Incidence of epidemic parotitis in different countries]

The authors analyzed the incidence of epidemic parotitis in various countries in 1960--1969 on the basis of the data published by the WHO. It can be supposed that there was no significant difference in the morbidity in various countries and that discrepancy in the official data of individual countries was apparently caused by the errors in recording. In the majority of the countries morbidity curve was fluctuating in character with a 4--5-year periodicity. In the countries of the northern hemisphere the greatest number of cases occurred in spring, and in the southern--in autumn. Monthly distribution of cases during the years with a high and low morbidity level displayed no significant changes.     

Three-dimensional Nuclear Telomere Organization in Multiple Myeloma

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Up to date, it is difficult to predict an individual's time to disease progression and the treatment response. To examine whether the nuclear telomeric architecture will unravel some of these questions, we carried out. Three-dimensional (3D) telomere analysis on samples from patients diagnosed with MGUS and MM, as well as from patients who went into relapse. Telomere signal intensity, number of telomere aggregates, nuclear volume, and the overall nuclear telomere distribution (a/c ratio) were analyzed. The telomeric profiles allowed for the differentiation of the disease stages. The telomeric profiles of myeloma cells obtained from blood and bone marrow aspirates were identical. Based on this study, we discuss the use of 3D telomere profiling as a potential future tool for risk stratification and personalized treatment decisions.     

Evolutionary response to coexistence with close relatives: increased resistance against specialist herbivores without cost for climatic‐stress resistance

Why can hosts coexist with conspecifics or phylogenetically proximate neighbours despite sharing specialist enemies? Do the hosts evolve increased enemy resistance? If so, does this have costs in terms of climatic‐stress resistance, or in such neighbourhoods, does climatic‐stress select for resistances that are multifunctional against climate and enemies? We studied oak (Quercus petraea) descendants from provenances of contrasting phylogenetic neighbourhoods and climates in a 25‐year‐old common garden. We found that descendants from conspecific or phylogenetically proximate neighbourhoods had the toughest leaves and fewest leaf miners, but no reduction in climatic‐stress resistance. Descendants from such neighbourhoods under cold or dry climates had the highest flavonol and anthocyanin levels and the thickest leaves. Overall, populations facing phylogenetically proximate neighbours can rapidly evolve herbivore resistance, without cost to climatic‐stress resistance, but possibly facilitating resistance against cold and drought via multifunctional traits. Microevolution might hence facilitate ecological coexistence of close relatives and thereby macroevolutionary conservatism of niches.     

Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350

SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0^4,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (K_i = 0.36 nM) and viral replication (replicon EC₅₀ = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics.     

Effects of methylphenidate: the cellular point of view

The psychostimulant methylphenidate (MPH) is the first choice of treatment in attention-deficit hyperactivity disorder and is based mainly on inhibition of dopamine transporter (DAT). Nonetheless, the complete cellular effects of MPH are still unknown. We attempted to determine whether MPH influences neurotransmitter levels, synaptic gene expression, and cell proliferation in a dose-dependent manner in rat pheochromocytoma cells (PC12) lacking DAT. PC12 were treated in a dose-dependent manner with MPH. Gene expression level of synaptotagmin (Syt) 1 and 4, syntaxin 1a (Stx1a), and synaptic vesicle glycoprotein 2C (SV2C) was measured using quantitative real-time RT-PCR. Different Neurotransmitter release was measured using high-performance liquid chromatography (HPLC). Differences in cell proliferation were evaluated via BrdU incorporation. Treatment with low-dose MPH (1-100 nM) altered intra-/extracellular neurotransmitter levels, down-regulated all investigated genes as well as enhanced cell proliferation significantly. These data point to diverse effects of MPH on cell metabolism independent of inhibiting DAT.     

The epidemiology of epidemic parotitis in the USSR.

Morbidity from epidemic parotitis in the USSR in the period from 1958 to 1972 ranged within the limits of 266.6 and 521.7 cases per 100 000 inhabitants. A 3--4 years cyclic recurrence of rises and falls in morbidity was observed. The bulk of cases of disease occur in the winter-spring period. In towns, parotitis is registered 3 times more frequently, in the mean, than in rural districts. More than 95% of patients in the USSR consisted of children under 15, while in Moscow, children aged 3--5 years were the most affected group. In Moscow in the period from February 1, 1972 to January 31, 1973, the morbidity in men was 493.2 per 100 000 and in women 339.5 per 100 000 (ratio 1:1.45).