This digest presents the most recent research from selected journals from the Nature Publishing Group -- Biotechnology, Genetics, Medicine, Methods, and Neuroscience -- as excerpted on The Scientific Lawyer. You are invited to download this digest's RSS feed:
June 29, 3:24 PM / Nature Methods / Summer reading: science in fictionThough somewhat rare, there are a few good fiction books to be found with refreshingly realistic biologists as central characters in laboratory settings.
June 29, 3:24 PM / Nature Methods / Limitations and possibilities of small RNA digital gene expression profiling
June 29, 3:24 PM / Nature Methods / RNAiCut: automated detection of significant genes from functional genomic screens
June 29, 3:24 PM / Nature Methods / Enabling IMAC purification of low abundance recombinant proteins from E. coli lysates
June 29, 3:24 PM / Nature Methods / A question of cultureTwo groups report culture conditions for long-term in vitro growth of intestinal tissue from the mouse.
June 29, 3:24 PM / Nature Methods / Fluorescent proteins: into the infraredAn engineered infrared fluorescent protein is the first member of a new class of genetically encodable probes, with special advantages over visible-wavelength fluorescent proteins for in vivo imaging.
June 29, 3:24 PM / Nature Methods / Going with the skewed flowComputational and experimental biologists teamed up to develop a new software tool to analyze the rich data generated by new and powerful flow cytometers.
June 29, 3:24 PM / Nature Methods / News in brief
June 29, 3:24 PM / Nature Methods / Grafting as a potent molecular toolGrafting two transgenic plants triggers lateral gene transfer at the graft site but does not elicit long-distance transport of DNA into the scion or root of the graft.
June 29, 3:24 PM / Nature Methods / Fluorescent false neurotransmittersA fluorescent probe designed to incorporate a fluorophore into the structure of a neurotransmitter finds activity-dependent heterogeneity in dopamine release at individual synapses.
June 29, 3:24 PM / Nature Methods / Will planets reveal the light of their life?Optical signatures from organic chemicals may help scientists detect traces of life on other planets.
June 29, 3:24 PM / Nature Methods / Finding multiple needles in one immune haystackAn approach using multiple fluorochrome combinations allows the simultaneous detection of many T-cell populations within a single blood sample.
June 29, 3:24 PM / Nature Methods / Downhill protein folding under pressureSub-microsecond, downhill-reaction protein folding can be investigated by a method to generate large and fast pressure drops. The approach is complementary to nanosecond temperature-jump methods and could provide new insights into the biophysics of protein folding.
June 29, 3:23 PM / Nature Methods / Genomics: catch me if you canNext-generation sequencing has made decoding entire genomes cheaper and faster. But what about those researchers who only want to sequence a small section of a genome or focus on a couple thousand specific exons? A wave of new technologies has recently emerged that should help these scientists target their sequencing efforts to sequences of interest.
June 29, 3:23 PM / Nature Methods / Corrigendum: A HUPO test sample study reveals common problems in mass spectrometry–based proteomics
June 29, 3:23 PM / Nature Methods / Erratum: Transposon-mediated genome manipulation in vertebrates
June 29, 3:23 PM / Nature Methods / Analysis of 5′ transcript heterogeneity by high-throughput sequencing of cDNA
June 29, 3:23 PM / Nature Methods / CYP2C9 and VKORC1 genotyping reagents from Idaho Technology: rapid turn-around, accurate results
June 29, 3:23 PM / Nature Methods / Fluidigm Dynamic Arrays provide a platform for single-cell gene expression analysis
June 26, 1:37 PM / Nature Genetics / Online MethodsMost of our readers access our articles online, in formats that deal well with increasingly complex research methods and the growing requirement for increased precision of citation. These considerations have now led us to publish Methods online.
June 26, 1:37 PM / Nature Genetics / High marks for GWASTwo genome-wide association studies for testicular cancer report associations at three new loci, including two candidate genes previously implicated in testicular development, KITLG (ligand for the receptor tyrosine kinase) and SPRY4 (sprouty 4). These studies are notable for the high effect sizes detected and the biological plausibility of the candidate genes.
June 26, 1:37 PM / Nature Genetics / TET2 mutations in myelodysplasia and myeloid malignanciesThe genetic basis of myelodysplasia has long been enigmatic, with few common targets of mutation known. A new study reports common mutations in the TET2 gene in myelodysplasia and related myeloid malignancies, suggesting that TET2 has an important role in hematopoiesis and in the pathogenesis of this disease.
