The Gr family of candidate gustatory and olfactory receptors in the yellow-fever mosquito Aedes aegypti

The gustatory receptor (Gr) protein family contains most of the diversity in the insect chemoreceptor superfamily, including within it not only taste receptors but select olfactory receptors as well. Manual annotation of the Gr family in the genome sequence of the yellow-fever mosquito, Aedes aegypti, yielded a total of 114 potential proteins encoded by 79 genes. In the sequenced genome, 23 of these genes and protein isoforms are pseudogenic, leaving 91 putatively functional Grs. Comparison with our previously published set of 76 Grs encoded by 52 genes in the distantly related Anopheles gambiae mosquito revealed 13 new AgGrs encoded by 8 genes. Phylogenetic analysis reveals the conservation of carbon dioxide, sugar, and several orphan receptors in these 2 mosquitoes and Drosophila flies. On the other hand, most of these Grs are unique to mosquitoes and many are specific to the Aedes or Anopheles lineages, indicating their involvement in mosquito-specific aspects of both gustatory and olfactory perception. In particular, most instances of alternative splicing in orthologous loci appear to have evolved after the culicine-anopheline split +/-150 million years ago.     

A systematic analysis of <Emphasis Type="Italic">Drosophila</Emphasis> gustatory receptor gene expression in abdominal neurons which project to the central nervous system

In Drosophila, the gustatory receptor (Gr) gene family contains 60 family members that encode 68 proteins through alternative splicing. Some gustatory receptors (Grs) are involved in the sensing of sugars, bitter substrates, CO₂, pheromones, and light. Here, we systematically examined the expression of all 68 Grs in abdominal neurons which project to the abdominal ganglion of the central nervous system using the GAL4/UAS system. Gr gene expression patterns have been successfully analyzed in previous studies by using the GAL4/UAS system to drive reporter gene expression. Interestingly, 21 Gr-GAL4 drivers showed abdominal ganglion projection, and 18 of these 21 Gr-GAL4 drivers labeled multidendritic neurons of the abdominal wall. 4 drivers also labeled neuronal processes innervating the reproductive organs. The peripheral expression of Gr-GAL4 drivers in abdominal multidendritic neurons or neurons innervating the reproductive organs suggests that these Grs have atypical sensory functions in these organs not limited to conventional taste sensing.     

Expiratory volume clamping: a new method to assess respiratory mechanics in sedated infants

During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pressure (P) were recorded in eight normal (N) infants, seven with reversible obstructive airway disease (ROAD), and seven with chronic lung disease (CLD). Intermittently, expiratory volume clamping (EVC) was applied, involving selective occlusion of the expiratory valve for three to five breaths. The latter produced cumulative increases in delta V that, due to progressive recruitment of the Hering-Breuer reflex, were accompanied by increasing expiratory plateaus in P (i.e., apneas). The resultant passive inflation delta V-P relationships were closely approximated by the expression: delta V = aP2 + bP + c, wherein a represented the pressure-related changes in chord compliance (Crs), b the Crs at P = 0, and c the difference between the dynamic end-expiratory and relaxation volumes of the respiratory system. Relative to N, the ROAD and CLD infants had significantly reduced weight-specific values of a/kg, their b/kg values were increased, whereas the c/kg measurements did not significantly vary. Moreover, for each subject we determined the net Crs/kg obtaining at P = 20 cmH2O (i.e., Crs20/kg), an estimate of the net deflation compliance; the passive respiratory time constant (tau rs) based on the slope of the expired delta V/V relationship; and the respiratory system conductance (Grs/kg). Relative to N, the mean Crs20/kg was significantly reduced only in the infants with CLD and, due to increases in tau rs, both patient groups depicted significantly diminished values of Grs/kg, suggesting the presence of airways obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adult stem cells in neural repair: Current options,limitations and perspectives

Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseasesthat defy doctors and researchers around the world. Stem cells can be divided into three main groups:(1) embryonic stem cells;(2) fetal stem cells; and(3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.     

Conventional, regulatory, and unconventional T cells in the immunologic response to Helicobacter pylori

Infection by the gastroduodenal pathogen Helicobacter pylori elicits a complex immunologic response in the mucosa involving neutrophils, plasma cells, eosinophils, and lymphocytes, of which T cells are the principal orchestrators of immunity. While so-called classical T cells (e.g. T-helper cells) that are activated by peptide fragments presented on antigen-presenting cells have received much attention in H. pylori infection, there exists a diverse array of other T cell populations that are potentially important for the outcome of the ensuing immune response, some of which have not been extensively studied in H. pylori infection. Pathogen-specific regulatory T cells that control and prevent the development of immunopathology associated with H. pylori infection have been investigated, but these cells can also benefit the bacterium in helping to prolong the chronicity of the infection by suppressing protective immune responses. An overlooked T cell population, the more recently described Th17 cells, may play a role in H. pylori-induced inflammation, due to triggering responses that ultimately lead to the recruitment of polymorphs, including neutrophils. The so-called innate or unconventional T cells, that include two conserved T cell subsets expressing invariant antigen-specific receptors, the CD1d-restricted natural killer T cells which are activated by glycolipids, and the mucosal-associated invariant T cells which play a role in defense against orally acquired pathogens in the intestinal mucosa, have only begun to receive attention. A greater knowledge of the range of T cell responses induced by H. pylori is required for a deeper understanding of the pathogenesis of this bacterium and its ability to perpetuate chronic infection, and could reveal new strategies for therapeutic exploitation.     

Stem cells: An eventual treatment option for heart diseases

Stem cells are of global excitement for various diseases including heart diseases. It is worth to understand the mechanism or role of stem cells in the treatment of heart failure. Bone marrow derived stem cells are commonly practiced with an aim to improve the function of the heart. The majority of studies have been conducted with acute myocardial infarction and a few has been investigated with the use of stem cells for treating chronic or dilated cardiomyopathy. Heterogeneity in the treated group using stem cells has greatly emerged. Ever increasing demand for any alternative made is of at most priority for cardiomyopathy. Stem cells are of top priority with the current impact that has generated among physicians. However, meticulous selection of proper source is required since redundancy is clearly evident with the present survey. This review focuses on the methods adopted using stem cells for heart diseases and outcomes that are generated so far with an idea to determine the best therapeutic possibility in order to fulfill the present demand.     

猪多能干细胞的研究进展

多能干细胞,如胚胎干细胞（embryonic stem cells,ESCs）、诱导多能干细胞（induced pluripotent stem cells,iPSCs）和成体干细胞（adultstemcells,ASCs）,是一类具有巨大潜能的独特细胞。猪作为试验材料,在遗传、代谢、生理生化及基因序列等方面较小鼠更接近于人类,正逐渐成为人类异种移植和再生医学研究的理想生物学模型。然而,目前对猪多能干细胞种类、来源、特征及机制的有限认识直接阻碍了其相关应用。该文将分别对猪ASCs的研究现状、猪类ESCs的分离培养、猪iPSCs的研究进展、多能干细胞间的联系和展望进行论述,以期为从事该领域研究的科研人员提供参考。     

Bovine mammary stem cells: cell biology meets production agriculture

Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and alter the function of bovine MaSC. In this review, we provide an overview of current knowledge of MaSC gained from studies using mouse and human model systems and present research on bovine MaSC within that context. Recent data indicate that MaSC retain labeled DNA for extended periods because of their selective segregation of template DNA strands during mitosis. Relying on this long-term retention of bromodeoxyuridine-labeled DNA, we identified putative bovine MaSC. These label-retaining epithelial cells (LREC) are in low abundance within mammary epithelium (<1%). They are predominantly estrogen receptor (ER)-negative and localized in a basal or suprabasal layer of the epithelium throughout the gland. Thus, the response of MaSC to estrogen, the major mitogen in mammary gland, is likely mediated by paracrine factors released by cells that are ER-positive. This is consistent with considerable evidence for cross-talk within and between epithelial cells and surrounding stromal cells. Excision of classes of cells by laser microdissection and subsequent microarray analysis will hopefully provide markers for MaSC and insights into their regulation. Preliminary analyses of gene expression in laser-microdissected LREC and non-LREC are consistent with the concept that LREC represent populations of stem cells and progenitor cells that differ with regard to their properties and location within the epithelial layer. We have attempted to modulate the MaSC number by infusing a solution of xanthosine through the teat canal and into the ductal network of the mammary glands of prepubertal heifers. This treatment increased the number of putative stem cells, as evidenced by an increase in the percentage of LREC and increased telomerase activity within the tissue. The exciting possibility that stem cell expansion can influence milk production is currently under investigation.     

