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1.
2.
Anonymous nuclear DNA markers in the American oyster and their implications for the heterozygote deficiency phenomenon in marine bivalves 总被引:4,自引:0,他引:4
A puzzling population-genetic phenomenon widely reported in allozyme
surveys of marine bivalves is the occurrence of heterozygote deficits
relative to Hardy-Weinberg expectations. Possible explanations for this
pattern are categorized with respect to whether the effects should be
confined to protein-level assays or are genomically pervasive and expected
to be registered in both protein- and DNA-level assays. Anonymous nuclear
DNA markers from the American oyster were employed to reexamine the
phenomenon. In assays based on the polymerase chain reaction (PCR), two
DNA-level processes were encountered that can lead to artifactual genotypic
scorings: (a) differential amplification of alleles at a target locus and
(b) amplification from multiple paralogous loci. We describe symptoms of
these complications and prescribe methods that should generally help to
ameliorate them. When artifactual scorings at two anonymous DNA loci in the
American oyster were corrected, Hardy-Weinberg deviations registered in
preliminary population assays decreased to nonsignificant values.
Implications of these findings for the heterozygote-deficit phenomenon in
marine bivalves, and for the general development and use of PCR-based
assays, are discussed.
相似文献
3.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
4.
Benjamin Maasoumy Kerstin Port Antoaneta Angelova Markova Beatriz Calle Serrano Magdalena Rogalska-Taranta Lisa Sollik Carola Mix Janina Kirschner Michael P. Manns Heiner Wedemeyer Markus Cornberg 《PloS one》2013,8(2)
Background
HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.Methods
All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.Results
208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.Conclusions
P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options. 相似文献5.
Water hyacinth Eichhornia crassipes is considered the most damaging aquatic weed in the world. However, few studies have quantified the impact of this weed economically and ecologically, and even fewer studies have quantified the benefits of its control. This paper focuses on water loss saving as the benefit derived from biological control of this plant between 1990 and 2013 at New Year’s Dam, Alicedale, Eastern Cape, South Africa. Estimates of water loss due to evapotranspiration from water hyacinth vary significantly; therefore, the study used three different rates, high, medium and low. A conservative raw agriculture value of R 0.26 per m3 was used to calculate the benefits derived by the water saved. The present benefit and cost values were determined using 10% and 5% discount rates. The benefit/cost ratio at the low evapotranspiration rate was less than one, implying that biological control was not economically viable but, at the higher evapotranspiration rates, the return justified the costs of biological control. However, at the marginal value product of water, the inclusion of the costs of damage to infrastructure, or the adverse effects of water hyacinth on biodiversity, would justify the use of biological control, even at the low transpiration rate. 相似文献
6.
7.
Marcello Tonelli Brenda Hemmelgarn Braden Manns George Pylypchuk Clara Bohm Karen Yeates Sita Gourishankar John S. Gill 《CMAJ》2004,171(6):577-582
Background
Despite the increase in the number of Aboriginal people with end-stage renal disease around the world, little is known about their health outcomes when undergoing renal replacement therapy. We evaluated differences in survival and rate of renal transplantation among Aboriginal and white patients after initiation of dialysis.Methods
Adult patients who were Aboriginal or white and who commenced dialysis in Alberta, Saskatchewan or Manitoba between Jan. 1, 1990, and Dec. 31, 2000, were recruited for the study and were followed until death, transplantation, loss to follow-up or the end of the study (Dec. 31, 2001). We used Cox proportional hazards models to examine the effect of race on patient survival and likelihood of transplant, with adjustment for potential confounders.Results
Of the 4333 adults who commenced dialysis during the study period, 15.8% were Aboriginal and 72.4% were white. Unadjusted rates of death per 1000 patient-years during the study period were 158 (95% confidence interval [CI] 144–176) for Aboriginal patients and 146 (95% CI 139–153) for white patients. When follow-up was censored at the time of transplantation, the age-adjusted risk of death after initiation of dialysis was significantly higher among Aboriginal patients than among white patients (hazard ratio [HR] 1.15, 95% CI 1.02–1.30). The greater risk of death associated with Aboriginal race was no longer observed after adjustment for diabetes mellitus and other comorbid conditions (adjusted HR 0.89, 95% CI 0.77–1.02) and did not appear to be associated with socioeconomic status. During the study period, unadjusted transplantation rates per 1000 patient-years were 62 (95% CI 52–75) for Aboriginal patients and 133 (95% CI 125–142) for white patients. Aboriginal patients were significantly less likely to receive a renal transplant after commencing dialysis, even after adjustment for potential confounders (HR 0.43, 95% CI 0.35–0.53). In an additional analysis that included follow-up after transplantation for those who received renal allografts, the age-adjusted risk of death associated with Aboriginal race (HR 1.36, 95% CI 1.21–1.52) was higher than when follow-up after transplantation was not considered, perhaps because of the lower rate of transplantation among Aboriginals.Interpretation
