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1.
Podosphaera leucotricha is the causal agent of powdery mildew (PM) in apple. To reduce the amount of fungicides required to control this pathogen, the development of resistant apple cultivars should become a priority. Resistance to PM was achieved in various crops by knocking out specific members of the MLO gene family that are responsible for PM susceptibility (S-genes). In apple, the knockdown of MdMLO19 resulted in PM resistance. However, since gene silencing technologies such as RNAi are perceived unfavorably in Europe, a different approach that exploits this type of resistance is needed. This work evaluates the presence of non-functional naturally occurring alleles of MdMLO19 in apple germplasm. The screening of the re-sequencing data of 63 apple individuals led to the identification of 627 single nucleotide polymorphisms (SNPs) in five MLO genes (MdMLO5, MdMLO7, MdMLO11, MdMLO18, and MdMLO19), 127 of which were located in exons. The T-1201 insertion of a single nucleotide in MdMLO19 caused the formation of an early stop codon, resulting in a truncated protein lacking 185 amino acids, including the calmodulin-binding domain. The presence of the insertion was evaluated in 115 individuals. It was heterozygous in 64 and homozygous in 25. Twelve of the 25 individuals carrying the insertion in homozygosity were susceptible to PM. After barley, pea, cucumber, and tomato, apple would be the fifth species for which a natural non-functional mlo allele has been found.  相似文献   
2.
The effect of exercise-induced oxidative stress on health and aging is not clearly explained. This study examined the effects of habitual sport practice, age, and submaximal exercise on the blood markers of oxidative stress, muscle damage, and antioxidant response. Seventy-two healthy men were grouped by their habitual sport practice: inactive (<1.5 h/week), recreational (3–8 h/week), and trained athletes (>8 h/week), and further divided by age: young (18–25 years), adult (40–55 years), and senior (>55 years). Blood samples were collected at rest and after submaximal effort. Hydroperoxides and superoxide dismutase, glutathione peroxidase, and catalase activities were measured by spectrophotometry. Nuclear DNA damage was analyzed by comet assay. The alpha-actin release was analyzed by Western blot. Alpha-tocopherol, retinol, and coenzyme-Q10 were quantified by high-performance liquid chromatography analysis. Data was analyzed through a factorial ANOVA and the Bonferroni post hoc test. Lipid peroxidation increased significantly with age and submaximal effort (p?<?0.05). However, the trained athlete group presented lower lipid peroxidation compared with the recreational group (MD?=?2.079, SED?=?0.58, p?=?0.002) and inactive group (MD?=?1.979, SED?=?0.61, p?=?0.005). Trained athletes showed significant higher alpha-actin levels (p?<?0.001) than the other groups. Recreational group showed lower nuclear DNA damage than trained athletes (MD?=?3.681, SED?=?1.28, p?=?0.015). Nevertheless, the inactive group presented significantly higher superoxide dismutase and catalase (p?<?0.05) than the other groups. Data suggested that habitual competitive training practice could prevent age-related increases of plasma lipid peroxidation, which, according with our results, cannot be entirely attributed to blood antioxidant defense systems.  相似文献   
3.
Introduction: B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease.

Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described.

Expert commentary: Although conventional strategies (genome sequencing, morphology assays, and immunophenotyping by flow cytometry and/or immunochemistry) have allowed the establishment of the disease stage based on different parameters, it is still necessary to utilize novel approaches (e.g., proteomics) that have the potential to simultaneously analyze thousands of molecules to improve understanding of CLL.  相似文献   

