High-energy scale revival and giant kink in the dispersion of a cuprate superconductor

In the present photoemission study of a cuprate superconductor Bi1.74Pb0.38Sr1.88CuO6+delta, we discovered a large scale dispersion of the lowest band, which unexpectedly follows the band structure calculation very well. The incoherent nature of the spectra suggests that the hopping-dominated dispersion occurs possibly with the assistance of local spin correlations. A giant kink in the dispersion is observed, and the complete self-energy containing all interaction information is extracted for a doped cuprate in the low energy region. These results recovered significant missing pieces in our current understanding of the electronic structure of cuprates.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Lett. on May 21, 200

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

3D multi-agent models for protein release from PLGA spherical particles with complex inner morphologies

In order to better understand and predict the release of proteins from bioerodible micro- or nanospheres, it is important to know the influences of different initial factors on the release mechanisms. Often though it is difficult to assess what exactly is at the origin of a certain dissolution profile. We propose here a new class of fine-grained multi-agent models built to incorporate increasing complexity, permitting the exploration of the role of different parameters, especially that of the internal morphology of the spheres, in the exhibited release profile. This approach, based on Monte-Carlo (MC) and Cellular Automata (CA) techniques, has permitted the testing of various assumptions and hypotheses about several experimental systems of nanospheres encapsulating proteins. Results have confirmed that this modelling approach has increased the resolution over the complexity involved, opening promising perspectives for future developments, especially complementing in vitro experimentation

The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time

Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections

A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin

<p>Abstract</p> <p>Background</p> <p>Current use of prescribed or over the counter non-steroidal anti-inflammatory drugs (NSAIDs) for pain and osteoarthritis (OA) have untoward gastrointestinal and cardiovascular related side effects, as a result the need for a safe and effective alternative has become unequivocally crucial.</p> <p>Method</p> <p>A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. Sixty subjects (age 40-75) with symptomatic OA of the hip or knee were assigned to 4 treatment groups (n = 15); Group A0 (Placebo, CMC capsule), Group A1 (UP446 250 mg/day), Group A2 (UP446 500 mg/day) and Group A3 (Celecoxib, 200 mg/day). MOS-SF-36 and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) data were collected at baseline and after 30, 60 and 90 days of treatment as a measure of efficacy. Erythrocyte sedimentation rate, C-reactive protein, plasma thrombin time (PTT), fructosamine, Hematology, clinical chemistry and fecal occult blood were monitored for safety.</p> <p>Results</p> <p>Statistically significant decrease in WOMAC pain score were observed for Group A1 at day 90, Group A2 at 30 and 90 days and Group A3 at 60 and 90 days. Statistically significant decrease in WOMAC stiffness score were observed for Group A1 and Group A2 at 30, 60 and 90 days; but not for Group A0 and Group A3. The mean change in WOMAC functional impairment scores were statistically significant for Group A1 and Group A2 respectively at 30 days (p = 0.006 and p = 0.006), at 60 days (p = 0.016 and p = 0.002) and at 90 days (p = 0.018 and p = 0.002), these changes were not significant for Group A0 and Group A3. Based on MOS -SF-36 questionnaires, statistically significant improvements in physical function, endurance and mental health scores were observed for all active treatment groups compared to placebo. No significant changes suggestive of toxicity in routine hematologies, serum chemistries, liver enzymes or PTT were noted in any of the treatment groups.</p> <p>Conclusion</p> <p>Based on current findings UP446 is safe and efficacious alternative to established anti-inflammatory medications for alleviating OA symptoms as measured by the WOMAC Index.</p

Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study

<p>Abstract</p> <p>Background</p> <p>DNA-methyltransferase-3B (DNMT3B), which plays a role in DNA methylation, is usually aberrant expression involved in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation in several cancers, thereby modulating the susceptibility to cancer.</p> <p>Methods</p> <p>DNMT3B -579G>T genotypes and -149C>T were determined by PCR-RFLP and sequencing in 137 colorectal cancer patients and 308 controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed colorectal cancer. The association between two SNPs of the <it>DNMT3B </it>promoter and the risk of the development of colorectal cancer was analyzed in a population of Chinese.</p> <p>Results</p> <p>The allele frequency of -149C >T among patients and controls was 0.73% versus 0.65%, respectively. The allele frequency of -597G>T for patients and controls was 6.57% versus 11.53%, respectively. Individuals with at least one -149C>T allele were no at a significantly increase risk of colorectal cancer compared with those having a -149TT genotype. However, Individuals with at least one 579G>T allele were decreased risk of colorectal cancer compared with those having a -579TT genotype.</p> <p>Conclusion</p> <p>The relative distribution of -149C>T <it>DNMT3B </it>SNPs among a Chinese population can not be used as a stratification marker to predict an individual's susceptibility to colorectal cancer. However, the DNMT3B -579G>T polymorphism may contribute to the genetic susceptibility to colorectal cancer.</p

