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

Alteration of volcaniclastic deposits at Minna Bluff : geochemical insights on mineralizing environment and climate during the Late Miocene in Antarctica

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 15 (2014): 3258–3280, doi:10.1002/2014GC005422.Secondary minerals in volcaniclastic deposits at Minna Bluff, a 45 km long peninsula in the Ross Sea, are used to infer processes of alteration and environmental conditions in the Late Miocene. Glassy volcaniclastic deposits are altered and contain phillipsite and chabazite, low to high-Mg carbonates, chalcedony, and clay. The δ18O of carbonates and chalcedony is variable, ranging from −0.50 to 21.53‰ and 0.68 to 10.37‰, respectively, and δD for chalcedony is light (−187.8 to −220.6‰), corresponding to Antarctic meteoric water. A mean carbonate 87Sr/86Sr ratio of 0.70327 ± 0.0009 (1σ, n = 12) is comparable to lava and suggests freshwater, as opposed to seawater, caused the alteration. Minerals were precipitated at elevated temperatures (91 and 104°C) based on quartz-calcite equilibrium, carbonate 13C-18C thermometry (Δ47 derived temperature = 5° to 43°C) and stability of zeolites in geothermal systems (>10 to ∼100°C). The alteration was a result of isolated, ephemeral events involving the exchange between heated meteoric water and glass during or soon after the formation of each deposit. Near-surface evaporative distillation can explain 18O-enriched compositions for some Mg-rich carbonates and chalcedony. The δ18Owater calculated for carbonates (−15.8 to −22.9‰) reveals a broad change, becoming heavier between ∼12 and ∼7 Ma, consistent with a warming climate. These findings are independently corroborated by the interpretation of Late Miocene sedimentary sequences recovered from nearby sediment cores. However, in contrast to a cold-based thermal regime proposed for ice flow at core sites, wet-based conditions prevailed at Minna Bluff; a likely consequence of high heat flow associated with an active magma system.This research was funded by a collaborative grant NSF OPP 05-38033. It also was supported by UNED/NSF 250550001146, NSF grants EAR-0949191, ARC-1215551, EAR-1325054, EAR-1352212, EAR-1049351, ACS grant 51182-DNI2, DOE grants DE-FG02-13ER16402, and DE-SC0010288, a Hellman Fellowship, and a Katzner grant (BGSU).2015-02-1

Petrology and Geochemistry of the AND-1B Core, ANDRILL McMurdo Ice Shelf Project, Antarctica

This section reports preliminary data and results on petrology and geochemistry of AND-1B core

Petrology and Geochemistry of the AND-1B Core, ANDRILL McMurdo Ice Shelf Project, Antarctica

This section reports preliminary data and results on petrology and geochemistry of AND-1B corePublishedin press2.3. TTC - Laboratori di chimica e fisica delle rocceN/A or not JCRreserve

Petrology and Geochemistry of the AND-1B Core, ANDRILL McMurdo Ice Shelf Project, Antarctica

This section reports preliminary data and results on petrology and geochemistry of AND-1B core

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

Late Pleistocene to Holocene Strata from Soft-Sediment Coring at the AND-1B Site, ANDRILL McMurdo Ice Shelf Project, Antarctica

Prior to rotary coring, a range of soft-sediment coring tools were deployed to recover the sediment-water interface and the upper few metres of strata, whose integrity was threatened by embedment of the sea riser for drilling of the ANDRILL (AND)-1A/1B holes. These coring options included (1) a sediment gravity corer deployed through the ice-shelf hole, and (2) a push corer deployed through the sea riser suspended a few metres above the seabed. Within the AND-1A hole (during an attempt at sea-riser embedment) an extended-nose corer was advanced in front of the sea riser with limited success. The hydraulic piston corer was not deployed as a consequence of the firmness of the Last Glacial Maximum (LGM) diamicton and the occurrence of outsized clasts that could damage the drill string and compromise the deeper coring options. Successive attempts at gravity and push coring recovered 12 cores up to a maximum of 1.56 metres below sea-floor (mbsf). The longest core was dedicated to sampling for microbial life and pore-water geochemical studies which were expected to show the greatest gradients in the upper few metres of the sediment column. All cores sampled Holocene sub-iceshelf sediments above the LGM diamicton, and displayed a similar stratigraphy to a previously obtained site survey core, 250 m to the southeast (McKay et al., in press), with an unconsolidated diamicton passing upwards into muddy sub-ice-shelf facies. The sediment cores record the retreat of the grounding line through the region about 10 000 years ago and a transition from grounding line proximal, through sub-ice-shelf to calving-line proximal environments

Molecular tweezers modulate 14-3-3 protein–protein interactions

Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein–protein interactions