RIG-I has guts： Identification of a role for RIG-I in colitis ：levelopment

Countries in North America and Europe have the highest incidence of inflammatory disorders of the gastrointestinal tract. The prevalence of inflammatory bowel diseases （IBD）, which comprise Crohn＇s disease （CD） and ulcerative colitis （UC）, now ranges from 10-200 cases per 100 000 individuals [ 1 ]. Although new therapeutic approaches have been developed to improve current treatments, the etiology of this disorder remains elusive. Crohn＇s disease and ulcerative colitis are known to show similar clinical and pathological characteristics; however it is now believed that these two forms of IBD are entirely different. Epidemio- logical studies have revealed that these differences might be explained by the fact that environmental and genetic factors play important roles in the pathogenesis and susceptibility to IBD [ 1 ].     

Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy

Inflammatory bowel disease(IBD), consisting primarily of ulcerative colitis and Crohn's disease, is a group of debilitating auto-immune disorders, which also increases the risk of colitis-associated cancer. However, due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs(e.g., approximately 30% non-responders to anti-TNFα agents), and related serious side effects, about half of all IBD patients(in millions) turn to alternative treatment options. In this regard, mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis. However, despite the increasing clinical realization of the significance of the concept of mucosal healing, its regulation and means of therapeutic targeting remain largely unclear. Here, stemcell therapy, which uses hematopoietic stem cells or mesenchymal stem cells, remains a promising option. Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells. The overreaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process. Moreover, by differentiating into the mature intestinal epithelial cells, the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction, the root cause of the IBD. In this article, we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient's quality of life.     

A statistical procedure to assess the significance level of barriers to gene flow

Although several methods are available to study the extent of isolation by distance （IBD） among natural populations, comparatively few exist to detect the presence of sharp genetic breaks in genetic distance datasets. In recent years, Monmonier＇s maximum-difference algorithm has been increasingly used by population geneticists. However, this method does not provide means to measure the statistical significance of such barriers, nor to determine their relative contribution to population differentiation with respect to IBD. Here, we propose an approach to assess the significance of genetic boundaries. The method is based on the calculation of a multiple regression from distance matrices, where binary matrices represent putative genetic barriers to test, in addition to geographic and genetic distances. Simulation results suggest that this method reliably detects the presence of genetic barriers, even in situations where IBD is also significant. We also illustrate the methodology by analyzing previously published datasets. Conclusions about the importance of genetic barriers can be misleading if one does not take into consideration their relative contribution to the overall genetic structure of species.     

Inflammatory bowel disease requires the interplay between innate and adaptive immune signals

Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide （NO） released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Thl cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-γ, （IFN-γ）-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-γ produced by Thl cells.     

For holistic control of reactive N: Regional, national and global perspectives

Reactive N is closely related to the global issues of climate change and regional pollutions. Nitrous oxide (N2O), the fourth important gas among greenhouse gases, is produced as an intermediate in nitrification and denitrification processes. As methane (CH4) is the end product in the anoxic decomposition of organic materials, mitigation options of N2O emission are different from those of CH4 emission. Nitrate is another reactive N bringing about the eutrification of aqueous environments and the hazard of drinking water. Mitigation of NO3 problem also relates closely to the N2O emission. Therefore, holistic approaches are necessary for solving the problems of Earth warming and environmental eutrification by reactive N at the same time. In this paper, the deforestation in the tropics, and the present situations of food supply and sustainable agriculture in Japan are re-evaluated in terms of N2O emission and NO3 discharge from the agricultural sector. The magnitude of N2O emission by deforestation in the tropics may fall within the similar order of magnitude by N fertilization. As more N is imported as foods and fodder than the amount of fertilized N in Japan, more attention should be paid to the phases of their consumption and waste treatment. Sole attention to the production stage is not enough for the total mitigation of various environmental problems by reactive N in relation to agriculture. Parameters holistically evaluating the impact of reactive N on the Earth and respective regions are urgently necessary.     

