PCR法检测外环境水中脊髓灰质炎病毒Ⅰ型基因的研究

应用聚合酶链反应（PCR）技术检测外环境水中分离的脊髓灰质炎病毒Ⅰ型（PVⅠ）毒株基因型,发现所分离的22株病毒．均为疫苗SabinⅠ相关株．脊髓灰质炎病毒的温度敏感（T特征）试验亦提示为弱毒株,与PCR试验相吻合。表明在实施强化免疫和常规免疫后,外环境中的脊髓灰质炎病毒已被疫苗相关株循环所取代。同时证实用PCR作为环境中PVⅠ病毒株的基因型分析的检测方法是特异和敏感的。     

Testable Hypotheses Implied by a Linear Hypothesis

ROY and ROY have shown that for any linear hypothesis H being not testable it is possible to construct a testable hypothesis which is implied by H. A maximal testable hypothesis implied by H is presented.     

Variable Parental Care in a Labrid Fish: How Care Might Evolve

Hypotheses for the evolution of parental care suggest several intermediate stages between no care and full care. To shed light on how care might evolve, I describe intermediate stages within one species. These include spawning behavior ranging from out-of-nest spawning, (which involves no parental care) to algal nests and associated male parental care (plus intermediate stages between the two previous categories), all observed in the same individual males of the peacock wrasse, Symphodus tinca. About 20% of males go through transitional stages from no care to full care as the season progresses. These stages are: 1) following females over large areas, 2) focusing on an area about 10 × 10 m, 3) chasing other fish, (both con- and heterospecific) from this area, 4) focusing spawns into a 1–2 m² area that he modifies by adding algae, and 5) remaining with the site day and night until the eggs hatch and the young disperse. This sequence of stages is similar to the evolutionary sequence suggested by previous theory, but differs in that site limitation is not necessary in order to lead to site attachment.     

Molecular mechanisms underlying glutamatergic dysfunction in schizophrenia: therapeutic implications

Early models for the etiology of schizophrenia focused on dopamine neurotransmission because of the powerful anti-psychotic action of dopamine antagonists. Nevertheless, recent evidence increasingly supports a primarily glutamatergic dysfunction in this condition, where dopaminergic disbalance is a secondary effect. A current model for the pathophysiology of schizophrenia involves a dysfunctional mechanism by which the NMDA receptor (NMDAR) hypofunction leads to a dysregulation of GABA fast- spiking interneurons, consequently disinhibiting pyramidal glutamatergic output and disturbing the signal-to-noise ratio. This mechanism might explain better than other models some cognitive deficits observed in this disease, as well as the dopaminergic alterations and therapeutic effect of anti-psychotics. Although the modulation of glutamate activity has, in principle, great therapeutic potential, a side effect of NMDAR overactivation is neurotoxicity, which accelerates neuropathological alterations in this illness. We propose that metabotropic glutamate receptors can have a modulatory effect over the NMDAR and regulate excitotoxity mechanisms. Therefore, in our view metabotropic glutamate receptors constitute a highly promising target for future drug treatment in this disease.     

南京1号与东非Bodo人类头骨化石:对中心和边缘假说的检测

中心和边缘假说认为非洲是人类演化的中心地区,东亚等地区是边缘地区。在边缘地区,人群的地区性形态特征出现较早,可上溯到直立人生活时期;在中心地区,人群的地区性形态特征出现较晚。Bodo人类头骨化石和南京1号人类头骨化石分别出自中心地区和边缘地区,二者年代都是距今60万年左右,二者都保留有面颅。因此,Bodo人类头骨化石和南京1号人类头骨化石是检测中心和边缘假说的最合适的材料。本文是对南京1号和Bodo头骨的面颅测量性特征作比较研究。研究结果表明:1.二者面颅测量性特征上的差别远大于这两个相应地区现代人群之间的差别,提示了人类的地区性体质形态差别早在60万年前就很明显;2.东亚的南京1号人类头骨和东非的Bodo人类头骨尽管同样古老,但各自与当地区的现代人群的面颅上的差异情况并不一致。Bodo头骨与东非现代人群显得差异较大,南京1号头骨与东亚现代人群显得较相近。这种相近,提示了在东亚这个边缘地区,现代人群的面颅测量性特征可追溯到以南京1号头骨为代表的远古人类那里,而在中心地区,现代人群的面颅测量性特征还很难与以Bodo为代表的远古人群相联系。本项研究结果与中心和边缘假说的推测相符合。     

