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511.
To better understand the evolutionary history of the genus Centaurium and its relationship to other genera of the subtribe Chironiinae (Gentianaceae: Chironieae), molecular analyses were performed using 80 nuclear ribosomal ITS and 76 chloroplast trnLF (both the trnL UAA intron and the trnL-F spacer) sequences. In addition, morphological, palynological, and phytochemical characters were included to a combined data matrix to detect possible non-molecular synapomorphies. Phylogenetic reconstructions support the monophyly of the Chironiinae and an age estimate of ca. 22 million years for the subtribe. Conversely, both molecular data sets reveal a polyphyletic Centaurium, with four well-supported main clades hereafter treated as separate genera. The primarily Mediterranean Centaurium s.s. is closely related to southern African endemics Chironia and Orphium, and to the Chilean species Centaurium cachanlahuen. The resurrected Mexican and Central American genus Gyrandra is closely related to Sabatia (from eastern North America). Lastly, the monospecific genus Exaculum (Mediterranean) forms a monophyletic group together with the two new genera: Schenkia (Mediterranean and Australian species) and Zeltnera (all other indigenous American centauries). Several biogeographical patterns can be inferred for this group, supporting a Mediterranean origin followed by dispersals to (1) North America, Central America, and South America, (2) southern Africa (including the Cape region), and (3) Australia and Pacific Islands. 相似文献
512.
513.
Lianbin Yao Sten Ohlson Brian W. Dymock 《Bioorganic & medicinal chemistry letters》2018,28(8):1357-1362
Inhibition of multiple signaling pathways in a cancer cell with a single molecule could result in better therapies that are simpler to administer. Efficacy may be achieved with reduced potency against individual targets if there is synergy through multiple pathway inhibition. To achieve this, it is necessary to be able to build multi-component ligands by joining together key pharmacophores in a way which maintains sufficient activity against the individual pathways. In this work, designed triple inhibiting ligands are explored aiming to block three completely different target types: a kinase (JAK2), an epigenetic target (HDAC) and a chaperone (HSP90). Although these enzymes have totally different functions they are related through inter-dependent pathways in the developing cancer cell. Synthesis of several complex multi-inhibiting ligands are presented along with initial enzyme inhibition data against 3 biological target classes of interest. A lead compound, 47, was discovered which had low micromolar activity for all 3 targets. Further development of these complex trispecific designed multiple ligands could result in a ‘transient drug’, an alternative combination therapy for treating cancer mediated via a single molecule. 相似文献
514.
Hossein Rajaei Sh Jan‐Frederic Struwe Michael J. Raupach Dirk Ahrens J. Wolfgang Wägele 《Zoological Journal of the Linnean Society》2013,169(1):70-83
We tested the hypothesis of species taxonomy in the genus Gnopharmia (Macariini, Ennominae) that was recently established in a review based on discrete morphological characters. For this objective we integrated both DNA‐based and morphometric approaches in order to infer species boundaries. A 658‐bp fragment of the mitochondrial cytochrome c oxidase subunit 1 (CO1) (DNA barcode) was analysed from populations of five species distributed throughout the Middle East to assess their consistency with traditionally defined morphospecies. Signals in the morphological variation of the aedeagus of all relevant populations were evaluated using geometric landmarks. Consistent groupings compatible with the current taxonomic classification were found with both approaches. The results strongly support the distinction of seven closely related species. © 2013 The Linnean Society of London 相似文献
515.
The last step in triacylglycerols (TAG) biosynthesis in oil seeds, the acylation of diacylglycerols (DAG), is catalysed by two types of enzymes: the acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). The relative contribution of these enzymes in the synthesis of TAG has not yet been defined in any plant tissue. In the presented work, microsomal preparations were obtained from sunflower and safflower seeds at different stages of development and used in DGAT and PDAT enzyme assays. The ratio between PDAT and DGAT activity differed dramatically between the two different species. DGAT activities were measured with two different acyl acceptors and assay methods using two different acyl-CoAs, and in all cases the ratio of PDAT to DGAT activity was significantly higher in safflower than sunflower. The sunflower DGAT, measured by both methods, showed significant higher activity with 18:2-CoA than with 18:1-CoA, whereas the opposite specificity was seen with the safflower enzyme. The specificities of PDAT on the other hand, were similar in both species with 18:2-phosphatidylcholine being a better acyl donor than 18:1-PC and with acyl groups at the sn-2 position utilised about fourfold the rate of the sn-1 position. No DAG:DAG transacylase activity could be detected in the microsomal preparations. 相似文献
516.
