Phase structure of black branes in grand canonical ensemble

This is a companion paper of our previous work [1] where we studied the thermodynamics and phase structure of asymptotically flat black $p$-branes in a cavity in arbitrary dimensions $D$ in a canonical ensemble. In this work we study the thermodynamics and phase structure of the same in a grand canonical ensemble. Since the boundary data in two cases are different (for the grand canonical ensemble boundary potential is fixed instead of the charge as in canonical ensemble) the stability analysis and the phase structure in the two cases are quite different. In particular, we find that there exists an analog of one-variable analysis as in canonical ensemble, which gives the same stability condition as the rather complicated known (but generalized from black holes to the present case) two-variable analysis. When certain condition for the fixed potential is satisfied, the phase structure of charged black $p$-branes is in some sense similar to that of the zero charge black $p$-branes in canonical ensemble up to a certain temperature. The new feature in the present case is that above this temperature, unlike the zero-charge case, the stable brane phase no longer exists and `hot flat space' is the stable phase here. In the grand canonical ensemble there is an analog of Hawking-Page transition, even for the charged black $p$-brane, as opposed to the canonical ensemble. Our study applies to non-dilatonic as well as dilatonic black $p$-branes in $D$ space-time dimensions.Comment: 32 pages, 2 figures, various points refined, discussion expanded, references updated, typos corrected, published in JHEP 1105:091,201

Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences

The mechanism by which protein-coding portions of eukaryotic genes came to be separated by long non-coding stretches of DNA, and the purpose for this perplexing arrangement, have remained unresolved fundamental biological problems for three decades. We report here a plausible solution to this problem based on analysis of open reading frame (ORF) length constraints in the genomes of nine diverse species. If primordial nucleic acid sequences were random in sequence, functional proteins that are innately long would not be encoded due to the frequent occurrence of stop codons. The best possible way that a long protein-coding sequence could have been derived was by evolving a split-structure from the random DNA (or RNA) sequence. Results of the systematic analyses of nine complete genome sequences presented here suggests that perhaps the major underlying structural features of split-genes have evolved due to the indigenous occurrence of split protein-coding genes in primordial random nucleotide sequence. The results also suggest that intron-rich genes containing short exons may have been the original form of genes intrinsically occurring in random DNA, and that intron-poor genes containing long exons were perhaps derived from the original intron-rich genes

Evolutionary Convergence on Highly-Conserved 3′ Intron Structures in Intron-Poor Eukaryotes and Insights into the Ancestral Eukaryotic Genome

The presence of spliceosomal introns in eukaryotes raises a range of questions about genomic evolution. Along with the fundamental mysteries of introns' initial proliferation and persistence, the evolutionary forces acting on intron sequences remain largely mysterious. Intron number varies across species from a few introns per genome to several introns per gene, and the elements of intron sequences directly implicated in splicing vary from degenerate to strict consensus motifs. We report a 50-species comparative genomic study of intron sequences across most eukaryotic groups. We find two broad and striking patterns. First, we find that some highly intron-poor lineages have undergone evolutionary convergence to strong 3′ consensus intron structures. This finding holds for both branch point sequence and distance between the branch point and the 3′ splice site. Interestingly, this difference appears to exist within the genomes of green alga of the genus Ostreococcus, which exhibit highly constrained intron sequences through most of the intron-poor genome, but not in one much more intron-dense genomic region. Second, we find evidence that ancestral genomes contained highly variable branch point sequences, similar to more complex modern intron-rich eukaryotic lineages. In addition, ancestral structures are likely to have included polyT tails similar to those in metazoans and plants, which we found in a variety of protist lineages. Intriguingly, intron structure evolution appears to be quite different across lineages experiencing different types of genome reduction: whereas lineages with very few introns tend towards highly regular intronic sequences, lineages with very short introns tend towards highly degenerate sequences. Together, these results attest to the complex nature of ancestral eukaryotic splicing, the qualitatively different evolutionary forces acting on intron structures across modern lineages, and the impressive evolutionary malleability of eukaryotic gene structures

Phase transitions and critical behavior of black branes in canonical ensemble

We study the thermodynamics and phase structure of asymptotically flat non-dilatonic as well as dilatonic black branes in a cavity in arbitrary dimensions ($D$). We consider the canonical ensemble and so the charge inside the cavity and the temperature at the wall are fixed. We analyze the stability of the black brane equilibrium states and derive the phase structures. For the zero charge case we find an analog of Hawking-Page phase transition for these black branes in arbitrary dimensions. When the charge is non-zero, we find that below a critical value of the charge, the phase diagram has a line of first-order phase transition in a certain range of temperatures which ends up at a second order phase transition point (critical point) as the charge attains the critical value. We calculate the critical exponents at that critical point. Although our discussion is mainly concerned with the non-dilatonic branes, we show how it easily carries over to the dilatonic branes as well.Comment: 37 pages, 6 figures, the validity of using the effective action discussed, references adde

