Waves on the surface of the Orion molecular cloud

Massive stars influence their parental molecular cloud, and it has long been suspected that the development of hydrodynamical instabilities can compress or fragment the cloud. Identifying such instabilities has proved difficult. It has been suggested that elongated structures (such as the `pillars of creation') and other shapes arise because of instabilities, but alternative explanations are available. One key signature of an instability is a wave-like structure in the gas, which has hitherto not been seen. Here we report the presence of `waves' at the surface of the Orion molecular cloud near where massive stars are forming. The waves seem to be a Kelvin-Helmholtz instability that arises during the expansion of the nebula as gas heated and ionized by massive stars is blown over pre-existing molecular gas.Comment: Preprint of publication in Natur

Formation of Multiple Populations in Globular Clusters: Another Possible Scenario

While chemical composition spreads are now believed to be a universal characteristic of globular clusters (GCs), not all of them present multiple populations in their color-magnitude diagrams (CMDs). Here we present a new scenario for the formation of GCs, in an attempt to qualitatively explain this otherwise intriguing observational framework. Our scenario divides GCs into three groups, depending on the initial mass (M_I) of the progenitor structure (PS), as follows. i) Massive PSs can retain the gas ejected by massive stars, including the ejecta of core-collapse SNe. ii) Intermediate-mass PSs can retain at least a fraction of the fast winds of massive stars, but none of the core-collapse SNe ejecta. iii) Low-mass PSs can only retain the slow winds of intermediate-mass stars. Members of the first group would include omega Centauri (NGC 5139), M54 (NGC 6715), M22 (NGC 6656), and Terzan 5, whereas NGC 2808 (and possibly NGC 2419) would be members of the second group. The remaining GCs which only present a spread in light elements, such as O and Na, would be members of the third group. According to our scenario, the different components in omega Cen should not display a sizeable spread in age. We argue that this is consistent with the available observations. We give other simple arguments in favor of our scenario, which can be described in terms of two main analytical relations: i) Between the actual observed ratio between first and second generation stars (R_SG^FG) and the fraction of first generation stars that have been lost by the GC (S_L); and ii) Between S_L and M_I. We also suggest a series of future improvements and empirical tests that may help decide whether the proposed scenario properly describes the chemical evolution of GCs.Comment: Accepted for publication in Astronomy and Astrophysic

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This 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

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Involvement of the cerebellum in structural connectivity enhancement in episodic migraine

Background: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. Methods: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. Results: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. Conclusions: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.info:eu-repo/semantics/publishedVersio

Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance. Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF

Comparative genomics in cyprinids: common carp ESTs help the annotation of the zebrafish genome

BACKGROUND: Automatic annotation of sequenced eukaryotic genomes integrates a combination of methodologies such as ab-initio methods and alignment of homologous genes and/or proteins. For example, annotation of the zebrafish genome within Ensembl relies heavily on available cDNA and protein sequences from two distantly related fish species and other vertebrates that have diverged several hundred million years ago. The scarcity of genomic information from other cyprinids provides the impetus to leverage EST collections to understand gene structures in this diverse teleost group. RESULTS: We have generated 6,050 ESTs from the differentiating testis of common carp (Cyprinus carpio) and clustered them with 9,303 non-gonadal ESTs from CarpBase as well as 1,317 ESTs and 652 common carp mRNAs from GenBank. Over 28% of the resulting 8,663 unique transcripts are exclusively testis-derived ESTs. Moreover, 974 of these transcripts did not match any sequence in the zebrafish or fathead minnow EST collection. A total of 1,843 unique common carp sequences could be stringently mapped to the zebrafish genome (version 5), of which 1,752 matched coding sequences of zebrafish genes with or without potential splice variants. We show that 91 common carp transcripts map to intergenic and intronic regions on the zebrafish genome assembly and regions annotated with non-teleost sequences. Interestingly, an additional 42 common carp transcripts indicate the potential presence of new splicing variants not found in zebrafish databases so far. The fact that common carp transcripts help the identification or confirmation of these coding regions in zebrafish exemplifies the usefulness of sequences from closely related species for the annotation of model genomes. We also demonstrate that 5' UTR sequences of common carp and zebrafish orthologs share a significant level of similarity based on preservation of motif arrangements for as many as 10 ab-initio motifs. CONCLUSION: Our data show that there is sufficient homology between the transcribed sequences of common carp and zebrafish to warrant an even deeper cyprinid transcriptome comparison. On the other hand, the comparative analysis illustrates the value in utilizing partially sequenced transcriptomes to understand gene structure in this diverse teleost group. We highlight the need for integrated resources to leverage the wealth of fragmented genomic data

Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction

A distal region of the human TGM1 promoter is required for expression in transgenic mice and cultured keratinocytes

BACKGROUND: TGM1(transglutaminase 1) is an enzyme that crosslinks the cornified envelope of mature keratinocytes. Appropriate expression of the TGM1 gene is crucial for proper keratinocyte function as inactivating mutations lead to the debilitating skin disease, lamellar ichthyosis. TGM1 is also expressed in squamous metaplasia, a consequence in some epithelia of vitamin A deficiency or toxic insult that can lead to neoplasia. An understanding of the regulation of this gene in normal and abnormal differentiation states may contribute to better disease diagnosis and treatment. METHODS: In vivo requirements for expression of the TGM1 gene were studied by fusing various lengths of promoter DNA to a reporter and injecting the DNA into mouse embryos to generate transgenic animals. Expression of the reporter was ascertained by Western blotting and immunohistochemistry. Further delineation of a transcriptionally important distal region was determined by transfections of progressively shortened or mutated promoter DNA into cultured keratinocytes. RESULTS: In vivo analysis of a reporter transgene driven by the TGM1 promoter revealed that 1.6 kilobases, but not 1.1 kilobases, of DNA was sufficient to confer tissue-specific and cell layer-specific expression. This same region was responsible for reporter expression in tissues undergoing squamous metaplasia as a response to vitamin A deprivation. Mutation of a distal promoter AP1 site or proximal promoter CRE site, both identified as important transcriptional elements in transfection assays, did not prevent appropriate expression. Further searching for transcriptional elements using electrophoretic mobility shift (EMSA) and transfection assays in cultured keratinocytes identified two Sp1 elements in a transcriptionally active region between -1.6 and -1.4 kilobases. While mutation of either Sp1 site or the AP1 site singly had only a small effect, mutation of all three sites eliminated nearly all the transcriptional activity. CONCLUSIONS: A distal region of the TGM1 gene promoter, containing AP1 and Sp1 binding sites, is evolutionarily conserved and responsible for high level expression in transgenic mice and in transfected keratinocyte cultures

WeederH: an algorithm for finding conserved regulatory motifs and regions in homologous sequences

BACKGROUND: This work addresses the problem of detecting conserved transcription factor binding sites and in general regulatory regions through the analysis of sequences from homologous genes, an approach that is becoming more and more widely used given the ever increasing amount of genomic data available. RESULTS: We present an algorithm that identifies conserved transcription factor binding sites in a given sequence by comparing it to one or more homologs, adapting a framework we previously introduced for the discovery of sites in sequences from co-regulated genes. Differently from the most commonly used methods, the approach we present does not need or compute an alignment of the sequences investigated, nor resorts to descriptors of the binding specificity of known transcription factors. The main novel idea we introduce is a relative measure of conservation, assuming that true functional elements should present a higher level of conservation with respect to the rest of the sequence surrounding them. We present tests where we applied the algorithm to the identification of conserved annotated sites in homologous promoters, as well as in distal regions like enhancers. CONCLUSION: Results of the tests show how the algorithm can provide fast and reliable predictions of conserved transcription factor binding sites regulating the transcription of a gene, with better performances than other available methods for the same task. We also show examples on how the algorithm can be successfully employed when promoter annotations of the genes investigated are missing, or when regulatory sites and regions are located far away from the genes