Supersymmetric Dark Matter in the Light of LEP 1.5

We discuss the lower limit on the mass of the neutralino $\chi$ that can be obtained by combining data from $e^+e^-$ annihilation at LEP and elsewhere with astrophysical and theoretical considerations. Loopholes in the purely experimental analysis of ALEPH data from the Z peak and LEP 1.5, which appear when $\mu<0$ for certain values of the sneutrino mass $m_{\tilde\nu}$ and the ratio $\tan\beta$ of supersymmetric Higgs vacuum expectation values, may be largely or totally excluded by data from lower-energy $e^+e^-$ data, the hypothesis that most of the cosmological dark matter consists of $\chi$ particles, and the assumption that electroweak symmetry breaking is triggered by radiative corrections due to a heavy top quark. The combination of these inputs imposes m_{\chi} \ge 21.4~\gev, if soft supersymmetry-breaking masses are assumed to be universal at the grand-unification scale.Comment: 22 pages. one Latex file + nine eps figure

Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation

Microtubules play crucial roles in cellular architecture, intracellular transport, and mitosis. The availability of free tubulin subunits affects polymerization dynamics and microtubule function. When cells sense excess free tubulin, they trigger degradation of the encoding mRNAs, which requires recognition of the nascent polypeptide by the tubulin-specific ribosome-binding factor TTC5. How TTC5 initiates the decay of tubulin mRNAs is unknown. Here, our biochemical and structural analysis reveals that TTC5 recruits the poorly studied protein SCAPER to the ribosome. SCAPER, in turn, engages the CCR4-NOT deadenylase complex through its CNOT11 subunit to trigger tubulin mRNA decay. SCAPER mutants that cause intellectual disability and retinitis pigmentosa in humans are impaired in CCR4-NOT recruitment, tubulin mRNA degradation, and microtubule-dependent chromosome segregation. Our findings demonstrate how recognition of a nascent polypeptide on the ribosome is physically linked to mRNA decay factors via a relay of protein-protein interactions, providing a paradigm for specificity in cytoplasmic gene regulation

Microwave alkylation of lithium tetrazolate

N1-substituted tetrazoles are interesting ligands in transition metal coordination chemistry, especially in the field of spin crossover. Their synthesis is performed in most cases according to the Franke-synthesis, using a primary amine as reagent introducing the substitution pattern. To enhance flexibility in means of substrate scope, we developed a new protocol based on alkylation of lithium tetrazolate with alkyl bromides. The N1–N2 isomerism of the tetrazole during the alkylation was successfully suppressed by use of highly pure lithium tetrazolate and 30 vol.% aqueous ethanol as solvent, leading to pure N1-substituted products. The feasibility of this reaction was demonstrated by a selection of different substrates.Austrian Science Fund (FWF

Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns

Human pre-catalytic spliceosomes contain several proteins that associate transiently just prior to spliceosome activation and are absent in yeast, suggesting that this critical step is more complex in higher eukaryotes. We demonstrate via RNAi coupled with RNA-Seq that two of these human-specific proteins, Smu1 and RED, function both as alternative splicing regulators and as general splicing factors and are required predominantly for efficient splicing of short introns. In vitro splicing assays reveal that Smu1 and RED promote spliceosome activation, and are essential for this step when the distance between the pre-mRNA's 5' splice site (SS) and branch site (BS) is sufficiently short. This Smu1-RED requirement can be bypassed when the 5' and 3' regions of short introns are physically separated. Our observations suggest that Smu1 and RED relieve physical constraints arising from a short 5'SS-BS distance, thereby enabling spliceosomes to overcome structural challenges associated with the splicing of short introns.Work in the J.V. laboratory was supported by Fundación Botín, Banco de Santander through its Santander Universities Global Division, the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU 2014-005153 and BFU 2017 89308-P) and the Centre of Excellence Severo Ochoa. Work in the R.L. laboratory was supported by a grant from the Deutsche Forschungsgemeinschaft SFB 860