The influence of paraquat on cell cycle--analysis of cell kinetics using DNA/BrdU staining]

We examined the in vitro and in vivo effects of paraquat on the cell cycle. After we exposed paraquat to the cultured cell (MDCK), we examined cell kinetics by flow cytometry with BrdU-PI double staining. And we administered paraquat intravenously to the rats, we collected and separated rat's liver and pulmonary cells, and we examined the cell kinetics by same method. Consequently our study found that the cells in the S-phase were noted to be abundant, and we suggested that paraquat apparently arrested the cell cycle at S time, and that DNA damage was importance in the mechanism of paraquat toxicity.     

Targeting gene-virotherapy of cancer

Due to concerns regarding the overlapping figures in this review that are identical to those contained in a reviewarticle that we have co-authored and published earlier,we retract the above paper we published in Cell Research.Weapologize for any confusion that may be caused by this matter,although we stand by the scientific contents containedin the Cell Research paper.     

An assessment of the impacts of molecular oxygen on the evolution of proteomes

Oxygen is not only one of life's essential elements but also a source of protein damage, mutagenesis, and ageing. Many proteome adaptations have been proposed to tackle such stresses and we assessed them using comparative genomics in a phylogenetic context. First, we find that aerobiosis is a trait with important phylogenetic inertia but that oxygen content in proteins is not. Instead, oxygen content is close to the expected values given the nucleotide composition. Accordingly, we find no evidence of oxygen being a scarce resource for protein synthesis even among anaerobes. Second, we searched for counterselection of amino acids more prone to oxidation among aerobes. Only cysteine follows the expected trend, whereas tryptophan follows the inverse one. When analyzing composition in the context of protein structures and residue accessibility, we find that all oxidable residues are avoided at the surface of proteins. Yet, there is no difference between aerobes and anaerobes in this respect, and the effect might be explained by the hydrophobicity of these residues. Third, we revisited the hypothesis that atmospheric enrichment in molecular oxygen led to the development of the communication capabilities of eukaryotes. With a larger data set and adequate controls, we confirm the trend of longer oxygen-rich outer domains in transmembrane proteins of eukaryotes. Yet, we find no significant association between oxygen concentration in the environment and this trait within prokaryotes, suggesting that this difference is clade specific and independent of oxygen availability. We find that genes involved in cellular responses to oxygen are much more frequent among aerobes, and we suggest that they erase most expected differences in terms of proteome composition between organisms facing high and low oxygen concentrations.     

Counterfactual thinking and emotions: regret and envy learning

Emotions like regret and envy share a common origin: they are motivated by the counterfactual thinking of what would have happened had we made a different choice. When we contemplate the outcome of a choice we made, we may use the information on the outcome of a choice we did not make. Regret is the purely private comparison between two choices that we could have taken, envy adds to this the information on outcome of choices of others. However, envy has a distinct social component, in that it adds the change in the social ranking that follows a difference in the outcomes. We study the theoretical foundation and the experimental test of this view.     

Complexity and approximability of double digest

We revisit the DOUBLE DIGEST problem, which occurs in sequencing of large DNA strings and consists of reconstructing the relative positions of cut sites from two different enzymes. We first show that DOUBLE DIGEST is strongly NP-complete, improving upon previous results that only showed weak NP-completeness. Even the (experimentally more meaningful) variation in which we disallow coincident cut sites turns out to be strongly NP-complete. In the second part, we model errors in data as they occur in real-life experiments: we propose several optimization variations of DOUBLE DIGEST that model partial cleavage errors. We then show that most of these variations are hard to approximate. In the third part, we investigate variations with the additional restriction that coincident cut sites are disallowed, and we show that it is NP-hard to even find feasible solutions in this case, thus making it impossible to guarantee any approximation ratio at all.     

Clustering humans: on biological boundaries

We inquire into the notions of 'boundary' and 'cluster' in the fields of medical genetics, pharmacogenetics, and population genetics. First we show that the two notions are not well discussed in literature. Then we propose a promising explication of them, in which we argue that clustering is always 'property laden', that is, fundamentally dependent on decisions about the properties to be taken into account. In particular we suggest three different kinds of properties (main properties, investigating properties, and catalyzing properties) that have a role in these decisions. That is, we conclude that boundaries and clusters among humans depend on our way of considering nature. Concepts of 'race' and 'ethnic group' are discussed too, since they are the most used clusters among humans.     

On the Relationship Between Memes and Genes: A Critique of Dennett

Dennett (1995) argues that memes or cultural replicators are largely autonomous of genes, and that they are fairly efficacious in determining who we are and what we do. I argue that Dennett's arguments are wrong in several aspects, which we can see by analyzing processes at appropriate levels. Specifically, I argue that it is not true that we as persons are created largely by memes, that our memes are not largely independent of our genes, and that we can use the universality of memes to make inferences about genetic predispositions. Finally, by suggesting an innate psychological mechanism for morality, I argue that morality may be largely the effect of genetic predispositions rather than autonomous.     