June 26, 1:37 PM / Nature Genetics / Tumors line up for a letdownMicroRNAs (miRNAs) and the pathways that regulate their expression have critical functions during normal development. A new study demonstrates that select cancer cells have appropriated one developmental mechanism of miRNA regulation, the inhibition of let-7 biogenesis by the Lin-28 and Lin-28B RNA binding proteins, to rid themselves of an antitumorigenic miRNA.
June 26, 1:37 PM / Nature Genetics / Research highlights
June 26, 1:36 PM / Nature Genetics / Corrigendum: Tiny RNAs associated with transcription start sites in animals
June 26, 1:36 PM / Nature Genetics / Erratum: Narcolepsy is strongly associated with the T-cell receptor alpha locus
June 25, 12:06 PM / Nature Neuroscience / Mining chemistry for psychiatryA new initiative aims to jump-start drug development for psychiatric diseases by inviting neuroscientists with unconventional ideas to avail themselves of an established high-throughput chemical screening platform.
June 25, 12:06 PM / Nature Neuroscience / Working on a Dream
June 25, 12:06 PM / Nature Neuroscience / A noseful of objectsHow are volatile molecules entering the nose converted to odor percepts in the brain? A fMRI study finds that distributed patterns of activity in the human posterior piriform cortex code the perceived category of odorants. This categorization of odors into objects is independent of their chemical structure.
June 25, 12:06 PM / Nature Neuroscience / Genetics meets epigenetics: HDACs and Wnt signaling in myelin development and regenerationA study shows that the histone deacetylases HDAC1 and HDAC2 stimulate oligodendrocyte differentiation by antagonizing the inhibitory action of Wnt signaling, linking genetic and epigenetic control of oligodendrocyte development.
June 25, 12:06 PM / Nature Neuroscience / Stop and go GABAA recent study shows that GABA switches from stimulating to inhibiting interneuron motility during neocortical development. This change in response is gated by the expression of the chloride transporter KCC2.
June 25, 12:06 PM / Nature Neuroscience / Reactive oxygen species are NOXious for neuronsMitochondria are considered to be the main source of reactive oxygen species during glutamate excitotoxicity. Data now support a prominent role in this process for NADPH oxidase, the enzyme that neutrophils use to kill bacteria.
June 25, 12:06 PM / Nature Neuroscience / Prefrontal cortex and cognitive control: motivating functional hierarchiesHow different frontal brain regions contribute to goal-directed behavior is not fully understood. A study now suggests a parallel functional architecture in medial and lateral prefrontal cortex for motivating and selecting behavior.
June 21, 0:00 AM / Nature Genetics / The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humansJames Lupski and colleagues provide evidence that a replication-based mechanism termed FoSTeS/MMBIR can mediate rearrangements in humans ranging in size from a few hundred base pairs to several megabases. They propose that FoSTeS/MMBIR could be an important mechanism for generating structural variation.
June 21, 0:00 AM / Nature Methods / Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimersUsing combinations of fluorescently labeled peptide–major histocompatability complex (pMHC) tetramers, T-cell populations with multiple antigen specificities can be monitored in parallel from small samples of human blood. Also in this issue, Newell et al. present a very similar combinatorial encoding method for this purpose.
June 21, 0:00 AM / Nature Methods / Simultaneous detection of many T-cell specificities using combinatorial tetramer stainingCombinations of fluorescently labeled peptide–major histocompatability (pMHC) tetramers are used to simultaneously detect T cells with multiple antigen specificities from human blood samples. Also in this issue, Hadrup et al. present a very similar combinatorial encoding approach.
June 21, 0:00 AM / Nature Genetics / The establishment of gene silencing at single-cell resolutionJasper Rine and colleagues examine the silencing of the HML locus in synchronous S. cerevisiae cells at single-cell resolution. They demonstrate that the establishment of silencing under native conditions occurs rapidly, within two cell cycles.
June 21, 0:00 AM / Nature Genetics / Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesisThomas Carroll and colleagues show that attenuation of Wnt9b signaling during kidney morphogenesis affects planar cell polarity and causes an increase in tubule diameter. Their analyses suggest that tubule diameter is established by convergent extension movements and subsequently maintained by polarized cell divisions.
June 21, 0:00 AM / Nature Neuroscience / Cellular and systems mechanisms of memory strength as a constraint on auditory fear reconsolidationMemories can be reconsolidated when reactivated. However, reconsolidation does not occur under certain boundary conditions. The authors show that these boundary conditions can be transient and that strong auditory fear memories in rats that initially did not undergo reconsolidation eventually did over time. Moreover, they find that the hippocampus is necessary for preventing reconsolidation from occuring in the amygdala, and that NR2B subunits, normally required for induction of reconsolidation in the amygdala, are downregulated when strong memories do not undergo reconsolidation.