Progenitor cells of the biliary epithelial cell lineage

Stem-like cells have been identified in liver that are able to differentiate in vivo and in culture to biliary epithelial cells (BEC), hepatocytes and oval cells. The growth factors/cytokines and signal pathways required for the differentiation processes are beginning to be evaluated. There is increasing evidence to suggest that these stem-like cells may originate from both the bone marrow population or from a precursor remnant from liver embryogenesis, as they share many of the same markers (CD34, c-kit, CD45). Most recently, it has been shown that a population of progenitor cells can copurify with mesenchymal bone marrow cells and differentiate under specific culture conditions to form both hepatic epithelial and also endothelial cells. The interaction of haemopoietic and mesenchymal stem cells needs further evaluation. The close association of ductular reactive cells and neovessels in end-stage cholestatic liver diseases and the relation to Jagged/Notch signalling pathway may be important in the regulation of stem cells to form both biliary epithelial and endothelial cells.     

间充质干细胞在动脉粥样硬化治疗中的研究进展

动脉粥样硬化是一种病因复杂的血管壁慢性炎症性疾病。动脉粥样硬化及其相关并发症已成为人类死亡的主要原因,然而,其病因和发病机制尚未完全阐明,治疗效果还不满意。目前已经证实,动脉内皮细胞功能发生障碍是动脉粥样硬化的始动过程,内皮细胞功能失调和内皮细胞丢失是动脉粥样硬化症的主要特点;而血管平滑肌细胞的异常增生在动脉粥样硬化的发生发展中也扮演着重要角色。因此,探索有效措施促进有益的内皮细胞再生并抑制平滑肌细胞增生是血管损伤防治的关键。近年来有研究发现,体外输注的间充质干细胞能够向受损部位募集,并进一步分化为内皮细胞,修复损伤血管。然而,也有研究显示体外输注的间充质干细胞还可以分化为血管平滑肌细胞进而在血管局部增生,参与血管再狭窄的发生。文中综述了间充质干细胞输注对动脉粥样硬化发展的最新研究进展,希望为后续开展的用间充质干细胞治疗动脉粥样硬化的研究提供一定的参考。     

Stem cells: their source,potency and use in regenerative therapies with focus on adipose-derived stem cells – a review

Stem cells can be defined as units of biological organization that are responsible for the development and the regeneration of organ and tissue systems. They are able to renew their populations and to differentiate into multiple cell lineages. Therefore, these cells have great potential in advanced tissue engineering and cell therapies. When seeded on synthetic or nature-derived scaffolds in vitro, stem cells can be differentiated towards the desired phenotype by an appropriate composition, by an appropriate architecture, and by appropriate physicochemical and mechanical properties of the scaffolds, particularly if the scaffold properties are combined with a suitable composition of cell culture media, and with suitable mechanical, electrical or magnetic stimulation. For cell therapy, stem cells can be injected directly into damaged tissues and organs in vivo. Since the regenerative effect of stem cells is based mainly on the autocrine production of growth factors, immunomodulators and other bioactive molecules stored in extracellular vesicles, these structures can be isolated and used instead of cells for a novel therapeutic approach called “stem cell-based cell-free therapy”. There are four main sources of stem cells, i.e. embryonic tissues, fetal tissues, adult tissues and differentiated somatic cells after they have been genetically reprogrammed, which are referred to as induced pluripotent stem cells (iPSCs). Although adult stem cells have lower potency than the other three stem cell types, i.e. they are capable of differentiating into only a limited quantity of specific cell types, these cells are able to overcome the ethical and legal issues accompanying the application of embryonic and fetal stem cells and the mutational effects associated with iPSCs. Moreover, adult stem cells can be used in autogenous form. These cells are present in practically all tissues in the organism. However, adipose tissue seems to be the most advantageous tissue from which to isolate them, because of its abundancy, its subcutaneous location, and the need for less invasive techniques. Adipose tissue-derived stem cells (ASCs) are therefore considered highly promising in present-day regenerative medicine.     

