The porous borders of the protein world

Fold switching may play a role in the evolution of new protein folds and functions. He et?al., in this issue of Structure, use protein design to illustrate that the same drastic change in a protein fold can occur via multiple different mutational pathways.     

The 19S cap puzzle: a new jigsaw piece

After elucidation of the atomic details of 20S proteasomes, current research focuses on the regulatory 19S particle. In this issue of Structure, He et?al. present the crystal structure of Rpn2 and use electron microscopy to examine differences between Rpn2 and Rpn1.     

Deterministic or stochastic choices in retinal neuron specification

There are two views on vertebrate retinogenesis: a deterministic model dependent on fixed lineages and a stochastic model in which choices of division modes and cell fates cannot be predicted. In this issue of Neuron, He et?al. (2012) address this question in zebrafish using live imaging and mathematical modeling.     

iPSCs: induced back to controversy

Several recent reports (Mayshar et?al., 2010; Laurent et?al., 2011; Lister et?al., 2011; Gore et?al., 2011; Hussein et?al., 2011) uncover genetic and epigenetic alterations in induced pluripotent stem cells, stimulating debate about their future. However, will these important findings really impact what we hope to gain?     

Converting human skin cells to neurons: a new tool to study and treat brain disorders?

Recent publications in Cell Stem Cell (Son et?al., 2011; Ambasudhan et?al., 2011), PNAS (Pfisterer et?al., 2011), and Nature (Caiazzo et?al., 2011; Pang et?al., 2011; Yoo et?al., 2011) report that functional neurons can be directly generated from human fibroblast cells without going through the pluripotent state.     

Comparative genomics of Neisseria weaveri clarifies the taxonomy of this species and identifies genetic determinants that may be associated with virulence

A group of bacterial strains formerly known as CDC group M-5 are opportunistic pathogens to humans. In 1993, a name, Neisseria weaveri, was proposed by two independent studies to harbor CDC group M-5 strains, namely N.?weaveri Holmes et?al. 1993 and N.?weaveri Andersen et?al. 1993, with two different 'type' strains. However, no study has been conducted on to the relatedness of the two 'type' strains, although the close relationship of the two taxa has long been accepted unofficially. Formally, the status of the name N.?weaveri Andersen et?al. 1993 is illegitimate because it is a later homonym of N.?weaveri Holmes et?al., 1993; but the name of the strain is still validly published. In this study, we attempt to resolve the confusion caused by the apparent duplication of the species N.?weaveri (with different type strains) using whole genome shotgun sequencing. We also sought to gain insight into the genetic characteristics of N.?weaveri by conducting comparative genomics. On the basis of genomic similarities revealed through a comparative genomic study, we propose that N.?weaveri Andersen et?al. 1993 should be re-classified as a later heterotypic synonym of N.?weaveri Holmes et?al., 1993.     

Movement, confusion, and orienting in frontal cortices

In this issue, two studies, by Ehrlich et?al. and Hill et?al., address the role of the frontal motor cortices in behavior of the rat and suggest a potential role for this structure in high-level control of diverse behaviors. Hill et?al. show that motor cortical neurons predict whisker movements even without sensory feedback and that their activity reflects efferent control. Surprisingly, Ehrlich et?al. report the participation of this same cortical region in the preparation and execution of orienting behaviors.     

How to remake a fibroblast into a neural stem cell

In this issue of Cell Stem Cell and in a recent issue of PNAS, Thier et?al. (2012), Han et?al. (2012), and Lujan et?al. (2012) report the derivation of multipotent neural stem/progenitor cells from cultured mouse fibroblasts using distinct reprograming approaches.     

Finally, Polyubiquitinated PCNA Gets Recognized

Studies from Ciccia et?al. (2012) and Yuan et?al. (2012) in this issue of Molecular Cell, together with Weston et?al. (2012), reveal that the translocase ZRANB3/AH2 can recognize K63-linked polyubiquitinated PCNA and plays an important role in restarting stalled replication forks.     

Synapses let loose for a change: inhibitory synapse pruning throughout experience-dependent cortical plasticity

In this issue of Neuron, Chen et?al. (2012) and van Versendaal et?al. (2012) used fluorescently tagged gephyrin to track inhibitory synapses in the mouse visual cortex in?vivo. Their studies show that visual experience-dependent plasticity is associated with clustered and location-specific pruning of inhibitory synapses.     

Lymphocyte choriomeningitis virus plays hide-and-seek with type 1 interferon

In this issue, Macal et?al. (2012); Walsh et?al. (2012), and Wang et?al. (2012) examine how adaptive immune responses to acute and chronic lymphocyte choriomeningitis virus infection are regulated by type 1 interferon produced early during infection by different cell types upon activation by intracellular nucleic acid sensors.     

