Current and Novel Inhibitors of HIV Protease

The design, development and clinical success of HIV protease inhibitors represent one of the most remarkable achievements of molecular medicine. This review describes all nine currently available FDA-approved protease inhibitors, discusses their pharmacokinetic properties, off-target activities, side-effects, and resistance profiles. The compounds in the various stages of clinical development are also introduced, as well as alternative approaches, aiming at other functional domains of HIV PR. The potential of these novel compounds to open new way to the rational drug design of human viruses is critically assessed

Price of Electricity vs Different Heating Technologies in Czech Republic

This paper analyses both individual components of the price of electricity and the electricity rates as related to individual modes of heating. The price development has been monitored and assessed since July 1, 2001, i.e. the date on which the 'Price Decree of the Energy Regulation Office, No. 5/2001' entered into force concerning introduction of new rates and prices of electricity for households and businesses. Primarily, the rate, D 02d, was chosen for assessment. This rate is used by the majority of households as they use gas or solid fuels for heating. Further, the rate, D45 d, for direct electric heating, and rates, D55 d and D 56 d, for heating by thermal pumps were also subject of assessment. Both the development trends and the comparison of the investigated rates of electricity make it obvious that prices of electricity will continue to be rising in the long-term perspective

Monitoring of Dilation Cracks and Vibrations Caused by Blasting Works at the Quarry of Mokra on Surrounding Construction Objects

The quarry of Mokra, whose locality comprises administrative area of three communities, has cooperated with our Institute for a longer time, communicating with the authorities and people, as regards environmental safety and quality of living in the area. Monitoring of the conditions by continual measurements of dilation cracking and blasting works seismic effects has been an indispensable part of the collaboration.The measurement equipment was developed especially for the needs and condition of the quarry of Mokra, but can be used universally. This paper reports on technicalities of its development and experience of using it in practice

Molecular phylogeny and biogeography of the genus Symbrenthia (Lepidoptera, Nymphalidae) correlates with the past geography of the Oriental region

Jesters, butterflies in the genus Symbrenthia Hübner, 1819, comprise 14 species mainly distributed in the Oriental region. Although this genus has attracted the attention of many researchers in the past, its taxonomy and biogeographic history remain unclear. In this study, we investigate phylogenetic and biogeographic relationships inferred from one mitochondrial (COI) and two nuclear genes (ArgKin, wingless), using both likelihood and Bayesian approaches. With the exception of S. hippalus, which we find to be either sister to Mynes Boisduval, 1832 or sister to Symbrenthia + Mynes + Araschnia, all species of Symbrenthia form a single monophyletic group. We describe a new genus Mynbrenthia Fric & Rindos gen. nov. to accommodate the taxon hippalus. The genus Symbrenthia splits into four sub-groups, “Brensymthia” (with S. niphanda and S. sinoides), “hypselis” (with S. hypselis, S. brabira, S. leoparda and S. doni), “intricata” (with S. intricata and S. hypatia) and “hippoclus” group (including S. platena and a complex of S. hippoclus and S. lilaea). The genus probably originated in Sundaland or continental Asia during the Eocene. The history of the genus Symbrenthia was more influenced by dispersal events and then by subsequent vicariances. Whereas the “hypselis” group colonised the Indo-Australian Archipelago from the Asian continent, the “hippoclus” group dispersed to continental Asia from the Indo-Australian Archipelago

Cross-continental phylogeography of two Holarctic Nymphalid butterflies, Boloria eunomia and Boloria selene

International audiencePleistocene glaciations had significant effects on the distribution and evolution of species inhabiting the Holarctic region. Phylogeographic studies concerning the entire region are still rare. Here, we compared global phylogeographic patterns of one boreo-montane and one boreo-temperate butterflies with largely overlapping distribution ranges across the Northern Hemisphere, but with different levels of range fragmentation and food specialization. We reconstructed the global phylogeographic history of the boreo-montane specialist Boloria eunomia (n = 223) and of the boreo-temperate generalist Boloria selene (n = 106) based on mitochondrial and nuclear DNA markers, and with species distribution modelling (SDM). According to the genetic structures obtained, both species show a Siberian origin and considerable split among populations from Nearctic and Palaearctic regions. According to SDMs and molecular data, both butterflies could inhabit vast areas during the moderate glacials. In the case of B. selene, high haplotype diversity and low geographic structure suggest long-lasting interconnected gene flow among populations. A stronger geographic struc-turing between populations was identified in the specialist B. eunomia, presumably due to the less widespread, heterogeneously distributed food resources, associated with cooler and more humid climatic conditions. Populations of both species show opposite patterns across major parts of North America and in the case of B. eunomia also across Asia. Our data underline the relevance to cover entire distribution ranges to reconstruct the correct phylogeographic history of species

Residues in the HIV-1 capsid assembly inhibitor binding site are essential for maintaining the assembly-competent quaternary structure of the capsid protein.

