Showing papers in "Science China-life Sciences in 2015"

Genetic basis and biotechnological manipulation of sexual dimorphism and sex determination in fish

Abstract: Aquaculture has made an enormous contribution to the world food production, especially to the sustainable supply of animal proteins. The utility of diverse reproduction strategies in fish, such as the exploiting use of unisexual gynogenesis, has created a typical case of fish genetic breeding. A number of fish species show substantial sexual dimorphism that is closely linked to multiple economic traits including growth rate and body size, and the efficient development of sex-linked genetic markers and sex control biotechnologies has provided significant approaches to increase the production and value for commercial purposes. Along with the rapid development of genomics and molecular genetic techniques, the genetic basis of sexual dimorphism has been gradually deciphered, and great progress has been made in the mechanisms of fish sex determination and identification of sex-determining genes. This review summarizes the progress to provide some directive and objective thinking for further research in this field.

The discovery of artemisinin and the Nobel Prize in Physiology or Medicine

Abstract: The 2015 Nobel Prize in Physiology or Medicine was awarded to Professor Youyou Tu for her key contributions to the discovery of artemisinin. Artemisinin has saved millions of lives and represents one of the significant contributions of China to global health. Many scientists were involved in the previously unknown 523 Project, and the Nobel Prize given to a single person has not been without controversy. Here we summarized some key events in the 523 Project and present our views on the Award to help the public better understand the rationale of the Nobel committee’s decision, the significance of the discovery, and current issues related to artimisinin in treating malaria.

Virus genomes and virus-host interactions in aquaculture animals

Abstract: Over the last 30 years, aquaculture has become the fastest growing form of agriculture production in the world, but its development has been hampered by a diverse range of pathogenic viruses. During the last decade, a large number of viruses from aquatic animals have been identified, and more than 100 viral genomes have been sequenced and genetically characterized. These advances are leading to better understanding about antiviral mechanisms and the types of interaction occurring between aquatic viruses and their hosts. Here, based on our research experience of more than 20 years, we review the wealth of genetic and genomic information from studies on a diverse range of aquatic viruses, including iridoviruses, herpesviruses, reoviruses, and rhabdoviruses, and outline some major advances in our understanding of virus-host interactions in animals used in aquaculture.

The hypoxia signaling pathway and hypoxic adaptation in fishes.

Abstract: The hypoxia signaling pathway is an evolutionarily conserved cellular signaling pathway present in animals ranging from Caenorhabditis elegans to mammals The pathway is crucial for oxygen homeostasis maintenance Hypoxia-inducible factors (HIF-1α and HIF-2α) are master regulators in the hypoxia signaling pathway Oxygen concentrations vary a lot in the aquatic environment To deal with this, fishes have adapted and developed varying strategies for living in hypoxic conditions Investigations into the strategies and mechanisms of hypoxia adaptation in fishes will allow us to understand fish speciation and breed hypoxia-tolerant fish species/strains This review summarizes the process of the hypoxia signaling pathway and its regulation, as well as the mechanism of hypoxia adaptation in fishes

Learning from berberine: Treating chronic diseases through multiple targets

Abstract: Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimers disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine (BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBRs molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.

Sensorimotor dysfunctions as primary features of autism spectrum disorders

Abstract: Motor impairments in autism spectrum disorders (ASD) have received far less research attention than core socialcommunication and cognitive features Yet, behavioral, neurophysiological, neuroimaging and histopathological studies have documented abnormal motor system development in the majority of individuals with ASD suggesting that these deficits may be primary to the disorder There are several unique advantages to studying motor development in ASD First, the neurophysiological substrates of motor skills have been well-characterized via animal and human lesion studies Second, many of the single- gene disorders associated with ASD also are characterized by motor dysfunctions Third, recent evidence suggests that the onset of motor dysfunctions may precede the emergence of social and communication deficits during the first year of life in ASD Motor deficits documented in ASD indicate disruptions throughout the neuroaxis affecting cortex, striatum, the cerebellum and brainstem Questions remain regarding the timing and development of motor system alterations in ASD, their association with defining clinical features, and their potential for parsing heterogeneity in ASD Pursuing these questions through neurobiologically informed translational research holds great promise for identifying gene-brain pathways associated with ASD

Three-dimensional bio-printing.

Abstract: Three-dimensional (3D) printing technology has been widely used in various manufacturing operations including automotive, defence and space industries. 3D printing has the advantages of personalization, flexibility and high resolution, and is therefore becoming increasingly visible in the high-tech fields. Three-dimensional bio-printing technology also holds promise for future use in medical applications. At present 3D bio-printing is mainly used for simulating and reconstructing some hard tissues or for preparing drug-delivery systems in the medical area. The fabrication of 3D structures with living cells and bioactive moieties spatially distributed throughout will be realisable. Fabrication of complex tissues and organs is still at the exploratory stage. This review summarize the development of 3D bio-printing and its potential in medical applications, as well as discussing the current challenges faced by 3D bio-printing.

Genetic and genomic analyses for economically important traits and their applications in molecular breeding of cultured fish.

Abstract: The traits of cultured fish must continually be genetically improved to supply high-quality animal protein for human consumption. Economically important fish traits are controlled by multiple gene quantitative trait loci (QTL), most of which have minor effects, but a few genes may have major effects useful for molecular breeding. In this review, we chose relevant studies on some of the most intensively cultured fish and concisely summarize progress on identifying and verifying QTLs for such traits as growth, disease and stress resistance and sex in recent decades. The potential applications of these major-effect genes and their associated markers in marker-assisted selection and molecular breeding, as well as future research directions are also discussed. These genetic and genomic analyses will be valuable for elucidating the mechanisms modulating economically important traits and to establish more effective molecular breeding techniques in fish.

NK cell-based cancer immunotherapy: from basic biology to clinical application

Abstract: Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.

Therapeutic potential of berberine against neurodegenerative diseases

Abstract: Berberine (BBR) is an organic small molecule isolated from various plants that have been used in traditional Chinese medicine. Isolation of this compound was its induction into modern medicine, and its usefulness became quickly apparent as seen in its ability to combat bacterial diarrhea, type 2 diabetes, hypercholesterolemia, inflammation, heart diseases, and more. However, BBR’s effects on neurodegenerative diseases remained relatively unexplored until its ability to stunt Alzheimer’s disease (AD) progression was characterized. In this review, we will delve into the multi-faceted defensive capabilities and bio-molecular pathways of BBR against AD, Parkinson’s disease (PD), and trauma-induced neurodegeneration. The multiple effects of BBR, some of which enhance neuro-protective factors/pathways and others counteract targets that induce neurodegeneration, suggest that there are many more branches to the diverse capabilities of BBR that have yet to be uncovered. The promising results seen provide a convincing and substantial basis to support further scientific exploration and development of the therapeutic potential of BBR against neurodegenerative diseases.

High quality reference genome of drumstick tree ( Moringa oleifera Lam.), a potential perennial crop

Abstract: The drumstick tree ( Moringa oleifera Lam.) is a perennial crop that has gained popularity in certain developing countries for its high-nutrition content and adaptability to arid and semi-arid environments. Here we report a high-quality draft genome sequence of M. oleifera . This assembly represents 91.78% of the estimated genome size and contains 19,465 protein-coding genes. Comparative genomic analysis between M. oleifera and related woody plant genomes helps clarify the general evolution of this species, while the identification of several species-specific gene families and positively selected genes in M. oleifera may help identify genes related to M. oleifera ’s high protein content, fast-growth, heat and stress tolerance. This reference genome greatly extends the basic research on M. oleifera , and may further promote applying genomics to enhanced breeding and improvement of M. oleifera .

Protein prenylation and human diseases: a balance of protein farnesylation and geranylgeranylation

Abstract: The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess CaaX motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase (GGPPS) catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.

Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

Abstract: Diabetic retinopathy (DR) is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of cells in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

Neuroendocrine regulation of somatic growth in fishes

Abstract: Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

Development and application of biological technologies in fish genetic breeding

Abstract: Fish genetic breeding is a process that remolds heritable traits to obtain neotype and improved varieties. For the purpose of genetic improvement, researchers can select for desirable genetic traits, integrate a suite of traits from different donors, or alter the innate genetic traits of a species. These improved varieties have, in many cases, facilitated the development of the aquaculture industry by lowering costs and increasing both quality and yield. In this review, we present the pertinent literatures and summarize the biological bases and application of selection breeding technologies (containing traditional selective breeding, molecular marker-assisted breeding, genome-wide selective breeding and breeding by controlling single-sex groups), integration breeding technologies (containing cross breeding, nuclear transplantation, germline stem cells and germ cells transplantation, artificial gynogenesis, artificial androgenesis and polyploid breeding) and modification breeding technologies (represented by transgenic breeding) in fish genetic breeding. Additionally, we discuss the progress our laboratory has made in the field of chromosomal ploidy breeding of fish, including distant hybridization, gynogenesis, and androgenesis. Finally, we systematically summarize the research status and known problems associated with each technology.

Defining language impairments in a subgroup of children with autism spectrum disorder

Abstract: Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge The majority of children are verbal but impaired in language, relative to age-matched peers One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI) An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis.

Abstract: Many randomized clinical controlled trials have confirmed the efficacy and safety of calcium dobesilate in treating diabetic retinopathy (DR) This systematic review critically evaluated the evidence that links calcium dobesilate to DR In this fixed-effects meta-analysis, a total of 221 pertinent English-language articles published between January 1975 and October 2013 were identified Systematic searches of PUBMED, Springer Link and the Cochrane Clinical Trials Database were conducted using the keywords “diabetic retinopathy” and “calcium dobesilate” The extracted information included the study design, inclusion and exclusion criteria, setting, sample size, participant mean age, treatment regime, mean change in best corrected visual acuity, laboratory parameters, capillary fragility, intraocular pressure and fundus manifestations based on the findings of fluorescent angiography The summary statistics indicated that calcium dobesilate was significantly associated with improving retinal microaneurysms (RR: 062, 95%CI: 042–090, P=001), retinalhemorrhages (RR: 039, 95% CI: 017–088, P=002); exudates (RR: 031, 95% CI: 012–081, P=002), reduction of whole blood viscosity (MD: −057 CP, 95% CI: −075 to −038, P<0001), plasma viscosity (MD: −036 CP, 95% CI: −063 to −009, P=001) and blood cholesterol (MD: −048 mg mL−1, 95% CI: −064−033, P<000001) Intraocular pressure was also significantly reduced (MD: −559 mmHg, 95% CI: −669 to −450, P<000001) The results indicate that calcium dobesilate effectively treats DR at the systematic and local ocular levels

Suppression dampens unpleasant emotion faster than reappraisal: Neural dynamics in a Chinese sample

Abstract: The timing dynamics of regulating negative emotion with expressive suppression and cognitive reappraisal were investigated in a Chinese sample. Event-Related Potentials were recorded while subjects were required to view, suppress emotion expression to, or reappraise emotional pictures. The results showed a similar reduction in self-reported negative emotion during both strategies. Additionally, expressive suppression elicited larger amplitudes than reappraisal in central-frontal P3 component (340-480 ms). More importantly, the Late Positive Potential (LPP) amplitudes were decreased in each 200 ms of the 800-1600 ms time intervals during suppression vs. viewing conditions. In contrast, LPP amplitudes were similar for reappraisal and viewing conditions in all the time windows, except for the decreased amplitudes during reappraisal in the 1400-1600 ms. The LPP (but not P3) amplitudes were positively related to negative mood ratings, whereas the amplitudes of P3, rather than LPP, predict self-reported expressive suppression. These results suggest that expressive suppression decreases emotion responding more rapidly than reappraisal, at the cost of greater cognitive resource involvements in Chinese individuals.

The calcium sensing receptor: from calcium sensing to signaling.

Abstract: The Ca2+-sensing receptor (the CaSR), a G-protein-coupled receptor, regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+ ([Ca2+]o) and responding to a diverse array of stimuli. Mutations in the Ca2+-sensing receptor result in hypercalcemic or hypocalcemic disorders, such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and autosomal dominant hypocalcemic hypercalciuria. Compelling evidence suggests that the CaSR plays multiple roles extending well beyond not only regulating the level of extracellular Ca2+ in the human body, but also controlling a diverse range of biological processes. In this review, we focus on the structural biology of the CaSR, the ligand interaction sites as well as their relevance to the disease associated mutations. This systematic summary will provide a comprehensive exploration of how the CaSR integrates extracellular Ca2+ into intracellular Ca2+ signaling.

Angiotensin II receptor blocker as a novel therapy in acute lung injury induced by avian influenza A H5N1 virus infection in mouse

Abstract: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China; Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China; State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610000, China

Using zebrafish as the model organism to understand organ regeneration

Abstract: The limited regenerative capacity of several organs, such as central nervous system (CNS), heart and limb in mammals makes related major diseases quite difficult to recover. Therefore, dissection of the cellular and molecular mechanisms underlying organ regeneration is of great scientific and clinical interests. Tremendous progression has already been made after extensive investigations using several model organisms for decades. Unfortunately, distance to the final achievement of the goal still remains. Recently, zebrafish became a popular model organism for the deep understanding of regeneration based on its powerful regenerative capacity, in particular the organs that are limitedly regenerated in mammals. Additionally, zebrafish are endowed with other advantages good for the study of organ regeneration. This review summarizes the recent progress in the study of zebrafish organ regeneration, in particular regeneration of fin, heart, CNS, and liver as the representatives. We also discuss reasons of the reduced regenerative capacity in higher vertebrate, the roles of inflammation during regeneration, and the difference between organogenesis and regeneration.

Contribution of epigenetics in diabetic retinopathy

Abstract: Diabetes has become the epidemic of the 21st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes (e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of microRNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.

Comparative transcriptome analysis of the lichen-forming fungus Endocarpon pusillum elucidates its drought adaptation mechanisms.

Abstract: The lichen-forming fungus was isolated from the desert lichen Endocarpon pusillum that is extremely drought resistant. To understand the molecular mechanisms of drought resistance in the fungus, we employed RNA-seq and quantitative real-time PCR to compare and characterize the differentially expressed genes in pure culture at two different water levels and with that in desiccated lichen. The comparative transcriptome analysis indicated that a total of 1781 genes were differentially expressed between samples cultured under normal and PEG-induced drought stress conditions. Similar to those in drought resistance plants and non-lichenized fungi, the common drought-resistant mechanisms were differentially expressed in E. pusillum. However, the expression change of genes involved in osmotic regulation in E. pusillum is different, which might be the evidence for the feature of drought adaptation. Interestingly, different from other organisms, some genes involved in drought adaption mechanisms showed significantly different expression patterns between the presence and absence of drought stress in E. pusillum. The expression of 23 candidate stress responsive genes was further confirmed by quantitative real-time PCR using dehydrated E. pusillum lichen thalli. This study provides a valuable resource for future research on lichen-forming fungi and shall facilitate future functional studies of the specific genes related to drought resistance.

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Abstract: This paper aims to observe the changes of the inflammatory cytokines in microglial BV2 cells stimulated by apelin, and investigate the mechanism of inflammatory cytokines secretion after apelin stimulation. Immunofluorescence and quantitative real-time PCR were performed to observe expression of TNF-α, IL-1β, IL-10, MIP-1α, and MCP-1 in BV2 cells. Western blot was used to investigate the expression of phosphorylation PI-3K/Akt and phosphorylation Erk signaling pathways in BV2 cells after stimulation by apelin. Furthermore, PI-3K/Akt inhibitor (LY294402) and Erk inhibitor (U0126) were used as antagonists to detect the secretion mechanisms of cytokines in BV2 cells stimulated by apelin. Exogenous recombinant apelin activated the expression of TNF-α, IL-1β, MCP-1 and MIP-1α in BV2 cells by the detection of fluorescence expression and mRNA. Apelin also unregulated the protein expression of p-PI-3K/Akt and p-Erk in BV2 cells induced by apelin. LY294002 and U0126 inhibited activation of p-PI-3K/Akt and p-Erk expression by Western blot and attenuated the expression of inflammation factors in BV2 cells by fluorescence staining. This study demonstrates that apelin is a potential activator of inflammation factors through the PI3K/Akt and Erk signaling pathway and is potential therapeutically relevant to inflammatory responses of microglia cells.

The role of miR156 in developmental transitions in Nicotiana tabacum

Abstract: Plants undergo a series of developmental transitions during their life cycle. After seed germination, plants pass through two distinct phases: the vegetative phase in which leaves are produced and the reproductive phase in which flowering occurs. Based on the reproductive competence and morphological changes, the vegetative phase can be further divided into juvenile and adult phases. Here, we demonstrate that the difference between juvenile and adult phase of Nicotiana tabacum is characterized by the changes in leaf size, leaf shape as well as the number of leaf epidermal hairs (trichomes). We further show that miR156, an age-regulated microRNA, regulates juvenile-to-adult phase transition in N. tabacum. Overexpression of miR156 results in delayed juvenile-to-adult transition and flowering. Together, our results support an evolutionarily conserved role of miR156 in plant developmental transitions.

Mechanisms of action of BCL6 during germinal center B cell development

Abstract: The transcriptional repressor B cell lymphoma 6 (BCL6) controls a large transcriptional network that is required for the formation and maintenance of germinal centers (GC). GC B cells represent the normal counterpart of most human B-cell lymphomas, which are often characterized by deregulated BCL6 expression or BCL6-mediated pathways. BCL6 suppresses gene transcription largely through recruitment of its co-repressors through its distinct repression domain. Understanding the precise biological roles of each repression domain in normal and malignant B cells is helpful for development of targeted inhibition of BCL6 functions that is emerging as the basis for design of anti-lymphoma therapies. This review focuses on recent progress in the molecular mechanisms of action of BCL6 in B cells and discusses remaining unresolved questions related to how these mechanisms are linked to normal and malignant B cell development.

Regulation of hematopoietic stem cells in the niche

Abstract: Hematopoiesis provides a suitable model for understanding adult stem cells and their niche. Hematopoietic stem cells (HSCs) continuously produce blood cells through orchestrated proliferation, self-renewal, and differentiation in the bone marrow (BM). Within the BM exists a highly organized microenvironment termed "niche" where stem cells reside and are maintained. HSC niche is the first evidence that a microenvironment contributes to protecting stem cell integrity and functionality in mammals. Although multiple models exist, recent progress has principally elucidated the cellular complexity of the HSC niche that maintains and regulates HSCs in BM. Here we introduce the development and summarize the achievements of HSC niche studies.

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

Abstract: Inhibitory leukocyte immunoglobulin-like receptors (LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase (SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.

Growth phase dependent changes in the structure and protein composition of nucleoid in Escherichia coli

Abstract: The genomic DNA of bacteria is highly compacted in a single or a few bodies known as nucleoids. Here, we have isolated Escherichia coli nucleoid by sucrose density gradient centrifugation. The sedimentation rates, structures as well as protein/ DNA composition of isolated nucleoids were then compared under various growth phases. The nucleoid structures were found to undergo changes during the cell growth; i. e., the nucleoid structure in the stationary phase was more tightly compacted than that in the exponential phase. In addition to factor for inversion stimulation (Fis), histone-like nucleoid structuring protein (H-NS), heat-unstable nucleoid protein (HU) and integration host factor (IHF) here we have identified, three new candidates of E. coli nucleoid, namely DNA-binding protein from starved cells (Dps), host factor for phage Qβ (Hfq) and suppressor of td- phenotype A (StpA). Our results reveal that the major components of exponential phase nucleoid are Fis, HU, H-NS, StpA and Hfq, while Dps occupies more than half of the stationary phase nucleoid. It has been known for a while that Dps is the main nucleoid-associated protein at stationary phase. From these results and the prevailing information, we propose a model for growth phase dependent changes in the structure and protein composition of nucleoid in E. coli.

Autism spectrum disorders in adolescence and adulthood: Long-term outcomes and relevant issues for treatment and research.

Abstract: The advances in research and treatment of autism spectrum disorders (ASD) over the past three decades have focused largely on early childhood and school-age years. Although ASD is a lifelong condition, there has been relatively little attention paid to ASD during the adolescent and adulthood periods. As the population of those with ASD continues to rise and age, the need to provide research and treatment for this group has become increasingly evident. This paper reviews the current literature available on symptoms, functioning, and treatment of adolescents and adults with ASD, as well as the unique issues that arise for individuals with ASD after childhood. Adulthood outcomes for ASD are generally poor, even for those with average to above average cognitive ability. Further research and additional clinical resources are needed for this rapidly increasing group.