How parasitoid females produce sexy sons: a causal link between oviposition preference, dietary lipids and mate choice in Nasonia

Sexual selection theory predicts that phenotypic traits used to choose a mate should reflect honestly the quality of the sender and thus, are often costly. Physiological costs arise if a signal depends on limited nutritional resources. Hence, the nutritional condition of an organism should determine both its quality as a potential mate and its ability to advertise this quality to the choosing sex. In insects, the quality of the offspring's nutrition is often determined by the ovipositing female. A causal connection, however, between the oviposition decisions of the mother and the mating chances of her offspring has never been shown. Here, we demonstrate that females of the parasitic wasp Nasonia vitripennis prefer those hosts for oviposition that have been experimentally enriched in linoleic acid (LA). We show by (13)C-labelling that LA from the host diet is a precursor of the male sex pheromone. Consequently, males from LA-rich hosts produce and release higher amounts of the pheromone and attract more virgin females than males from LA-poor hosts. Finally, males from LA-rich hosts possess three times as many spermatozoa as those from LA-poor hosts. Hence, females making the right oviposition decisions may increase both the fertility and the sexual attractiveness of their sons.     

Hacking the Code of Amyloid Formation: The Amyloid Stretch Hypothesis

Many research efforts in the last years have been directed towards understanding the factors determining protein misfolding and amyloid formation. Protein stability and amino acid composition have been identified as the two major factors in vitro. The research of our group has been focused on understanding the relationship between amino acid sequence and amyloid formation. Our approach has been the design of simple model systems that reproduce the biophysical properties of natural amyloids. An amyloid sequence pattern was extracted that can be used to detect amyloidogenic hexapeptide stretches in proteins. We have added evidence supporting that these amyloidogenic stretches can trigger amyloid formation by nonamyloidogenic proteins. Some experimental results in other amyloid proteins will be analyzed under the conclusions obtained in these studies. Our conclusions together with evidences from other groups suggest that amyloid formation is the result of the interplay between a decrease of protein stability, and the presence of highly amyloidogenic regions in proteins. As many of these results have been obtained in vitro, the challenge for the next years will be to demonstrate their validity in in vivo systems.     

Schizophrenia is not associated with the ERBB3 gene in a Han Chinese population sample: Results from case-control and family-based studies

ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3), encoding a receptor of neuregulin-1 (NRG1), has been considered a functional candidate gene for schizophrenia susceptibility. In order to investigate a relationship between ERBB3 gene and schizophrenia in the Chinese population, case-control and family-based studies were carried out in 470 cases matched by controls, and in 532 family trios. Our results failed to show any evidence of significant association between the ERBB3 rs2292238 polymorphism and schizophrenia.     

Polymorphism of the Serotonin Receptor Type 2A (5-HTR2A) Gene and Verbal Fluency in Normalcy and in Schizophrenia

To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the internal vocabulary), the T102C polymorphism of the serotonin receptor type 2A (5-HTR2A) gene was tested for association with verbal fluency in 108 patients with schizophrenia or disorders of the schizophrenic spectrum and 97 mentally healthy individuals. A significant association was observed only in male schizophrenics (n = 67), with homozygotes A2A2 having lower verbal fluency. The results do not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia.     

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness¹ and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them². This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia³. The male-to-female ratio of mutation rate is estimated at about 4–6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males⁴. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.     

