Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff,Latvia

Luk?evi?s, E., Ahlberg, P.E., Stinkulis, ?., Vasi?kova, J. & Zupi??, I. 2011: Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff, Latvia. Lethaia, Vol. 45, pp. 356–370. The siliciclastic sequence of the Upper Devonian of Kurzeme, Western Latvia, is renowned for abundant vertebrate fossils, including the stem tetrapods Obruchevichthys gracilis and Ventastega curonica. During the first detailed taphonomic study of the vertebrate assemblage from the Ogre Formation cropping out at the Langsēde Cliff, Imula River, abundant vertebrate remains have been examined and identified as belonging to one psammosteid, two acanthodian and three sarcopterygian genera; the placoderm Bothriolepis maxima dominates the assemblage. Besides fully disarticulated placoderm and psammosteid plates, separate sarcopterygian scales and teeth, and acanthodian spines, partly articulated specimens including complete distal segments of Bothriolepis pectoral fins, Bothriolepis head shields and sarcopterygian lower jaws have been found. The size distribution of the placoderm bones demonstrates that the individuals within the assemblage are of approximately uniform age. Distinct zones have been traced within the horizontal distribution of the bones. These linear zones are almost perpendicular to the dominant dip azimuth of the cross‐beds and ripple‐laminae and most probably correspond to the depressions between subaqueous dunes. Concavity ratio varies significantly within the excavation area. The degree of fragmentation of the bones and disarticulation of the skeletons suggest that the carcasses were reworked and slightly transported before burial. Sedimentological data suggest deposition in a shallow marine environment under the influence of rapid currents. The fossiliferous bed consists of a basal bone conglomerate covered by a cross‐stratified sandstone with mud drapes, which is in turn overlain by ripple laminated sandstone, indicating the bones were buried by the gradual infilling of a tidal channel. All the Middle–Upper Devonian vertebrate bone‐beds from Latvia are associated with sandy to clayey deposits and have been formed in a sea‐coastal zone during rapid sedimentation episodes, but differ in fossil abundance and degree of preservation. □Agnathans, Devonian, facies analysis, fish, fossil assemblage, palaeoenvironment.     

TPCK targets elements of mitotic spindle and induces cell cycle arrest in prometaphase

The serine protease inhibitor N-α-tosyl-ε-phenylalanyl chloromethyl ketone (TPCK) has been long used in studies of cellular processes including apoptosis. Depending on the experimental conditions, TPCK either induces or inhibits changes associated with apoptosis but there has been little progress in identifying the relevant targets for TPCK. Our group recently showed that the largest subunit of the RNA polymerase II is one of the intracellular targets of TPCK. The complex effects of TPCK on apoptosis, however, suggested the existence of additional apoptosis-relevant targets in cells. Using our unique polyclonal anti-tosyl antibody, here we report the identification of the mitotic spindle as another intracellular target for TPCK. We also provide data that TPCK-mediated labeling of the mitotic spindle correlates with cell cycle arrest in prometaphase.     

A tree-based method for the rapid screening of chemical fingerprints

Background  

The fingerprint of a molecule is a bitstring based on its structure, constructed such that structurally similar molecules will have similar fingerprints. Molecular fingerprints can be used in an initial phase of drug development for identifying novel drug candidates by screening large databases for molecules with fingerprints similar to a query fingerprint.     

Recrafting the neighbor-joining method

Background  

The neighbor-joining method by Saitou and Nei is a widely used method for constructing phylogenetic trees. The formulation of the method gives rise to a canonical Θ(n ³) algorithm upon which all existing implementations are based.     

SequenceLDhot: detecting recombination hotspots

MOTIVATION: There is much local variation in recombination rates across the human genome--with the majority of recombination occurring in recombination hotspots--short regions of around approximately 2 kb in length that have much higher recombination rates than neighbouring regions. Knowledge of this local variation is important, e.g. in the design and analysis of association studies for disease genes. Population genetic data, such as that generated by the HapMap project, can be used to infer the location of these hotspots. We present a new, efficient and powerful method for detecting recombination hotspots from population data. RESULTS: We compare our method with four current methods for detecting hotspots. It is orders of magnitude quicker, and has greater power, than two related approaches. It appears to be more powerful than HotspotFisher, though less accurate at inferring the precise positions of the hotspot. It was also more powerful than LDhot in some situations: particularly for weaker hotspots (10-40 times the background rate) when SNP density is lower (< 1/kb). AVAILABILITY: Program, data sets, and full details of results are available at: http://www.maths.lancs.ac.uk/~fearnhea/Hotspot.     

Application of coalescent methods to reveal fine-scale rate variation and recombination hotspots

There has been considerable recent interest in understanding the way in which recombination rates vary over small physical distances, and the extent of recombination hotspots, in various genomes. Here we adapt, apply, and assess the power of recently developed coalescent-based approaches to estimating recombination rates from sequence polymorphism data. We apply full-likelihood estimation to study rate variation in and around a well-characterized recombination hotspot in humans, in the beta-globin gene cluster, and show that it provides similar estimates, consistent with those from sperm studies, from two populations deliberately chosen to have different demographic and selectional histories. We also demonstrate how approximate-likelihood methods can be used to detect local recombination hotspots from genomic-scale SNP data. In a simulation study based on 80 100-kb regions, these methods detect 43 out of 60 hotspots (ranging from 1 to 2 kb in size), with only two false positives out of 2000 subregions that were tested for the presence of a hotspot. Our study suggests that new computational tools for sophisticated analysis of population diversity data are valuable for hotspot detection and fine-scale mapping of local recombination rates.     

Maximum-likelihood estimation of coalescence times in genealogical trees

We develop a method for maximum-likelihood estimation of coalescence times in genealogical trees, based on population genetics data. For this purpose, a Viterbi-type algorithm is constructed to maximize the joint likelihood of the coalescence times. Marginal confidence intervals for the coalescence times based on the profile likelihoods are also computed. Our method of finding MLEs and calculating C.I.'s appears to be more accurate than alternative numerical maximization methods, and maximum-likelihood inference appears to be more accurate than other existing model-free approaches to estimating coalescent times. We demonstrate the method on two different data sets: human Y chromosome DNA data and fungus DNA data.     

A novel method with improved power to detect recombination hotspots from polymorphism data reveals multiple hotspots in human genes

We introduce a new method for detection of recombination hotspots from population genetic data. This method is based on (a) defining an (approximate) penalized likelihood for how recombination rate varies with physical position and (b) maximizing this penalized likelihood over possible sets of recombination hotspots. Simulation results suggest that this is a more powerful method for detection of hotspots than are existing methods. We apply the method to data from 89 genes sequenced in African American and European American populations. We find many genes with multiple hotspots, and some hotspots show evidence of being population-specific. Our results suggest that hotspots are randomly positioned within genes and could be as frequent as one per 30 kb.     

Inhibition of protein synthesis and JNK activation are not required for cell death induced by anisomycin and anisomycin analogues

Anisomycin was identified in a screen of clinical compounds as a drug that kills breast cancer cells (MDA16 cells, derived from the triple negative breast cancer cell line, MDA-MB-468) that express high levels of an efflux pump, ABCB1. We show the MDA16 cells died by a caspase-independent mechanism, while MDA-MB-468 cells died by apoptosis. There was no correlation between cell death and either protein synthesis or JNK activation, which had previously been implicated in anisomycin-induced cell death. In addition, anisomycin analogues that did not inhibit protein synthesis or activate JNK retained the ability to induce cell death. These data suggest that either a ribosome-ANS complex is a death signal in the absence of JNK activation or ANS kills cells by binding to an as yet unidentified target.