International audienceMorphogenesis of infectious HIV-1 involves budding of immature virions followed by proteolytic disassembly of the Gag protein shell and subsequent assembly of processed capsid proteins (CA) into the mature HIV-1 core. The dimeric interface between C-terminal domains of CA (C-CA) has been shown to be important for both immature and mature assemblies. We previously reported a CA-binding peptide (CAI) that blocks both assembly steps in vitro. The three-dimensional structure of the C-CA/CAI complex revealed an allosteric effect of CAI that alters the C-CA dimer interface. Based on this structure, we now investigated the phenotypes of mutations in the binding pocket. CA variants carrying mutations Y169A, L211A, or L211S had a reduced affinity for CAI and were unable to form mature-like particles in vitro. These mutations also blocked morphological conversion to mature virions in tissue culture and abolished infectivity. X-ray crystallographic analyses of the variant C-CA domains revealed that these alterations induced the same allosteric change at the dimer interface observed in the C-CA/CAI complex. These results point to a role of key interactions between conserved amino acids in the CAI binding pocket of C-CA in maintaining the correct conformation necessary for mature core assembly

Life History Traits Reflect Changes in Mediterranean Butterfly Communities Due to Forest Encroachment

<div><p>The biodiversity of the Southern Balkans, part of the Mediterranean global biodiversity hot-spot, is threatened by land use intensification and abandonment, the latter causing forest encroachment of formerly open habitats. We investigated the impact of forest encroachment on butterfly species richness, community species composition and the representation of life history traits by repeated seasonal visits of 150 one-hectare sites in five separate regions in three countries—Greece, Bulgaria, and the Republic of Macedonia (FYROM—the Former Yugoslav Republic of Macedonia)— 10 replicates for each habitat type of grasslands, open formations and scrub forest within each region. Grasslands and open formations sites hosted in average more species and more red-listed species than scrub forest, while no pattern was found for numbers of Mediterranean species. As shown by ordination analyses, each of the three habitat types hosted distinct butterfly communities, with Mediterranean species inclining either towards grasslands or open formations. Analysing the representation of life history traits revealed that successional development from grasslands and open formations towards scrub forest shifts the community composition towards species overwintering in earlier stages, having fewer generations per year, and inhabiting large European or Eurosiberian (e.g. northern) ranges; it decreases the representation of Mediterranean endemics. The loss of grasslands and semi-open formations due to forest encroachment thus threatens exactly the species that should be the focus of conservation attention in the Mediterranean region, and innovative conservation actions to prevent ongoing forest encroachment are badly needed.</p></div

Results of Redundancy analyses analyzing butterfly species composition.

<p>Summary of single-term ordinations of predictors of interest (<i>Forest encroachment</i> and <i>Canopy)</i> and potential covariates (site characteristics and visit circumstances) as well as partial RDA ordinations assessing the effect of predictors of interest on butterfly species community composition (BSC) after controlling for site characteristics and visit circumstances (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152026#sec002" target="_blank">Methods</a> for details).</p

Results of life history traits analysis.

<p>Traits-based interpretation of partial RDA ordinations of Southern Balkans butterfly community species composition (BSC) that assessed the response to <i>Forest encroachment</i> and <i>Canopy</i> models including significant covariates and controlled for phylogeny.</p

Impact of <i>Forest encroachment</i> and <i>Canopy</i> on butterfly species richness (A-B) and Red-listed species (C-D) recorded during 2012–2013 from 150 sites in the Southern Balkans.

<p>The box plots show values of species richness (A) and Red-listed species (C) predicted by the generalised linear model (glm) with <i>Forest Encroachment</i> treated as 3-level factors, no covariates included. The lines in (B–D) show glm predicted values with <i>Canopy</i> covers treated as linear predictor after inclusion of covariates for Species Richness (B) and without covariates for Red-listed species (D). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152026#pone.0152026.t001" target="_blank">Table 1</a> for details.</p