L-type Ca2+ channels in Ca2+ channelopathies

Voltage-gated L-type Ca2+ channels (LTCCs) mediate depolarization-induced Ca2+ entry in electrically excitable cells, including muscle cells, neurons, and endocrine and sensory cells. In this review we summarize the role of LTCCs for human diseases caused by genetic Ca2+ channel defects (channelopathies). LTCC dysfunction can result from structural aberrations within pore-forming alpha1 subunits causing incomplete congenital stationary night blindness, malignant hyperthermia sensitivity or hypokalemic periodic paralysis. However, studies in mice revealed that LTCC dysfunction also contributes to neurological symptoms in Ca2+ channelopathies affecting non-LTCCs, such as Ca(v)2.1 alpha1 in tottering mice. Ca2+ channelopathies provide exciting molecular tools to elucidate the contribution of different LTCC isoforms to human diseases.     

Structural analysis of the envelope gp120 V3 loop for some HIV-1 variants circulating in the countries of Eastern Europe

The V3 loop on gp120 from human immunodeficiency virus type 1 (HIV-1) is a focus of many research groups involved in anti-AIDS drug development because this region of the protein is a principal target for neutralizing antibodies and a major determinant for cell tropism and syncytium formation. In this study, the nucleotide sequences of the env gene region coding the V3 loop were determined by DNA sequencing methods for four novel HIV-1 strains that circulate in the countries of Eastern Europe, such as Russia, Belarus, Ukraine, etc. Based on the empirical data obtained, the 3D structures of the V3 loops associated with these viral modifications were generated by computer modeling and then compared to discover similarities in the spatial arrangement of this functionally important site of gp120. Despite the HIV-1 genetic variety, several regions of the V3 loop that contain residues critical for cell tropism were shown to be structurally invariant, which may explain its exceptional role in a co-receptor usage. These data together with those on the biological activity of the V3 individual residues clearly show that these conserved structural motifs of gp120 represent potential HIV-1 weak points most suitable for therapeutic intervention.     

A new scaphognathid pterosaur from western Liaoning,China

A partial skeleton of a new pterosaur, Jianchangnathus robustus gen. et sp. nov. from western Liaoning, China, is described. The specimen (IVPP V16866) was collected near Linglongta, Jianchang County, whose deposits have a disputed age that range from Middle Jurassic to Early Cretaceous. The new species shares several features with the non-pterodactyloid Scaphognathus from the Late Jurassic deposits of southern Germany, such as a deep anterior end of the lower jaw, a piriform lower temporal fenestra with the ventral margin broader than the dorsal one and the interalveolar spacing of the maxillary teeth about three alveolar spaces, allowing its allocation to the Scaphognathidae. The main diagnostic features of J. robustus include the large maxillary process of the jugal, the convex alveolar margin of the lower jaw and the procumbent disposition of the first three pairs of dentary teeth. The new Chinese taxon also differs from Fenghuangopterus lii, which comes from the same deposit and is here regarded as Scaphognathidae incertae sedis, mainly by the lower number of teeth and several proportions of the wing elements. The discovery of J. robustus demonstrates a larger diversity in the pterosaur fauna of the Linglongta region so far dominated by the non-pterodactyloid clade Wukongopteridae.     

Spore morphology of the north Asian members of Cystopteridaceae

Spores of Cystopteridaceae from northern Asia were examined using scanning electron microscopy. To evaluate the utility of spore morphology in the taxonomy of each genus, we examined spores of 14 species: seven species each of Gymnocarpium and Cystopteris. Among these are 12 species occurring in northern Asia and two species from other regions for comparative studies. The study focused particularly on perispore characters and spore size. Spores of all species examined are monolete, bean-shaped, with a range in spore size of 26–56 × 18–37 μm for Cystopteris and 25–48 × 16–34 μm for Gymnocarpium. The perispore is morphologically diverse within Cystopteris, but less so within Gymnocarpium. The perispore of the Cystopteris spores is characterised by folds and spines that are separate or form complex sculptural elements. Sacci, ridges and flanges, sometimes on the same spore, are characteristic of the perispore of Gymnocarpium. Spores have straight laesura over which the perispore forms a crest. The crest represents a high and flat fold, which is entire, foveolate or reticulate.     

Parallel-Stranded Duplex DNA and Self-Assembled Quartet Structures Formed by Isoguanine and Related Bases

Abstract

Parallel-stranded (ps) oligonucleotide duplexes are described containing isoguanine-cytosine and/or 5-methylisocytosine-guanine base pairs. A parallel hybrid is also formed when 5-aza-7-deazaguanine base pairs with guanine while the base pair with isoguanine results in an antiparallel duplex. Oligomers such as d(T₄isoG₄T₄) form selfassembled tetraplexes which show a cation selectivity different from that of the G-quartet.     

Parallel-Stranded DNA Formed by New Base Pairs Related to the Isoguanine-Cytosine or Isocytosine-Guanine Motifs

Abstract

Parallel-stranded (ps) oligonucleotide duplexes containing several new base pairs formed between 7-deazaisoguanine and cytosine, 8-aza-7-deaza-isoguanine and cytosine, and 5-aza-7-deaza guanine and guanine are described. The stability of the pshybrids increased if the duplex contains 8-aza-7-deazaisoguanine instead of isoguanine and is decreased by 7-deazaisoguanine incorporation. The purine-purine base pair between 5-aza-7-deazaguanine and guanine was found to be more stable than that of 5-methylisocytosine with guanine.     

