Molecular Tweezers with Varying Anions: A Comparative Study

Selective binding of the phosphate-substituted molecular tweezer 1a to protein lysine residues was suggested to explain the inhibition of certain enzymes and the aberrant aggregation of amyloid petide Aβ42 or α-synuclein, which are assumed to be responsible for Alzheimer’s and Parkinson’s disease, respectively. In this work we systematically investigated the binding of four water-soluble tweezers 1a−d (substituted by phosphate, methanephosphonate, sulfate, or O-methylenecarboxylate groups) to amino acids and peptides containing lysine or arginine residues by using fluorescence spectroscopy, NMR spectroscopy, and isothermal titration calorimetry (ITC). The comparison of the experimental results with theoretical data obtained by a combination of QM/MM and ab initio 1H NMR shift calculations provides clear evidence that the tweezers 1a−c bind the amino acid or peptide guest molecules by threading the lysine or arginine side chain through the tweezers’ cavity, whereas in the case of 1d the guest molecule is preferentially positioned outside the tweezer’s cavity. Attractive ionic, CH-π, and hydrophobic interactions are here the major binding forces. The combination of experiment and theory provides deep insight into the host−guest binding modes, a prerequisite to understanding the exciting influence of these tweezers on the aggregation of proteins and the activity of enzymes

Sedimentology and stratigraphy of the ANDRILL McMurdo Ice Shelf (AND-1B) core

During the 2006-2007 austral summer, the ANDRILL McMurdo Ice Shelf Project recovered a core 1285 m long (AND-1B) from Windless Bight in McMurdo Sound. This core contains a range of lithologies, including both siliciclastic and volcanic diamictites, sandstones and mudstones; diatomites; and volcanic ash/tuff and one phonolitic lava flow. This sequence has been subdivided into eight lithostratigraphic units and 25 subunits, based on lithological abundances. Eleven lithofacies have been identified, ranging from open marine diatomites and mudstones to turbidites to ice-proximal massive and stratified diamictites. More than 50 glacimarine sequences have been recognized, bounded by glacial surfaces of erosion. Three distinct stacking patterns are present, showing evidence of glacial advance/retreat/advance with varying degrees of preservation. Carbonate and pyrite are the dominant secondary phases in the core. The pyrite overprint is especially notable in volcanic sediments below ~400 mbsf, where it often obscures stratification and sediment texture

Sedimentology and stratigraphy of the ANDRILL McMurdo Ice Shelf (AND-1B) core

During the 2006-2007 austral summer, the ANDRILL McMurdo Ice Shelf Project recovered a core 1285 m long (AND-1B) from Windless Bight in McMurdo Sound. This core contains a range of lithologies, including both siliciclastic and volcanic diamictites, sandstones and mudstones; diatomites; and volcanic ash/tuff and one phonolitic lava flow. This sequence has been subdivided into eight lithostratigraphic units and 25 subunits, based on lithological abundances. Eleven lithofacies have been identified, ranging from open marine diatomites and mudstones to turbidites to ice-proximal massive and stratified diamictites. More than 50 glacimarine sequences have been recognized, bounded by glacial surfaces of erosion. Three distinct stacking patterns are present, showing evidence of glacial advance/retreat/advance with varying degrees of preservation. Carbonate and pyrite are the dominant secondary phases in the core. The pyrite overprint is especially notable in volcanic sediments below ~400 mbsf, where it often obscures stratification and sediment texture

Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854)

Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of congenital non-syndromic sensorineural hearing loss. Two large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30), cause hearing loss in individuals homozygous, or compound heterozygous for these deletions or one such deletion and a mutation in GJB2. Recently, we have demonstrated that the del(GJB6-D13S1830) deletion contributes to hearing loss due to an allele-specific lack of GJB2 mRNA expression and not as a result of digenic inheritance, as was postulated earlier. In the current study we investigated the smaller del(GJB6-D13S1854) deletion, which disrupts the expression of GJB2 at the transcriptional level in a manner similar to the more common del(GJB6-D13S1830) deletion. Interestingly, in the presence of this deletion, GJB2 expression remains minimally but reproducibly present. The relative allele-specific expression of GJB2 was assessed by reverse-transcriptase PCR and restriction digestions in three probands who were compound heterozygous for a GJB2 mutation and del(GJB6-D13S1854). Each individual carried a different sequence variant in GJB2. All three individuals expressed the mutated GJB2 allele in trans with del(GJB6-D13S1854), but expression of the GJB2 allele in cis with the deletion was almost absent. Our study clearly corroborates the hypothesis that the del(GJB6-D13S1854), similar to the larger and more common del(GJB6-D13S1830), removes (a) putative cis-regulatory element(s) upstream of GJB6 and narrows down the region of location

Top Production in Hadron-Hadron Collisions and Anomalous Top-Gluon Couplings

We discuss the influence of anomalous tbar-t-G couplings on total and differential tbar-t production cross sections in hadron-hadron collisions. We study in detail the effects of a chromoelectric and a chromomagnetic dipole moment, d' and \mu', of the top quark. In the d'-\mu' plane, we find a whole region where the anomalous couplings give a zero net contribution to the total top production rate. In differential cross sections, the anomalous moments have to be quite sizable to give measurable effects. We estimate the values of d' and \mu' which are allowed by the present Tevatron experimental results on top production. A chromoelectric dipole moment of the top violates CP invariance. We discuss a simple CP-odd observable which allows for a direct search for CP violation in top production.Comment: footnote pg. 4 changed, acknowledgments extende

Spectrum of Genetic Changes in Patients with Non-Syndromic Hearing Impairment and Extremely High Carrier Frequency of 35delG GJB2 Mutation in Belarus

The genetic nature of sensorineural hearing loss (SNHL) has so far been studied for many ethnic groups in various parts of the world. The single-nucleotide guanine deletion (35delG) of the GJB2 gene coding for connexin 26 was shown to be the main genetic cause of autosomal recessive deafness among Europeans. Here we present the results of the first study of GJB2 and three mitochondrial mutations among two groups of Belarusian inhabitants: native people with normal hearing (757 persons) and 391 young patients with non-syndromic SNHL. We have found an extremely high carrier frequency of 35delG GJB2 mutation in Belarus −5.7%. This point deletion has also been detected in 53% of the patients with SNHL. The 312del14 GJB2 was the second most common mutation in the Belarus patient cohort. Mitochondrial A1555G mt-RNR1 substitution was found in two SNHL patients (0.55%) but none were found in the population cohort. No individuals carried the A7445G mutation of mitochondrial mt-TS1. G7444A as well as T961G substitutions were detected in mitochondrial mt-RNR1 at a rate of about 1% both in the patient and population cohorts. A possible reason for Belarusians having the highest mutation carrier frequency in Europe 35delG is discussed