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Multidisciplinary perspectives on mechanisms of activity of popular immune-enhancing herbal supplements used by athletes
David S. SENCHINA, Justus E. HALLAM, David J. CHENEY
Front Biol    2013, 8 (1): 78-100.
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This paper examines cellular and molecular mechanisms that may underpin the purported effects of five herbal supplements in the context of athlete immune function. Ginseng and echinacea are used frequently by athletes, whereas astragalus and elderberry are used infrequently and pequi is just emerging as a possible supplement. In vivo studies of these products on athlete immune function have yielded heterogeneous results, likely due to experimental design differences. Ginseng, echinacea, elderberry, and pequi are considered asterids sensu lato. Ginseng appears to exert strongest effects on components of adaptive immunity, in particular maintaining Th1/Th2 balance of CD4+ T cells and their downstream effects, via its ginsenosides, flavonoids, and polysaccharides. Echinacea alkamides, caffeic acid derivatives, and polysacchardies may target both innate and adaptive immunity, though perhaps the former more consistently. Elderberry harbors anthocyanins and lectins which may modulate innate immunity. Data on pequi is limited but suggests that carotenoids, phenols, and fatty acids may alter circulating leukocyte populations. More phylogenetically distant, astragalus is a rosid sensu lato and may influence the innate immune system through flavonoids, polysaccharides, and saponins. Supplements generally demonstrate no effects on physiologic parameters such as lactate, oxygen dynamics, or athletic performance. Bioavailability studies indicate that purported bioactive molecules of these supplements may reach circulation in low but therapeutically-relevant quantities. Difficulties in cross-comparisons due to study design differences, coupled with an overall dearth of research on the topic, currently hamper any formal conclusions regarding the efficacy of these supplements as immunoregulators for athletes.

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MicroRNAs and drug modulation in cancer: an intertwined new story
Francesca FANINI, Ivan VANNINI, Muller FABBRI
Front Biol    2011, 6 (5): 351-356.
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MicroRNAs (miRNAs) are endogenous small non-coding RNAs (ncRNAs) which play important regulatory roles in physiological processes such as cellular differentiation, proliferation, development, apoptosis and stem cell self-renewal. An increasing number of papers have clearly claimed their involvement in cancer, providing, in some cases, also the molecular mechanisms implicated. Several studies led to the conclusion that miRNAs can be effectively used as anticancer agents alone or in combination with existing anticancer drugs. In particular, miRNAs can be effectively used to overcome drug resistance, one of the main factors responsible for anticancer treatment insuccess. One of the main questions remains how to modulate the expression of miRNAs in cancer cells. Interestingly, a few studies have shown that the expression of miRNAs is affected by drugs (including some drugs currently used as anticancer agents), therefore providing the rationale for an intertwined scenario in which miRNAs can be modulated by drugs and, in turn, can affect drug sensitivity of cancer cells.

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Single-cell genomics: An overview
Qichao WANG, Xianmin ZHU, Yun FENG, Zhigang XUE, Guoping FAN
Front Biol    2013, 8 (6): 569-576.
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The newly developed next-generation sequencing platforms, in combination with genome-scale amplification methods, provide a powerful tool to study genomics from a single cell. This mini-review summarizes the technologies of single cell genomics and their applications in several areas of biomedical research including stem cells, cancer biology and reproductive medicine. Particularly, it highlights recent advances in single cell exome sequencing, RNA-seq, and genome sequencing. The application of these powerful techniques will shed new light on the fundamental principles of gene transcription and genome organization at single-cell level and improve our understanding of cellular heterogeneity and diversity in multicellular organisms.

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Progress in Brucella vaccine development
Xinghong YANG, Jerod A. SKYBERG, Ling CAO, Beata CLAPP, Theresa THORNBURG, David W. PASCUAL
Front Biol    2013, 8 (1): 60-77.
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Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines.

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The stomata frontline of plant interaction with the environment-perspectives from hormone regulation
Mengmeng ZHU, Shaojun DAI, Sixue CHEN
Front Biol    2012, 7 (2): 96-112.
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Plants have evolved elaborate mechanisms to perceive and integrate signals from various environmental conditions. On leaf surface, stomata formed by pairs of guard cells mediate gas exchange, water transpiration as well as function in response to abiotic and biotic stresses. Stomatal closure could be induced by drought, salt, pathogen and other adverse conditions. This constitutes an instant defense response to prevent further damage to plants. Abscisic acid (ABA) is a major plant hormone involved in stress responses. Stress-activated ABA synthesis causes stomatal closure and prevents opening to reduce water loss and cell dehydration. Key regulatory receptor complex and other important components in the ABA signaling pathway have been identified. However, our knowledge of ABA signal transduction in guard cells is far from complete. Jasmonates are a group of phytohormones generally known to be important for plant defense against insects and necrotrophic pathogens. The increased levels of methyl jasmonate (MeJA) induced by herbivory and pathogen invasion show a similar effect on stomatal movement associated with ROS production as ABA. Investigation of guard cell signaling networks involving the two important phytohormones is significant and exciting. Information about protein and metabolite components and how they interact in guard cells is lacking. Here we review recent advances on hormone signaling networks in guard cells and how the networks integrate environmental signals to plant physiological output.

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Insights into the role of jasmonic acid-mediated defenses against necrotrophic and biotrophic fungal pathogens
Christopher J. ANTICO, Chad COLON, Taylor BANKS, Katrina M. RAMONELL
Front Biol    2012, 7 (1): 48-56.
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Jasmonic acid (JA) is a natural hormone regulator involved in development, responses against wounding and pathogen attack. Upon perception of pathogens, JA is synthesized and mediates a signaling cascade initiating various defense responses. Traditionally, necrotrophic fungi have been shown to be the primary activators of JA-dependent defenses through the JA-receptor, COI1. Conversely, plants infected with biotrophic fungi have classically been associated with suppressing JA-mediated responses. However, recent evidence has shown that certain biotrophic fungal species also trigger activation of JA-mediated responses and mutants deficient in JA signaling show an increase in susceptibility to certain biotrophic fungal pathogens. These findings suggest a new role for JA in defense against fungal biotrophs. This review will focus on recent research advancing our knowledge of JA-dependant responses involved in defense against both biotrophic and necrotrophic fungi.

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An epigenetic perspective on the failing heart and pluripotent-derived-cardiomyocytes for cell replacement therapy
Joshua D. TOMPKINS,Arthur D. RIGGS
Front. Biol.    2015, 10 (1): 11-27.
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As life expectancy rises, the prevalence of heart failure is steadily increasing, while donors for organ transplantation remain in short supply (Zwi-Dantsis and Gepstein, 2012). Indeed, myocardial infarction represents the foremost cause of death within industrialized nations (Henning, 2011) and further, approximately 1% of all newborns harbor a congenital heart defect. Although medical interventions allow>80% of those with cardiac defects to survive to adulthood, there are often extreme emotional and financial burdens that accompany such congenital anomalies, and many individuals will remain at a heightened risk for myocardial infarction throughout the remainder of their lives (Verheugt et al., 2010; Amianto et al., 2011). In this review, we will discuss the nature of the failing heart and strategies for repair from an epigenetic standpoint. Significant focus will reside on pluripotent-to-cardiomyocyte differentiation for cell replacement, epigenetic mechanisms of cardiomyocyte differentiation, epigenetic “memories,” and epigenetic control of cardiomyocyte cell fate toward translational utility.

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Approaches in extracellular matrix engineering for determination of adhesion molecule mediated single cell function
Front Biol    2013, 8 (1): 32-49.
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The native extracellular matrix (ECM) and the cells that comprise human tissues are together engaged in a complex relationship; cells alter the composition and structure of the ECM to regulate the material and biologic properties of the surrounding environment while the composition and structure of the ECM modulates cellular processes that maintain healthy tissue and repair diseased tissue. This reciprocal relationship occurs via cell adhesion molecules (CAMs) such as integrins, selectins, cadherins and IgSF adhesion molecules. To study these cell-ECM interactions, researchers use two-dimensional substrates or three-dimensional matrices composed of native proteins or bioactive peptide sequences to study single cell function. While two-dimensional substrates provide valuable information about cell-ECM interactions, three-dimensional matrices more closely mimic the native ECM; cells cultured in three-dimensional matrices have demonstrated greater cell movement and increased integrin expression when compared to cells cultured on two-dimensional substrates. In this article we review a number of cellular processes (adhesion, motility, phagocytosis, differentiation and survival) and examine the cell adhesion molecules and ECM proteins (or bioactive peptide sequences) that mediate cell functionality.