Decision making: singin' in the brain

Which neurons in the brain "decide" to initiate particular behaviors in response to sensory information? In this issue of Neuron, two papers (Kohatsu et?al. and von Philipsborn et?al.) identify candidates in the courtship circuitry of Drosophila. The activity of these neurons is both regulated by sex pheromones and necessary and sufficient to trigger male love song.     

Lack of an Additive Effect between the Deletions of Klf5 and Nkx3-1 in Mouse Prostatic Tumorigenesis

Prostate cancer is one of the most common malignancies.The development and progression of prostate cancer are driven by a series of genetic and epigenetic events including gene amplification that activates oncogenes and chromosomal deletion that inactivates tumor suppressor genes.Whereas gene amplification occurs in human prostate cancer,gene deletion is more common,and a large number of chromosomal regions have been identified to have frequent deletion in prostate cancer,suggesting that tumor suppressor inactivation is more common than oncogene activation in prostatic carcinogenesis (Knuutila et al.,1998,1999;Dong,2001).Among the most frequently deleted chromosomal regions in prostate cancer,target genes such as NKX3-1 from 8p21,PTENfrom 10q23 andATBF1 from 16q22 have been identified by different approaches (He et al.,1997;Li et al.,1997;Sun et al.,2005),and deletion of these genes in mouse prostates has been demonstrated to induce and/or promote prostatic carcinogenesis.For example,knockout of Nkx3-1 in mice induces hyperplasia and dysplasia (Bhatia-Gaur et al.,1999;Abdulkadir et al.,2002) and promotes prostatic tumorigenesis (Abate-Shen et al.,2003),while knockout of Pten alone causes prostatic neoplasia (Wang et al.,2003).Therefore,gene deletion plays a causal role in prostatic carcinogenesis (Dong,2001).     

Calcium and repression in malaria sex: knowing when the time is right

Plasmodium falciparum PfEMP1 is a malaria virulence protein whose expression is epigenetically regulated. The parasite's ability to express exclusively only one of the sixty var genes that encode PfEMP1 is essential for disease pathogenesis. Two recent papers identify key molecular players in determining whether a var gene is active or silenced (Volz et?al., 2012; Zhang et?al., 2011).     

Moving right along: how PP1 helps clear the checkpoint

Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et?al., 2011) and one in Current Biology (Rosenberg et?al., 2011), begin to show how phosphatase PP1-gamma connects chromosome-microtubule attachment with anaphase entry.     

Understanding metastasis in pancreatic cancer: a call for new clinical approaches

Although metastasis is a major cause of morbidity and mortality in patients with pancreatic cancer, the requisite events are currently unknown. In this issue of Cell, Haeno et?al. and Rhim et?al. propose that metastasis occurs much earlier than previously anticipated, with clear implications for improving patient care.     

A genetic push to understand motion detection

Two articles in this issue of Neuron (Eichner et?al. and Clark et?al.) attack the problem of explaining how neuronal hardware in Drosophila implements the Reichardt motion detector, one of the most famous computational models in neuroscience, which has proven intractable up to now.     

Epigenetic Variations in Plant Hybrids and Their Potential Roles in Heterosis

Heterosis,one of the most important biological phenomena,refers to the phenotypic superiority of a hybrid over its genetically diverse parents with respect to many traits such as biomass,growth rate and yield.Despite its successful application in breeding and agronomic production of many crop and animal varieties,the molecular basis of heterosis remains elusive.The classic genetic explanations for heterosis centered on three hypotheses:dominance (Davenport,1908;Bruce,1910;Keeble and Pellew,1910;Jones,1917),overdominance (East,1908;Shull,1908) and epistasis (Powers,1944;Yu et al.,1997).However,these hypotheses are largely conceptual and not connected to molecular principles,and are therefore insufficient to explain the molecular basis of heterosis (Birchler et al.,2003).Recently,many studies have explored the molecular mechanism of heterosis in plants at a genome-wide level.These studies suggest that global differential gene expression between hybrids and parental lines potentially contributes to heterosis in plants (e.g.,Swanson-Wagner et al.,2006;Zhang et al.,2008;Wei et al.,2009;Song et al.,2010).Research suggests that genetic components,including cis-acting elements and trans-acting factors,are critical regulators of differential gene expression in hybrids (Hochholdinger and Hoecker,2007;Springer and Stupar,2007;Zhang et al.,2008).However,other research indicates that epigenetic components,the regulators of chromatin states and genome activity,also have the potential to impact heterosis (e.g.,Ha et al.,2009;He et al.,2010;Groszmann et al.,2011;Barber et al.,2012;Chodavarapu et al.,2012;Greaves et al.,2012a;Shen et al.,2012).