June 21, 0:00 AM / Nature Methods / Filter-based hybridization capture of subgenomes enables resequencing and copy-number detectionConcatenated PCR products serve as subgenomic traps in this targeted genome capture technique; subsequent high-throughput sequencing allows the detection of nucleotide and structural variations in the captured genomic regions.
June 21, 0:00 AM / Nature Neuroscience / Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distributionThe authors examine the effect of increased synthesis of AMPAR subunits on their subcellular distribution in hippocampal neurons. Virally expressing AMPARs caused an accumulation in cell bodies with little effect on dendritic amounts. Stargazin coexpression enhanced dendritic GluR1 levels by protecting it from lysosomal degradation but didn't increase surface or synaptic GluR1 levels.
June 14, 0:00 AM / Nature Genetics / Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune responseAicardi-Goutieres syndrome is a genetically determined encephalopathy that is associated with an increased production of interferon alpha, which in turn is central to the pathogenesis of systemic lupus erythematosus. Yanick Crow and colleagues now identify homozygous mutations in an interferon-inducible nuclear gene encoding SAMHD1 in AGS-affected individuals across several pedigrees and characterize its function in modulating an innate immune response.
June 14, 0:00 AM / Nature Neuroscience / Adenosine A2A receptor mediates microglial process retractionOrr and colleagues identify a molecular pathway in microglia that converts ATP-dependent process extension into process retraction during inflammation. This reversal is dependant on A2A adenosine receptor upregulation and P2Y12 downregulation.
June 14, 0:00 AM / Nature Neuroscience / Awake replay of remote experiences in the hippocampusHippocampal replay is thought to be essential for the consolidation of event memories. Sleep replay involves the reactivation of stored representations in the absence of specific sensory inputs, whereas awake replay is thought to reflect input from the current environment. Here the authors find that the hippocampus consistently replays past experiences during brief pauses in waking behavior, suggesting a role for waking replay in memory consolidation and retrieval.
June 14, 0:00 AM / Nature Neuroscience / Adult birdsong is actively maintained by error correctionYoung birds rely on auditory feedback when learning to imitate the songs of adult birds. Here the authors find that, as with humans, birds use auditory feedback to correct vocal errors in adulthood. This suggests that lifelong error correction may be a general principle of learned vocal behavior.
June 14, 0:00 AM / Nature Neuroscience / Twin-spot MARCM to reveal the developmental origin and identity of neuronsThe mosaic analysis with repressible cell markers (MARCM) technique allows for lineage tracing in Drosophila. Here, the authors report an improvement on this technique, twin-spot MARCM, which permits high-resolution lineage tracing of both sister clones.
June 14, 0:00 AM / Nature Genetics / Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20Justin Rubio and colleagues report results of a genome-wide association study of multiple sclerosis using cases from Australia and New Zealand. Their findings confirm several published risk loci for MS and identify two new risk loci on chromosomes 12 and 20.
June 14, 0:00 AM / Nature Neuroscience / Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesinPolyQ-Htt inhibits fast axonal transport in cellular and animal Huntington's disease models. Here, the authors show that this effect is a result of the activation of JNK3. PolyQ-Htt–activated JNK3 reduces kinesin-1 binding to microtubules.
June 14, 0:00 AM / Nature Methods / Mapping the structure and conformational movements of proteins with transition metal ion FRETFluorescence resonance energy transfer (FRET) between a small-molecule fluorophore donor and a transition metal ion acceptor, a method called 'transition metal ion FRET,' works over shorter distances than the classical FRET approach and can thus be used to monitor very small conformational changes in proteins.
June 14, 0:00 AM / Nature Genetics / RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infectionJutta Gartner and colleagues identify five pathologic mutant alleles in the RNASET2 gene that compromise its enzymatic activity and that are responsible for the CMV infection–like neurological disorder cystic leukoencephalopathy without megalencephaly (CLM).
June 14, 0:00 AM / Nature Neuroscience / Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticityAlthough the role of Notch signaling in CNS glial development is well established, its participation in peripheral glial development is still unclear. This paper shows that Notch signaling regulates the differentiation of Schwann cell precursors and the proliferation of Schwann cells, and acts as a break on myelination of peripheral nerves.
June 14, 0:00 AM / Nature Methods / In vivo fluorescence imaging with high-resolution microlensesA combination of gradient refractive index lenses with plano-convex lenses produces high-resolution microlenses with image quality similar to a conventional high quality microscope objective. The microlenses are capable of imaging dendritic spines on hippocampal neurons in live mice.