Historical diversification of a terra-firme forest bird superspecies: a phylogeographic perspective on the role of different hypotheses of Amazonian diversification

Among those few hypotheses of Amazonian diversification amenable to falsification by phylogenetic and population genetics methods, three can be singled out because of their general application to vertebrates: the riverine barrier, the refuge, and the Miocene marine incursion hypotheses. I used phylogenetic and population genetics methods to reconstruct the diversification history of the upland (terra-firme) forest superspecies Xiphorhynchus spixii/elegans (Aves: Dendrocolaptidae) in Amazonia, and to evaluate predictions of the riverine barrier, refuge, and Miocene marine incursion hypotheses. Phylogeographic and population genetics analyses of the X. spixiilelegans superspecies indicated that the main prediction of the riverine barrier hypothesis (that sister lineages occur across major rivers) hold only for populations separated by "clear-water" rivers located on the Brazilian shield, in central and eastern Amazonia; in contrast, "white-water" rivers located in western Amazonia did not represent areas of primary divergence for populations of this superspecies. The main prediction derived from the refuge hypothesis (that populations of the X. spixii/elegans superspecies would show signs of past population bottlenecks and recent demographic expansions) was supported only for populations found in western Amazonia, where paleoecological data have failed to support past rainforest fragmentation and expansion of open vegetation types; conversely, populations from the eastern and central parts of Amazonia, where paleoecological data are consistent with an historical interplay between rainforest and open vegetation types, did not show population genetics attributes expected under the refuge hypothesis. Phylogeographic and population genetics data were consistent with the prediction made by the Miocene marine incursion hypothesis that populations of the X. spixii/elegans superspecies found on the Brazilian shield were older than populations from other parts of Amazonia. In contrast, the phylogeny obtained for lineages of this superspecies falsified the predicted monophyly of Brazilian shield populations, as postulated by the Miocene marine incursion hypothesis. In general, important predictions of both riverine barrier and Miocene marine incursion hypotheses were supported, indicating that they are not mutually exclusive; in fact, the data presented herein suggest that an interaction among geology, sea level changes, and hydrography created opportunities for cladogenesis in the X. spixii/elegans superspecies at different temporal and geographical scales.     

Translation Driven by Picornavirus IRES Is Hampered from Sindbis Virus Replicons: Rescue by Poliovirus 2A Protease

Alphavirus replicons are very useful for analyzing different aspects of viral molecular biology. They are also useful tools in the development of new vaccines and highly efficient expression of heterologous genes. We have investigated the translatability of Sindbis virus (SV) subgenomic mRNA bearing different 5′-untranslated regions, including several viral internal ribosome entry sites (IRESs) from picornaviruses, hepatitis C virus, and cricket paralysis virus. Our findings indicate that all these IRES-containing mRNAs are initially translated in culture cells transfected with the corresponding SV replicon but their translation is inhibited in the late phase of SV replication. Notably, co-expression of different poliovirus (PV) non-structural genes reveals that the protease 2A (2A^pro) is able to increase translation of subgenomic mRNAs containing the PV or encephalomyocarditis virus IRESs but not of those of hepatitis C virus or cricket paralysis virus. A PV 2A^pro variant deficient in eukaryotic initiation factor (eIF) 4GI cleavage or PV protease 3C, neither of which cleaves eIF4GI, does not increase picornavirus IRES-driven translation, whereas L protease from foot-and-mouth disease virus also rescues translation. These findings suggest that the replicative foci of SV-infected cells where translation takes place are deficient in components necessary to translate IRES-containing mRNAs. In the case of picornavirus IRESs, cleavage of eIF4GI accomplished by PV 2A^pro or foot-and-mouth disease virus protease L rescues this inhibition. eIF4GI co-localizes with ribosomes both in cells electroporated with SV replicons bearing the picornavirus IRES and in cells co-electroporated with replicons that express PV 2A^pro. These findings support the idea that eIF4GI cleavage is necessary to rescue the translation driven by picornavirus IRESs in baby hamster kidney cells that express SV replicons.     