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DISC1 genetics, biology and psychiatric illness
Pippa A. THOMSON, Elise L.V. MALAVASI, Ellen GRüNEWALD, Dinesh C. SOARES, Malgorzata BORKOWSKA, J. Kirsty MILLAR
Front Biol    2013, 8 (1): 1-31.
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Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.

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Application of reprogrammed patient cells to investigate the etiology of neurological and psychiatric disorders
Kimberly M. CHRISTIAN, Hongjun SONG, Guo-li MING
Front Biol    2012, 7 (3): 179-188.
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Cellular reprogramming allows for the de novo generation of human neurons and glial cells from patients with neurological and psychiatric disorders. Crucially, this technology preserves the genome of the donor individual and thus provides a unique opportunity for systematic investigation of genetic influences on neuronal pathophysiology. Although direct reprogramming of adult somatic cells to neurons is now possible, the majority of recent studies have used induced pluripotent stem cells (iPSCs) derived from patient fibroblasts to generate neural progenitors that can be differentiated to specific neural cell types. Investigations of monogenic diseases have established proof-of-principle for many aspects of cellular disease modeling, including targeted differentiation of neuronal populations and rescue of phenotypes in patient iPSC lines. Refinement of protocols to allow for efficient generation of iPSC lines from large patient cohorts may reveal common functional pathology and genetic interactions in diseases with a polygenic basis. We review several recent studies that illustrate the utility of iPSC-based cellular models of neurodevelopmental and neurodegenerative disorders to identify novel phenotypes and therapeutic approaches.

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A power analysis for future clinical trials on the potential adverse effects of SSRIs on amygdala reactivity
M. A. Bottelier,A. Schrantee,G. van Wingen,H. G. Ruhé,M. B. de Ruiter,L. Reneman
Front. Biol.    2016, 11 (3): 256-259.
Abstract   HTML   PDF (125KB)

Treatment of adolescents with antidepressants may induce an increased risk for suicidality in this population. The activity of the amygdala during processing of emotional faces with functional Magnetic Resonance Imaging (fMRI) is a well-known measure of emotional dysregulation. Based upon data of our prematurely ended randomized clinical trial with fluoxetine (NTR3103) in anxious and or depressed girls (12–14 years of age) we calculated that with the found effect size of r = 0.66, compared to placebo, only 8 subjects are needed to demonstrate increased amygdala activity following 16 weeks of treatment with fluoxetine.

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Alternative splicing switching in stem cell lineages
Front Biol    2013, 8 (1): 50-59.
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The application of stem cells to regenerative medicine depends on a thorough understanding of the molecular mechanisms underlying their pluripotency. Many studies have identified key transcription factor-regulated transcriptional networks and chromatin landscapes of embryonic and a number of adult stem cells. In addition, recent publications have revealed another interesting molecular feature of stem cells— a distinct alternative splicing pattern. Thus, it is possible that both the identity and activity of stem cells are maintained by stem cell-specific mRNA isoforms, while switching to different isoforms ensures proper differentiation. In this review, we will discuss the generality of mRNA isoform switching and its interaction with other molecular mechanisms to regulate stem cell pluripotency, as well as the reprogramming process in which differentiated cells are induced to become pluripotent stem cell-like cells (iPSCs).

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Growth factor receptor trafficking as a potential therapeutic target in pediatric cancer
Peter E. ZAGE, Andrew J. BEAN
Front Biol    2012, 7 (1): 1-13.
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Growth factor receptors (GFRs) are often aberrantly expressed in tumor cells, and altered GFR expression and activity contribute to the pathogenesis of many types of cancer. A variety of mechanisms have been identified that result in enhanced GFR expression and activity in cancer cells. Defects in the pathways responsible for GFR internalization and intracellular trafficking are likely to be involved in altered GFR expression in a variety of cancers. The roles of GFR trafficking pathways in the regulation of GFR expression, in the pathogenesis of tumors, and in the response of tumors to treatment have not been fully delineated, but the likely contributions of GFR signaling to the development and progression of various malignancies suggest that therapies that modify GFR trafficking may be effective as anticancer treatments.