Survival among dialysis patients was similar for Aboriginal and white patients after adjustment for comorbidity. However, despite universal access to health care, Aboriginal people had a significantly lower rate of renal transplantation, which might have adversely affected their survival when receiving renal replacement therapy.In North America and the Antipodes, the incidence of diabetes among adolescent and adult Aboriginals has risen dramatically,1,2,3,4 with corresponding increases in the prevalence of diabetic nephropathy.5,6,7 Aboriginal people in Canada have experienced disproportionately high incidence rates of end-stage renal disease (ESRD), with an 8-fold increase in the number of prevalent dialysis patients between 1980 and 2000.8 Although the incidence of ESRD appears to have decreased in recent years, the prevalence of diabetes mellitus and its complications are rising, especially among young people.9,10,11Most work evaluating health outcomes among Aboriginal people considers either the general population12or diseases for which interventions are implemented over a short period, such as alcohol abuse,13 injury14 or critical illness.15 Death and markers of poor health are significantly more common among Aboriginal people than among North Americans of European ancestry, perhaps because of the greater prevalence of diabetes mellitus, adverse health effects due to lower socioeconomic status16 and reduced access to primary care.17 Aboriginal patients may also face unique barriers to care, including mistrust of non-Aboriginal providers, institutional discrimination or preference for traditional remedies.18 These factors may be most relevant when contact with physicians is infrequent, which obstructs development of a therapeutic relationship. In contrast, ESRD is a chronic illness that requires ongoing care from a relatively small, stable multidisciplinary team.Although recent evidence highlights racial inequalities in morbidity and mortality among North Americans with ESRD, most studies have focused on black or Hispanic populations.19We conducted this study to evaluate rates of death and renal transplantation among Aboriginal people after initiation of dialysis in Alberta, Saskatchewan and Manitoba. 相似文献8.
Losing balance: cytokine signaling and cell death in the context of hepatocyte injury and hepatic failure 总被引:6,自引:0,他引:6
Fulminant hepatic failure (FHF) represents a clinical scenario that is associated with high morbidity and mortality, and very limited treatment options. Therefore, great efforts have been made recently on defining its biological mechanisms. This article gives an overview of the cellular processes that are linked to the loss of hepatocytes as a reaction to various agents that cause hepatic failure, and summarizes recent results from clinical and experimental studies of the role of pro- and antiapoptotic cytokines and their intracellular signaling in this context. 相似文献
9.
Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells
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Satyanarayana A Wiemann SU Buer J Lauber J Dittmar KE Wüstefeld T Blasco MA Manns MP Rudolph KL 《The EMBO journal》2003,22(15):4003-4013
Telomere shortening limits the regenerative capacity of primary cells in vitro by inducing cellular senescence characterized by a permanent growth arrest of cells with critically short telomeres. To test whether this in vitro model of cellular senescence applies to impaired organ regeneration induced by telomere shortening in vivo, we monitored liver regeneration after partial hepatectomy in telomerase-deficient mice. Our study shows that telomere shortening is heterogeneous at the cellular level and inhibits a subpopulation of cells with critically short telomeres from entering the cell cycle. This subpopulation of cells with impaired proliferative capacity shows senescence-associated beta-galactosidase activity, while organ regeneration is accomplished by cells with sufficient telomere reserves that are capable of additional rounds of cell division. This study provides experimental evidence for the existence of an in vivo process of cellular senescence induced by critical telomere shortening that has functional impact on organ regeneration. 相似文献
10.
Kornelius Schulze Tobias J. Weismüller Michael Bubenheim Peter Huebener Roman Zenouzi Henrike Lenzen Christian Rupp Daniel Gotthardt Philipp de Leuw Andreas Teufel Vincent Zimmer Florian P. Reiter Christian Rust Lars Tharun Alexander Quaas S?ren A. Weidemann Frank Lammert Christoph Sarrazin Michael P. Manns Ansgar W. Lohse Christoph Schramm German PSC Study Group 《PloS one》2015,10(10)