The free energy of mechanically unstable phases

Phase diagrams provide ‘roadmaps’ to the possible states of matter. Their determination traditionally rests on the assumption that all phases, even unstable ones, have well-defined free energies under all conditions. However, this assumption is commonly violated in condensed phases due to mechanical instabilities. This long-standing problem impedes thermodynamic database development, as pragmatic attempts at solving this problem involve delicate extrapolations that are highly nonunique and that lack an underlying theoretical justification. Here we propose an efficient computational solution to this problem that has a simple interpretation, both as a topological partitioning of atomic configuration space and as a minimally constrained physical system. Our natural scheme smoothly extends the free energy of stable phases, without relying on extrapolation, thus enabling a formal assessment of widely used extrapolation schemes

A panel of cultivate specific marker based on polymorphisms at microsatellite markers for Iranian cultivated Almonds (Prunus dulcis).

Molecular markers developed for Prunus also offer a powerful tool to study the evolution of the genome, and for understanding of genome structure and determinants of genetic diversity. Two hundred eighty almond genotypes/cultivars from different origins distributed throughout Iran besides some foreign cultivars and their hybrids with Iranian ones were collected. Microsatellite analysis was carried out using 9 pair flanking SSR sequences previously cloned and sequenced specifically in almond. The total number of detected alleles was 152 (9 to 20 alleles per locus with an average of 16.87). The mean PIC value of the polymorphic loci wasrelatively high (0.81) and the mean value for He was 0.83, so that we were able to distinguish 98% of the genotypes using 5 loci. Incluster analysis, the genotypes were divided into 2 major groups, foreign cultivars and Iranian almond genotypes. Principal coordinate analysis based on Shared Allele method indicated proper distribution of the studied markers through the genome. Some specific markers were recorded among the germ plasm which can be used efficiently in rapid and precise identification of the related genotypes and also in breeding programs through MAS. Genotypes were coded using our suggested coding method for genotype molecular identification

A panel of cultivate specific marker based on polymorphisms at microsatellite markers for Iranian cultivated almonds (Prunus dulcis).

Abstract Molecular markers developed for Prunus also offer a powerful tool to study the evolution of the genome, and for understanding of genome structure and determinants of genetic diversity. Two hundred eighty almond genotypes/cultivars from different origins distributed throughout Iran besides some foreign cultivars and their hybrids with Iranian ones were collected. Microsatellite analysis was carried out using 9 pair flanking SSR sequences previously cloned and sequenced specifically in almond. The total number of detected alleles was 152 (9 to 20 alleles per locus with an average of 16.87). The mean PIC value of the polymorphic loci was relatively high (0.81) and the mean value for H e was 0.83, so that we were able to distinguish 98% of the genotypes using 5 loci. In cluster analysis, the genotypes were divided into 2 major groups, foreign cultivars and Iranian almond genotypes. Principal coordinate analysis based on Shared Allele method indicated proper distribution of the studied markers through the genome. Some specific markers were recorded among the germplasm which can be used efficiently in rapid and precise identification of the related genotypes and also in breeding programs through MAS. Genotypes were coded using our suggested coding method for genotype molecular identification

The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells

Regulatory T cells (Tregs) have a central role in maintaining immune homoeostasis through various mechanisms. Although the Forkhead transcription factor Foxp3 defines the Treg cell lineage and functions, the molecular mechanisms of Foxp3 induction and maintenance remain elusive. Here we show that Foxp3 is one of the direct targets of Nr4a2. Nr4a2 binds to regulatory regions of Foxp3, where it mediates permissive histone modifications. Ectopic expression of Nr4a2 imparts Treg-like suppressive activity to naïve CD4+ T cells by inducing Foxp3 and by repressing cytokine production, including interferon-γ and interleukin-2. Deletion of Nr4a2 in T cells attenuates induction of Tregs and causes aberrant induction of Th1, leading to the exacerbation of colitis. Nr4a2-deficeint Tregs are prone to lose Foxp3 expression and have attenuated suppressive ability both in vitro and in vivo. Thus, Nr4a2 has the ability to maintain T-cell homoeostasis by regulating induction, maintenance and suppressor functions of Tregs, and by repression of aberrant Th1 induction

