Synthesis and Properties of ApA Analogues with Shortened Phosphonate Internucleotide Linkage

A complete series of the 2 ′–5 ′ and 3 ′–5 ′ regioisomeric types of r(ApA) and 2 ′-d(ApA) analogues with the α-hydroxy-phosphonate C3 ′-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 ′-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 ′-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 ′(2 ′)-O-P-CH₂-C4 ″ linkage lacking the 5 ′-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 ′-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.     

Zooplankton of the drying lake Orog (Mongolia)

Interannual differences in zooplankton parameters of the drying lake Orog depend on the water level and the influence of the lake’s tributary. When the water level is high and pastures are especially close to the shoreline, the zooplankton structure indicates a hypertrophic status. When the water level decreases, pastures are far from the shoreline, and a large proportion of the body of water comes from the tributary, the zooplankton structure characterizes the lake as an oligotrophic waterbody; when the tributary dries up, it is characterized as mesotrophic.     

Chemoimmunotherapy of chronic hepatitis B virus infection in the woodchuck model overcomes immunologic tolerance and restores T-cell responses to pre-S and S regions of the viral envelope protein

Treatment of chronic hepatitis B virus (HBV) infection could combine potent antiviral drugs and therapeutic vaccines to overcome immunological tolerance and induce the recovery phenotype to protect against disease progression. Conventional vaccination of woodchucks chronically infected with the woodchuck hepatitis virus (WHV) elicited differential T-cell response profiles depending on whether or not carriers were treated with the potent antiviral drug clevudine (CLV), which significantly reduces viral and antigen loads. The differential T-cell responses defined both CLV-dependent and CLV-independent epitopes of the pre-S and S regions of the WHV envelope protein. Only combined treatment involving CLV and conventional vaccine therapeutically restored the T-cell response profile of chronic WHV carrier woodchucks to that seen in prophylactic vaccination and in recovery from acute WHV infection. The results have implications for mechanisms of immunological tolerance operating in chronic HBV infection and suggest that such combined chemoimmunotherapy may be useful for treatment of humans with chronic HBV infection.     

Mercury content in muscles of fish of the Selenga River and lakes of its basin (Russia)

Differences between the muscle mercury contents in fish from lakes Gusinoye and Karasinoye and the Selenga River may indicate an inconsiderable income of mercury in aquatic ecosystems with atmospheric precipitation, along with a more intensive migration of mercury with the riverine flux. The minimal concentration of mercury (less than 0.15 mg/kg, dry weight) has been registered in the muscles of Amur sleeper from Lake Karasinoye and of Baikal omul from Lake Baikal, while the maximal concentration (1.0–2.3 mg/kg, dry weight) has been revealed in the fish caught in the Selenga River delta (in predatory pike, Amur catfish, and perch, as well as in omnivorous roach and ide). The muscle metal content in dace decreased along the downstream direction.     

Age and growth comparisons of Hovsgol grayling (Thymallus nigrescens Dorogostaisky, 1923), Baikal grayling (T. baicalensis Dybowski, 1874), and lenok (Brachymystax lenok Pallas, 1773) in lentic and lotic habitats of Northern Mongolia

Despite concern over the conservation status of many Mongolian salmonids and the importance of their ecological role in Mongolia's aquatic ecosystems, little is known about their basic biology. Hovsgol grayling (Thymallus nigrescens) is endemic to Lake Hovsgol, Mongolia and listed as endangered on the Mongolian Red List. Baikal grayling (T. baicalensis) and lenok (Brachymystax lenok) are found in lakes and rivers throughout the Selenge drainage. A detailed study of the age and growth of these three salmonids was conducted based on 1,682 samples collected from July 2006 to July 2013 in Lake Hovsgol, its outlet the Eg River, and one of the Eg's largest tributaries, the Uur River. Our results suggest that Hovsgol grayling in particular can reach a much older maximum age (17 years in our samples) than previously believed based on aging from scales. Female Hovsgol grayling were heavier at a given length than their male counterparts. Lenok had a greater average length‐at‐age in Lake Hovsgol compared to the rivers and greater weight‐at‐length in the warmer Uur River than in the Eg; female lenok from the rivers had a greater average length‐at‐age than their male counterparts. This study provides critical new information for the management and conservation of these threatened salmonid species in Mongolia.     