June 14, 0:00 AM / Nature Genetics / Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility lociPhilip De Jager and colleagues report results of a large genome-wide association and replication study for multiple sclerosis. The work uncovers three new susceptibility loci for MS, including common and rare variants at TNFRSF1A and common variants at IRF8 and CD6.
June 14, 0:00 AM / Nature Methods / Quantitative analysis of gene expression in a single cell by qPCRThere have been many attempts to measure gene expression in single cells but counting several different mRNAs in the same cell has been a challenge. A reusable single-cell cDNA library immobilized on beads allows quantitative measurement of multiple mRNAs in a single cell with a large dynamic range and small experimental error.
June 14, 0:00 AM / Nature Methods / Agouti C57BL/6N embryonic stem cells for mouse genetic resourcesMouse embryonic stem cell lines from the C57BL/6 strain are reported. The lines are highly germline competent, suitable for high-throughput genetic manipulation and will enable the generation of large knockout mouse resources.
June 9, 5:47 PM / Nature Biotechnology / Taiwan builds biotech runway
June 9, 5:47 PM / Nature Biotechnology / Science communication reconsideredAs new media proliferate and the public's trust and engagement in science are influenced by industry involvement in academic research, an interdisciplinary workshop provides some recommendations to enhance science communication.
June 9, 5:47 PM / Nature Biotechnology / First GM trial in Belgium since 2002
June 9, 5:47 PM / Nature Biotechnology / Phase zero launch
June 9, 5:47 PM / Nature Biotechnology / Ariad's NFκB patent claims shot down on appeal
June 9, 5:47 PM / Nature Biotechnology / A day late and a few million dollars shortThe pitfalls of seeking and obtaining a patent term extension.
June 9, 5:47 PM / Nature Biotechnology / Structure of a multidrug transporterCrystal structures of a mammalian multidrug efflux pump bound to peptide inhibitors may reveal drug-binding sites.
June 9, 5:47 PM / Nature Biotechnology / Profiting from pandemics
June 9, 5:46 PM / Nature Biotechnology / Still strapped for cash
June 9, 5:46 PM / Nature Biotechnology / Genzyme takes Campath bet
June 9, 5:46 PM / Nature Biotechnology / Shining light on a new class of hydrogelsAddition of a photodegradable group to the backbone of synthetic hydrogels enables real-time control of the material's chemical and physical properties.
June 9, 5:46 PM / Nature Biotechnology / India's first true stem cell trials
June 9, 5:46 PM / Nature Biotechnology / Cause and expressBiological validation of a cadre of new obesity genes supports the power of studies that exploit 'expression quantitative trait loci'.
June 9, 5:46 PM / Nature Biotechnology / Mixed news for Avastin
June 9, 5:46 PM / Nature Biotechnology / Pharma's role is not to bankroll biotech
June 9, 5:46 PM / Nature Biotechnology / Pig patent revolt
June 9, 5:46 PM / Nature Biotechnology / TNF-blocker triple approval
June 9, 5:46 PM / Nature Biotechnology / Conflating MTAs and patents
June 9, 5:46 PM / Nature Biotechnology / Boardroom tensions rise as investors push for liquidation
June 9, 5:46 PM / Nature Biotechnology / US regulator wades into stem cell therapies for heart disease
June 9, 5:46 PM / Nature Biotechnology / Masters of their universeNature Biotechnology talks to some of the leading characters behind the Genentech legend.
June 9, 5:46 PM / Nature Biotechnology / Reflect: augmented browsing for the life scientist
June 9, 5:46 PM / Nature Biotechnology / Career interruptedA sound game plan can help you roll with the punches in uncertain times.
June 9, 5:46 PM / Nature Biotechnology / A European perspective on immunogenicity evaluation
June 9, 5:46 PM / Nature Biotechnology / Flu vaccine makers upgrade technology—and pray for time
June 9, 5:46 PM / Nature Biotechnology / Vaccine market boostersRecent commercial success belies conventional wisdom that vaccines are a low-margin, moribund sector. But will the trend continue? Cormac Sheridan investigates.
June 9, 5:46 PM / Nature Biotechnology / Wasting cash—the decline of the British biotech sectorUndercapitalization and overgenerous boardroom compensation for management have been major contributors to the poor performance of UK biotech.
June 9, 5:46 PM / Nature Biotechnology / Extrapolating from sequence—the 2009 H1N1 'swine' influenza virus
June 9, 5:46 PM / Nature Biotechnology / Strangled at birth? Forest biotech and the Convention on Biological DiversityAgainst the Cartagena Protocol and widespread scientific support for a case-by-case approach to regulation, the Convention on Biological Diversity has become a platform for imposing broad restrictions on research and development of all types of transgenic trees.
