Comparison of micronuclei frequencies in mono-, bi- and poly-nucleated lymphocytes from subjects of a residential suburb and subjects living near a metallurgical plant

Spontaneous baseline frequencies of micronuclei in mono-, bi- and poly-nucleated lymphocytes were analyzed, using the cytokinesis-block technique, in 103 subjects living in a residential suburb (Genova-Nervi), and in 203 subjects living in an urban industrialized area near a metallurgical plant and a coke factory (Genova-Cornigliano). Statistical analysis showed that the average frequency of micronucleated binucleated lymphocytes (MnBNL) was significantly higher (1.42-fold) in donors of Nervi than in donors of Cornigliano living in a contaminated environment. In contrast, the average frequency of micronucleated polynucleated lymphocytes (MnPNL) was significantly higher (1.66-fold) in donors of Cornigliano than in donors of Nervi. The existence in the whole population examined of a positive correlation between frequency of MnBNL and frequency of MnPNL and the absence of a positive correlation between frequency of bi- and poly-nucleated lymphocytes and frequency of MnPNL suggest that the formation of MnPNL is a consequence of genetic damage and not of mitotic errors arising during the division of bi- and poly-nucleated cells. In agreement with previous findings the frequency of MnBNL increased with age and was significantly higher in females than in males; unexpectedly it was higher in non-smokers/non-drinkers than in smokers/drinkers.     

Assessing Nephrological Competence among Geriatricians: A Proof of Concept Internet Survey

Chronic kidney disease (CKD) is highly prevalent in the elderly and negatively impacts survival and health status. Thus, nephrological competence is mandatory for a skilled geriatrician. The present study aimed to assess nephrological competence in a sample of geriatricians recruited through a web survey. To this aim, a 12-items questionnaire was produced by an expert panel of nephrologists and geriatricians and was available online for members of the Italian Society of Gerontology and Geriatrics (SIGG). Two-hundred-eighty-seven geriatricians volunteered to fill in the questionnaire. The majority of them indirectly estimated the glomerular filtration rate (GFR) using mainly the Cockroft-Gault (C-G) formula. Selected nephrological exams, such as urinary Na and serum D-vitamin measurements, did not qualify as routine exams although the majority of geriatricians supplemented their patients with fat-soluble secosteroids. Ten percent of geriatricians asked for nephrological consultation only for stage 5 CKD patients and 30,9% only for stage 4 or 5. Erythropoietin supplementation was common practice for the majority of geriatricians, while only one third of them systematically used a procedure intended to prevent the contrast induced nephropathy (CIN). Finally, an alleged 50% adherence to the international guidelines for the management of CKD patients emerged from the questionnaire. Overall, results from this survey strongly recommend promoting nephrological education among geriatricians. Didactic standards for in training geriatricians need to be updated and the cooperation between geriatrics and nephrological societies promoted.     

Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation

Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels.     

Occurrence,diversity and distribution of Trypanosoma infections in cattle around the Akagera National Park,Rwanda

BackgroundAfrican Trypanosomiases threaten the life of both humans and animals. Trypanosomes are transmitted by tsetse and other biting flies. In Rwanda, the African Animal Trypanosomiasis (AAT) endemic area is mainly around the tsetse-infested Akagera National Park (NP). The study aimed to identify Trypanosoma species circulating in cattle, their genetic diversity and distribution around the Akagera NP.MethodologyA cross-sectional study was carried out in four districts, where 1,037 cattle blood samples were collected. The presence of trypanosomes was determined by microscopy, immunological rapid test VerY Diag and PCR coupled with High-Resolution Melt (HRM) analysis. A parametric test (ANOVA) was used to compare the mean Packed cell Volume (PCV) and trypanosomes occurrence. The Cohen Kappa test was used to compare the level of agreement between the diagnostic methods.FindingsThe overall prevalence of trypanosome infections was 5.6%, 7.1% and 18.7% by thin smear, Buffy coat technique and PCR/HRM respectively. Microscopy showed a low sensitivity while a low specificity was shown by the rapid test (VerY Diag). Trypanosoma (T.) congolense was found at a prevalence of 10.7%, T. vivax 5.2%, T. brucei brucei 2% and T. evansi 0.7% by PCR/HRM. This is the first report of T.evansi in cattle in Rwanda. The non-pathogenic T. theileri was also detected. Lower trypanosome infections were observed in Ankole x Friesian breeds than indigenous Ankole. No human-infective T. brucei rhodesiense was detected. There was no significant difference between the mean PCV of infected and non-infected animals (p>0.162).ConclusionsOur study sheds light on the species of animal infective trypanosomes around the Akagera NP, including both pathogenic and non-pathogenic trypanosomes. The PCV estimation is not always an indication of trypanosome infection and the mechanical transmission should not be overlooked. The study confirms that the area around the Akagera NP is affected by AAT, and should, therefore, be targeted by the control activities. AAT impact assessment on cattle production and information on the use of trypanocides are needed to help policymakers prioritise target areas and optimize intervention strategies. Ultimately, these studies will allow Rwanda to advance in the Progressive Control Pathway (PCP) to reduce or eliminate the burden of AAT.     

Characterization and Evolution of mariner Elements from Closely Related Species of Fruit Flies (Diptera: Tephritidae)

Mariner elements were amplified using the polymerase chain reaction from two species of tephritid flies, Ceratitis rosa and Trirhithrum coffeae. The sequences were ∼1.3 kb in length. None of these elements appeared to be functional, as in every case the open reading frame (ORF) was disrupted by the presence of frameshifts or stop codons. These elements, Crmar1 and Tcmar1, are very similar to the Ccmar1 element previously amplified from the closely related tephritid species C. capitata and are members of the mellifera subfamily of mariner elements. The phylogeny and pattern of divergence of these elements were examined in relation to the phylogeny of the host species. It is highly probable that the elements were present in the ancestral lineage prior to the divergence of the three species. The copy numbers of the elements within each species are very different, ranging from about 10 in T. coffeae to 5,000 in C. rosa. The possible mechanisms which determine the copy number of an element in the host genome are discussed. Received: 25 April 1997 / Accepted: 31 July 1997     

芦鹀种群中的文化、遗传和形态进化的同时比较

我们比较了芦 (Emberizaschoeniclus)两个亚种组 ,即北部的薄喙亚种组和南部的厚喙亚种组的 10个种群中的文化、遗传和形态变异。使用了四个不同的变异标记物 ,其中两个用来测量文化分化 ,一个用来测量遗传分化 ,即微卫星等位基因的频次 ,一个用来测量种群的形态分化 ,即喙的高度。将遗传分化作为进化时间的尺度 ,我们计算了亚种组间和组内分化指标与所估计的进化率之间的相关性 ,发现只有文化定量指标和遗传分化与种群的形态分化相关 ,而两个文化分化指标之间没有关系 ,文化分化与遗传分化之间也没有关系。使用文化 -定量分化指标 ,发现亚种组间的文化进化率高于亚种内的文化进化率 ,提示鸣唱在防止杂交方面只有微弱的、也许是次要的作用。鸣唱定量特征的变异与微卫星频次相同 ,实际上在自然界中更可能是遗传决定的 ,这可以解释由于分析两个文化变异指标所得出的结果的不一致性。鸣唱的声学特性可能由于栖息地的差异或形态上的限制而发生了演变 ,而文化传播单位 (Meme)的特性可能由于学习鸣唱和文化传播而受到了影响