The intracellular trafficking of GFRs is regulated by a number of protein complexes and by protein ubiquitination. Many of the proteins required for this trafficking are products of tumor suppressor genes, and the expression and function of the protein machinery utilized for intracellular trafficking is frequently altered in tumor cells, consistent with the likely role of GFR trafficking in tumorigenesis. Many of the proteins involved in GFR trafficking have been identified as potential targets for anticancer treatment, and novel treatments directed against these targets are currently in preclinical development and in clinical trials. Ubiquitin ligases are critical for GFR trafficking and represent potentially important targets for the development of novel therapies.

The genes for the ubiquitin ligases c-Cbl and UBE4B are located in chromosome regions commonly altered in a variety of tumors and therefore are likely to be important for tumorigenesis. c-Cbl ubiquitinates a number of GFRs and directs them for degradation. Mutations in c-Cbl have been identified in cases of myeloid leukemia and myelodysplasia, providing a link between GFR ubiquitination and trafficking and leukemogenesis. We have shown that UBE4B plays a crucial role in GFR trafficking and degradation in tumor cells, suggesting a previously uncharacterized link between UBE4B and tumorigenesis. With the critical need for new and effective therapies for pediatric malignancies, the recently identified roles for the GFR trafficking pathway in the pathogenesis of various forms of cancer confirm the importance of the further development of novel therapies targeting this pathway in children with cancer.

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Advances in plant proteomics-key techniques of proteome
RUAN Songlin, MA Huasheng, WANG Shiheng, XIN Ya, QIAN Lihua, TONG Jianxing, WANG Jie
Front. Biol.    2008, 3 (3): 245-258.
Abstract   HTML   PDF (149KB)
Following the completion of genome sequencing of model plants, such as rice (Oryza sativa L.) and Arabidopsis thaliana, the era of functional plant genomics has arrived which provides a solid basis for the development of plant proteomics. We review the background and concepts of proteomics, as well as the key techniques which include: (1) separation techniques such as 2-DE (two-dimensional electrophoresis), RP-HPLC (reverse phase high performance liquid chromatography) and SELDI (surface enhanced laser desorption/ionization) protein chip; (2) mass spectrometry such as MALDI-TOF-MS (matrix assisted laser desorption/ionization-time of flight- mass spectrometry) and ESI-MS/MS (electrospray ionization mass spectrometry/mass spectrometry); (3) Peptide sequence tags; (4) databases related to proteomics; (5) quantitative proteome; (6) TAP (tandem affinity purification) and (7) yeast two-hybrid system. In addition, the challenges and prospects of proteomics are also discussed.
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Degradome sequencing reveals endogenous small RNA targets in rice ( Oryza sativa L. ssp . indica )
Ming ZHOU, Lianfeng GU, Pingchuan LI, Xianwei SONG, Liya WEI, Zhiyu CHEN, Xiaofeng CAO
Front. Biol.    2010, 5 (1): 67-90.
Abstract   PDF (861KB)
MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) regulate gene expression in eukaryotes. Plant miRNAs modulate their targets mainly via messenger RNA (mRNA) cleavage. Small RNA (sRNA) targets have been extensively investigated in Arabidopsis using computational prediction, experimental validation, and degradome sequencing. However, small RNA targets are largely unknown in rice (Oryza sativa). Here, we report global identification of small RNA targets using high throughput degradome sequencing in the rice indica cultivar 93-11 (Oryza sativa L. ssp. indica). One hundred and seventy-seven transcripts targeted by a total of 87 unique miRNAs were identified. Of targets for the conserved miRNAs between Arabidopsis and rice, transcription factors comprise around 70% (58 in 82), indicating that these miRNAs act as masters of gene regulatory nodes in rice. In contrast, non-conserved miRNAs targeted diverse genes which provide more complex regulatory networks. In addition, 5 AUXIN RESPONSE FACTORs (ARFs) cleaved by the TAS3 derived ta-siRNAs were also detected. A total of 40 sRNA targets were further validated via RNA ligase-mediated 5′ rapid amplification of cDNA ends (RLM 5′-RACE). Our degradome results present a detailed sRNA-target interaction atlas, which provides a guide for the study of the roles of sRNAs and their targets in rice.
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BMP signaling pathway and spinal cord development
Zhihui XIE, Nengyin SHENG, Naihe JING
Front Biol    2012, 7 (1): 24-29.
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The development of spinal cord is a precisely and sequentially regulated process, which is controlled by signaling pathways and transcription factors in each stage. Overwhelming data have shown the essential roles of BMP signaling in different stages of this developmental process. It is also clear that the proper functions of BMP signaling require its cross-talk with several other signaling pathways including Notch, Wnt and retinoic acid (RA) pathways. Here, we highlight the recent advancement in understanding the roles of BMP signaling during neurogenesis, neural tube patterning, axon development and glial differentiation in the spinal cord, and emphasize its integrations with other pathways during these processes.