June 9, 5:46 PM / Nature Biotechnology / The genome-assisted barnyardIn contrast to the slow translation of human genome information into medicine, animal genomics is likely to have a rapid and tangible impact on agriculture.
June 9, 5:46 PM / Nature Biotechnology / Reply to Conflating MTAs and patents
June 9, 5:46 PM / Nature Biotechnology / Recent patent applications in genomic assays
June 9, 5:46 PM / Nature Biotechnology / Research highlights
June 9, 5:46 PM / Nature Biotechnology / People
June 7, 0:00 AM / Nature Genetics / REL, encoding a member of the NF-κB family of transcription factors, is a newly defined risk locus for rheumatoid arthritisPeter Gregersen and colleagues report that common variants at the REL locus are associated with risk of rheumatoid arthritis. REL encodes a member of the NF-κB family of transcription factors, which play key roles in coordinating immune and inflammatory responses.
June 7, 0:00 AM / Nature Neuroscience / Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylationThe authors use high-resolution total reflection fluorescence microscopy to study the mechanisms of AMPA receptor synaptic delivery. They report that palmitoylation of the GluR1 subunit modulates phosphorylation by PKC. This enhances protein 4.1N binding to GluR1, thereby facilitating GluR1 insertion.
June 7, 0:00 AM / Nature Genetics / Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemiaShaoguang Li and colleagues identify Alox5 as a key gene that regulates the function of leukemia stem cells but not normal hematopoietic stem cells in mice, highlighting how cancer and normal stem cells distinctly self-renew and differentiate.
June 7, 0:00 AM / Nature Neuroscience / NADPH oxidase is the primary source of superoxide induced by NMDA receptor activationNMDA-induced superoxide production, which can lead to cell death at excessive levels, is widely believed to originate from mitochondria. Here, the authors find that, in both cultured neurons and mouse hippocampus, NADPH oxidase is actually the primary source of NMDA-induced superoxide production.
June 7, 0:00 AM / Nature Neuroscience / Motivation and cognitive control in the human prefrontal cortexUsing functional magnetic resonance imaging, the authors investigate how the prefrontal cortex (PFC) combines the motivation and selection processes underlying cognitive control. They find that these functions are physically separable, represented in different areas of the PFC, and that these areas may subserve the integration of motivation and cognitive control for decision making.
June 7, 0:00 AM / Nature Genetics / Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axonsWilliam Talbot and colleagues show that a kinesin motor protein, Kif1b, is required for the specific localization of mRNAs that encode myelin proteins in central nervous system glia and mediates the development of myelinated axons. Kif1b has previously been linked to the susceptibility of multiple sclerosis, and damage to myelinated axons is central to the symptoms associated with multiple sclerosis. This suggests mechanisms by which defects in Kif1b may contribute to the disease.
June 7, 0:00 AM / Nature Methods / 'Injecting' yeastUsing a topographically patterned substrate for immobilization of single yeast cells and a piezo-impact micromanipulator to transiently disrupt the cell wall, molecules can be physically introduced into yeast.
June 7, 0:00 AM / Nature Methods / Doxycycline-dependent photoactivated gene expression in eukaryotic systemsActivation of caged doxycycline or cyanodoxycycline by biologically innocuous doses of UV light allows for precise temporal and spatial control of transgene expression in hippocampal slices, mouse embryos and Xenopus laevis tadpoles.
June 7, 0:00 AM / Nature Neuroscience / HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin–TCF interactionPrevious work has suggested that the histone deacetylase HDAC1 promotes and canonical Wnt signaling antagonizes oligodendrocyte differentiation. Here, Ye et al. show that HDAC1/2 directly interferes with canonical Wnt signaling in oligodendrocyte precursors by competing with β-catenin for interaction with the transcriptional co-factor TCF7L2. TCF7L2 itself is shown to be crucial for oligodendrocyte development.
June 7, 0:00 AM / Nature Neuroscience / Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's diseaseMutations in LRRK2 can cause Parkinson's disease. The authors create a transgenic mouse model of LRRK2 that recapitulates several cardinal features of the disease.
June 7, 0:00 AM / Nature Neuroscience / βCaMKII controls the direction of plasticity at parallel fiber–Purkinje cell synapsesSynaptic plasticity at the cerebellar parallel fiber–Purkinje cell is mediated by calcium/calmodulin kinase II. In a knockout mouse line lacking the beta subunit of CaMKII, the authors show a bidirectional inversion of synaptic plasticity accompanying movement disorders and impaired motor learning.