Comparative actualistic study hints at origins of alleged Miocene coprolites of Poland

Excrement-shaped ferruginous masses have been recovered from the Miocene of Turów mine in south-western Poland. These siderite masses have been the subject of much controversy, having been interpreted either as being coprolites, cololithes or pseudofossils created by mechanical deformation of plastic sediment. Here we present the results of mineralogical, geochemical, petrographic and microtomographical analyses. Our data indicate that these masses consist of siderite and iron oxide rather than phosphate, and rarely contain recognizable food residues, which may suggest abiotic origins of these structures. On the other hand, evidence in support of a fecal origin include: (i) the presence of two distinct morphotypes differing in size and shape, (ii) the presence of rare hair-like structures or coalified inclusions and (iii) the presence of rare fine striations on the surface. Importantly, comparative actualistic study of recent vertebrate feces shows overall resemblance of the first morphotype (sausage-shaped with rare coalified debris) to excrements of testudinoid turtles (Testudinoidea), whose shell fragment was found in the investigated locality. The second morphotype (rounded to oval-shaped with hair-like structures), in turn, is similar to the feces of some snakes (Serpentes), the remains of which were noted in the Miocene of the neighborhood areas. Other potential producers (such as lizards and crocodiles) and even abiotic origins cannot be fully excluded but are less likely

Comparative actualistic study hints at origins of alleged Miocene coprolites of Poland

Excrement-shaped ferruginous masses have been recovered from the Miocene of Turów mine in south-western Poland. These siderite masses have been the subject of much controversy, having been interpreted either as being coprolites, cololithes or pseudofossils created by mechanical deformation of plastic sediment. Here we present the results of mineralogical, geochemical, petrographic and microtomographical analyses. Our data indicate that these masses consist of siderite and iron oxide rather than phosphate, and rarely contain recognizable food residues, which may suggest abiotic origins of these structures. On the other hand, evidence in support of a fecal origin include: (i) the presence of two distinct morphotypes differing in size and shape, (ii) the presence of rare hair-like structures or coalified inclusions and (iii) the presence of rare fine striations on the surface. Importantly, comparative actualistic study of recent vertebrate feces shows overall resemblance of the first morphotype (sausage-shaped with rare coalified debris) to excrements of testudinoid turtles (Testudinoidea), whose shell fragment was found in the investigated locality. The second morphotype (rounded to oval-shaped with hair-like structures), in turn, is similar to the feces of some snakes (Serpentes), the remains of which were noted in the Miocene of the neighborhood areas. Other potential producers (such as lizards and crocodiles) and even abiotic origins cannot be fully excluded but are less likely

The Grizzly, October 16, 1987

Campus Crackdown Affects All • Police to Halt Under-Age Drinking • Rafuse Paint Crew: Loud, Leering and Surly? • Students Study Abroad • Musser Returns to Dark Ages • Letter: Grizzly Errs • G.E. Attends U.C. Luncheon • The International Job Scene • Commuter Communication Gap • Bears Hope for Winning Season • Soccer Sinks Washington • Athlete of the Week: Walder Forwards Record • Meet the 1987 Homecoming Queen Candidates • Football to Face Gettysburg • Hockey Halted by West Chester • Myrin Catalog System On Line • Busie Body Needs a Bodyhttps://digitalcommons.ursinus.edu/grizzlynews/1196/thumbnail.jp

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation

Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies for HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases

Single-Nucleosome Mapping of Histone Modifications in S. cerevisiae

Covalent modification of histone proteins plays a role in virtually every process on eukaryotic DNA, from transcription to DNA repair. Many different residues can be covalently modified, and it has been suggested that these modifications occur in a great number of independent, meaningful combinations. Published low-resolution microarray studies on the combinatorial complexity of histone modification patterns suffer from confounding effects caused by the averaging of modification levels over multiple nucleosomes. To overcome this problem, we used a high-resolution tiled microarray with single-nucleosome resolution to investigate the occurrence of combinations of 12 histone modifications on thousands of nucleosomes in actively growing S. cerevisiae. We found that histone modifications do not occur independently; there are roughly two groups of co-occurring modifications. One group of lysine acetylations shows a sharply defined domain of two hypo-acetylated nucleosomes, adjacent to the transcriptional start site, whose occurrence does not correlate with transcription levels. The other group consists of modifications occurring in gradients through the coding regions of genes in a pattern associated with transcription. We found no evidence for a deterministic code of many discrete states, but instead we saw blended, continuous patterns that distinguish nucleosomes at one location (e.g., promoter nucleosomes) from those at another location (e.g., over the 3′ ends of coding regions). These results are consistent with the idea of a simple, redundant histone code, in which multiple modifications share the same role

Training genetic programming classifiers by vicinal-risk minimization

We propose and motivate the use of vicinal-risk minimization (VRM) for training genetic programming classifiers. We demonstrate that VRM has a number of attractive properties and demonstrate that it has a better correlation with generalization error compared to empirical risk minimization (ERM) so is more likely to lead to better generalization performance, in general. From the results of statistical tests over a range of real and synthetic datasets, we further demonstrate that VRM yields consistently superior generalization errors compared to conventional ERM

Quantitative Phosphoproteomics of CXCL12 (SDF-1) Signaling

CXCL12 (SDF-1) is a chemokine that binds to and signals through the seven transmembrane receptor CXCR4. The CXCL12/CXCR4 signaling axis has been implicated in both cancer metastases and human immunodeficiency virus type 1 (HIV-1) infection and a more complete understanding of CXCL12/CXCR4 signaling pathways may support efforts to develop therapeutics for these diseases. Mass spectrometry-based phosphoproteomics has emerged as an important tool in studying signaling networks in an unbiased fashion. We employed stable isotope labeling with amino acids in cell culture (SILAC) quantitative phosphoproteomics to examine the CXCL12/CXCR4 signaling axis in the human lymphoblastic CEM cell line. We quantified 4,074 unique SILAC pairs from 1,673 proteins and 89 phosphopeptides were deemed CXCL12-responsive in biological replicates. Several well established CXCL12-responsive phosphosites such as AKT (pS473) and ERK2 (pY204) were confirmed in our study. We also validated two novel CXCL12-responsive phosphosites, stathmin (pS16) and AKT1S1 (pT246) by Western blot. Pathway analysis and comparisons with other phosphoproteomic datasets revealed that genes from CXCL12-responsive phosphosites are enriched for cellular pathways such as T cell activation, epidermal growth factor and mammalian target of rapamycin (mTOR) signaling, pathways which have previously been linked to CXCL12/CXCR4 signaling. Several of the novel CXCL12-responsive phosphoproteins from our study have also been implicated with cellular migration and HIV-1 infection, thus providing an attractive list of potential targets for the development of cancer metastasis and HIV-1 therapeutics and for furthering our understanding of chemokine signaling regulation by reversible phosphorylation