DNA barcoding, phylogeny and phylogeography of the cyst nematode species of the Avenae group from the genus Heterodera (Tylenchida: Heteroderidae)

Among the recognised species groups of Heterodera, the Avenae group is one of the largest with a total of 12 species. Ten of them, H. arenaria, H. aucklandica, H. australis, H. avenae, H. filipjevi, H. mani, H. pratensis, H. riparia, H. sturhani and H. ustinovi, are morphologically closely related and represent the H. avenae species complex, and the other two, H. hordecalis and H. latipons, are morphologically more distinct from this complex. In this study we provide comprehensive phylogenetic analyses of several hundred COI and ITS rRNA gene sequences from the Avenae group using Bayesian inference, maximum likelihood and statistical parsimony. Some 220 COI and 11 ITS rRNA new gene sequences from 147 nematode populations collected in 26 countries were obtained in this study. Our study showed that the COI gene is a powerful DNA barcoding marker for identification of populations and species from the Avenae group. A putatively new cyst nematode species related to H. latipons was revealed from the analysis of COI and ITS rRNA gene datasets. COI gene sequences allow distinguishing H. arenaria, H. australis and H. sturhani from each other and other species. Problems of species delimiting of these species are discussed. The results of the analysis showed that COI haplotypes corresponded to certain pathotypes of the cereal cyst nematodes. It is recommended that information on COI haplotypes of studied populations be included in research with these nematodes. Based on the results of phylogeographical analysis and age estimation of clades with a molecular clock approach, it was hypothesised that several species of the Avenae group primarily originated and diversified in the Irano-Anatolian hotspot during the Pleistocene and Holocene periods and then dispersed from this region across the world. Different geographic barriers, centres and times of origin might explain current known distribution patterns for species of the Avenae group. Possible pathways, including a long distance trans-Atlantic dispersal, and secondary centres of diversification are proposed and discussed. © 2018 by Koninklijke Brill NV, Leiden, The Netherlands

THYROID FUNCTION IN MALIGNANT PEDIATRIC PATIENTS AFTER RADIOTHERAPY

Introduction. Malignancy is seen in pediatrics, frequently. Radiotherapy as a common procedure in malignancy management may has many side effects and complications, especially about endocrine system. In this study, we evaluate the incidence of post radiotherapy hypothyroidism In malignant pediatric patients.
 Methods. In a cross sectional study one hundred and eighty children between 1 to 20 years old that survived of malignancy were selected. They have been treated in Sayyed-Alshohada hospital (affiliated to Isfahan University of Medical Sciences) from 1993 Sep. until 1998 Sep. by radiotherapy.
 Baseline characteristics (e.g. sex, age, dose, location and number of radiotherapy fraction, type of malignancy) were derived from medical records. Subjects were invited by letters to evaluate their thyroid functions in 1999. Serum T4 and FT4 concentrations assayed by RIA and TSH by IRMA methods.
 Results. The incidence of hypothyroidism was 13.3 percent (1.2 percent secondary hypothyroidism and 12.1 percent primary hypothyroidism). There was no statistical difference in age and sex distribution between patients with or without hypothyroidism. History of cervical region radiotherapy was taken in 45.8 percent of hypothyroid patients. There was no significant difference in dose and number of radiotherapy fraction between hypothyroid and euthyroid patients.
 Discussion. Radiotherapy may have a role in developing hypothyroidism in patients who received radiotherapy. This role has no relation to age and sex, dose and number of radiation fraction in development of hypothyroidism. Region of radiotherapy is important. It is suggested that this study continues and data will be collected during several years in future. Of course, many of hypothyroid patients will become euthyroid spontaneously

Apolipoprotein A-I proteolysis in aortic valve stenosis: role of cathepsin S

Aortic valve stenosis (AVS) is the most common valvular heart disease in the Western world. Therapy based on apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins, results in AVS regression in experimental models. Nevertheless, apoA-I degradation by proteases might lead to suboptimal efficacy of such therapy. An activatable probe using a quenched fluorescently labeled full-length apoA-I protein was generated to assess apoA-I-degrading protease activity in plasma derived from 44 men and 20 women with severe AVS (age 65.0 ± 10.4 years) as well as from a rabbit model of AVS. In human and rabbit AVS plasma, apoA-I-degrading protease activity was significantly higher than in controls (humans: 0.038 ± 0.009 vs 0.022 ± 0.005 RFU/s, p < 0.0001; rabbits: 0.033 ± 0.016 vs 0.017 ± 0.005 RFU/s, p = 0.041). Through the use of protease inhibitors, we identified metalloproteinases (MMP) as exerting the most potent proteolytic effect on apoA-I in AVS rabbits (67%, p < 0.05 vs control), while the cysteine protease cathepsin S accounted for 54.2% of apoA-I degradation in human plasma (p < 0.05 vs control) with the maximum effect seen in women (68.8%, p < 0.05 vs men). Accordingly, cathepsin S activity correlated significantly with mean transaortic pressure gradient in women (r = 0.5, p = 0.04) but not in men (r = - 0.09, p = 0.60), and was a significant independent predictor of disease severity in women (standardized beta coefficient 0.832, p < 0.001) when tested in a linear regression analysis. ApoA-I proteolysis is increased in AVS. Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease

Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis

BACKGROUND Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown. METHODS AND RESULTS We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( < 0.05). Accordingly, AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%,  < 0.0001). Both ADAMTS-13 activity and HMWM correlated significantly with aortic transvalvular gradients, thereby showing opposing correlations ( = 0.3,  = 0.018 and  = -0.4,  = 0.003, respectively). Administration of an apoA-I mimetic peptide reduced ADAMTS-13 activity in AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec,  < 0.05). Similarly, a negative correlation was found between ADAMTS-13 activity and HDL cholesterol levels in patients with AVS ( = -0.3,  = 0.045). CONCLUSION Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS