Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: A quantitative approach

The epithelial amiloride-sensitive sodium channel (ENaC) controls transepithelial Na+ movement in Na+-transporting epithelia and is associated with Liddle syndrome, an autosomal dominant form of salt-sensitive hypertension. Detailed analysis of ENaC channel properties and the functional consequences of mutations causing Liddle syndrome has been, so far, limited by lack of a method allowing specific and quantitative detection of cell-surface-expressed ENaC. We have developed a quantitative assay based on the binding of 125I-labeled M2 anti-FLAG monoclonal antibody (M2Ab*) directed against a FLAG reporter epitope introduced in the extracellular loop of each of the α, β, and γ ENaC subunits. Insertion of the FLAG epitope into ENaC sequences did not change its functional and pharmacological properties. The binding specificity and affinity (Kd = 3 nM) allowed us to correlate in individual Xenopus oocytes the macroscopic amiloride-sensitive sodium current (INa) with the number of ENaC wild-type and mutant subunits expressed at the cell surface. These experiments demonstrate that: (i) only heteromultimeric channels made of α, β, and γ ENaC subunits are maximally and efficiently expressed at the cell surface; (ii) the overall ENaC open probability is one order of magnitude lower than previously observed in single-channel recordings; (iii) the mutation causing Liddle syndrome (β R564stop) enhances channel activity by two mechanisms, i.e., by increasing ENaC cell surface expression and by changing channel open probability. This quantitative approach provides new insights on the molecular mechanisms underlying one form of salt-sensitive hypertension.

Retinoid-related orphan receptor γ (RORγ) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis

To identify the physiological functions of the retinoid-related orphan receptor γ (RORγ), a member of the nuclear receptor superfamily, mice deficient in RORγ function were generated by targeted disruption. RORγ−/− mice lack peripheral and mesenteric lymph nodes and Peyer's patches, indicating that RORγ expression is indispensable for lymph node organogenesis. Although the spleen is enlarged, its architecture is normal. The number of peripheral blood CD3+ and CD4+ lymphocytes is reduced 6- and 10-fold, respectively, whereas the number of circulating B cells is normal. The thymus of RORγ−/− mice contains 74.4% ± 8.9% fewer thymocytes than that of wild-type mice. Flow cytometric analysis showed a decrease in the CD4+CD8+ subpopulation. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining demonstrated a 4-fold increase in apoptotic cells in the cortex of the thymus of RORγ−/− mice. The latter was supported by the observed increase in annexin V-positive cells. RORγ−/− thymocytes placed in culture exhibit a dramatic increase in the rate of “spontaneous” apoptosis. This increase is largely associated with CD4+CD8+ thymocytes and may, at least in part, be related to the greatly reduced level of expression of the anti-apoptotic gene Bcl-XL. Flow cytometric analysis demonstrated a 6-fold rise in the percentage of cells in the S phase of the cell cycle among thymocytes from RORγ−/− mice. Our observations indicate that RORγ is essential for lymphoid organogenesis and plays an important regulatory role in thymopoiesis. Our findings support a model in which RORγ negatively controls apoptosis in thymocytes.

Transcriptome of a mouse kidney cortical collecting duct cell line: Effects of aldosterone and vasopressin

Aldosterone and vasopressin are responsible for the final adjustment of sodium and water reabsorption in the kidney. In principal cells of the kidney cortical collecting duct (CCD), the integral response to aldosterone and the long-term functional effects of vasopressin depend on transcription. In this study, we analyzed the transcriptome of a highly differentiated mouse clonal CCD principal cell line (mpkCCDcl4) and the changes in the transcriptome induced by aldosterone and vasopressin. Serial analysis of gene expression (SAGE) was performed on untreated cells and on cells treated with either aldosterone or vasopressin for 4 h. The transcriptomes in these three experimental conditions were determined by sequencing 169,721 transcript tags from the corresponding SAGE libraries. Limiting the analysis to tags that occurred twice or more in the data set, 14,654 different transcripts were identified, 3,642 of which do not match known mouse sequences. Statistical comparison (at P < 0.05 level) of the three SAGE libraries revealed 34 AITs (aldosterone-induced transcripts), 29 ARTs (aldosterone-repressed transcripts), 48 VITs (vasopressin-induced transcripts) and 11 VRTs (vasopressin-repressed transcripts). A selection of the differentially-expressed, hormone-specific transcripts (5 VITs, 2 AITs and 1 ART) has been validated in the mpkCCDcl4 cell line either by Northern blot hybridization or reverse transcription–PCR. The hepatocyte nuclear transcription factor HNF-3-α (VIT39), the receptor activity modifying protein RAMP3 (VIT48), and the glucocorticoid-induced leucine zipper protein (GILZ) (AIT28) are candidate proteins playing a role in physiological responses of this cell line to vasopressin and aldosterone.

Emaranhamento de feixes de fótons por meio do campo magnético

Foi proposta uma experiência na qual seria possível produzir um emaranhamento quântico de feixes de fótons com diferentes frequências, movendo-se em uma mesma direção, controlado por meio de um campo magnético externo. Nessa experiência, a interação entre o campo magnético e fótons é realizada por intermédio de elétrons, que interagem tanto com os fótons quanto com o campo magnético externo. Foi desenvolvida uma teoria que descreve processos físicos. Derivamos medidas de emaranhamento de informação e de Schmidt para um sistema geral de dois qubits e a medida residual para um sistema geral de três qubits. Usando a informação obtida da análise dos sistemas de dois e de três quase-fótons, calculamos medidas de emaranhamento. Criamos um programa para cálculo numérico, nesses casos, através do qual construímos gráficos de dependência das medidas de emaranhamentos em feixes de dois e de três fótons. Os resultados obtidos nos permitem ver como a medida de emaranhamento depende dos parâmetros, que caracterizam o sistema em questão. Por exemplo, se ambas as polarizações dos fótons coincidem, então, nenhum emaranhamento ocorre. O emaranhamento acontece apenas se as polarizações do fóton forem opostas.

Brownian Carnot engine

The Carnot cycle imposes a fundamental upper limit to the efficiency of a macroscopic motor operating between two thermal baths. However, this bound needs to be reinterpreted at microscopic scales, where molecular bio-motors and some artificial micro-engines operate. As described by stochastic thermodynamics, energy transfers in microscopic systems are random and thermal fluctuations induce transient decreases of entropy, allowing for possible violations of the Carnot limit. Here we report an experimental realization of a Carnot engine with a single optically trapped Brownian particle as the working substance. We present an exhaustive study of the energetics of the engine and analyse the fluctuations of the finite-time efficiency, showing that the Carnot bound can be surpassed for a small number of non-equilibrium cycles. As its macroscopic counterpart, the energetics of our Carnot device exhibits basic properties that one would expect to observe in any microscopic energy transducer operating with baths at different temperatures. Our results characterize the sources of irreversibility in the engine and the statistical properties of the efficiency-an insight that could inspire new strategies in the design of efficient nano-motors.

On nomenclature and identity of Scarabaeus aeruginosus Linnaeus, S. aeruginosus Drury and S. speciosissimus Scopoli (Coleoptera: Scarabaeoidea: Cetoniinae and Rutelinae)

The valid name for the largest European species of Cetoniinae is Protaetia speciosissima (Scopoli, 1786), with Protaetia aeruginosa (Medvedev, 1964) as a junior synonym. The specimen illustrated by Scopoli in the original description is designated as the lectotype of Scarabaeus speciosissimus Scopoli, 1786. Since the lectotype is lost, a neotype from Piedmont, Italy, is designated and deposited in the Museo Civico di Storia Naturale Carmagnola, Italy. The name Scarabaeus aeruginosus Drury, 1773 is unavailable since Drury did not describe a new species but misidentified Scarabaeus aeruginosus Linné, 1767. A specimen figured by Gronovius in 1764 and cited by Linné is designated as the lectotype of Scarabaeus aeruginosus Linné, 1767. This species remains dubious, but it can be assigned to the ruteline subtribe Anticheirina.