Camilla Rams Rathleff William Neill Baird Jens Lykkegaard Olesen Ewa Maria Roos Sten Rasmussen Michael Skovdal Rathleff 《PloS one》2013,8(11)
Background
One of the rationales behind using strength training in the treatment of adolescents with Patellofemoral Pain (PFP) is that reduced strength of the lower extremity is a risk factor for PFP and a common deficit. This rationale is based on research conducted on adolescents >15 years of age but has never been investigated among young adolescents with PFP.Objectives
To compare isometric muscle strength of the lower extremity among adolescents with PFP compared to age- and gender-matched pain-free adolescents.Methods
In 2011 a population-based cohort (APA2011-cohort) consisting of 768 adolescents aged 12–15 years from 8 local schools was formed. In September 2012, all adolescents who reported knee pain in September 2011 were offered a clinical examination if they still had knee pain. From these, 20 adolescents (16 females) were diagnosed with PFP. Pain-free adolescents from the APA2011-cohort (n = 20) were recruited on random basis as age- and gender-matched pairs. Primary outcome was isometric knee extension strength normalized to body weight (%BW) and blinded towards subject information. Secondary outcomes included knee flexion, hip abduction/adduction and hip internal/external rotation strength. Demographic data included Knee Injury and Osteoarthritis Outcome Score (KOOS) and symptom duration.Results
Adolescents with PFP reported long symptom duration and significantly worse KOOS scores compared to pain-free adolescents. There were no significant differences in isometric knee extension strength (Δ0.3% BW, p = 0.97), isometric knee flexion strength (Δ0.4% BW, p = 0.84) or different measures of hip strength (Δ0.4 to 1.1% BW, p>0.35).Conclusion
Young symptomatic adolescents with PFP between 12 and 16 years of age did not have decreased isometric muscle strength of the knee and hip. These results question the rationale of targeting strength deficits in the treatment of adolescents with PFP. However, strength training may still be an effective treatment for those individuals with PFP suffering from strength deficits. 相似文献517.
Rab Nawaz Samo Arshad Altaf Ajmal Agha Omrana Pasha Shafquat Rozi Ashraf Memon Saleem Azam Meridith Blevins Sten H. Vermund Sharaf Ali Shah 《PloS one》2013,8(12)
Background
The incidence of HIV among persons who inject drugs (PWIDU) has fallen in many nations, likely due to successes of clean needle/syringe exchange and substance abuse treatment and service programs. However in Pakistan, prevalence rates for PWID have risen dramatically. In several cities, prevalence exceeded 20% by 2009 compared to a 2003 baseline of just 0.5%. However, no cohort study of PWID has ever been conducted.Methods
We enrolled a cohort of 636 HIV seronegative PWID registered with three drop-in centers that focus on risk reduction and basic social services in Karachi. Recruitment began in 2009 (March to June) and PWID were followed for two years. We measured incidence rates and risk factors associated with HIV seroconversion.Results
Incidence of HIV was 12.4 per 100 person-years (95% exact Poisson confidence interval [CI]: 10.3–14.9). We followed 474 of 636 HIV seronegative persons (74.5%) for two years, an annual loss to follow-up of <13 per 100 person years. In multivariable Cox regression analysis, HIV seroconversion was associated with non-Muslim religion (Adjusted risk ratio [ARR] = 1.7, 95%CI:1.4, 2.7, p = 0.03), sharing of syringes (ARR = 2.3, 95%CI:1.5, 3.3, p<0.0001), being homeless (ARR = 1.7, 95%CI:1.1, 2.5, p = 0.009), and daily injection of drugs (ARR = 1.1, 95%CI:1.0, 1.3, p = 0.04).Conclusions
Even though all members of the cohort of PWID were attending risk reduction programs, the HIV incidence rate was very high in Karachi from 2009–2011. The project budget was low, yet we were able to retain three-quarters of the population over two years. Absence of opiate substitution therapy and incomplete needle/syringe exchange coverage undermines success in HIV risk reduction. 相似文献518.
