be associated with dissatisfaction and civil unrest. This knowledge may help inform development of policies with greater potential to improve welfare. Overall, results of this study suggested that gender, government anti-corruption initiatives, and the country’s economic condition are important in explaining appraisal of the political environment as stable or unstable. Implications for welfare and scholarship are discussed

Impact of Autosomal Recessive Juvenile Parkinson’s Disease Mutations on the Structure and Interactions of the Parkin Ubiquitin-like Domain

Autosomal recessive juvenile parkinsonism (ARJP) is an early onset familial form of Parkinson\u27s disease. Approximately 50% of all ARJP cases are attributed to mutations in the gene park2, coding for the protein parkin. Parkin is a multidomain E3 ubiquitin ligase with six distinct domains including an N-terminal ubiquitin-like (Ubl) domain. In this work we examined the structure, stability, and interactions of the parkin Ubl domain containing most ARJP causative mutations. Using NMR spectroscopy we show that the Ubl domain proteins containing the ARJP substitutions G12R, D18N, K32T, R33Q, P37L, and K48A retained a similar three-dimensional fold as the Ubl domain, while at least one other (V15M) had altered packing. Four substitutions (A31D, R42P, A46P, and V56E) result in poor folding of the domain, while one protein (T55I) showed evidence of heterogeneity and aggregation. Further, of the substitutions that maintained their three-dimensional fold, we found that four of these (V15M, K32T, R33Q, and P37L) lead to impaired function due to decreased ability to interact with the 19S regulatory subunit S5a. Three substitutions (G12R, D18N, and Q34R) with an uncertain role in the disease did not alter the three-dimensional fold or S5a interaction. This work provides the first extensive characterization of the structural effects of causative mutations within the ubiquitin-like domain in ARJP

The moderating impact of temporal separation on the association between intention and physical activity: a meta-analysis

Previous meta-analyses have estimated that the intention-behaviour association in physical activity (PA) is large in magnitude. However, these prior meta-analyses have also revealed a large degree of heterogeneity, suggesting the presence of moderating variables. This study examines the impact of one such moderator, testing the hypothesis that the magnitude of the association between intention and behaviour decreases as the temporal separation between the two increases. A systematic literature search was used to identify published and unpublished studies that met the inclusion criteria. A random-effects meta-regression was conducted to test the study hypothesis. A total of 78 journal articles and 11 unpublished dissertations were identified, yielding 109 effect sizes. The mean number of weeks between the measurement of intention and behaviour was 5.4 (SD = 6.6, range = .43, 26). The average correlation between intention and behaviour was r = 0.51. In line with theoretical predictions, temporal separation was a significant moderator of the intention-behaviour correlation (B = −.014, p \u3c .001) and explained 24% of the between-study variance. This result remained unchanged when entered simultaneously with several control variables. The results of this analysis have important implications both for researchers and for intervention designers aiming to increase rates of PA

Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

Background: Family studies support a genetic predisposition to inflammatory bowel diseases (IBD), but known genetic variants only partially explain the disease heritability. Families with multiple affected individuals potentially harbour rare and high-impact causal variants. Long regions of homozygosity due to recent inbreeding may increase the risk of individuals bearing homozygous loss-of-function variants. This study aimed to identify rare and homozygous genetic variants contributing to IBD. Methods: Four families with known consanguinity and multiple cases of IBD were recruited. In a family-specific analysis, we utilised homozygosity mapping complemented by whole-exome sequencing. Results: We detected a single region of homozygosity shared by Crohn's disease cases from a family of Druze ancestry, spanning 2.6 Mb containing the NOD2 gene. Whole-exome sequencing did not identify any potentially damaging variants within the region, suggesting that non-coding variation may be involved. In addition, affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1, WHAMM, DENND3, and C5. Conclusion: This study examined the potential contribution of rare, high-impact homozygous variants in consanguineous families with IBD. While the analysis was not designed to achieve statistical significance, our findings highlight genes or loci that warrant further research. Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn's disease

