From Genotype �� Environment Interaction to Gene �� Environment Interaction

Historically in plant breeding a large number of statistical models has been developed and used for studying genotype × environment interaction. These models have helped plant breeders to assess the stability of economically important traits and to predict the performance of newly developed genotypes evaluated under varying environmental conditions. In the last decade, the use of relatively low numbers of markers has facilitated the mapping of chromosome regions associated with phenotypic variability (e.g., QTL mapping) and, to a lesser extent, revealed the differetial response of these chromosome regions across environments (i.e., QTL × environment interaction). QTL technology has been useful for marker-assisted selection of simple traits; however, it has not been efficient for predicting complex traits affected by a large number of loci. Recently the appearance of cheap, abundant markers has made it possible to saturate the genome with high density markers and use marker information to predict genomic breeding values, thus increasing the precision of genetic value prediction over that achieved with the traditional use of pedigree information. Genomic data also allow assessing chromosome regions through marker effects and studying the pattern of covariablity of marker effects across differential environmental conditions. In this review, we outline the most important models for assessing genotype × environment interaction, QTL × environment interaction, and marker effect (gene) × environment interaction. Since analyzing genetic and genomic data is one of the most challenging statistical problems researchers currently face, different models from different areas of statistical research must be attempted in order to make significant progress in understanding genetic effects and their interaction with environment.     

From Mallory to Mallory-Denk bodies: what, how and why?

Frank B. Mallory described cytoplasmic hyaline inclusions in hepatocytes of patients with alcoholic hepatitis in 1911. These inclusions became known as Mallory bodies (MBs) and have since been associated with a variety of other liver diseases including non-alcoholic fatty liver disease. Helmut Denk and colleagues described the first animal model of MBs in 1975 that involves feeding mice griseofulvin. Since then, mouse models have been instrumental in helping understand the pathogenesis of MBs. Given the tremendous contributions made by Denk to the field, we propose renaming MBs as Mallory-Denk bodies (MDBs). The major constituents of MDBs include keratins 8 and 18 (K8/18), ubiquitin, and p62. The relevant proteins and cellular processes that contribute to MDB formation and accumulation include the type of chronic stress, the extent of stress-induced protein misfolding and consequent proteasome overload, a K8-greater-than-K18 ratio, transamidation of K8 and other proteins, presence of p62 and autophagy. Although it remains unclear whether MDBs serve a bystander, protective or injury promoting function, they do serve an important role as histological and potential progression markers in several liver diseases.     

From protein structure to biochemical function?

Here we describe various methods currently under development aimed at identifying a proteins function from its three-dimensional structure. We are combining a number of these methods to create a pipeline of applications, called ProFunc, which will take a given 3D structure, run all the applications on it and compile and summarise the results obtained. The aim is to provide a best guess as to the proteins function from the evidence provided by the different methods. Here we present three examples, using structures solved by the Midwest Center for Structural Genomics consortium, illustrating the strengths and weaknesses of current approaches.     

From Skin Cells to Ovarian Follicles?

Generating oocytes from cells derived from skin in vitro may provide a valuable modelfor identifying factors involved in germ cell formation and oocyte differentiation. In addition, the“oocytes” produced could potentially be useful for therapeutic cloning, and thus offer newpossibilities for tissue therapy. We recently reported the differentiation of cells derived fromporcine fetal skin into cells resembling germ cells and oocytes. A subpopulation of these cellsexpressed germ cell markers and formed aggregate like oocyte-cumulus complexes that secretedovarian steroid hormones and responded to gonadotropin stimulation. Some of these aggregatesextruded large oocyte-like cells that expressed markers appropriate to oocytes. We now showfurther evidence of germ cell marker expression during differentiation. We have also comparedthe oocyte-like cells with natural oocytes for their expression levels of Oct4, growthdifferentiation factor-9b (GDF9b), the deleted in azoospermia -like (DAZL) gene, vasa, zonapellucida (ZP), and the meiosis marker synaptonemal complex protein 3 (SCP3), and haverevealed interesting similarities and differences.     

From symptomatic treatments to causative therapy?

The search for genes that predispose individuals to develop common chronic diseases such as asthma, diabetes and Alzheimer's promises to give insights into their molecular pathogenesis. This will lead to the development of therapies that modulate the pathology, rather than the physiology of these diseases. As academia and the pharmaceutical industry increasingly focus on this challenge, the genetic dissection of Alzheimer's is spearheading attempts to shift the therapeutic paradigm away from symptomatic to curative treatments.     

From exotic spice to modern drug?

The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.     

The Angiomotins – From discovery to function

Angiomotins were originally identified as angiostatin binding proteins and implicated in the regulation of endothelial cell migration. Recent studies have shed light on the role of Angiomotins and other members of the Motin protein family in epithelial cells and in pathways directly linked to the pathogenesis of cancer. In particular, Motins have been shown to play a role in signaling pathways regulated by small G-proteins and the Hippo–YAP pathway. In this review the role of the Motin protein family in these signaling pathways will be described and open questions will be discussed.     

From Peirce’s Semiotics to Information-Sign-Symbol

Peirce is the father of semiotics. However, his theory was developed long before the developments in information theory. The codification procedures studied by the latter turn out to be crucial also for biology. At the root of both information and semiosis there are equivalence classes. In the case of biological systems, we speak of functional equivalence classes. Equivalence classes represent the grid that organism impose on biochemical processes and signals of the external or internal environment. The whole feedback circuit that is built in this way allows information control. Symbolic systems represent another kind of dealing-with-information as far as they deal with the matching of our concepts with the world.     

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

The field of cholecystokinin (CCK) stimulation of exocrine pancreatic secretion has experienced major changes in the recent past. This review attempts to summarize the present status of the field. CCK production in the intestinal I cells, the molecular forms of CCK produced and subsequently circulated in the blood, the presence or absence of CCK receptors on the isolated pancreatic acinar cells and the associated signaling for acinar cell secretion, and the actual circuits and sites of action for CCK regulation of exocrine pancreatic secretion in vivo are reviewed in different animal species with an emphasis on birds, rodents, and humans. Clear differences in the relative importance of neural and direct modes of CCK action on pancreatic acinar cells were identified. Rodents seem to be endowed with both modes of action, whereas in humans the neural mode may predominate. In birds, such as duck, the direct mode needs further assistance from pituitary adenylate cyclase-activating peptide/VIP receptors. However, much further work needs to be directed to the neural mode to map out all sites of CCK action and details of the full circuits, and we foresee a major revival for this field of research in the near future.     

Membrane pores—From biology to track-etched membranes

Flow of ions through narrow pores, either induced in biological membranes or created in synthetic membrane filters, exhibits, under appropriate conditions: 1) rapid switching of ion current between high and low conducting states; 2) selectivity between different ions; 3) inhibition by protons or divalent cations with an order of efficacy usually H⁺ >Zn²⁺>Ca²⁺ >Mg²⁺. It seems reasonable to conclude that these common properties arise from a common cause-the nature of the flow of ions close to a charged surface.     

Editorial. Peptides – From Discovery to Therapeutics

International Journal of Peptide Research and Therapeutics -     

Introduction to the thematic issue “From brain function to therapy”

<正>This thematic issue of Science China Life Sciences,"From brain function to therapy",highlights some of the exciting research being undertaken in the Joint Laboratory of Neuroscience and Cognition,an international scientific collaboration between the Queensland Brain Institute(QBI)at The