456 research outputs found

    Catalytic and mechanistic studies into the epoxidation of styrenes using manganese complexes of structurally similar polyamine ligands

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    The synthesis and catalytic activity of manganese(ii) complexes of two polyamine ligands is reported which highlights how a small structural change in the ligand affects the overall catalytic behaviour.</p

    Torn Between the Real Me and the Social Me: Educated Women’s Perspectives of Surviving Marital Abuse

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    The perspectives of educated women on surviving abusive marital relationships have not been adequately explored, thus implying a gap in the literature regarding the role of education in enhancing or mitigating the prevalence of intimate partner violence (IPV). In this context, the question is how do educated women perceive surviving abusive relationships? Interpretative Phenomenological Analysis (IPA), using flexible semi-structured face-to-face interviews, was conducted to understand the experiences of eight highly educated women (master’s, Ph.D.) in abusive marriage. Four superordinate interrelated themes were developed: (a) developing an awareness of self-respect generating role confusion, (b) being torn between traditions and ambitions, (c) normalizing abuse as part of marriage, and (d) challenging abuse by self-promotion. Like other survivors of abuse, educated women tried to justify, blame themselves, work harder to please the perpetrator, and promote themselves; finally, they continued to live their lives by embracing abuse to bring peace and save their marriage. The effect of sociocultural context on educated women’s perspectives seems to play a crucial role in women’s decisions to stay in abusive relationships, despite the assumptions of empowerment and independence

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

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    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

    Structural and Compositional Changes in Aging Bone: Osteopenia in Lumbar Vertebrae of Wistar Female Rats

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    Changes in vertebral bone mineral content and density during aging were quantified in female Wistar rats. This study represents a longitudinal follow up utilizing single photon absorptiometry for the measurement of bone mineral content (BMC), quantitative computed tomography (OCT) for the measurement of bone mineral density (BMD), and image analysis histomorphometry for the measurement of trabecular bone volume (TBV) and bone cortical area (BCA). The above measurements were accompanied by biochemical assays of calcium concentrations in the respective bones. All aging animals experienced significant decreases in BMC, BMD, TBV, BCA and in the calcium content of their bones. The above features have been further emphasized through the use of scanning electron micrographs showing the age-related structural changes in a three-dimentional fashion. New, advanced technologies will enable the quantitation of 3-dimensional images that are currently obtained from the scanning electron micrograph; thus will provide new consideration as related to trabecular bone compactness (density). Energy dispersive x-ray spectroscopy indicated that the nature of crystals in aging bones does not differ markedly from that encountered in young specimens. Data are also provided with regard to the health of the animals, and it became apparent that aging rats undergo changes in their kidneys yet do not show any significant change in renal functional parameters as measured in both the serum and the urine. Hence, new noninvasive methodologies are currently available for longitudinal studies related to the skeleton in laboratory animals enabling reliable monitoring of age-related and hormonally induced changes in bones (spine and hip) of well defined experimental models

    A QCD Sum Rule Approach to the sdγs\to d\gamma Contribution to the ΩΞγ\Omega^-\to \Xi^-\gamma Radiative Decay

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    QCD sum rules are used to calculate the contribution of short-distance single-quark transition sdγs\rightarrow d \gamma, to the amplitudes of the hyperon radiative decay, ΩΞγ\Omega^-\rightarrow \Xi^-\gamma. We re-evaluate the Wilson coefficient of the effective operator responsible for this transition. We obtain a branching ratio which is comparable to the unitarity limit.Comment: 15 pages, Revtex, 13 figures available as a uuencoded, gz-compressed ps fil

    Right hemithoracic pseudocyst with splenic artery aneurysm: two rare complications of an uncommon disease

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    Pleural involvement is an uncommon but well recognized complication of chronic pancreatitis, mainly in the form of pleural effusion affecting the left hemithorax. Pancreatic pseudocyst extending to the posterior mediastinum with or without communication with the pleural space is another rare form of this involvement.The treatment of chronic pancreatic pleural effusions and pancreatic pseudocysts generally starts with a conservative approach including bowel rest, drainage of the pleural effusion by repeated thoracentesis or a chest tube, and total parenteral nutrition (TPN) for a period of time determined by the clinical course. Other treatment modalities including percutaneous drainage, endoscopic retrograde cholangiopancreatogram (ERCP) with stenting of the pancreatic duct and surgical drainage are used if conservative approaches fail.We report a patient with a complicated pancreatic pseudocyst who showed an involvement of the posterior mediastinum and right pleural space, with conspectus sparing of the left hemithorax. The patient had a prolonged and complicated course that included recurrence of the pseudocyst with oral feedings and the development of a splenic artery aneurysm. Some of the above findings have been reported separately as uncommon complications of chronic pancreatitis and pancreatic pseudcyst, but to our knowledge a single case with all these complications was not published in the English literature

    Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation

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    Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC) and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC) and fetal membrane (Mb-MSC) through morphological and fluorescent-activated cell sorting (FACS). MSC frequency is higher in membrane than placenta (2.14%  ± 0.65 versus 15.67%  ± 0.29%). Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration

    Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

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    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

    Long Distance Contribution to sdγs \to d\gamma and Implications for ΩΞγ,BsBdγ\Omega^-\to \Xi ^-\gamma, B_s \to B_d^*\gamma and bsγb \to s\gamma

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    We estimate the long distance (LD) contribution to the magnetic part of the sdγs \to d\gamma transition using the Vector Meson Dominance approximation (V=ρ,ω,ψi)(V=\rho,\omega,\psi_i). We find that this contribution may be significantly larger than the short distance (SD) contribution to sdγs \to d\gamma and could possibly saturate the present experimental upper bound on the ΩΞγ\Omega^-\to \Xi^-\gamma decay rate, ΓΩΞγMAX3.7×109\Gamma^{\rm MAX}_{\Omega^-\to \Xi^-\gamma} \simeq 3.7\times10^{-9}eV. For the decay BsBdγB_s \to B^*_d\gamma, which is driven by sdγs \to d\gamma as well, we obtain an upper bound on the branching ratio BR(BsBdγ)<3×108BR(B_s \to B_d^*\gamma)<3\times10^{-8} from ΓΩΞγMAX\Gamma^{\rm MAX}_{\Omega^-\to \Xi^-\gamma}. Barring the possibility that the Quantum Chromodynamics coefficient a2(ms)a_2(m_s) be much smaller than 1, ΓΩΞγMAX\Gamma^{\rm MAX}_{\Omega^-\to \Xi^-\gamma} also implies the approximate relation 23igψi2(0)mψi212gρ2(0)mρ2+16gω2(0)mω2\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 bsγb \to s\gamma are small. We find that these amount to an increase of (4±2)%(4\pm2)\% in the magnitude of the bsγb \to s \gamma transition amplitude, relative to the SD contribution alone.Comment: 16 pages, LaTeX fil

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

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    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
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