Apparent non-canonical trans-splicing is generated by reverse transcriptase in vitro

Trans-splicing, the in vivo joining of two RNA molecules, is well characterized in several groups of simple organisms but was long thought absent from fungi, plants and mammals. However, recent bioinformatic analyses of expressed sequence tag (EST) databases suggested widespread trans-splicing in mammals^1-2^. Splicing, including the characterised trans-splicing systems, involves conserved sequences at the splice junctions. Our analysis of a yeast non-coding RNA revealed that around 30% of the products of reverse transcription lacked an internal region of 117 nt, suggesting that the RNA was spliced. The junction sequences lacked canonical splice-sites but were flanked by direct repeats, and further analyses indicated that the apparent splicing actually arose because reverse transcriptase can switch templates during transcription^3^. Many newly identified, apparently trans-spliced, RNAs lacked canonical splice sites but were flanked by short regions of homology, leading us to question their authenticity. Here we report that all reported categories of non-canonical splicing could be replicated using an in vitro reverse transcription system with highly purified RNA substrates. We observed the reproducible occurrence of ostensible trans-splicing, exon shuffling and sense-antisense fusions. The latter generate apparent antisense non-coding RNAs, which are also reported to be abundant in humans^4^. Different reverse transcriptases can generate different products of template switching, providing a simple diagnostic. Many reported examples of splicing in the absence of canonical splicing signals may be artefacts of cDNA preparation

The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes

Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6–7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing

Intron Dynamics in Ribosomal Protein Genes

The role of spliceosomal introns in eukaryotic genomes remains obscure. A large scale analysis of intron presence/absence patterns in many gene families and species is a necessary step to clarify the role of these introns. In this analysis, we used a maximum likelihood method to reconstruct the evolution of 2,961 introns in a dataset of 76 ribosomal protein genes from 22 eukaryotes and validated the results by a maximum parsimony method. Our results show that the trends of intron gain and loss differed across species in a given kingdom but appeared to be consistent within subphyla. Most subphyla in the dataset diverged around 1 billion years ago, when the “Big Bang” radiation occurred. We speculate that spliceosomal introns may play a role in the explosion of many eukaryotes at the Big Bang radiation

Both Size and GC-Content of Minimal Introns Are Selected in Human Populations

Background: We previously have studied the insertion and deletion polymorphism by sequencing no more than one hundred introns in a mixed human population and found that the minimal introns tended to maintain length at an optimal size. Here we analyzed re-sequenced 179 individual genomes (from African, European, and Asian populations) from the data released by the 1000 Genome Project to study the size dynamics of minimal introns. Principal Findings: We not only confirmed that minimal introns in human populations are selected but also found two major effects in minimal intron evolution: (i) Size-effect: minimal introns longer than an optimal size (87 nt) tend to have a higher ratio of deletion to insertion than those that are shorter than the optimal size; (ii) GC-effect: minimal introns with lower GC content tend to be more frequently deleted than those with higher GC content. The GC-effect results in a higher GC content in minimal introns than their flanking exons as opposed to larger introns ($125 nt) that always have a lower GC content than that of their flanking exons. We also observed that the two effects are distinguishable but not completely separable within and between populations. Conclusions: We validated the unique mutation dynamics of minimal introns in keeping their near-optimal size and GC content, and our observations suggest potentially important functions of human minimal introns in transcript processin

Malignant peripheral nerve sheath tumor of the breast: case report

<p>Abstract</p> <p>Background</p> <p>Malignant peripheral nerve sheath tumor is a rare soft tissue sarcoma of ectomesenchymal origin. It is the malignant counterpart of benign soft tissue tumors like neurofibromas and schwannomas and may often follow them. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an extremely rare location of this lesion and presentation as a breast lump in the absence of pain or previous benign neural tumor is even rarer.</p> <p>Case presentation</p> <p>A 38-year-old female presented with complaints of painless, hard breast lump for three months which was clinically suspected to be a ductal carcinoma with inconclusive fine needle aspiration cytology. Histopathology revealed a malignant spindle cell tumor which was confirmed to be malignant peripheral nerve sheath tumor on the basis of immunopositivity for vimentin, neurone specific enolase and S-100.</p> <p>Conclusion</p> <p>To the best of our knowledge only six such case reports have been published in literature. The differential diagnosis of malignant peripheral nerve sheath tumor should be considered by the clinician as well as the pathologists in the work-up of a breast neoplasm as treatment and prognosis of this rare malignancy is different.</p