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Finding biomarkers for non-small cell lung cancer diagnosis and prognosis
Tian XIAO, Lei BAO, Hongbin JI
Front Biol    2012, 7 (1): 14-23.
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Despite of several decades of efforts, lung cancer remains one of most deadly diseases, with a 5-year survival rate approximately 15% worldwide. In China, the situation is even worse. Although there is no official data released yet, the 5-year survival rate is estimated to be around 10%. In past 30 years, there was a dramatic increase of lung cancer related death about 465% in mainland China. Annually, about 400000 people die of lung cancer and the number is still climbing. At the same time, the number of new lung cancer cases also increase rapidly. The high mortality of lung cancer is mainly ascribed to two factors: the lack of effective ways to identify early diagnostic biomarkers and to treat metastatic cancer. Lung cancer can be pathologically divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), among which NSCLC accounts for about 80% of all cases. In this review, we will focus on the recent efforts and progress in finding biomarkers in NSCLC. Since biomarkers are derived from both invasive and non-invasive ways, we divide them into these two categories and review them separately. We hope the discovery of biomarkers will eventually change the current clinical practice in NSCLC patients and improve their quality of life.

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Drosophila embryo syncytial blastoderm cellular architecture and morphogen gradient dynamics: Is there a correlation?
Front Biol    2012, 7 (1): 73-82.
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During embryo development in many metazoan animals, the first differentiated cell type to form is an epithelial cell. This epithelial layer is modified by developmental cues of body axes formation to give rise to various tissues. The cells that arise are mesenchymal in nature and are a source of other tissue types. This epithelial to mesenchymal transition is used for tissue type formation and also seen in diseases such as cancer. Here we discuss recent findings on the cellular architecture formation in the Drosophila embryo and how it affects the developmental program of body axes formation. In particular these studies suggest the presence of compartments around each nucleus in a common syncytium. Despite the absence of plasma membrane boundaries, each nucleus not only has its own endoplasmic reticulum and Golgi complex but also its own compartmentalized plasma membrane domain above it. This architecture is potentially essential for morphogen gradient restriction in the syncytial Drosophila embryo. We discuss various properties of the dorso-ventral and the antero-posterior morphogen gradients in the Drosophila syncytium, which are likely to depend on the syncytial architecture of the embryo.

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Signal convergence through the lenses of MAP kinases: paradigms of stress and hormone signaling in plants
Kundan KUMAR, Dhammaprakash Pandhari WANKHEDE, Alok Krishna SINHA
Front Biol    2013, 8 (1): 109-118.
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Common mechanisms plants use to translate the external stimuli into cellular responses are the activation of mitogen-activated protein kinase (MAPK) cascade. These MAPK cascades are highly conserved in eukaryotes and consist of three subsequently acting protein kinases, MAP kinase kinase kinase (MAPKKK), MAP kinase kinase (MAPKK) and MAP kinase (MAPK) which are linked in various ways with upstream receptors and downstream targets. Plant MAPK cascades regulate numerous processes, including various environmental stresses, hormones, cell division and developmental processes. The number of MAPKKs in Arabidopsis and rice is almost half the number of MAPKs pointing important role of MAPKKs in integrating signals from several MAPKKKs and transducing signals to various MAPKs. The cross talks between different signal transduction pathways are concentrated at the level of MAPKK in the MAPK cascade. Here we discussed the insights into MAPKK mediated response to environmental stresses and in plant growth and development.