In Putin’s Shadow: Dmitry Medvedev’s presidency. OSW Point of View, November 2011

Dmitry Medvedev’s presidency was an experiment carried out by the Russian ruling elite. Even though the new president has been a loyal member of the ruling camp, this decision involved certain risk that the extensive constitutional powers could eventually encourage the new president to seek emancipation, which could provoke internal conflicts and splits in the elite. This paper analyses Medvedev’s presidency and tries to answer the question why this scenario did not take place and why Medvedev failed to overcome the restrictions imposed on him at the start of his presidential term. The paper also presents the activation of certain social groups during Medvedev’s presidency and their calls for a new social contract with the government.

Russia's strategy towards Moldova: continuation or change? OSW Commentary No. 74, 2012-04-19

The nomination on 21 March of deputy prime minister Dmitri Rogozin to the newly created post of the Russian president’s special representative for Transnistria and to the post of co-chairman of the Russian-Moldovan intergovernmental committee demonstrates the Kremlin’s increased interest in Moldova, and may be a sign of a change in Russia’s strategy towards this country. Other developments which may suggest a revival of Russia’s policy towards Moldova include the appointment on 5 April of Farit Mukhametshin as Russia’s new ambassador in Chisinau. Mukhametshin is a high-ranking official who had previously headed the Federal Agency for the Commonwealth of Independent States, Compatriots Living Abroad and International Humanitarian Cooperation (Rossotrudnichestvo), which is one of the major instruments of Russia’s ‘soft power’ policy towards the post-Soviet states. The Kremlin’s growing interest in Moldova has further been confirmed by an unprecedented visit by Russia’s defence minister Anatoly Serdyukov to Transnistria on 12 April, and a two-day visit by Dmitri Rogozin to Chisinau and Tiraspol on 16–17 April.

Turbulence ahead: disputes within the Russian ruling elite are gathering force. OSW Commentary No. 91, 2012-09-27

The last month has seen a public confrontation between Igor Sechin, the president of Rosneft, and Arkady Dvorkovich, the deputy prime minister, concerning the consolidation of the energy sector. This is the latest in a series of disputes between the Kremlin & businessmen from Putin’s inner circle on one side, and the government & Prime Minister Medvedev on the other. These disputes have been wide-ranging in nature, concerning economic policy, the scope of competency of individual members of the elite, but also the ‘tough line’ adopted by the Kremlin since Vladimir Putin’s return to the presidency. The Kremlin, which is still the main decision-making centre in Russia, has been effectively forcing its opinions through in its short-term disputes with the government. However, a new element in the ongoing conflicts, which is unfavourable to President Putin, is their exceptional strength, their much more public nature, and their wide range (which has included criticism of the president himself) and ever-changing context, especially the worsening socio-economic situation. These conflicts have been overlapping with signs of dissent among Putin’s business supporters, and their declining political willingness to support the leader unconditionally. The Kremlin’s response to the unrest consists of intensifying efforts to discipline the elite and weakening those groups in which Vladimir Putin has limited confidence. The elite’s support is crucial to the stability of his government; to maintain this support, the Kremlin is ready to introduce restrictive and repressive actions against both parliamentarians and government officials. In the short term, such a policy will force the Kremlin’s supporters back into obedience, but fears of a further increase in repression are also starting to be expressed on the sidelines.

Simfonii͡a dli͡a orkestra = [music] : Symphonie für Orchester : Op. 10 /

Re-issued from the plates of Universal-Edition, originally those of State Music Publishers, Moscow.

Symphony no. 4, op. 43. [music] /

Mode of access: Internet.

Kitaĭsko-russkiĭ slovar : po graficheskoĭ sistemi︠e︡ /

Chinese title at head of t.p.

Vozstanīe Uota Taĭlera : ocherki iz istorīi razlozhenīi︠a︡ feodalʹnago stroi︠a︡ v Anglīi /

Includes bibliographical references.