On the epistemology of mental illness.

The most important epistemological problem in psychiatry is the detection of malingering. This is a consequence of the fact that there is no objective way to confirm any psychiatric diagnosis. Psychiatric diagnosis is based on subjective complaints. The discovery of objective markers for psychiatric diagnosis is problematic because it presupposes we can tell valid from faked subjective symptoms. But this is the difficulty. If we use pervasive irrationality as a sign of mental illness, we encounter the problem of identifying pervasive irrationality. To understand someone's behaviour, we have to assume it is largely rational. This precludes us from using behaviour to separate genuine from faked mental illness. There are a number of strategies used to solve any epistemological problem, and the most successful is the hypothetico-deductive method. If we use this, we can solve our epistemological problem. Genuine mental illness can be identified when it is the best explanation of the person's overall behaviour. Consilience of inductions is critical in supporting the validity of such explanations. This implies that it is merely a hypothesis that mental illness exists, and that we might discover that many mental illnesses, perhaps all, do not exist. We must embrace this possibility--only if we take a risk will we gain any knowledge.     

A global phenomenological model of ischemic stroke with stress on spreading depressions

In this paper, we establish a new global phenomenological model of ischemic stroke. It takes into account local ischemia, energy reduction, propagation of spreading depressions (SD), damages to the cells and cellular death by apoptosis or necrosis. The spatial diffusion of the ions in the extracellular space which triggers the propagation of SD is a central point here. First we expose the various biological hypotheses that we have made in this model, and then we explain how to determine the parameters and solve the system of equations that we obtain. Next we present some results of this model: we simulate a KCl injection and then a local ischemia. Finally we discuss results and propose some improvements for this model.     

Systems biology of lactic acid bacteria: a critical review

Understanding the properties of a system as emerging from the interaction of well described parts is the most important goal of Systems Biology. Although in the practice of Lactic Acid Bacteria (LAB) physiology we most often think of the parts as the proteins and metabolites, a wider interpretation of what a part is can be useful. For example, different strains or species can be the parts of a community, or we could study only the chemical reactions as the parts of metabolism (and forgetting about the enzymes that catalyze them), as is done in flux balance analysis. As long as we have some understanding of the properties of these parts, we can investigate whether their interaction leads to novel or unanticipated behaviour of the system that they constitute. There has been a tendency in the Systems Biology community to think that the collection and integration of data should continue ad infinitum, or that we will otherwise not be able to understand the systems that we study in their details. However, it may sometimes be useful to take a step back and consider whether the knowledge that we already have may not explain the system behaviour that we find so intriguing. Reasoning about systems can be difficult, and may require the application of mathematical techniques. The reward is sometimes the realization of unexpected conclusions, or in the worst case, that we still do not know enough details of the parts, or of the interactions between them. We will discuss a number of cases, with a focus on LAB-related work, where a typical systems approach has brought new knowledge or perspective, often counterintuitive, and clashing with conclusions from simpler approaches. Also novel types of testable hypotheses may be generated by the systems approach, which we will illustrate. Finally we will give an outlook on the fields of research where the systems approach may point the way for the near future.     

Insights from social transmission of information in rodents

Direct exposure to stimuli in their environment is not the only way that animals learn about important information. Individuals can infer fear from a social context through observation. Like humans, rats are very social animals, and may learn to infer information about their environment through their interactions with conspecifics. Here, we first review different models for social transmission of information in rodents. Second, we examine different modes of communication that are important to social learning. Then, we cover the different proximate factors that are thought to modulate the social transmission of information. Next, we identify social and environmental conditions that impact social learning, and finally, we conclude by revisiting social transmission through the lens of the Tinbergen framework.     

Snx5, as a Mind bomb-binding protein, is expressed in hematopoietic and endothelial precursor cells in zebrafish

Notch signaling has an evolutionarily conserved function for cell fate determination and stem cell maintenance. Previously, we identified a novel component of the Notch signaling pathway in zebrafish, mind bomb, which encodes an E3 ubiquitin ligase essential for Notch signal activation. Further studies showed that Mind bomb(-/-) mouse embryos exhibited pan-Notch phenotypes in various tissues, suggesting that Mind bomb function is conserved in mammals. Therefore we sought to understand the various molecular partners of Mind bomb using yeast two-hybrid screening. In this search we identified Sorting nexin 5 (Snx5) as a novel interacting partner of Mind bomb. Furthermore we demonstrated that Snx5 colocalizes with Mind bomb in early endosomal compartments, suggesting that Snx5 is important for Mind bomb trafficking. In addition, we identified zebrafish orthologue of Snx5 and showed that snx5 is predominantly expressed in hematopoietic and endothelial precursor cells in zebrafish. We also found defects in hematopoiesis and blood vessel development in snx5 morpholino-injected embryos. Taken together, we show that Snx5, a novel interacting partner of Mind bomb, may have an essential role for cell fate determination in early development.     