Geochemistry and clay mineralogy of soils eaten by Japanese macaques

Three groups of soils from two Japanese monkey parks at Arashiyama (Honshu) and Takasakiyama (Kyushu) were analyzed for their geochemistry and clay and primary mineral content. Two groups (Y and T) of soils are regularly eaten by Japanese macaques; a third group (N) is not eaten. Of the elements analyzed, soil group N (not eaten) is within the range of all elements in the Y group, and is very different from the T group. These preliminary data suggest there is no chemical stimulus in soil eating behaviour. We also analyzed the mineralogy of the clay fraction (<2 μm) but could find only a possible stimulus from ingesting plagioclase and orthoclase minerals. The clay mineral content consists of small to trace amounts of metahalloysite that might play a role in countering the effects of diarrhea. However, from the available data there are no clear trends that would provide a stimulus for geophagic behaviour.     

A Highly Pathogenic Strain of Porcine Deltacoronavirus Caused Watery Diarrhea in Newborn Piglets

Porcine deltacoronavirus(PDCoV) is a newly identified virus that causes watery diarrhea in newborn piglets and results in significant economic losses to the pig industry. Since first reported in Hong Kong in 2012, PDCoV has been subsequently detected in USA, South Korea, Thailand, and mainland China. Here we isolated a strain of PDCoV, named CHN-GD-2016,from the intestinal content of a diseased newborn piglet with severe diarrhea in a pig farm in Guangdong, China. PDCoV CHN-GD-2016 could be identified by immunofluorescence with PDCoV specific rabbit antisera, and typical crown-shaped particles with spiky surface projections of this PDCoV were observed with electron microscopy. Genomic analysis showed that the PDCoV CHN-GD-2016 was closely related to other Chinese PDCoV strains, with the highest sequence similarity with the strain CHN/Tianjin/2016. Importantly, inoculation of newborn piglets with 1×10~5 TCID_(50) of CHN-GD-2016 by oral feeding successfully reproduced clear clinical symptoms, including vomiting, dehydration, and severe diarrhea in piglets. In addition, the virus RNA in rectal swabs from 1 to 7 days post inoculation was detected, macroscopic and microscopic lesions in small intestine were observed, and viral antigen was also detected in the small intestines with immunohistochemical staining. Collectively, the data show in this study confirms that PDCoV is present in Guangdong,China and is highly pathogenic in newborn piglets.     

Melatonin in the seasonal response of the aphid Acyrthosiphon pisum

Aphids display life cycles largely determined by the photoperiod.During the warm long-day seasons.most aphid species reproduce by viviparous parthenogenesis.The shortening of the photoperiod in autumn induces a switch to sexual reproduction.Males and sexual females mate to produce overwintering resistant eggs.In addition to this full life cycle(holocycle),there are anholocyelic lineages that do not respond to changes in photoperiod and reproduce continuously by parthenogenesis.The molecular or hormonal events that trigger the scasonal response(i.c,induction of the sexual phenotypes)are still unknown.Although circadian synthesis of melatonin is known to play a key role in vertebrate photoperiodism,the involvement of the circadian clock and/or of the hor-mone melatonin in insect seasonal responses is not so well established.Here we show that melatonin levels in the aphid Acyrthosiphon pisum are significantly higher in holocyclice aphids reared under short days than under long days,while no differences were found between anholoeyelic aphids under the same conditions.We also found that melatonin is localized in the aphid suboesophageal ganglion(SOG)and in the thoracic ganglionic mass(TGM).In analogy to vertcbrates,insect-type arylalkxylamine N-acetyltransferases(i-AANATs)are thought to play a key role in melatonin synthesis.We measured the expression of four I-AANAT genes identified in A.pisum and localized two of them in situ in the insect central nervous systems(CNS).Levels of expression of these genes were compatible with the quantities of melatonin observed.Moreover,like melatonin,expression of these genes was found in the SOG and the TGM.     

Preliminary investigation of sequence-independent DNA binding proteins in rat skeletal muscle sarcoplasmic reticulum and their function

To observe the binding of plasmid DNA to non-nuclear DNA binding proteins in sar-coplasmic reticulum (SR) and the effects of this binding on SR function, sarcoplasmic reticulum proteins in rat skeletal muscle were isolated by differential centrifuge and sucrose density-gradient centrifuge. The results showed that there are two sequence-independent DNA binding proteins in SR proteins, the molecular weights of which are 83 and 58 ku, respectively. Ca2 uptake and release of SR were remarkably promoted by the binding of plasmid DNA to DNA binding proteins in SR, the mechanism is probably through increasing of Ca2 -ATPase activity in SR and changing of character of Ca2 release channel ryanodine receptors induced by the binding. These results suggest that there exist DNA binding proteins in SR and its binding to DNA may affect Ca2 transport of SR.     

Msx homeobox gene family and craniofacial development

Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the phenotypic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice.     

我国婴幼儿中存在不同基因型杯状病毒的感染

Human caliciviruses were detected from stool specimens collected from infants with diarrhea from Beijing and Anhui Province by using RT PCR PCR products with molecular weight around 330 were obtained by using the primer pair of 289/290,which is proved to be able to amplify both Norwalk like and Sapporo like human caliciviruses The PCR products amplified from specimens collected in Beijing(CR480) and Anhui(A141) were cloned into the T A cloning vector pUCm T and sequenced The cDNA fragment amplified from CR480 is 319bp in length,which is consistent with the molecular weight of the cDNA fragment amplified from Norwalk like viruses with the primer pair 289/290,whereas the cDNA fragment amplified from A141 is 331 bp in length,which is the size of the cDNA fragment from Sapporo like viruses The sequence analysis revealed that the cDNA from CR480(the stool specimen collected in Beijing) shared higher nucleotide and amino acid identities with selected Norwalk like viruses (from 60% to 97% and 62% to 99%,respectively)than with selected Sapporo like viruses(less than 58%),having the highest identity with Takl 1999 jp and ARG320,which belong to genotype Ⅱ of Norwalk like viruses The sequence of the cDNA from A141 (collected form Anhui Province) shared higher nucleotide and amino acid identities with selected Sapporo like viruses(from 68% to 92% and 75% to 96%,respectively) than with selected Norwalk like viruses(less than 52%) It suggests that both Norwalk like and Sapporo like human caliciviruses are circulating in China and cause diarrhea in infants and young childeren     

Studies on the mitotic chromosome scaffold of Allium sativum

An argentophilic structure is present in the metaphase chromosomes of garlic(Allium sativum),Cytochemical studies indicate that the main component of the structure is non-histone proteins(NHPs).The results of light and electron microscopic observations reveal that the chromosme NHP scaffold is a network which is composed of fibres and granules and distributed throughout the chromosomes.In the NHP network,there are many condensed regions that are connected by redlatively looser regions.The distribution of the condensed regions varies in individual chromosomes.In some of the chromosomes the condensed regions are lognitudinally situsted in the central part of a chromatid while in others these regions appear as coillike transverse bands.At early metaphase.scaffolds of the sister chromatids of a chromosome are linked to each other in the centromeric region,meanwhile,they are connected by scafold materials along the whole length of the chromosome.At late metaphase,however,the connective scaffold materials between the two sister chromatids disappear gradually and the chromatids begin to separate from one another at their ends.but the chromatids are linked together in the centromeric region until anaphase.This connection seems to be related to the special structure of the NHP scaffold formed in the centromeric region.The morphological features and dynamic changes of the chromosome scaffold are discussed.     