The first case of morphological differentiation of Altai Osman <Emphasis Type="Italic">Oreoleuciscus potanini</Emphasis> (Cyprinidae,Actinopterigii) in a river

The variability of osteological characters has been investigated in cyprinid fish of the genus Oreoleuciscus (Potanin Altai osman) from the river Zavkhan; this fish species is endemic for water bodies of Central Asia. Multivariate analysis of 13 quantitative parameters of the size of the cerebral and visceral skull and the pectoral girdle and the construction of ontogenetic channels allowed the detection of morphologically distinct forms in the fluvial habitats. The result obtained provides additional proof of the possibility of sympatric diversification of fish in river ecosystems. One of the two fluvial forms discovered has been shown to be identical (with regard to the osteological characters) to a previously described herbivorous form of O. potanini from the standing water bodies of the Great Lakes Hollow (Western Mongolia).     

Structure–activity study of macropin,a novel antimicrobial peptide from the venom of solitary bee Macropis fulvipes (Hymenoptera: Melittidae)

A novel antimicrobial peptide, designated macropin (MAC‐1) with sequence Gly‐Phe‐Gly‐Met‐Ala‐Leu‐Lys‐Leu‐Leu‐Lys‐Lys‐Val‐Leu‐NH₂, was isolated from the venom of the solitary bee Macropis fulvipes. MAC‐1 exhibited antimicrobial activity against both Gram‐positive and Gram‐negative bacteria, antifungal activity, and moderate hemolytic activity against human red blood cells. A series of macropin analogs were prepared to further evaluate the effect of structural alterations on antimicrobial and hemolytic activities and stability in human serum. The antimicrobial activities of several analogs against pathogenic Pseudomonas aeruginosa were significantly increased while their toxicity against human red blood cells was decreased. The activity enhancement is related to the introduction of either l ‐ or d ‐lysine in selected positions. Furthermore, all‐d analog and analogs with d ‐amino acid residues introduced at the N‐terminal part of the peptide chain exhibited better serum stability than did natural macropin. Data obtained by CD spectroscopy suggest a propensity of the peptide to adopt an amphipathic α‐helical secondary structure in the presence of trifluoroethanol or membrane‐mimicking sodium dodecyl sulfate. In addition, the study elucidates the structure–activity relationship for the effect of d ‐amino acid substitutions in MAC‐1 using NMR spectroscopy. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Strance double helix of poly(dA-dT) in high-salt solution

³¹P and ¹H NMR studies indicate that double stranded poly(dA-dT) adopts an unusual structure in high-CsF solution, in which the dA residues occur in a unique geometry. This structure is different from the high-salt form of poly(dG-dC).     

Synthesis and utilization of 13C and 15N backbone-labeled proline: NMR study of synthesized oxytocin with backbone-labeled C-terminal tripeptide amide

Summary. The ¹³C and ¹⁵N backbone-labeled proline was prepared using Oppolzer’s method based on application of a sultam as chiral auxiliary. This isotopomer was used in the synthesis of the ¹³C, ¹⁵N backbone-labeled C-terminal tripeptide amide fragment of neurohypophyseal hormone oxytocin. Finally, this tripeptide amide was coupled by segment condensation with N-Boc- or N-Fmoc-tocinoic acid, followed by N-deprotection with TFA or piperidine. The labeled oxytocin exhibited biological activity identical with that of natural oxytocin. A detailed ¹H, ¹³C and ¹⁵N NMR study confirmed the assigned oxytocin conformation containing a β-turn in the cyclic part of the molecule, stabilized by H-bond(s) that can be perturbed by the C-terminal tripeptide amide moiety as indicated by comparison of NMR data for both the tocine ring in oxytocin and tocinoic acid.