Polyploidization has provided much genetic variation for plant adaptive evolution, but the mechanisms by which the molecular evolution of polyploid genomes establishes genetic architecture underlying species differentiation are unclear. Brassica is an ideal model to increase knowledge of polyploid evolution. Here we describe a draft genome sequence of Brassica oleracea, comparing it with that of its sister species B. rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of transposable elements, differential gene co-retention for specific pathways and variation in gene expression, including alternative splicing, among a large number of paralogous and orthologous genes. Genes related to the production of anticancer phytochemicals and morphological variations illustrate consequences of genome duplication and gene divergence, imparting biochemical and morphological variation to B. oleracea. This study provides insights into Brassica genome evolution and will underpin research into the many important crops in this genus.

Mammalian cell totipotency is a subject that has fascinated scientists for generations. A long lasting question whether some of the somatic cells retains totipotency was answered by the cloning of Dolly at the end of the 20th century. The dawn of the 21st has brought forward great expectations in harnessing the power of totipotentcy in medicine. Through stem cell biology, it is possible to generate any parts of the human body by stem cell engineering. Considerable resources will be devoted to harness the untapped potentials of stem cells in the foreseeable future which may transform medicine as we know today. At the molecular level, totipotency has been linked to a singular transcription factor and its expression appears to define whether a cell should be totipotent. Named Oct4, it can activate or repress the expression of various genes. Curiously, very little is known about Oct4 beyond its ability to regulate gene expression. The mechanism by which Oct4 specifies totipotency remains entirely unresolved. In this review, we summarize the structure and function of Oct4 and address issues related to Oct4 function in maintaining totipotency or pluripotency of embryonic stem cells.

Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-gamma production and lytic degranulation during human tuberculosis. We demonstrated that specific Ag-stimulation increased CD3+PD-1+ lymphocytes in peripheral blood and pleural fluid from tuberculosis patients in direct correlation with IFN-gamma production from these individuals. Moreover, M. tuberculosis-induced IFN-gamma participated in the up-regulation of PD-1 expression. Blockage of PD-1 or PD-1 and its ligands (PD-Ls: PD-L1, PD-L2) enhanced the specific degranulation of CD8+ T cells and the percentage of specific IFN-gamma-producing lymphocytes against the pathogen, demonstrating that the PD-1:PD-Ls pathway inhibits T cell effector functions during active M. tuberculosis infection. Furthermore, the simultaneous blockage of the inhibitory receptor PD-1 together with the activation of the costimulatory protein signaling lymphocytic activation molecule led to the promotion of protective IFN-gamma responses to M. tuberculosis, even in patients with weak cell-mediated immunity against the bacteria. Together, we demonstrated that PD-1 interferes with T cell effector functions against M. tuberculosis, suggesting that PD-1 has a key regulatory role during the immune response of the host to the pathogen.

BACKGROUND

Nucleosome positioning participates in many cellular activities and plays significant roles in regulating cellular processes. With the avalanche of genome sequences generated in the post-genomic age, it is highly desired to develop automated methods for rapidly and effectively identifying nucleosome positioning. Although some computational methods were proposed, most of them were species specific and neglected the intrinsic local structural properties that might play important roles in determining the nucleosome positioning on a DNA sequence.

RESULTS

Here a predictor called 'iNuc-PseKNC' was developed for predicting nucleosome positioning in Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster genomes, respectively. In the new predictor, the samples of DNA sequences were formulated by a novel feature-vector called 'pseudo k-tuple nucleotide composition', into which six DNA local structural properties were incorporated. It was observed by the rigorous cross-validation tests on the three stringent benchmark datasets that the overall success rates achieved by iNuc-PseKNC in predicting the nucleosome positioning of the aforementioned three genomes were 86.27%, 86.90% and 79.97%, respectively. Meanwhile, the results obtained by iNuc-PseKNC on various benchmark datasets used by the previous investigators for different genomes also indicated that the current predictor remarkably outperformed its counterparts.