Preparing normal tissue cells for space flight experiments

Deterioration of health is a problem in modern space flight business. In order to develop countermeasures, research has been done on human bodies and also on single cells. Relevant experiments on human cells in vitro are feasible when microgravity is simulated by devices such as the Random Positioning Machine or generated for a short time during parabolic flights. However, they become difficult in regard to performance and interpretation when long-term experiments are designed that need a prolonged stay on the International Space Station (ISS). One huge problem is the transport of living cells from a laboratory on Earth to the ISS. For this reason, mainly rapidly growing, rather robust human cells such as cancer cells, embryonic cells, or progenitor cells have been investigated on the ISS up to now. Moreover, better knowledge on the behavior of normal mature cells, which mimic the in vivo situation, is strongly desirable. One solution to the problem could be the use of redifferentiable cells, which grow rapidly and behave like cancer cells in plain medium, but are reprogrammed to normal cells when substances like retinoic acid are added. A list of cells capable of redifferentiation is provided, together with names of suitable drugs, in this review.     

胚胎干细胞起源的探讨

目前胚胎干细胞(ESCs)建系的取材来源包括桑椹胚的卵裂球、囊胚的内细胞团(ICM)、上胚层细胞和原始生殖细胞(PGCs),甚至从新生鼠睾丸细胞也分离得到类ES样细胞系。这就提出了一个问题,什么是ESCs最接近的体内细胞来源。传统观念常常把ESCs等同于ICM细胞,也有学者认为ESCs更象上胚层细胞,而在已知的分子标记基因方面,ESCs所具有的特征更接近体内早期生殖细胞。不清楚ESCs最接近的体内细胞来源,可能是制约许多品系小鼠和大多哺乳类动物建系成功率提高的原因之一。ESCs系与EG细胞系的分离条件不同表明,加强对ESCs多能性维持基因调控研究具有重要意义。本文从ESCs的经典概念及其发展,早期胚胎细胞和生殖细胞发育规律,早期胚胎细胞、早期生殖细胞和ESCs的关系等方面进行综合分析,认为ESCs可能有多种接近的体内细胞来源。进一步应通过对ESCs建系不同的取材细胞和不同品系的ESCs间进行比较研究,以便弄清ESCs的来源和转化机制,为提高不同物种ESCs建系效率提供理论支持。     

Autophagy in stem cells

Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future.     

Induced pluripotent stem (iPS) cells from human fetal stem cells (hFSCs)

Introduction

(1) Human embryonic stem (ES) cells are pluripotent but are difficult to be used for therapy because of immunological, oncological and ethical barriers. (2) Pluripotent cells exist in vivo, i.e., germ cells and epiblast cells but cannot be isolated without sacrificing the developing embryo. (3) Reprogramming to pluripotency is possible from adult cells using ectopic expression of OKSM and other integrative and non-integrative techniques. (4) Hurdles to overcome include i.e stability of the phenotype in relation to epigenetic memory.

Sources of data

We reviewed the literature related to reprogramming, pluripotency and fetal stem cells.

Areas of agreement

(1) Fetal stem cells present some advantageous characteristics compared with their neonatal and postnatal counterparts, with regards to cell size, growth kinetics, and differentiation potential, as well as in vivo tissue repair capacity. (2) Amniotic fluid stem cells are more easily reprogrammed to pluripotency than adult fibroblast. (3) The parental population is heterogeneous and present an intermediate phenotype between ES and adult somatic stem cells, expressing markers of both.

Areas of controversy

(1) It is unclear whether induced pluripotent stem (iPS) derived from amniotic fluid stem cells are fully or partially reprogrammed. (2) Optimal protocols to ensure highest efficiency and phenotype stability remains to be determined. (3) The “level” of reprogramming, fully vs partial, of iPS derived from amniotic fluid stem cells remain to be determined.

Growing points

Banking of fully reprogrammed cells may be important both for (1) autologous and allogenic applications in medicine, and (2) disease modeling.     

Evidence for somatostatin,gastrin and pancreatic polypeptide-like substances in the mucosa cells of the gut in fishes with and without stomach

Gastrin, pancreatic polypeptide and somatostatin immunoreactive cells in the gut of two fish with stomachs (perch and catfish) and a stomachless fish (carp) were studied by immunocytochemistry. In the gastric mucosa of perch and catfish, cells showing gastrin and somatostatin-like immunoreactivity are found, scattered among the surface mucous cells and mucous neck cells. No pancreatic polypeptide (P.P.) immunoreactive cells are detected in the gastric mucosa. Cells showing gastrin and P.P.-like immunoreactivity are observed in the intestinal mucosa of perch, catfish and carp. In this location no somatostatin immunoreactive cells are found.