Increased heat loss affects hibernation in golden-mantled ground squirrels

During hibernation at ambient temperatures (T(a)) above 0 degrees C, rodents typically maintain body temperature (T(b)) approximately 1 degrees C above T(a), reduce metabolic rate, and suspend or substantially reduce many physiological functions. We tested the extent to which the presence of an insulative pelage affects hibernation. T(b) was recorded telemetrically in golden-mantled ground squirrels (Spermophilus lateralis) housed at a T(a) of 5 degrees C; food intake and body mass were measured at regular intervals throughout the hibernation season and after the terminal arousal. Animals were subjected to complete removal of the dorsal fur or a control procedure after they had been in hibernation for 3-4 wk. Shaved squirrels continued to hibernate with little or no change in minimum T(b), bout duration, duration of periodic normothermic bouts, and food intake during normothermia. Rates of rewarming from torpor were, however, significantly slower in shaved squirrels, and rates of body mass loss were significantly higher, indicating increased depletion of white adipose energy stores. An insulative pelage evidently conserves energy over the course of the hibernation season by decreasing body heat loss and reducing energy expenditure during periodic arousals from torpor and subsequent intervals of normothermia. This prolongs the hibernation season by several weeks, thereby eliminating the debilitating consequences associated with premature emergence from hibernation.     

Chromosomal Dynamism in Progeny of Outbreak-Related Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:NM

Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:NM (nonmotile) is a unique clone that causes outbreaks of hemorrhagic colitis and hemolytic-uremic syndrome. In well-defined clusters of cases, we have observed significant variability in pulsed-field gel electrophoresis (PFGE) patterns which could indicate coinfection by different strains. An analysis of randomly selected progeny colonies of an outbreak strain after subcultivation demonstrated that they displayed either the cognate PFGE outbreak pattern or one of four additional patterns and were <89% similar. These profound alterations were associated with changes in the genomic position of one of two Shiga toxin 2-encoding genes (stx₂) in the outbreak strain or with the loss of this gene. The two stx₂ alleles in the outbreak strain were identical but were flanked with phage-related sequences with only 77% sequence identity. Neither of these phages produced plaques, but one lysogenized E. coli K-12 and integrated in yecE in the lysogens and the wild-type strain. The presence of two stx₂ genes which correlated with increased production of Stx2 in vitro but not with the clinical outcome of infection was also found in 14 (21%) of 67 SF EHEC O157:NM isolates from sporadic cases of human disease. The variability of PFGE patterns for the progeny of a single colony must be considered when interpreting PFGE patterns in SF EHEC O157-associated outbreaks.     

Bromide does not bind to the Mn4Ca complex in its S1 state in Cl(-)-depleted and Br(-)-reconstituted oxygen-evolving photosystem II: evidence from X-ray absorption spectroscopy at the Br K-edge

Chloride is an important cofactor in photosynthetic water oxidation. It can be replaced by bromide with retention of the oxygen-evolving activity of photosystem II (PSII). Binding of bromide to the Mn(4)Ca complex of PSII in its dark-stable S(1) state was studied by X-ray absorption spectroscopy (XAS) at the Br K-edge in Cl(-)-depleted and Br(-)-substituted PSII membrane particles from spinach. The XAS spectra exclude the presence of metal ions in the first and second coordination spheres of Br(-). EXAFS analysis provided tentative evidence of at least one metal ion, which may be manganese or calcium, at a distance of approximately 5 A to Br(-). The native Cl(-) ion may bind at a similar distance. Accordingly, water oxidation may not require binding of a halide directly to the metal ions of the Mn complex in its S(1) state.     

Abundance of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) and urban transmission of visceral leishmaniasis in Campo Grande, state of Mato Grosso do Sul, Brazil

The outspread and urbanization of visceral leishmaniasis (VL) in Campo Grande, state of Mato Grosso do Sul, lead us to undertake the present study over diversity and abundance of sand flies in the urban area to compare with previous search carried out during 1999/2000, before the identification of the disease in the human population.The captures were carried out with automatic light traps, weekly, from February 2004 to February 2005 on three sites including a forested area (Zé Pereira), two peridomicilies (shelters of domestic animals and cultivation areas), and intradomicilie. In the present study 110 collections were obtained during 13 months for 1320 h of collections, resulting in 5004 specimens, 3649 males and 1355 females belonging to the 20 following species: Brumptomyia avellari, Brumptomyia sp., Bichromomyia flaviscutellata, Evandromyia lenti, E. termitophila, E. cortelezzii, E. borrouli, Lutzomyia sp., L. longipalpis, Micropygomyia quinquefer, N. antunesi, N. whitmani, Pintomyia christenseni, Pi. damascenoi, Psathyromyia aragaoi, Ps. campograndensis, Ps. hermanlenti, Ps. shannoni, Pychodopygus claustrei, and Sciopemyia sordellii. L. longipalpis was the most abundant species in the anthropic environment with 92.22% of the captures. This shows an increase of sixty times in the density of L. longipalpis compared to the last sand fly evaluation in 1999/2000. The high density of L. longipalpis in Campo Grande is the main factor of risk in transmission of the disease to human in the urban area. The capture of N. antunesi, typical specie from Amazonian region, in Mato Grosso do Sul is reported for the first time.