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Quantitative analysis of FRET assay in biology New developments in protein interaction affinity and protease kinetics determinations in the SUMOylation cascade
Yan LIU, Yang SONG, Ling JIANG, Jiayu LIAO
Front Biol    2012, 7 (1): 57-64.
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F?rster resonance energy transfer (FRET) techniques have been widely used in biological studies in vitro and in vivo and are powerful tools for elucidating protein interactions in many regulatory cascades. FRET occurs between oscillating dipoles of two fluorophores with overlapping emission and excitation wavelengths and is dependent on the spectroscopic and geometric properties of the donor-acceptor pair. Various efforts have been made to develop quantitative FRET methods to accurately determine the interaction affinity and kinetics parameters. SUMOylation is an important post-translational protein modification with key roles in multiple biological processes. Conjugating SUMO to substrates requires an enzymatic cascade. Sentrin/SUMO-specific proteases (SENP) act as endopeptidases to process the pre-SUMO or an isopeptidase to deconjugate SUMO from its substrate. Here we also summarize recent developments of theoretical and experimental procedures for determining the protein interaction dissociation constant, Kd, and protease kinetics parameters, kcat and Km, in the SUMOylation pathway. The general principles of these quantitative FRET-based measurements can be applied to other protein interactions and proteases.

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Advances in medical decision support systems for diagnosis of acute graft-versus-host disease: molecular and computational intelligence joint approaches
Maurizio FIASCHé, Maria CUZZOLA, Giuseppe IRRERA, Pasquale IACOPINO, Francesco Carlo MORABITO
Front Biol    2011, 6 (4): 263-273.
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Acute graft-versus-host disease (aGVHD) is a serious systemic complication of allogeneic hematopoietic stem cell transplantation (HSCT) causing considerable morbidity and mortality. Acute GVHD occurs when alloreactive donor-derived T cells recognize host-recipient antigens as foreign. These trigger a complex multiphase process that ultimately results in apoptotic injury in target organs. The early events leading to GVHD seem to occur very soon, presumably within hours from the graft infusion. Therefore, when the first signs of aGVHD clinically manifest, the disease has been ongoing for several days at the cellular level, and the inflammatory cytokine cascade is fully activated. So, it comes as no surprise that progress in treatment based on clinical diagnosis of aGVHD has been limited in the past 30 years. It is likely that a pre-emptive strategy using systemic high-dose corticosteroids as early as possible could improve the outcome of aGVHD. Due to the deleterious effects of such treatment particularly in terms of infection risk posed by systemic steroid administration in a population that is already immune-suppressed, it is critical to identify biomarker signatures for approaching this very complex task. Some research groups have begun addressing this issue through molecular and proteomic analyses, combining these approaches with computational intelligence techniques, with the specific aim of facilitating the identification of diagnostic biomarkers in aGVHD. In this review, we focus on the aGVHD scenario and on the more recent state-of-the-art. We also attempt to give an overview of the classical and novel techniques proposed as medical decision support system for the diagnosis of GVHD.

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Metabolomics in Schizophrenia and Major Depressive Disorder
Iva Petrovchich,Alexandra Sosinsky,Anish Konde,Abigail Archibald,David Henderson,Mirjana Maletic-Savatic,Snezana Milanovic
Front. Biol.    2016, 11 (3): 222-231.
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Defining pathophenotype, a systems level consequence of a disease genotype, together with environmental and stochastic influences, is an arduous task in psychiatry. It is also an appealing goal, given growing need for appreciation of brain disorders biological complexity, aspiration for diagnostic tests development and ambition to identify novel drug targets. Here, we focus on the Schizophrenia and Major Depressive Disorder and highlight recent advances in metabolomics research. As a systems biology tool, metabolomics holds a promise to take part in elucidating interactions between genes and environment, in complex behavioral traits and psychopathology risk translational research.

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Adult neurogenesis in the mammalian brain
Simon M.G. BRAUN, Sebastian JESSBERGER
Front Biol    2013, 8 (3): 295-304.
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New neurons are generated throughout life in distinct areas of the mammalian brain. This process, called adult neurogenesis, has challenged previously held concepts about adult brain plasticity and opened novel therapeutic avenues to treat certain neuro-psychiatric diseases. Here, we review the current knowledge regarding the fate and potency of neural stem cells (NSCs), as well as the mechanisms underlying neuronal differentiation and subsequent integration. Furthermore, we discuss the functional significance of adult neurogenesis in health and disease, and offer brief insight into the future directions of the adult neurogenesis field.