BACKGROUND

A user-friendly web-server, iNuc-PseKNC is freely accessible at http://lin.uestc.edu.cn/server/iNuc-PseKNC.

The infection of the nervous system by the cystic larvae of Taenia solium (neurocysticercosis) is a frequent cause of seizure disorders. Neurocysticercosis is endemic or presumed to be endemic in many low-income countries. The lifecycle of the worm and the clinical manifestations of neurocysticercosis are well established, and CT and MRI have substantially improved knowledge of the disease course. Improvements in immunodiagnosis have further advanced comprehension of the pathophysiology of this disease. This knowledge has led to individualised treatment approaches that account for the involvement of parenchymal or extraparenchymal spaces, the number and form of parasites, and the extent of degeneration and associated inflammation. Clinical investigations are focused on development of effective treatments and reduction of side-effects induced by treatment, such as seizures, hydrocephalus, infarcts, and neuroinjury.

Honeybee colony collapse is a sanitary and ecological worldwide problem. The features of this syndrome are an unexplained disappearance of adult bees, a lack of brood attention, reduced colony strength, and heavy winter mortality without any previous evident pathological disturbances. To date there has not been a consensus about its origins. This report describes the clinical features of two professional bee-keepers affecting by this syndrome. Anamnesis, clinical examination and analyses support that the depopulation in both cases was due to the infection by Nosema ceranae (Microsporidia), an emerging pathogen of Apis mellifera. No other significant pathogens or pesticides (neonicotinoids) were detected and the bees had not been foraging in corn or sunflower crops. The treatment with fumagillin avoided the loss of surviving weak colonies. This is the first case report of honeybee colony collapse due to N. ceranae in professional apiaries in field conditions reported worldwide.

The pseudo oligonucleotide composition, or pseudo K-tuple nucleotide composition (PseKNC), can be used to represent a DNA or RNA sequence with a discrete model or vector yet still keep considerable sequence order information, particularly the global or long-range sequence order information, via the physicochemical properties of its constituent oligonucleotides. Therefore, the PseKNC approach may hold very high potential for enhancing the power in dealing with many problems in computational genomics and genome sequence analysis. However, dealing with different DNA or RNA problems may need different kinds of PseKNC. Here, we present a flexible and user-friendly web server for PseKNC (at http://lin.uestc.edu.cn/pseknc/default.aspx) by which users can easily generate many different modes of PseKNC according to their need by selecting various parameters and physicochemical properties. Furthermore, for the convenience of the vast majority of experimental scientists, a step-by-step guide is provided on how to use the current web server to generate their desired PseKNC without the need to follow the complicated mathematical equations, which are presented in this article just for the integrity of PseKNC formulation and its development. It is anticipated that the PseKNC web server will become a very useful tool in computational genomics and genome sequence analysis.

Occurring at adenine (A) with the consensus motif GAC, N(6)-methyladenosine (m(6)A) is one of the most abundant modifications in RNA, which plays very important roles in many biological processes. The nonuniform distribution of m(6)A sites across the genome implies that, for better understanding the regulatory mechanism of m(6)A, it is indispensable to characterize its sites in a genome-wide scope. Although a series of experimental technologies have been developed in this regard, they are both time-consuming and expensive. With the avalanche of RNA sequences generated in the postgenomic age, it is highly desired to develop computational methods to timely identify their m(6)A sites. In view of this, a predictor called "iRNA-Methyl" is proposed by formulating RNA sequences with the "pseudo dinucleotide composition" into which three RNA physiochemical properties were incorporated. Rigorous cross-validation tests have indicated that iRNA-Methyl holds very high potential to become a useful tool for genome analysis. For the convenience of most experimental scientists, a web-server for iRNA-Methyl has been established at http://lin.uestc.edu.cn/server/iRNA-Methyl by which users can easily get their desired results without needing to go through the mathematical details.