Commentary on de Cock Buning: A United Kingdom Perspective

de Cock Buning (1998) highlighted the existence of alternative and more favorable options available to xenotransplantation. Clearly, there is a need to emphasize a review of existing organ procurement programs worldwide. A tree interest in the welfare of animals encourages increased liaison between transplant communities throughout the world to discuss the experiences of various procurement programs.     

A Novel Theory on the Origin of the Genetic Code: A GNC-SNS Hypothesis

We have previously proposed an SNS hypothesis on the origin of the genetic code (Ikehara and Yoshida 1998). The hypothesis predicts that the universal genetic code originated from the SNS code composed of 16 codons and 10 amino acids (S and N mean G or C and either of four bases, respectively). But, it must have been very difficult to create the SNS code at one stroke in the beginning. Therefore, we searched for a simpler code than the SNS code, which could still encode water-soluble globular proteins with appropriate three-dimensional structures at a high probability using four conditions for globular protein formation (hydropathy, α-helix, β-sheet, and β-turn formations). Four amino acids (Gly [G], Ala [A], Asp [D], and Val [V]) encoded by the GNC code satisfied the four structural conditions well, but other codes in rows and columns in the universal genetic code table do not, except for the GNG code, a slightly modified form of the GNC code. Three three-amino acid systems ([D], Leu and Tyr; [D], Tyr and Met; Glu, Pro and Ile) also satisfied the above four conditions. But, some amino acids in the three systems are far more complex than those encoded by the GNC code. In addition, the amino acids in the three-amino acid systems are scattered in the universal genetic code table. Thus, we concluded that the universal genetic code originated not from a three-amino acid system but from a four-amino acid system, the GNC code encoding [GADV]-proteins, as the most primitive genetic code. Received: 11 June 2001 / Accepted: 11 October 2001     

Association of the hSERT and SLC6A4 Polymorphic Markers of the Serotonin Transporter Gene with Schizophrenia in Two Ethnic Groups

Insertion/deletion and VNTR polymorphisms of the serotonin transporter gene were tested for association with schizophrenia in patients of different ethnicity. A difference in genetic predisposition was observed for continuous and shift-like schizophrenia forms, the former tending to be associated with genotype 12/12 in Tatars and L/L in Russians.     

Mesenchymal-to-Endothelial Transition in Kaposi Sarcoma: A Histogenetic Hypothesis Based on a Case Series and Literature Review

Objectives

Although several studies have been conducted regarding Kaposi sarcoma (KS), its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature.

Methods

In 15 cases of KSs diagnosed during 2000–2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF), COX-2, c-KIT, smooth muscle antigen (SMA), and stem cell surface marker CD105.

Results

Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs.

Conclusions

KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.     

A role of myocardial stiffness in cell-based cardiac repair: a hypothesis

Determining which time point is optimal for bone marrow-derived cell (BMC) transplantation for acute myocardial infarction (AMI) has attracted a great deal of attention. Studies have verified the interaction between cell treatment effect and transfer timing and have suggested that the optimal time frame for BMC therapy is day 4 to day 7 after AMI. However, the potential mechanism underlying the time-dependent therapeutic response remains unclear. Recently, a growing body of in vitro evidence has suggested that stem cells are able to feel and respond to the stiffness of their microenvironment to commit to a relevant lineage, indicating that soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Simultaneously, considering the fact that the myocardium post-infarction experiences a time-dependent stiffness change from flexible to rigid as a result of myocardial remodelling following tissue necrosis and massive extracellular matrix deposition, we presume that the myocardial stiffness within a certain time frame (possibly day 4–7) post-AMI might provide a more favourable physical microenvironment for the phenotypic plasticity and functional specification of engrafted BMCs committed to some cell lineages, such as endothelial cells, vascular smooth muscle cells or cardiomyocytes. The beneficial effect facilitates angiogenesis and myocardiogenesis in the infarcted heart, and subsequently leads to more amelioration of cardiac functions. If the present hypothesis were true, it would be of great help to understand the mechanism underlying the optimal timing for BMC transplantation and to establish a direction for the time selection of cell therapy.