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Adult neurogenesis in Provence: Where history meets science
Mirjana Maletic-Savatic,Michael Valenzuela
Front. Biol.    2016, 11 (3): 149-150.
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Stress, hippocampal neurogenesis and cognition: functional correlations
Paul J. Lucassen,Charlotte A. Oomen
Front. Biol.    2016, 11 (3): 182-192.
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The brain of many species including humans, harbors stem cells that continue to generate new neurons up into adulthood. This form of structural plasticity occurs in a limited number of brain regions, i.e. the subventricular zone and the hippocampal dentate gyrus and is regulated by environmental and hormonal factors. In this minireview, we provide an overview of the effects of stress and glucocorticoid hormones on adult hippocampal neurogenesis and discuss how these effects may be relevant for cognitive function and possibly, brain disease. While its exact functional role remains elusive, adult neurogenesis has been implicated in learning and memory, fear and mood regulation and recently, adult-born neurons were found to be involved in specific cognitive functions such as pattern separation (i.e. the ability to form unique memory representations) and cognitive flexibility. The process of adult neurogenesis is influenced by several factors; whereas e.g. exercise stimulates, exposure to stress and stress hormones generally inhibit neurogenesis. Effects of acute, mild stress are generally short-lasting and recover quickly, but chronic or severe forms of stress can induce lasting reductions in adult neurogenesis. Some of the inhibitory effects of stress can be rescued by exercise, by allowing a period of recovery from stress, by drugs that target the stress system, or by some, but not all, antidepressants. Stress may, partly through its effects on adult neurogenesis, alter structure and plasticity of the hippocampal circuit. This can lead to subsequent changes in stress responsivity and aspects of memory processing, which may be particularly relevant for stress related psychopathology or brain diseases that involve perturbed memory processing.

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Annual plants in arid and semi-arid desert regions
LI Xuehua, LI Xiaolan, JIANG Deming, LIU Zhimin, YU Qinghe
Front. Biol.    2008, 3 (3): 259-264.
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Annual plants are the main vegetation in arid and semi-arid desert regions. Because of their unique traits, they are the optimal experimental subjects for ecological studies. In this article, we summarize annual plants’ seed germination strategies, seedling adaptability mechanism to environments, seed dispersal, and soil seed banks. We also discuss the biotic and abiotic factors affecting the composition and dynamics of annual plant populations and communities. Because annual plants have important ecological functions in desert vegetation systems, this study on annual plants will be of great benefit to the conservation and restoration of desert ecosystems, the rational utilization of resources, and the sustainable development of desert regions.
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Combined immunohistochemical and retrograde tracing reveals little evidence of innervation of the rat dentate gyrus by midbrain dopamine neurons
Charlotte M. Ermine,Jordan L. Wright,Clare L. Parish,Davor Stanic,Lachlan H. Thompson
Front. Biol.    2016, 11 (3): 246-255.
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Although the functional neuroanatomy of the midbrain dopamine (mDA) system has been well characterized, the literature regarding its capacity to innervate the hippocampal formation has been inconsistent. The lack of expression of definitive markers for dopaminergic fibers, such as the dopamine transporter, in the hippocampus has complicated studies in this area. Here we have used immunohistochemical techniques to characterize the tyrosine hydroxylase expressing fiber network in the rat hippocampus, combined with retrograde tracing from the dentate gyrus to assess the capacity for afferent innervation by mDA neurons. The results indicate that virtually all tyrosine hydroxylase fibers throughout the hippocampus are of a noradrenergic phenotype, while the overlying cortex contains both dopaminergic and noradrenergic fiber networks. Furthermore, retrograde tracing from the dentate gyrus robustly labels tyrosine hydroxylase-immunoreactive noradrenergic neurons in the locus coeruleus but not mDA neurons.