Cancer remains a major killer worldwide. Traditional methods of cancer treatment are expensive and have some deleterious side effects on normal cells. Fortunately, the discovery of anticancer peptides (ACPs) has paved a new way for cancer treatment. With the explosive growth of peptide sequences generated in the post genomic age, it is highly desired to develop computational methods for rapidly and effectively identifying ACPs, so as to speed up their application in treating cancer. Here we report a sequence-based predictor called iACP developed by the approach of optimizing the g-gap dipeptide components. It was demonstrated by rigorous cross-validations that the new predictor remarkably outperformed the existing predictors for the same purpose in both overall accuracy and stability. For the convenience of most experimental scientists, a publicly accessible web-server for iACP has been established at http://lin.uestc.edu.cn/server/iACP, by which users can easily obtain their desired results.

Over the last twenty years, there has been rapid growth of a new approach to understanding the evolution of organismic form. This evolutionary developmental biology, or 'evo-devo', is focused on the developmental genetic machinery that lies behind embryological phenotypes, which were all that could be studied in the past. Are there any general concepts emerging from this new approach, and if so, how do they impact on the conceptual structure of traditional evolutionary biology? In providing answers to these questions, this review assesses whether evo-devo is merely filling in some missing details, or whether it will cause a large-scale change in our thinking about the evolutionary process.

Meiosis is essential for eukaryotic sexual reproduction, with two consecutive rounds of nuclear divisions, allowing production of haploid gametes. Information regarding the meiotic transcriptome should provide valuable clues about global expression patterns and detailed gene activities. Here we used RNA sequencing to explore the transcriptome of a single plant cell type, the Arabidopsis male meiocyte, detecting the expression of approximately 20 000 genes. Transcription of introns of >400 genes was observed, suggesting previously unannotated exons. More than 800 genes may be preferentially expressed in meiocytes, including known meiotic genes. Of the 3378 Pfam gene families in the Arabidopsis genome, 3265 matched meiocyte-expressed genes, and 18 gene families were over-represented in male meiocytes, including transcription factor and other regulatory gene families. Expression was detected for many genes thought to encode meiosis-related proteins, including MutS homologs (MSHs), kinesins and ATPases. We identified more than 1000 orthologous gene clusters that are also expressed in meiotic cells of mouse and fission yeast, including 503 single-copy genes across the three organisms, with a greater number of gene clusters shared between Arabidopsis and mouse than either share with yeast. Interestingly, approximately 5% transposable element genes were apparently transcribed in male meiocytes, with a positive correlation to the transcription of neighboring genes. In summary, our RNA-Seq transcriptome data provide an overview of gene expression in male meiocytes and invaluable information for future functional studies.

Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-γ alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M. tuberculosis infection, but the role of IL-17-producing cells in human TB remains to be understood. Therefore, we investigated the induction and regulation of IFN-γ and IL-17 during the active disease. TB patients were classified as High and Low Responder individuals according to their T cell responses against the antigen, and cytokine expression upon M. tuberculosis stimulation was investigated in peripheral blood and pleural fluid. Afterwards, the potential correlation among the proportions of cytokine-producing cells and clinical parameters was analyzed. In TB patients, M. tuberculosis induced IFN-γ and IL-17, but in comparison with BCG-vaccinated healthy donors, IFN-γ results were reduced significantly, and IL-17 was markedly augmented. Moreover, the main source of IL-17 was represented by CD4(+)IFN-γ(+)IL-17(+) lymphocytes, a Th1/Th17 subset regulated by IFN-γ. Interestingly, the ratio of antigen-expanded CD4(+)IFN-γ(+)IL-17(+) lymphocytes, in peripheral blood and pleural fluid from TB patients, was correlated directly with clinical parameters associated with disease severity. Indeed, the highest proportion of CD4(+)IFN-γ(+)IL-17(+) cells was detected in Low Responder TB patients, individuals displaying severe pulmonary lesions, and longest length of disease evolution. Taken together, the present findings suggest that analysis of the expansion of CD4(+)IFN-γ(+)IL-17(+) T lymphocytes in peripheral blood of TB patients might be used as an indicator of the clinical outcome in active TB.