Geochemical characteristics and 40Ar- 39Ar ages of the amphibolites and gabbros in Tarlang area: Implications for tectonic evolution of the Chinese Altai

Amphibolitic and gabbroic rocks occur in Tarlang area in Chinese Altay. Amphibolites are metamorphosed products of mafic magmatic rocks (SiO 2 = 45.42% - 52.96%) and contain high Al 2O 3 (13.14% - 17.92%), Fe 2O 3 T (9.08% - 16.88%) and TiO 2 (0.82% - 3.23%) contents. The amphibolite samples show relatively flat REE patterns, without significant fractionations of REEs (La/Yb N = 1.53 - 1.79). These samples are depleted in HFSEs slightly, with slightly Ti-Nb-Ta negative anomalies, which suggest a subtle relation to subduction-related environment. The gabbroic samples (SiO 2 = 46.96% - 49.86%) have intermediate TiO 2 (0.38% - 1.89%) and relatively low K 2 O contents (K 2 O = 0.34% - 1.03%), belonging to subalkali rocks (Na 2 O > K 2 O). They have relatively high Al 2O 3 (15.0% - 20.81%), CaO (10.13% - 11.60%) and moderate MgO (7.3% - 8.3% ) contents. The gabbroic samples show two types of REE patterns. One is characterized by slight fractionation of REEs (La/Yb N = 1.10 - 1.67) and weak Eu anomalies (δEu = 1.03 - 1.10), while the other is enriched in LREE s (La/Yb N = 5.97 - 6.39), with significantly positive Eu anomalies (δEu = 1.31 - 1.44), which may reflect accumulation of plagioclase in the magma chamber. These gabbroic rocks all exhibit Ti-Nb-Ta troughs and Pb-Sr spikes, also implying a subduction-related origin. The 40Ar/ 39Ar spectrum of the gabbroic sample is simple and flat (plateau age of 266.9 ± 4.2Ma; isochron age of 261 ± 23Ma), indicating that its K-Ar isotopic system was not seriously disturbed by subsequent thermal events and may reflect the intrusion time of the gabbro. However, 40Ar- 39Ar analysis of the amphibolite give rise to a saddle-like spectrum, and its youngest plateau (297.3 ± 6.1Ma) probably reflects the last metamorphic event. The difference on age and geochemistry between the amphibolitic and gabbroic rocks implies that they probably represent different mafic magma. The protolith of amphibolites probably formed in a seamount near a subduction zone and subsequently accreated to the Altai. The gabbro exhibits subduction-releted characteristics and was coeval with transtensional movement in the Chinese Altai, probably reflecting a tectonic transition in the Permian.阿爾泰塔爾浪地區出露一些斜長角閃巖和輝長巖。其中,斜長角閃巖為基性巖漿巖變質的產物,SiO_2含量為45.42%～52.96%,具有較高的Al_2O_3(13.14%～17.92%)、Fe_2O_3~T(9.08%～16.88%)和TiO_2(0.82%～3.23%)含量。斜長角閃巖樣品稀土元素曲線比較平坦,輕重稀土元素分餾不明顯(La/Yb_N=1.53～1.79),無明顯的Nb和Ta虧損。通過野外產狀及地球化學特征分析,認為該斜長角閃巖形成于海山的構造環境。輝長巖SiO_2(46.96%～49.86%)含量稍低,TiO_2(0.38%～1.89%)變化較大,并富Al_2O_3(15.0%～20.81%)、CaO(10.13%～11.60%),具有中等至較高MgO含量(7.3%～8.3%)和相對較低的鉀含量(K_2O=0.34%～1.03%),屬亞堿性巖石系列(Na_2O>K_2O)。輝長巖呈現兩種稀土元素組成特征。一種輕重稀土分餾不明顯,配分曲線比較平坦(La/Yb_N=1.10～1.67),具有輕微的Eu正異常(δEu=1.03～1.10);另一種輕重稀土元素分餾較明顯(La/Yb_N=5.97～...published_or_final_versio

Selection for Replicases in Protocells

PMCID: PMC3649988This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies