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.     

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?     

Evicting the pneumococcus from its nasopharyngeal lodgings

Adenylylation of Rab proteins appears to be an intriguing mechanism that Legionella pneumophila uses to modulate their activity during infection. Now the reverse reaction (deadenylylation) (Neunuebel et?al., 2011; Tan and Luo, 2011) and a new posttranslational modification (phosphocholination) of Rab1 (Mukherjee et?al., 2011) have been reported.     

Unveiled α-neurexins take center stage

Neurexins are presynaptic transmembrane proteins that play an essential role in synapse function. The crystal structures of α-neurexin extracellular domains (Chen et?al., 2011; Miller et?al., 2011) provide important insights into their conformational freedom and their putative spatial arrangement with binding partners in the synaptic cleft.     

Double take on Piwi protein/piRNA complex structure

Two recent studies by the Carlomagno/Pillai labs (Simon et?al., 2011) and the Patel group (Tian et?al., 2011) report the structures of complexes of Piwi PAZ domains with piRNA, utilizing two major methods in structural biology, NMR spectroscopy, and X-ray crystallography, and derive very similar structures with similar resolution.     

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.     

Transmitter time: synaptic plasticity and metabolic memory in the hypothalamus

Hunger elicits feeding behavior by activating Agouti-related peptide (AgRP) neurons. Two recent studies show how fasting, or the hunger hormone ghrelin, promote excitatory glutamate release onto AgRP neurons (Yang et?al., 2011) and increase postsynaptic glutamate receptor-mediated drive (Liu et?al., 2012).     

Breaking the cell cycle of HSCs by p57 and friends

The cell cycle regulators involved in maintaining the quiescence, and thereby the self-renewal capacity, of somatic stem cells have long been elusive. Two new Cell Stem Cell articles in this issue (Matsumoto et?al., 2011; Zou et?al., 2011) now show that the CDK inhibitor p57 is a crucial brake for cycling HSCs, and links self-renewal activity to cell cycle quiescence.     

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).     

UBAP1: a new ESCRT member joins the cl_Ub

The ESCRTs play multiple roles within the cell, including degradation of ubiquitinated membrane proteins by sorting them into multivesicular bodies (MVBs). Two recent studies provide structural and functional insights into how the newly identified ESCRT-I component UBAP1 dedicates ESCRT-I function for sorting ubiquitinated proteins at the MVB (Agromayor et?al., 2012 [this issue of Structure]; Stefani et?al., 2011).     

Converted neural cells: induced to a cure?

Many neurodegenerative disorders such as Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and others often occur as a result of progressive loss of structure or function of neurons. Recently, many groups were able to generate neural cells, either differentiated from induced pluripotent stem cells (iPSCs) or converted from somatic cells. Advances in converted neural cells have opened a new era to ease applications for modeling diseases and screening drugs. In addition, the converted neural cells also hold the promise for cell replacement therapy (Kikuchi et al., 2011; Krencik et al., 2011; Kriks et al., 2011; Nori et al., 2011; Rhee et al., 2011; Schwartz et al., 2012). Here we will mainly discuss most recent progress on using converted functional neural cells to treat neurological diseases and highlight potential clinical challenges and future perspectives.     

Gimme phospho-serine five! Capping enzyme guanylyltransferase recognition of the RNA polymerase II CTD

In this issue of Molecular Cell, two papers on the structure of murine capping enzyme guanylyltransferase (Ghosh et?al., 2011) and yeast studies of the recognition of the RNA polymerase II CTD (Schwer and Shuman, 2011) describe the mechanism of recruitment of the capping apparatus to nascent pre-mRNAs.     

Early human dispersals into the Iberian Peninsula: a comment on Martínez et al.(2010) and Garcia et al. (2011)

Garcia et al. (2011) recently discussed early human dispersals into the Iberian Peninsula, describing several putative lithic artifacts (Martínez et al., 2010) recovered from layer 7 of the Vallpara díssection (Madurell-Malapeira et al., 2010) in Terrassa (Vallès-Penedès Basin, Catalonia, Spain). According to the authors' opinion, such evidence (1) fills a gap in the chronology of early human occupation in Iberia, (2) indicates that these populations had primary and early access to carcasses, and (3) confirms that early human populations were equipped with advanced cultural traits enabling them to survive in unfavourable climatic conditions. We argue below that the record of human activity at Vallparadís (Martínez et al., 2010;Garcia et al., 2011) is doubtful and even that if confirmed, a chronological gap would remain (contra Garcia et al., 2011). Additional remarks on assertions by these authors on the Vallparadís geology, taphonomy and paleonvironment are also provided.     

Human rhinovirus C infection is associated with asthma in children determined by xTAG respiratory viral panel FAST

<正>Dear Editor,Cumulative evidence supports the role of early-life viral infections,especially respiratory syncytial virus(RSV)and human rhinovirus(HRV),as major antecedents of childhood asthma(Lemanske,2002;Jackson et al.,2008).In this study,the x TAG respiratory viral panel FAST(RVP FAST)assay,a multiplex polymerase chain reaction(PCR)-based method(Arens et al.,2010;BaladaLlasat et al.,2011;Gharabaghi et al.,2011;Selvaraju,2012),was used to investigate the association of infec-     

Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure

Methamphetamine exposure in utero leads to a variety of higher‐order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long‐lasting route‐based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine‐induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131–141, 2016. © 2016 Wiley Periodicals, Inc.     

ATM signals miRNA biogenesis through KSRP

In this issue of Molecular Cell, Zhang and colleagues (Zhang et?al., 2011) describe a critical link between the DNA damage response and the miRNA pathway, in which DNA double-strand breaks (DSBs) induce ATM-dependent KSRP phosphorylation to facilitate pri-miRNA processing.     

Tolerance induction by allogeneic hematopoietic stem cells

In this issue of Cell Stem Cell, Zheng et?al. (2011) report that HSCs expressing PD-L1 display enhanced engraftment in irradiated allogeneic recipients. Independently in Nature, Fujisaki et?al. (2011) observe allogeneic HSCs persisting in proximity to regulatory T?cells in nonirradiated recipients, further connecting HSCs and immune tolerance.