Knop FK Vilsbøll T Højberg PV Larsen S Madsbad S Holst JJ Krarup T 《Regulatory peptides》2007,144(1-3):123-130
BACKGROUND: The incretin effect is reduced and the insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is abolished in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE AND DESIGN: To evaluate the causality of this deficiency we investigated 8 patients with chronic pancreatitis (CP) and normal glucose tolerance (NGT) (fasting plasma glucose (FPG): 5.5 (4.5-6.0) mM (mean (range); HbA(1c): 5.8 (5.4-6.3) %) and 8 patients with CP and secondary diabetes not requiring insulin (FPG: 7.1 (6.0-8.8) mM; HbA(1c): 7.0 (5.8-10.0) %) during three 15-mM hyperglycaemic clamps with continuous iv infusion of saline, glucagon-like peptide-1 (GLP-1) or GIP. RESULTS: The initial (0-20 min) insulin and C-peptide responses were enhanced significantly in both groups by GLP-1 and GIP, respectively, compared to saline (P<0.05). In both groups GLP-1 infusion resulted in significantly greater insulin and C-peptide responses from 20-120 min compared with saline infusion. During GIP infusion the late-phase insulin response (20-120 min) was 3.1+/-1.0 fold greater than during saline infusion in the group of patients with CP and NGT (P<0.05), whereas there was no significant differences in patients with CP and DM. CONCLUSIONS: The lack of GIP amplification of the late insulin response to iv glucose develops alongside the deterioration of glucose tolerance in patients with CP, suggesting that the same may be true for the loss of the GIP effect in patients with T2DM. 相似文献
519.
Troy D. Moon Ezequiel B. Ossemane Ann F. Green Elisée Ndatimana Eurico José Charlotte P. Buehler C. William Wester Sten H. Vermund Omo Olupona 《PloS one》2014,9(10)
Objective
To generate maps reflecting the intersection of community-based Voluntary Counseling and Testing (VCT) delivery points with facility-based HIV program demographic information collected at the district level in three districts (Ile, Maganja da Costa and Chinde) of Zambézia Province, Mozambique; in order to guide planning decisions about antiretroviral therapy (ART) program expansion.Methods
Program information was harvested from two separate open source databases maintained for community-based VCT and facility-based HIV care and treatment monitoring from October 2011 to September 2012. Maps were created using ArcGIS 10.1. Travel distance by foot within a 10 km radius is generally considered a tolerable distance in Mozambique for purposes of adherence and retention planning.Results
Community-based VCT activities in each of three districts were clustered within geographic proximity to clinics providing ART, within communities with easier transportation access, and/or near the homes of VCT volunteers. Community HIV testing results yielded HIV seropositivity rates in some regions that were incongruent with the Ministry of Health’s estimates for the entire district (2–13% vs. 2% in Ile, 2–54% vs. 11.5% in Maganja da Costa, and 23–43% vs. 14.4% in Chinde). All 3 districts revealed gaps in regional disbursement of community-based VCT activities as well as access to clinics offering ART.Conclusions
Use of geospatial mapping in the context of program planning and monitoring allowed for characterizing the location and size of each district’s HIV population. In extremely resource limited and logistically challenging settings, maps are valuable tools for informing evidence-based decisions in planning program expansion, including ART. 相似文献520.
Bart Victor Meridith Blevins Ann F. Green Elisée Ndatimana Lázaro González-Calvo Edward F. Fischer Alfredo E. Vergara Sten H. Vermund Omo Olupona Troy D. Moon 《PloS one》2014,9(9)