TRAIL expression in vascular smooth muscle

TRAIL is a cell-associated tumor necrosis factor-related apoptosis-inducing ligand originally identified in immune cells. The ligand has the capacity to induce apoptosis after binding to cell surface receptors. To examine TRAIL expression in murine vascular tissue, we employed in situ hybridization and immunohistochemistry. In these studies, we found that TRAIL mRNA and protein were specifically localized throughout the medial smooth muscle cell layer of the pulmonary artery. Notably, a similar pattern of expression was observed in the mouse aorta. Consistent with these findings, we found that cultures of primary human aorta and pulmonary artery smooth muscle cells express abundant TRAIL mRNA and protein. We also found that these cells and endothelial cells undergo cell lysis in response to exogenous addition of TRAIL. Last, we confirmed that TRAIL specifically activated a death program by confirming poly(ADP ribose) polymerase cleavage. Overall, we believe that these findings are relevant to understanding the factors that regulate cell turnover in the vessel wall.     

贵州盘县中三叠统混鱼龙类化石的初步研究

记述贵州省盘县新民乡羊圈村中三叠统关岭组上段的混鱼龙3种,其中有一新种:Mixosaurus mao-taiensis Young,1965,emend.nov.,Mixosaurus cornalianus(Bassani),1886和Mixosaurus yangjuanensis sp.nov.。与混鱼龙类化石同层产出的有真颌鱼类和龙鱼类化石,真颌鱼类的特征比意大利和瑞士边界地区安尼-拉丁期和拉丁期早期普罗山头组(Prosanto Formation)所产的始真颌鱼Eoeugnathus进步,混鱼龙新种也比意-瑞边界地区安尼-拉丁期过渡期的混鱼龙进步。因此,我们推测当前混鱼龙类化石的层位可能包括从下安尼阶上部到拉丁阶下部的一段地层,不是简单的一个化石层,此问题尚待进一步深入研究。     

Aquatic animals, cognitive ethology, and ethics: questions about sentience and other troubling issues that lurk in turbid water

In this general, strongly pro-animal, and somewhat utopian and personal essay, I argue that we owe aquatic animals respect and moral consideration just as we owe respect and moral consideration to all other animal beings, regardless of the taxonomic group to which they belong. In many ways it is more difficult to convince some people of our ethical obligations to numerous aquatic animals because we do not identify or empathize with them as we do with animals with whom we are more familiar or to whom we are more closely related, including those species (usually terrestrial) to whom we refer as charismatic megafauna. Many of my examples come from animals that are more well studied but they can be used as models for aquatic animals. I follow Darwinian notions of evolutionary continuity to argue that if we feel pain, then so too do many other animals, including those that live in aquatic environs. Recent scientific data ('science sense') show clearly that many aquatic organisms, much to some people's surprise, likely suffer at our hands and feel their own sorts of pain. Throughout I discuss how cognitive ethology (the study of animal minds) is the unifying science for understanding the subjective, emotional, empathic, and moral lives of animals because it is essential to know what animals do, think, and feel as they go about their daily routines. Lastly, I argue that when we are uncertain if we are inflicting pain due to our incessant, annoying, and frequently unnecessary intrusions into the lives of other animals as we go about 'redecorating nature' (removing animals or moving them from place to place), we should err on the side of the animals and stop engaging in activities that cause pain and suffering.     

Deconstructing death in paleodemography

In 1992 in this Journal (Konigsberg and Frankenberg [1992] Am. J. Phys. Anthropol. 89:235-256), we wrote about the use of maximum likelihood methods for the "estimation of age structure in anthropological demography." More specifically, we presented a particular method (the "iterated age-length key") from the fisheries literature and suggested that the method could be used in human and primate demography and paleodemography as well. In our paper (section titled "Some Future Directions"), we spelled out two broad areas that we expected to see develop over the ensuing years. First, we felt that the use of explicit likelihood methods would open up interest in basic estimation issues, such as the calculation of standard errors for demographic estimates and the formulation of tests for whether samples differed in their demographic structure. Second, we felt that the time was ripe for hazards analyses that would incorporate the uncertainty in estimation that follows from using age "indicators" rather than known ages. While some of these developments have occurred during the last decade, few have been reported in the American Journal of Physical Anthropology. In this paper we resolve some issues from our 1992 paper, and attempt to redress this deficit in the literature by reviewing some recent developments in paleodemography over the past decade.     

Publication bias and merit in ecology

Bias, or any set of factors that influence the general expression of merit, is common in science and is an inevitable by-product of an imperfect but otherwise reasonably objective human pursuit to understand the world we inhabit. In this paper, we explore the conceptual significance of a relatively tractable form of bias, namely publication and dissemination bias. A specific definition is developed, a working model of classification for publication bias is proposed, and an assessment of what we can measure is described. Finally, we offer expectations for ecologists with respect to the significance of bias in the publication process within our discipline. We argue that without explicit consideration of both the qualitative and quantitative aspects of publication bias in ecology, we limit our capacity to fairly assess and best use the science that we as a community produce.