Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

International audienc

cluster: Searching for Unique Low Energy Minima of Structures Using a Novel Implementation of a Genetic Algorithm

A new flexible implementation of a genetic algorithm for locating unique low energy minima of isomers of clusters is described and tested. The strategy employed can be applied to molecular or atomic clusters and has a flexible input structure so that a system with several different elements can be built up from a set of individual atoms or from fragments made up of groups of atoms. This cluster program is tested on several systems, and the results are compared to computational and experimental data from previous studies. The quality of the algorithm for locating reliably the most competitive low energy structures of an assembly of atoms is examined for strongly bound Si–Li clusters, and ZnF₂ clusters, and the more weakly interacting water trimers. The use of the nuclear repulsion energy as a duplication criterion, an increasing population size, and avoiding mutation steps without loss of efficacy are distinguishing features of the program. For the Si–Li clusters, a few new low energy minima are identified in the testing of the algorithm, and our results for the metal fluorides and water show very good agreement with the literature

An Olivella Grooved Rectangle Bead Cluster from San Nicolas Island, California

A survey on San Nicolas Island found a cluster of over 4,200 shell beads associated with Middle Holocene archaeological deposits eroded from a coastal dune at CA-SNI-12. Among the 12 bead types recovered were more than 146 Olivella Grooved Rectangle (OGR) beads, including a previously unknown subtype with diagonal grooves, >3,000 Olivella cap beads, and nearly 400 Olivella spire-removed beads. Direct AMS radiocarbon dates (~5,000 cal B.P.) on two bead fragments con rm the Middle Holocene age of the feature. Between approximately 5,400 and 4,400 cal B.P., California’s southern Channel Islands appear to have been the focal point of OGR bead production and use, though these beads have been found in a variety of archaeological contexts across western North America. The broad distribution but short temporal duration of these beads makes them an important Middle Holocene indicator of bead production and exchange in California and the Great Basin

An Olivella Grooved Rectangle Bead Cluster from San Nicolas Island, California

A survey on San Nicolas Island found a cluster of over 4,200 shell beads associated with Middle Holocene archaeological deposits eroded from a coastal dune at CA-SNI-12. Among the 12 bead types recovered were more than 146 Olivella Grooved Rectangle (OGR) beads, including a previously unknown subtype with diagonal grooves, >3,000 Olivella cap beads, and nearly 400 Olivella spire-removed beads. Direct AMS radiocarbon dates (~5,000 cal B.P.) on two bead fragments con rm the Middle Holocene age of the feature. Between approximately 5,400 and 4,400 cal B.P., California’s southern Channel Islands appear to have been the focal point of OGR bead production and use, though these beads have been found in a variety of archaeological contexts across western North America. The broad distribution but short temporal duration of these beads makes them an important Middle Holocene indicator of bead production and exchange in California and the Great Basin

Changes in Marine Subsistence on San Miguel Island from 8,500 to 2,400 Years Ago: Analysis of Bulk Samples from Cave of the Chimneys (CA-SMI-603)

We present a detailed faunal analysis of bulk samples excavated from Cave of the Chimneys, located on the northeast coast of San Miguel Island. The site contains at least six discrete cultural components in a well-strati ed and well- preserved sequence spanning roughly 6,000 years, from about 8,500 to 2,400 years ago. Although species composition and shell sh richness changed over time, rocky intertidal shell sh dominate the faunal assemblage. The Early Holocene strata predominantly consist of California mussels (Mytilus californianus) with other species present in low numbers. The contribution of other shell sh taxa in the Middle Holocene strata greatly increases so that no single species dominates the assemblage. Fish remains are present throughout, but vary in abundance and dietary importance. We discuss these trans-Holocene patterns in the context of other San Miguel Island sites and general patterns of maritime subsistence developed for the Santa Barbara Channel region

Changes in Marine Subsistence on San Miguel Island from 8,500 to 2,400 Years Ago: Analysis of Bulk Samples from Cave of the Chimneys (CA-SMI-603)

We present a detailed faunal analysis of bulk samples excavated from Cave of the Chimneys, located on the northeast coast of San Miguel Island. The site contains at least six discrete cultural components in a well-strati ed and well- preserved sequence spanning roughly 6,000 years, from about 8,500 to 2,400 years ago. Although species composition and shell sh richness changed over time, rocky intertidal shell sh dominate the faunal assemblage. The Early Holocene strata predominantly consist of California mussels (Mytilus californianus) with other species present in low numbers. The contribution of other shell sh taxa in the Middle Holocene strata greatly increases so that no single species dominates the assemblage. Fish remains are present throughout, but vary in abundance and dietary importance. We discuss these trans-Holocene patterns in the context of other San Miguel Island sites and general patterns of maritime subsistence developed for the Santa Barbara Channel region

Quantitative Profiling for Substrates of the Mitochondrial Presequence Processing Protease Reveals a Set of Nonsubstrate Proteins Increased upon Proteotoxic Stress

The majority of mitochondrial preproteins are targeted via N-terminal presequences that are cleaved upon import into the organelle. The essential mitochondrial processing protease (MPP) is assumed to cleave the majority of incoming precursors; however, only a small fraction of mitochondrial precursors have been experimentally analyzed limiting the information on MPP recognition and substrate specificity. Here we present the first systematic approach for identification of authentic MPP substrate proteins using a temperature-sensitive mutant of the MPP subunit Mas1. Inactivation of MPP at nonpermissive temperature leads to accumulation of immature precursors in mitochondria, which were measured by quantitative N-terminal ChaFRADIC. This led to the identification of 66 novel MPP substrates. Deduction of the cleaved presequences determines arginine in position −2 of the cleavage site as a main factor for MPP recognition. Interestingly, a set of nonprocessed proteins was also increased in <i>mas1</i> mutant mitochondria. Additionally, <i>mas1</i> mitochondria respond to temperature elevation with an increase in membrane potential and oxygen consumption. These changes might indicate that <i>mas1</i> cells exert a response to balance the proteotoxic stress induced by MPP dysfunction