Translation is a key process for gene expression. Timely identification of the translation initiation site (TIS) is very important for conducting in-depth genome analysis. With the avalanche of genome sequences generated in the postgenomic age, it is highly desirable to develop automated methods for rapidly and effectively identifying TIS. Although some computational methods were proposed in this regard, none of them considered the global or long-range sequence-order effects of DNA, and hence their prediction quality was limited. To count this kind of effects, a new predictor, called "iTIS-PseTNC," was developed by incorporating the physicochemical properties into the pseudo trinucleotide composition, quite similar to the PseAAC (pseudo amino acid composition) approach widely used in computational proteomics. It was observed by the rigorous cross-validation test on the benchmark dataset that the overall success rate achieved by the new predictor in identifying TIS locations was over 97%. As a web server, iTIS-PseTNC is freely accessible at http://lin.uestc.edu.cn/server/iTIS-PseTNC. To maximize the convenience of the vast majority of experimental scientists, a step-by-step guide is provided on how to use the web server to obtain the desired results without the need to go through detailed mathematical equations, which are presented in this paper just for the integrity of the new prection method.

Although research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammation of the small intestine and colon caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. A number of fermented dairy products contain lactic acid bacteria (LAB) and bifidobacteria, some of which have been characterized as probiotics that can modify the gut microbiota and may be beneficial for the treatment and the prevention of IBD. The objective of this review was to carry out a systematic search of LAB and bifidobacteria probiotics and IBD, using the PubMed and Scopus databases, defined by a specific equation using MeSH terms and limited to human clinical trials. The use of probiotics and/or synbiotics has positive effects in the treatment and maintenance of UC, whereas in CD clear effectiveness has only been shown for synbiotics. Furthermore, in other associated IBD pathologies, such as pouchitis and cholangitis, LAB and bifidobacteria probiotics can provide a benefit through the improvement of clinical symptoms. However, more studies are needed to understand their mechanisms of action and in this way to understand the effect of probiotics prior to their use as coadjuvants in the therapy and prevention of IBD conditions.

CONCLUSIONS

The avalanche of genomic sequences generated in the post-genomic age requires efficient computational methods for rapidly and accurately identifying biological features from sequence information. Towards this goal, we developed a freely available and open-source package, called PseKNC-General (the general form of pseudo k-tuple nucleotide composition), that allows for fast and accurate computation of all the widely used nucleotide structural and physicochemical properties of both DNA and RNA sequences. PseKNC-General can generate several modes of pseudo nucleotide compositions, including conventional k-tuple nucleotide compositions, Moreau-Broto autocorrelation coefficient, Moran autocorrelation coefficient, Geary autocorrelation coefficient, Type I PseKNC and Type II PseKNC. In every mode, >100 physicochemical properties are available for choosing. Moreover, it is flexible enough to allow the users to calculate PseKNC with user-defined properties. The package can be run on Linux, Mac and Windows systems and also provides a graphical user interface.

METHODS

The package is freely available at: http://lin.uestc.edu.cn/server/pseknc.

Tuberculous pleurisy allows the study of specific cells at the site of Mycobacterium tuberculosis infection. Among pleural lymphocytes, natural killer (NK) cells are a major source of interferon gamma (IFN-gamma), and their functions are regulated by activating and inhibitory receptors. Programmed death-1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are recognized inhibitory receptors in adaptive immunity, but their role during innate immunity remains poorly understood. We investigated the PD-1:PD-L1/PD-L2 pathway on NK cell effector functions in peripheral blood and pleural fluid from patients with tuberculosis. M. tuberculosis stimulation significantly up-regulated PD-1, PD-L1, and PD-L2 levels on NK cells. Interestingly, a direct correlation between PD-1 and IFN-gamma expression on NK cells was observed. Moreover, blockade of the PD-1 pathway markedly augmented lytic degranulation and IFN-gamma production of NK cells against M. tuberculosis. Furthermore, PD-1(+) NK cells displayed a diminished IFN-gamma mean fluorescence intensity, denoting the relevance of PD-1 on IFN-gamma regulation. Together, we described a novel inhibitory role played by PD-1:PD-L interactions in innate immunity in tuberculosis.

