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.     

RAD in the realm of next-generation sequencing technologies

The first North American RAD Sequencing and Genomics Symposium, sponsored by Floragenex (http://www.floragenex.com/radmeeting/), took place in Portland, Oregon (USA) on 19 April 2011. This symposium was convened to promote and discuss the use of restriction-site-associated DNA (RAD) sequencing technologies. RAD sequencing is one of several strategies recently developed to increase the power of data generated via short-read sequencing technologies by reducing their complexity (Baird et al. 2008; Huang et al. 2009; Andolfatto et al. 2011; Elshire et al. 2011). RAD sequencing, as a form of genotyping by sequencing, has been effectively applied in genetic mapping and quantitative trait loci (QTL) analyses in a range of organisms including nonmodel, genetically highly heterogeneous organisms (Table 1; Baird et al. 2008; Baxter et al. 2011; Chutimanitsakun et al. 2011; Pfender et al. 2011). RAD sequencing has recently found applications in phylogeography (Emerson et al. 2010) and population genomics (Hohenlohe et al. 2010). Considering the diversity of talks presented during this meeting, more developments are to be expected in the very near future.     

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?     

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.     

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.     

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.     

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.     

FEN nucleases: bind, bend, fray, cut

In this issue, Orans et al. (2011) and Tsutakawa et al. (2011) report exciting insights into the molecular principles governing diverse endo- and exonucleolytic cleavage specificities of members of the RAD2/FEN superfamily of nucleases, which have critical roles in DNA replication and maintenance.     

PP2A targets SAS-5 in centriole assembly

In this issue of Developmental Cell, Kitagawa et al. (2011a) and Song et al. (2011) show that the protein phosphatase PP2A regulates SAS-5 to control centriole duplication. Two paradigms are presented to explain how PP2A regulates SAS-5.     

Translocation mapping exposes the risky lifestyle of B cells

Recurrent chromosomal translocations can drive oncogenesis, but how they form has remained elusive. Now, Chiarle et al. (2011) and Klein et al. (2011) characterize the genome-wide spectrum of translocations that form from a single double-stranded break, revealing that specific loci have an intrinsic predisposition for frequent chromosomal rearrangements.     

Old enzymes, new tricks: sirtuins are NAD(+)-dependent de-acylases

Seven mammalian sirtuins are nicotinamide adenine dinucleotide (NAD)(+)-dependent deacetylases and are important modulators of energy metabolism and stress resistance. Two new studies by Du et al. (2011) and Peng et al. (2011) identify a new enzymatic activity for SIRT5, expanding the cellular repertoire of posttranslational modifications targeted by the sirtuins.     

Clever leukemic stem cells branch out

Individual tumors harbor heterogeneous populations of genetically distinct subclones. Two recent papers in Nature by Notta et al. (2011) and Anderson et al. (2011) reveal genetic heterogeneity in functional leukemic stem cells, which has important implications for how both cancer and normal stem cell populations may adapt to selective pressure.     

Recognition of centromeric histone variant CenH3s by their chaperones

Comment on: Zhou et al. Nature 2011; 47:234-237, Hu et al. Genes Dev 2011; 25:901-6 and Cho et al. Proc Natl Acad Sci USA 2011; 108:9367-71.     

Tales from the crypt: the expanding role of slow cycling intestinal stem cells

Similar to other highly self-renewing tissues, the intestinal epithelium contains both slowly and rapidly cycling progenitor/stem cells, though their relationship has been largely unexplored. Two recent reports in Nature (Tian et al., 2011) and Science (Takeda et al., 2011) shed new light on their dynamic interplay.     

Gene editing in stem cells hits the target

Two recent reports describe promising, highly efficient methods to modify genes in pluripotent stem cells using zinc finger nuclease (ZFN)-mediated (Soldner et?al., 2011) or helper-dependent adenovirus (HDAdV)-mediated (Liu et?al., 2011b) gene modification. These technical developments will have far ranging effects on the rapidly growing field of regenerative medicine.     

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.