Small supernumerary marker chromosomes--progress towards a genotype-phenotype correlation

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they are too small to be characterized for their chromosomal origin by traditional banding techniques, but require molecular cytogenetic techniques for their identification. Apart from the correlation of about one third of the sSMC cases with a specific clinical picture, i.e. the i(18p), der(22), i(12p) (Pallister Killian syndrome) and inv dup(22) (cat-eye) syndromes, most of the remaining sSMC have not yet been correlated with clinical syndromes. Recently, we reviewed the available >1600 sSMC cases (Liehr T, sSMC homepage: http://mti-n.mti.uni-jena.de/~huwww/MOL_ZYTO/sSMC.htm). A total of 387 cases (including the 45 new cases reported here) have been molecularly cytogenetically characterized with regard to their chromosomal origin, the presence of euchromatin, heterochromatin and satellite material. Based on analysis of these cases we present the first draft of a basic genotype-phenotype correlation for sSMC for all human chromosomes apart from the chromosomes Y, 10, 11 and 13.     

Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients

In previous cross-sectional studies, we demonstrated that, in most patients with chronic hepatitis C, the composition and complexity of the circulating hepatitis C virus (HCV) population do not coincide with those of the virus replicating in the liver. In the subgroup of patients with similar complexities in both compartments, the ratio of quasispecies complexity in the liver to that in serum (liver/serum complexity ratio) of paired samples correlated with disease stage. In the present study we investigated the dynamic behavior of viral population parameters in consecutive paired liver and serum samples, obtained 3 to 6 years apart, from four chronic hepatitis C patients with persistently normal transaminases and stable liver histology. We sequenced 359 clones of a genomic fragment encompassing the E2(p7)-NS2 junction, in two consecutive liver-serum sample pairs from the four patients and in four intermediate serum samples from one of the patients. The results show that the liver/serum complexity ratio is not stable but rather fluctuates widely over time. Hence, the liver/serum complexity ratio does not identify a particular group of patients but a particular state of the infecting quasispecies. Phylogenetic analysis and signature mutation patterns showed that virtually all circulating sequences originated from sequences present in the liver specimens. The overall behavior of the circulating viral quasispecies appears to originate from changes in the relative replication kinetics of the large mutant spectrum present in the infected liver.     

Electrochemical treatment of mouse Ehrlich tumor with direct electric current.

Electrochemical treatment of cancer utilizes direct electric current (DEC) to produce direct alterations and chemical changes in tumors. However, the DEC treatment is not established and mechanisms are not well understood. In vivo studies were conducted to evaluate the effectiveness of DEC on animal tumor models. Ehrlich tumors were implanted subcutaneously in sixty male BALB/c mice. When the tumor volumes reached 850 mm(3), four platinum electrodes were inserted into the tumors. DEC of 4 mA was applied for 21 min to the treated group; the total charge was 5 C. The healthy and sick control groups were subjected to the same conditions but without DEC. Hematological and chemical parameters as well as histopathological and peritumoral findings were studied. After the electrochemical therapy it was observed that both tumor volume decrease and necrosis percentage increase were significant in the treated group. Moreover, 24 h after treatment an acute inflammatory response, as well as sodium ion decrease, and potassium ion and spleen weight increase were observed in this group. It was concluded that both electrochemical reactions (fundamentally those in which reactive oxygen species are involved), and immune system stimulation induced by cytotoxic action of the DEC could constitute the most important antitumor mechanisms.     

Meiotic behaviour of sex chromosomes and polymeiosis in three species of insectivores

A study of male meiosis has been carried out on air-dried testicular preparations from three insectivore species: Crocidura russula, Neomys anomalus and Talpa occidentalis.Two particularities in relation to the meiotic process were found. The sex-chromosomes show a special allocycly. In the zygotene and pachytene stages, only some cells (a maximum of 50% in some individuals) present a typical sex-vesicle. In the majority of cells in these stages, the X-chromosome appears unfolded, isopycnotic or negatively heteropycnotic, with the ends of the arms together. The Y-chromosome is more condensed and it is associated with the ends of the X-chromosome. At diakinesis and metaphase I the sex chromosomes show end-to-end pairing. A second interesting feature in these species is the existence of spontaneous polymeiosis in a relative high frequency.The origin of this phenomenon, and the influence of these two particularities on fertility and the relation with the phylogeny of these species are discussed.     

The synaptic sequence in hydroxyurea-treated spermatocytes of Pitymys duodecimcostatus (Rodentia, Microtidae)

A number of Pitymys duodecimcostatus males from a natural population were treated with hydroxyurea, which produces a gap in the spermatogenic line, to study the synaptic sequence of meiotic prophase. The use of substaging criteria, based on the morphological characteristics of the meiotic cells themselves, gave rise to a classification scheme consistent with the chronological sequence revealed by hydroxyurea treatment, which supports the usefulness of these independent criteria. The characteristics of meiotic prophase in P. duodecimcostatus are also described and discussed.     

Synthesis,antimycobacterial activity and influence on mycobacterial InhA and PknB of 12-membered cyclodepsipeptides

In recent years, several small natural cyclopeptides and cyclodepsipeptides were reported to have antimycobacterial activity. Following this lead, a synthetic pathway was developed for a small series of 12-membered ring compounds with one amide and two ester bonds (cyclotridepsipeptides). Within the series, the ring system proved to be necessary for growth inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis in the low micromolar range. Open-chain precursors and analogues were inactive. The compounds modulated autophosphorylation of the mycobacterial protein kinase B (PknB). PknB inhibitors were active at µM concentration against mycobacteria while inducers were inactive. PknB regulates the activity of the mycobacterial reductase InhA, the target of isoniazid. The activity of the series against Mycobacterium bovis BCG InhA overexpressing strains was indistinguishable from that of the parental strain suggesting that they do not inhibit InhA. All substances were not cytotoxic (HeLa?>?5?µg/ml) and did not show any significant antiproliferative effect (HUVEC?>?5?µg/ml; K-562?>?5?µg/ml). Within the scope of this study, the molecular target of this new type of small cyclodepsipeptide was not identified, but the data suggest interaction with PknB or other kinases may partly cause the activity.     

C. elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent Pathologies

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Pinus pollen season trend in South Spain

In Andalusia (southern Spain), Pinus species are found in mountainous areas and nature reserves, though some species are also grown as ornamentals in cities. Annual airborne pollen trends are regarded as an indicator of variations in climate prompted by overall climate change. Airborne pollen concentration also provides a useful tool for analyzing alterations in the distribution of vegetation in response to environmental factors and to changes in land use. The present study analyzed the Pinus pollen season over 22 years (1993–2014) in 4 Andalusian cities (Córdoba, Granada, Jaén, and Málaga), and examined correlations between airborne pollen concentrations and meteorological parameters (temperature and rainfall). Pinus pollen season lasted from March to June, starting first in Málaga and later in eastern Andalusia. Differences between the pollen curves for each city were attributable to differing proportions of pine species in each province. Temperatures during the months prior to flowering tended to fall, prompting delayed onset of the pollen season in most cities. No significant results were observed for rainfall patterns in most cities. Total pollen concentrations increased at most sites, suggesting that the recorded decline in pine-nut output was not influenced by flowering rates, but to the impact of a local pest.