4.
The study of the evolutionary interrelationships among the species encompassed in the Neotropical genus Argia (Zygoptera: Coenagrionidae) has been neglected. The goal of this study is to infer the phylogenetic relationships among 36 species of Argia Rambur, 1842, using complementary data sets (i.e., larval morphology and mitochondrial DNA). The morphological data set comprises 76% of the larvae currently described for this genus and includes 97 morphological characters. From those, 47 characters have not been previously used in taxonomic studies involving dragonflies’ larvae. This is the first cladistic study based on larvae morphology for species within the suborder Zygoptera. Data partitions were analyzed individually, as well as total evidence, using parsimony and Bayesian inference as criteria for optimal-tree selection. The results support the monophyly of the North American species of Argia. This genus can be identified by the combination of eight synapomorphies, four of which are exclusively found in Argia. According to the optimal trees, the individual data sets (i.e., morphology and DNA sequences) have a high level of homoplasy, resulting in soft polytomies and low support for several nodes. The specific relationships of the terminal units differ between the phylogenies; nonetheless, there is historical congruence among them. Within Argia, five clades were consistently recovered. Most of those clades have been identified, at least in part, in previous phylogenetic and taxonomic studies. Indubitably, the morphological characters from larvae have historical signal useful for cladistic and taxonomic inference. Therefore, it should be a priority to pay more attention to this source of characters.  相似文献   
5.
Biological systems often have to measure extremely low concentrations of chemicals with high precision. When dealing with such small numbers of molecules, the inevitable randomness of physical transport processes and binding reactions will limit the precision with which measurements can be made. An important question is what the lower bound on the noise would be in such measurements. Using the theory of diffusion-influenced reactions, we derive an analytical expression for the precision of concentration estimates that are obtained by monitoring the state of a receptor to which a diffusing ligand can bind. The variance in the estimate consists of two terms, one resulting from the intrinsic binding kinetics and the other from the diffusive arrival of ligand at the receptor. The latter term is identical to the fundamental limit derived by Berg and Purcell (Biophys. J., 1977), but disagrees with a more recent expression by Bialek and Setayeshgar. Comparing the theoretical predictions against results from particle-based simulations confirms the accuracy of the resulting expression and reaffirms the fundamental limit established by Berg and Purcell.  相似文献   
6.
Toll-like receptors (TLRs) play a crucial role in innate- and adaptive immunity. The TLR pathways were shown to play key functional roles in experimental acute and chronic kidney injury, including the allo-immune response after experimental renal transplantation. Data about the precise impact of TLRs and their negative regulators on human renal transplant outcomes however are limited and contradictory. We studied twelve non-synonymous single nucleotide polymorphisms (SNPs) of which eleven in TLR1-8 and one in SIGIRR in a final cohort comprising 1116 matching donors and recipients. TLR3 p.Leu412Phe and SIGIRR p.Gln312Arg significantly deviated from Hardy-Weinberg equilibrium and were excluded. The frequency distribution of the minor alleles of the remaining 10 TLR variants were compared between patients with end-stage renal disease (recipients) and controls (kidney donors) in a case-control study. Secondly, the associations between the minor allele frequency of the TLR variants and delayed graft function, biopsy-proven acute rejection and death-censored graft failure after transplantation were investigated with Cox regression. Carrier frequencies of the minor alleles of TLR1 p.His305Leu (OR = 4.79, 95% CI = 2.35–9.75, P = 0.0002), TLR1 p.Asn248Ser (OR = 1.26, 95% CI = 1.07–1.47, P = 0.04) and TLR8 p.Met1Val (OR = 1.37, 95% CI = 1.14–1.64, P = 0.008) were significantly higher in patients with ESRD, with little specificity for the underlying renal disease entity (adjusted for age, gender and donor-recipient relatedness). The minor allele frequency of none of the TLR variants significantly associated with the surrogate and definite outcomes, even when multivariable models were created that could account for TLR gene redundancy. In conclusion, genetic variants in TLR genes were associated with the prevalence of ESRD but not renal transplant outcomes. Therefore, our data suggests that specific TLR signaling routes might play a role in the final common pathway of primary renal injury. A role for TLR signaling in the context of renal transplantation is probably limited.  相似文献   
7.

Objective

The detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.

Methods

We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.

Results

Of the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death.

Conclusion

Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.  相似文献   
8.
9.
ObjectiveTo evaluate the capability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis determined by histopathology in type 2 diabetic patients.MethodsFifty-nine type 2 diabetic patients (49 women, 10 men; mean age, 54 ± 9 years) were submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional approval and patient consent were obtained. Pure molecular-based (D), perfusion-related (D*), and vascular fraction (f) were calculated using a double exponential model and least squares curve fitting. D, D*, and f were compared between patients with and without steatohepatitis and between patients with and without fibrosis. The variables were compared by using the Ranksum test and Student t-test.ResultsSteatohepatitis was observed in 22 patients and fibrosis in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p<0.05) and a lower D* median (34.39 s/mm2 vs. 45.23 s/mm2, p<0.05) were observed among those with steatohepatitis. A lower D median (0.70 s/mm2 vs. 0.82 s/mm2, p<0.05) and a lower D* median (35.01 s/mm2 vs. 44.76 s/mm2, p=0.05) were also observed among those with fibrosis.ConclusionIVIM-DWI has the potential to aid in the characterization of steatohepatitis and fibrosis.  相似文献   
10.
Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D’ = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.  相似文献   
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