ABA-Mediated Inhibition of Germination Is Related to the Inhibition of Genes Encoding Cell-Wall Biosynthetic and Architecture： Modifying Enzymes and Structural Proteins in Medicago truncatula Embryo Axis

Radicle emergence and reserves mobilization are two distinct programmes that are thought to control germination. Both programs are influenced by abscissic acid （ABA） but how this hormone controls seed germination is still poorly known. Phenotypic and microscopic observations of the embryo axis of Medicago truncatula during germination in mitotic inhibition condition triggered by 10 μM oryzalin showed that cell division was not required to allow radicle emergence. A suppressive subtractive hybridization showed that more than 10% of up-regulated genes in the embryo axis encoded proteins related to cell-wall biosynthesis. The expression of α-expansins, pectin-esterase, xylogucan-endotransglycosidase, cellulose synthase, and extensins was monitored in the embryo axis of seeds germinated on water, constant and transitory ABA. These genes were overexpressed before completion of germination in the control and strongly inhibited by ABA. The expression was re-established in the ABA transitory-treatment after the seeds were transferred back on water and proceeded to germination. This proves these genes as contributors to the completion of germination and strengthen the idea that cell-wall loosening and remodeling in relation to cell expansion in the embryo axis is a determinant feature in germination. Our results also showed that ABA controls germination through the control of radicle emergence, namely by inhibiting cell-wall loosening and expansion.     

A genetic solution for the global food security crisis

<正>Due to the rapid increase in population and the decreasing availability of arable land and freshwater resources per capita,global crop production will need to double by 2050 to meet human food demand.In early March,the World Bank and the Food and Agriculture Organization(FAO) of the United Nations released a report saying that 45 countries are in urgent need of food aid and millions of people are in severe hunger(https://www.worldbank.org/en/topic/agriculture/brief/food-security-update)...     

Anti-Hepatitis B Virus Drugs in Clinical and Preclinical Development

Up to date, there are two types of drugs approved to treat hepatitis B interferons and nucleos (t) ide analogues. However, the therapies are limited in the clinical context because of the negative side effects of interferon-α and the development of substantial viral resistance to nucleos (t) idic inhibitors. Therefore, new drugs with novel structures and mechanisms are needed. In this article, the drugs approved by FDA or the European Commission for treating chronic hepatitis B virus infection, as well as those under clinical trials, and several compounds in preclinical studies are reviewed. Additionally, some potential targets and strategies to combat chronic hepatitis B virus infection are discussed.     

Computational Models to Synthesize Human Walking

The synthesis of human walking is of great interest in biomechanics and biomimetic engineering due to its predictive capabilities and potential applications in clinical biomechanics, rehabilitation engineering and biomimetic robotics. In this paper, the various methods that have been used to synthesize humanwalking are reviewed from an engineering viewpoint. This involves a wide spectrum of approaches, from simple passive walking theories to large-scale computational models integrating the nervous, muscular and skeletal systems. These methods are roughly categorized under four headings： models inspired by the concept of a CPG （Central Pattern Generator）, methods based on the principles of control engineering, predictive gait simulation using optimisation, and models inspired by passive walking theory. The shortcomings and advantages of these methods are examined, and future directions are discussed in the context of providing insights into the neural control objectives driving gait and improving the stability of the predicted gaits. Future advancements are likely to be motivated by improved understanding of neural control strategies and the subtle complexities of the musculoskeletal system during human locomotion. It is only a matter of time before predictive gait models become a practical and valuable tool in clinical diagnosis, rehabilitation engineering and robotics.     