PROTEIN STRUCTURE REPORT Solution structure of the E3 ligase HOIL-1 Ubl domain

Abstract: The E3 ligases HOIL-1 and parkin are each comprised of an N-terminal ubiquitin-like (Ubl) domain followed by a zinc-binding region and C-terminal RING-In-between-RING-RING domains. These two proteins, involved in the ubiquitin-mediated degradation pathway, are the only two known E3 ligases to share this type of multidomain architecture. Further, the Ubl domain of both HOIL-1 and parkin has been shown to interact with the S5a subunit of the 26S proteasome. The solution structure of the HOIL-1 Ubl domain was solved using NMR spectroscopy to compare it with that of parkin to determine the structural elements responsible for S5a intermolecular interactions. The final ensemble of 20 structures had a b-grasp Ubl-fold with an overall backbone RMSD of 0.59 6 0.10 Å in the structured regions between I55 and L131. HOIL-1 had a unique extension of both b1 and b2 sheets compared to parkin and other Ubl domains, a result of a four-residue insertion in this region. A similar 15-residue hydrophobic core in the HOIL-1 Ubl domain resulted in a comparable stability to the parkin Ubl, but significantly lower than that observed for ubiquitin. A comparison with parkin and other Ubl domains indicates that HOIL-1 likely uses a conserved hydrophobic patch (W58, V102, Y127, Y129) found on the b1 face, the b3-b4 loop and b5, as well as a C-terminal basic residue (R134) to recruit the S5a subunit as part of the ubiquitin-mediated proteolysis pathway

Coadministration of Anti-Viral Monoclonal Antibodies With Routine Pediatric Vaccines and Implications for Nirsevimab Use: A White Paper

Routine childhood vaccinations are key for the protection of children from a variety of serious and potentially fatal diseases. Current pediatric vaccine schedules mainly cover active vaccines. Active vaccination in infants is a highly effective approach against several infectious diseases; however, thus far, for some important viral pathogens, including respiratory syncytial virus (RSV), vaccine development and license by healthcare authorities have not been accomplished. Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants. In this manuscript, we consider the potential implications for the introduction of an anti-viral mAb, such as nirsevimab, into the routine pediatric vaccine schedule, as well as considerations for coadministration. Specifically, we present evidence on the general mechanism of action of anti-viral mAbs and experience with palivizumab, the only approved mAb for the prevention of RSV infection in preterm infants, infants with chronic lung disease of prematurity and certain infants with hemodynamically significant heart disease. Palivizumab has been used for over two decades in infants who also receive routine vaccinations without any alerts concerning the safety and efficacy of coadministration. Immunization guidelines (Advisory Committee on Immunization Practices, Joint Committee on Vaccination and Immunization, National Advisory Committee on Immunization, Centers for Disease Control and Prevention, American Academy of Pediatrics, The Association of the Scientific Medical Societies in Germany) support coadministration of palivizumab with routine pediatric vaccines, noting that immunobiologics, such as palivizumab, do not interfere with the immune response to licensed live or inactivated active vaccines. Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit

The hypertension cascade of care in the midst of conflict: the case of the Gaza Strip

Although hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers

Long Distance Contribution to s→dγs \to d\gamma and Implications for Ω−→Ξ−γ,Bs→Bd∗γ\Omega^-\to \Xi ^-\gamma, B_s \to B_d^*\gamma and b→sγb \to s\gamma

We estimate the long distance (LD) contribution to the magnetic part of the $s \to d\gamma$ transition using the Vector Meson Dominance approximation $(V=\rho,\omega,\psi_i)$. We find that this contribution may be significantly larger than the short distance (SD) contribution to $s \to d\gamma$ and could possibly saturate the present experimental upper bound on the $\Omega^-\to \Xi^-\gamma$ decay rate, $\Gamma^{\rm MAX}_{\Omega^-\to \Xi^-\gamma} \simeq 3.7\times10^{-9}$eV. For the decay $B_s \to B^*_d\gamma$, which is driven by $s \to d\gamma$ as well, we obtain an upper bound on the branching ratio $BR(B_s \to B_d^*\gamma)<3\times10^{-8}$ from $\Gamma^{\rm MAX}_{\Omega^-\to \Xi^-\gamma}$. Barring the possibility that the Quantum Chromodynamics coefficient $a_2(m_s)$ be much smaller than 1, $\Gamma^{\rm MAX}_{\Omega^-\to \Xi^-\gamma}$ also implies the approximate relation $\frac{2}{3} \sum_i \frac{g^2_{\psi_i}(0)}{m^2_{\psi_i}} \simeq \frac{1}{2} \frac{g^2_\rho(0)}{m^2_\rho} + \frac{1}{6}\frac{g^2_\omega(0)}{m^2_\omega}$. This relation agrees quantitatively with a recent independent estimate of the l.h.s. by Deshpande et al., confirming that the LD contributions to $b \to s\gamma$ are small. We find that these amount to an increase of $(4\pm2)\%$ in the magnitude of the $b \to s \gamma$ transition amplitude, relative to the SD contribution alone.Comment: 16 pages, LaTeX fil