Response bias shows up in many fields of behavioural and healthcare research where self-reported data are used. We demonstrate how to use stochastic frontier estimation (SFE) to identify response bias and its covariates. In our application to a family intervention, we examine the effects of participant demographics on response bias before and after participation; gender and race/ethnicity are related to magnitude of bias and to changes in bias across time, and bias is lower at post-test than at pre-test. We discuss how SFE may be used to address the problem of 'response shift bias' - that is, a shift in metric from before to after an intervention which is caused by the intervention itself and may lead to underestimates of programme effects.

The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

In eukaryotic genes, exons are generally interrupted by introns. Accurately removing introns and joining exons together are essential processes in eukaryotic gene expression. With the avalanche of genome sequences generated in the postgenomic age, it is highly desired to develop automated methods for rapid and effective detection of splice sites that play important roles in gene structure annotation and even in RNA splicing. Although a series of computational methods were proposed for splice site identification, most of them neglected the intrinsic local structural properties. In the present study, a predictor called "iSS-PseDNC" was developed for identifying splice sites. In the new predictor, the sequences were formulated by a novel feature-vector called "pseudo dinucleotide composition" (PseDNC) into which six DNA local structural properties were incorporated. It was observed by the rigorous cross-validation tests on two benchmark datasets that the overall success rates achieved by iSS-PseDNC in identifying splice donor site and splice acceptor site were 85.45% and 87.73%, respectively. It is anticipated that iSS-PseDNC may become a useful tool for identifying splice sites and that the six DNA local structural properties described in this paper may provide novel insights for in-depth investigations into the mechanism of RNA splicing.

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org/ and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.

OBJECTIVE

Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals.

OBJECTIVE

In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis.

METHODS

Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed.

RESULTS

Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms.

CONCLUSIONS

Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry.

Cytochrome P450 (CYP) superfamily members CYP2C8 and CYP2C9 are polymorphically expressed enzymes that are involved in the metabolic inactivation of several drugs, including, among others, antiepileptics, NSAIDs, oral hypoglycemics, and anticoagulants. Many of these drugs have a narrow therapeutic index, and growing evidence indicates a prominent role of CYP2C8 and CYP2C9 polymorphisms in the therapeutic efficacy and in the development of adverse effects among patients treated with drugs that are CYP2C8 or CYP2C9 substrates. In this review, we summarize present knowledge on human variability in the frequency of variant CYP2C8 and CYP2C9 alleles. Besides an expected interethnic variability in allele frequencies, a large intraethnic variability exists. Among Asian subjects, for example, statistically significant differences (p < 0.0001) in CYP2C9*3 allele frequencies between Chinese and Japanese individuals have been reported. In addition, individuals from East Asia present different allele frequencies for CYP2C9*2 and CYP2C9*3 compared with South Asian subjects (p < 0.0001). Among Caucasian Europeans, statistically significant differences for the frequency of CYP2C8*3, CYP2C9*2, and CYP2C9*3 exist (p < 0.0001). This indicates that Asian individuals or Caucasian European individuals cannot be considered as homogeneous groups regarding CYP2C8 or CYP2C9 allele frequencies. Caucasian American subjects also show a large variability in allele frequencies, which is likely to be related to ethnic ancestry. A higher frequency of variant CYP2C8 and CYP2C9 alleles is expected among Caucasian Americans with South European ancestry than in individuals with North European ancestry. The findings summarized in this review suggest that among individuals with Asian or European ancestry, intraethnic differences in the risk of developing adverse effects with drugs that are CYP2C8 or CYP2C9 substrates are to be expected. In addition, the observed intraethnic variability reinforces the need for proper selection of control subjects and points against the use of surrogate control groups for studies involving association of CYP2C8 or CYP2C9 alleles with adverse drug reactions or spontaneous diseases.