Biomass estimation of demersal resources in the Persian Gulf and Oman Sea by swept area method

Regarding to monitor of demersal resources in the Persian Gulf and Oman Sea, and also biomass and CPUA estimation of them, ten research cruises were carried out by using R/V Ferdows-1 equipped with bottom trawl, covering the area from 49º 00´ E in the west (north-west Persian Gulf) to 61º 25´ E in the east (borderline with Pakistan) from 2012 to 2014 The study area was stratified into 17 strata (A to Q) of which 10 strata (A to J) were in the Persian Gulf and 7 strata (K to Q) were in the Oman Sea, covering the depths of 10-50 m in the Persian Gulf and 10-100 m in the Oman Sea. A total of 316 stations were randomly selected and the biomass and CPUA were estimated by swept area method during this three years period, the strat A and B weren’t covered. The comparison between two regions indicated that the percentage of density of demersal fishes in the Persian Gulf during years 2012, 2013 and 2014 were 1.0, 1.4 and 1.6 times more than the Oman Sea and totally 50-60% of total biomass was found for the Persian Gulf. Also a comparison among 17 strata the highest biomass was found for K region (Sirik to Jask) in the Oman Sea in 2012 & 2014; and C region (Genaveh to Bordkhoon) in 2013 in the Persian Gulf. The same comparison was done for CPUA of commercial, non-commercial and total in both water bodies and it was found that in years 2012 to 2014 the region K (Sirik to Jask) in the Oman Sea and Stratum Q (Bersi to Gwatr) had the highest value of CPUA. On the contrary, the stratum M (Biahi to Galak estuary) showed the lowest value of biomass for both commercial and non-commercial fishes. With review the mean CPUA in different depth layers for years 2012, 2013 and 2014, it was concluded that in the Oman Sea with increasing the depth, the mean CPUA is decreased and the lowest CPUA belongs to depths of 30-50 m The comparison between commercial and non-commercial groups in both ecosystems, it concluded that the density of commercial species were higher than non-commercial ones; and for years 2009, 2010 and 2011 the commercial species consist of 63.4, 65.0 and 59.7 % of total biomass. In all years the Persian Gulf indicated higher values than the Oman Sea. The most abundant fishes were Rays, Ribbon fishes, Carangids, Grunts, Japanese threadfin bream, Lizardfish and Barracuda for both Persian Gulf and Oman Sea

Developmental Transcriptional Networks Are Required to Maintain Neuronal Subtype Identity in the Mature Nervous System

During neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and Tv4), we test whether the subtype transcription factor networks that direct differentiation during development are required persistently for long-term maintenance of subtype identity. By conditional transcription factor knockdown in adult Tv neurons after normal development, we find that most transcription factors within the Tv1/Tv4 subtype transcription networks are indeed required to maintain Tv1/Tv4 subtype-specific gene expression in adults. Thus, gene expression profiles are not simply “locked-in,” but must be actively maintained by persistent developmental transcription factor networks. We also examined the cross-regulatory relationships between all transcription factors that persisted in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory relationships that had existed between these transcription factors during development were no longer present in the mature adult neuron. This points to key differences between developmental and maintenance transcriptional regulatory networks in individual neurons. Together, our results provide novel insight showing that the maintenance of subtype identity is an active process underpinned by persistently active, combinatorially-acting, developmental transcription factors. These findings have implications for understanding the maintenance of all long-lived cell types and the functional degeneration of neurons in the aging brain

Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning

Schizophrenia: do all roads lead to dopamine or is this where they start? Evidence from two epidemiologically informed developmental rodent models