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Asexual and sexual reproductive strategies in clonal plants
ZHANG Yufen, ZHANG Dayong
Front. Biol.    2007, 2 (3): 256-262.
Abstract   PDF (274KB)
Most plants can reproduce both sexually and asexually (or vegetatively), and the balance between the two reproductive modes may vary widely between and within species. Extensive clonal growth may affect the evolution of life history traits in many ways. First, in some clonal species, sexual reproduction and sex ratio vary largely among populations. Variation in sexual reproduction may strongly affect plant’s adaptation to local environments and the evolution of the geographic range. Second, clonal growth can increase floral display, and thus pollinator attraction, while it may impose serious constraints and evolutionary challenges on plants through geitonogamy that may strongly influence pollen dispersal. Geitonogamous pollination can bring a cost to plant fitness through both female and male functions. Some co-evolutionary interactions, therefore, may exist between the spatial structure and the mating behavior of clonal plants. Finally, a trade-off may exist between sexual reproduction and clonal growth. Resource allocation to the two reproductive modes may depend on environmental conditions, competitive dominance, life span, and genetic factors. If different reproductive modes represent adaptive strategies for plants in different environments, we expect that most of the resources should be allocated to sexual reproduction in habitats with fluctuating environmental conditions and strong competition, while clonal growth should be dominant in stable habitats. Yet we know little about the consequence of natural selection on the two reproductive modes and factors which control the balance of the two reproductive modes. Future studies should investigate the reproductive strategies of clonal plants simultaneously from both sexual and asexual perspectives.
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Origin and differentiation of endemism in the flora of China
WU Zhengyi, SUN Hang, ZHOU Zhekun, PENG Hua, LI Dezhu
Front. Biol.    2007, 2 (2): 125-143.
Abstract   PDF (313KB)
The present paper analyzed 239 endemic genera in 67 families in the flora of seed plants in China. The results showed that there are five families containing more than ten endemic genera, namely, Gesneriaceae (27), which hereafter refers to the number of endemic genera in China, Composite (20), Labiatae (12), Cruciferae (11), and Umbelliferae (10), 15 families with two endemic genera, and another 30 families with only one endemic genus. Four monotypic families (Ginkgoaceae, Davidiaceae, Eucommiaceae and Acanthochlamydaceae) are the most ancient, relict and characteristic in the flora of seed plants in China. Based on integrative data of systematics, fossil history, and morphological and molecular evidence of these genera, their origin, evolution and relationships were discussed. In gymnosperms, all endemic genera are relicts of the Arctic-Tertiary flora, having earlier evolutionary history, and can be traced back to the Cretaceous or to the Jurassic and even earlier. In angiosperms, the endemic genera are mostly relicts, and are represented in all lineages in the Eight-Class System of Classification of Angiosperms , and endemism can be found in almost every evolutionary stage of extant angiosperms. The relict genera once occupied huge areas in the northern hemisphere in the Tertiary or the late Cretaceous, while neo-endemism mostly originated in the late Tertiary. They came from Arctic-Tertiary, Paleo-tropical-Tertiary and Tethys-Tertiary florisitic elements, and the blend of the three elements with many genera of autochthonous origin. The endemism was formed when some dispersal routes such as the North Atlantic Land Bridge, and the Bering Bridge became discontinuous during the Tertiary, as well as the climate change and glaciations in the late Tertiary and the Quaternary. Therefore, the late Tertiary is the starting point of extant endemism of the flora in China.
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Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation
Martha Hvoslef-Eide,Charlotte A. Oomen
Front. Biol.    2016, 11 (3): 168-181.
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The ability to discriminate and store similar inputs as distinct representations in memory is thought to rely on a process called pattern separation in the dentate gyrus of the hippocampus. Recent computational and empirical findings support a role for adult-born granule neurons in spatial pattern separation. We reviewed rodent studies that have manipulated both hippocampal adult neurogenesis and assessed pattern separation. The majority of studies report a supporting role of adult born neurons in pattern separation as measured at the behavioral level. However, closer evaluation of the published findings reveals variation in both pattern separation tasks and in the interpretation of behavioral performance that, taken together, suggests that the role of hippocampal adult neurogenesis in pattern separation may be less established than is currently assumed. Assessment of pattern separation at the network level through the use of immediate early gene expression, optogenetic, pharmacogenetic and/or in vivo electrophysiology studies could be instrumental in further confirming a role of adult born neurons in pattern separation further. Finally, hippocampal adult neurogenesis and pattern separation are not an exclusive pair, as evidence for hippocampal adult neurogenesis contributing to the temporal separation of events in memory, forgetting and cognitive flexibility has also been found. We conclude that whereas current empirical evidence for the involvement of hippocampal adult neurogenesis in pattern separation seems supportive, there is a need for careful interpretation of behavioral findings and an integration of the various proposed functions of adult born neurons.

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