Patterns of tree phenological diversity in dry tropics

Recent phenological studies in tropical deciduous forests revealed a mosaic of vegetation composed of several pheno-phases that are evolved as an adaptation by the species to overcome seasonal drought in different ways. These pheno-phases represent extent of annual deciduousness (～leaflessness) and triggering factors for buds break (e.g. vegetative and flower). Thus, studying patterns of various pheno-phases (phonological diversity) in tropical forest have been thought to provide a potential tool to address critical questions related to climate change modeling and monitoring. In tropics, tree species represent a gradient of deciduousness (from leaf-exchanging species to >6 months deciduous species) and flowering initiation (breaking of flower buds in various part of annual cycle). Both processes are mostly triggered by variation in day length and/or temperature during late dry season/autumn, and/or first significant rain during rainy season. In addition, few factors like drought induced leaf fall and sporadic winter rains are supposed to affect these processes temporarily. Besides, the abundances of pheno-phases (i.e. leafing and flowering) also vary among tropical deciduous forest trees. Presence of such variations in tropical tree pheno-phases and their abundances are reported to vary due to micro-climatic variables and has specific implications in tropical forests. Present paper discusses the existing information on various pheno-phases and their abundances in tropical forests and role of climatic factors on tree phonological diversity. Further, we emphasized the need to develop predicting understanding of impending climatic change (i.e. precipitation and temperature) on diversity of pheno-phases by collecting long-term data on tree pheno-phases through a network of phonological stations in dry tropics.     

Patterns of tree phenological diversity in dry tropics

Recent phenological studies in tropical deciduous forests revealed a mosaic of vegetation composed of several pheno-phases that are evolved as an adaptation by the species to overcome seasonal drought in different ways. These pheno-phases represent extent of annual deciduousness (～leaflessness) and triggering factors for buds break (e.g. vegetative and flower). Thus, studying patterns of various pheno-phases (phonological diversity) in tropical forest have been thought to provide a potential tool to address critical questions related to climate change modeling and monitoring. In tropics, tree species represent a gradient of deciduousness (from leaf-exchanging species to >6 months deciduous species) and flowering initiation (breaking of flower buds in various part of annual cycle). Both processes are mostly triggered by variation in day length and/or temperature during late dry season/autumn, and/or first significant rain during rainy season. In addition, few factors like drought induced leaf fall and sporadic winter rains are supposed to affect these processes temporarily. Besides, the abundances of pheno-phases (i.e. leafing and flowering) also vary among tropical deciduous forest trees. Presence of such variations in tropical tree pheno-phases and their abundances are reported to vary due to micro-climatic variables and has specific implications in tropical forests. Present paper discusses the existing information on various pheno-phases and their abundances in tropical forests and role of climatic factors on tree phonological diversity. Further, we emphasized the need to develop predicting understanding of impending climatic change (i.e. precipitation and temperature) on diversity of pheno-phases by collecting long-term data on tree pheno-phases through a network of phonological stations in dry tropics.     

Double-gating mechanism and diversity of an adenosine triphosphate (ATP)-sensitive K~ channel in neurons acutely dissociated from rat neocortex

Classically, ion channels are classified into 2 groups: chemical-sensitive (ligand-gated) and voltage-sensitive channels. Single ATP-sensitive K (K-ATP) channel currents were recorded in acutely dissociated rat neo-cortical neurons using patch clamp technique. A type of K-ATP channel has been found to be gated not only by intra-cellular ATP, but also by membrane potential ( Vm) , and proved to be a novel mechanism underlying the gating of ion channels, namely bi-gating mechanism. The results also show that the K-ATP channels possess heterogeneity and di-versity. These types of K-ATP channels have been identified in 40.12% of all patches, which are different in activa-tion-threshold and voltage-sensitivity. The present experiment studied the type-3 K-ATP channel with a unitary con-ductance of about 80 pS in detail ( n = 15). Taking account of all the available data, a variety of K-ATP channels are suggested to exist in body, and one type of them is bi-gated by both chemical substances and membrane poten     

Mesenchymal stem cells in ischemic tissue regeneration

Diseases caused by ischemia are one of the leading causes of death in the world. Current therapies for treating acute myocardial infarction, ischemic stroke, and critical limb ischemia do not complete recovery. Regenerative therapies opens new therapeutic strategy in the treatment of ischemic disorders. Mesenchymal stem cells(MSCs) are the most promising option in the field of cell-based therapies, due to their secretory and immunomodulatory abilities, that contribute to ease inflammation and pr...