The idea that there is some sort of abnormality in dopamine (DA) signalling is one of the more enduring hypotheses in schizophrenia research. Opinion leaders have published recent perspectives on the aetiology of this disorder with provocative titles such as ‘Risk factors for schizophrenia—all roads lead to dopamine' or ‘The dopamine hypothesis of schizophrenia—the final common pathway'. Perhaps, the other most enduring idea about schizophrenia is that it is a neurodevelopmental disorder. Those of us that model schizophrenia developmental risk-factor epidemiology in animals in an attempt to understand how this may translate to abnormal brain function have consistently shown that as adults these animals display behavioural, cognitive and pharmacological abnormalities consistent with aberrant DA signalling. The burning question remains how can in utero exposure to specific (environmental) insults induce persistent abnormalities in DA signalling in the adult? In this review, we summarize convergent evidence from two well-described developmental animal models, namely maternal immune activation and developmental vitamin D deficiency that begin to address this question. The adult offspring resulting from these two models consistently reveal locomotor abnormalities in response to DA-releasing or -blocking drugs. Additionally, as adults these animals have DA-related attentional and/or sensorimotor gating deficits. These findings are consistent with many other developmental animal models. However, the authors of this perspective have recently refocused their attention on very early aspects of DA ontogeny and describe reductions in genes that induce or specify dopaminergic phenotype in the embryonic brain and early changes in DA turnover suggesting that the origins of these behavioural abnormalities in adults may be traced to early alterations in DA ontogeny. Whether the convergent findings from these two models can be extended to other developmental animal models for this disease is at present unknown as such early brain alterations are rarely examined. Although it is premature to conclude that such mechanisms could be operating in other developmental animal models for schizophrenia, our convergent data have led us to propose that rather than all roads leading to DA, perhaps, this may be where they start

Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors

Degeneration of dopamine neurons in the midbrain causes symptoms of the movement disorder, Parkinson disease. Dopamine neurons are generated from proliferating progenitor cells localized in the embryonic ventral midbrain. However, it remains unclear for how long cells with dopamine progenitor character are retained and if there is any potential for reactivation of such cells after cessation of normal dopamine neurogenesis. We show here that cells expressing Lmx1a and other progenitor markers remain in the midbrain aqueductal zone beyond the major dopamine neurogenic period. These cells express dopamine receptors, are located in regions heavily innervated by midbrain dopamine fibres and their proliferation can be stimulated by antagonizing dopamine receptors, ultimately leading to increased neurogenesis in vivo. Furthermore, treatment with dopamine receptor antagonists enhances neurogenesis in vitro, both from embryonic midbrain progenitors as well as from embryonic stem cells. Altogether our results indicate a potential for reactivation of resident midbrain cells with dopamine progenitor potential beyond the normal period of dopamine neurogenesis

Intelligent mining of large-scale bio-data: bioinformatics applications

Today, there is a collection of a tremendous amount of bio-data because of the computerized applications worldwide. Therefore, scholars have been encouraged to develop effective methods to extract the hidden knowledge in these data. Consequently, a challenging and valuable area for research in artificial intelligence has been created. Bioinformatics creates heuristic approaches and complex algorithms using artificial intelligence and information technology in order to solve biological problems. Intelligent implication of the data can accelerate biological knowledge discovery. Data mining, as biology intelligence, attempts to find reliable, new, useful and meaningful patterns in huge amounts of data. Hence, there is a high potential to raise the interaction between artificial intelligence and bio-data mining. The present paper argues how artificial intelligence can assist bio-data analysis and gives an up-to-date review of different applications of bio-data mining. It also highlights some future perspectives of data mining in bioinformatics that can inspire further developments of data mining instruments. Important and new techniques are critically discussed for intelligent knowledge discovery of different types of row datasets with applicable examples in human, plant and animal sciences. Finally, a broad perception of this hot topic in data science is given