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 27, 12:53 PM / Nature Methods / Byte-ing off more than you can chewWith access to high-throughput technologies, researchers struggle to store their raw data. Many just give up.
June 27, 12:53 PM / Nature Methods / Fish fingers on the menuZebrafish researchers rejoice! Reverse genetics is now on the menu, thanks to zinc-finger nucleases.
June 27, 12:53 PM / Nature Methods / Living dropletsTiny droplets of water in oil can serve as miniature culture vessels for living single cells and multicellular organisms.
June 27, 12:53 PM / Nature Methods / Chemical biology: New electrophilic probes slide inRecently discovered electrophilic probes open the door to activity-based protein profiling (ABPP) studies of a broader range of proteins.
June 27, 12:53 PM / Nature Methods / News in brief
June 27, 12:53 PM / Nature Methods / Live-cell map questA high-resolution interactome map that describes how proteins interact in living yeast cells is an invaluable reference for the research community.
June 27, 12:53 PM / Nature Methods / The beginning of the end for microarrays?Two complementary approaches, both using next-generation sequencing, have successfully tackled the scale and the complexity of mammalian transcriptomes, at once revealing unprecedented detail and allowing better quantification.
June 27, 12:53 PM / Nature Methods / Hunting hidden transcriptsStrategies for the comprehensive identification of transcript isoforms produced from specific genomic loci make use of and expand existing tools and resources.
June 27, 12:53 PM / Nature Methods / Microfluidics: streamlining discovery in worm biologyAdvances in the application of microfluidics technology to biological assays using the model organism Caenorhabditis elegans help to automate otherwise time-consuming experiments.
June 27, 12:53 PM / Nature Methods / Imaging and detection: focusing on softwareIn designing microscopy software to take advantage of better hardware, developers are facing challenges of accessibility, functionality and usability.
June 27, 12:53 PM / Nature Methods / Rapid, fail-early identification of toxic compounds in secondary screening
June 27, 0:00 AM / Nature Methods / Whispering-gallery-mode biosensing: label-free detection down to single molecules
June 26, 11:45 AM / Nature Genetics / All in the mindFindings of an excess of de novo structural variants in cases of autism and schizophrenia have raised hopes that neuropsychiatric conditions may yet prove genetically tractable. Past experience suggests that success in finding causative variants will require exceptional rigor and caution.
June 26, 11:45 AM / Nature Genetics / ESR1 gene amplification in breast cancer: a common phenomenon?
June 26, 11:45 AM / Nature Genetics / Reply to “ESR1 gene amplification in breast cancer: a common phenomenon?”
June 26, 11:45 AM / Nature Genetics / ESR1 gene amplification in breast cancer: a common phenomenon?
June 26, 11:45 AM / Nature Genetics / HDAC2 deficiency and histone acetylation
June 26, 11:45 AM / Nature Genetics / ESR1 gene amplification in breast cancer: a common phenomenon?
June 26, 11:45 AM / Nature Genetics / Reply to “HDAC2 deficiency and histone acetylation”
June 26, 11:45 AM / Nature Genetics / ESR1 gene amplification in breast cancer: a common phenomenon?
June 26, 11:45 AM / Nature Genetics / Blood-strong love
June 26, 11:45 AM / Nature Genetics / Research highlights
June 26, 11:45 AM / Nature Genetics / Conflicting evidence on the frequency of ESR1 amplification in breast cancerAn earlier report of high-frequency ESR1 amplification in breast cancer is now challenged by correspondence from four groups. This discussion of whether or not there is something 'FISHy' about ESR1 amplification highlights the difficulty of validating such observations, leaving the frequency and clinical significance of ESR1 amplification in breast cancer an open question.
June 26, 11:45 AM / Nature Genetics / Bringing age-related macular degeneration into focusGenetic studies of age-related macular degeneration (AMD), the most prevalent blinding condition among the elderly, have had both great success and deep controversy. A new study now begins to resolve contradictory views over two candidate genes at a major AMD locus on chromosome 10q26 by suggesting a functional variant in one of these genes.
June 26, 11:45 AM / Nature Genetics / A new identity for the elusive intestinal stem cellThe tremendous regenerative power of the intestinal epithelium has attracted considerable attention to the crypt as a model for adult stem cell biology. A new study now identifies the Polycomb group protein Bmi1 as a specific marker of intestinal stem cells in vivo.
June 26, 11:45 AM / Nature Genetics / Lung stem cells in the balanceWnt ligands are secreted glycoproteins with critical roles in organogenesis, cancer initiation and progression, and maintenance of stem cell pluripotency. A new study strengthens considerably our understanding of the role of Wnt signaling in progenitor cells of the lung epithelium during development and injury.
June 26, 11:45 AM / Nature Genetics / Shedding light on skin cancerPigmentation traits are known risk factors for skin cancer. Now, three new studies provide insights into the genetic factors underlying these effects, and the results reveal a surprisingly complex picture of the relationship between pigmentation traits and disease risk.
June 26, 11:45 AM / Nature Genetics / Corrigendum: Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta
June 26, 11:45 AM / Nature Genetics / Corrigendum: Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome
June 26, 11:45 AM / Nature Genetics / Corrigendum: Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy
June 26, 11:45 AM / Nature Genetics / Giuseppe Attardi 1923–2008
June 26, 0:00 AM / Nature Genetics / Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene databaseLars Bertram and colleagues report the creation of an online database, SzGene, containing all published genetic association studies for schizophrenia. A series of meta-analyses reveals 24 variants in 16 genes to be associated with the disease with nominal significance, and four of these have strong epidemiological support.
June 25, 1:14 PM / Nature Neuroscience / Awake and asleep
June 25, 1:14 PM / Nature Neuroscience / Corrigendum: Decision-making with multiple alternatives
June 25, 1:14 PM / Nature Neuroscience / Erratum: Cognitive neuroscience: new kids on the block?
June 25, 1:14 PM / Nature Neuroscience / Adult neurogenesis finds its niche
June 25, 1:14 PM / Nature Neuroscience / Catecholaminergic neuron survival: getting hooked on GDNFPascual et al. conditionally delete glial cell line-derived neurotrophic factor (GDNF) expression in adult mice. They report that GDNF is indispensable for the survival of adult catecholaminergic neurons.
June 25, 1:14 PM / Nature Neuroscience / Corrigendum: Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter
June 25, 1:14 PM / Nature Neuroscience / Cocaine-evoked synaptic plasticity: a key to addiction?Drugs of abuse are known to induce changes in synaptic strength in the reward neurons of the brain. Two recent studies shed some light on how drug-induced plasticity might mediate addictive behavior long after drug use.
June 25, 1:14 PM / Nature Neuroscience / Out of control in the dendritesAlthough voltage-clamp recordings remain a favorite method for studying synaptic transmission, the space-clamp problems that are associated with somatic voltage-clamp recordings have never been directly measured. A study by Williams and Mitchell in this issue now measures the experimental errors associated with this technique.
June 25, 1:14 PM / Nature Neuroscience / The shape of faces (to come)Have facial expressions evolved randomly or do their different shapes support some adaptive purpose? New work offers evidence of a selection pressure that may have shaped fearful and disgusted expressions.
June 25, 1:14 PM / Nature Neuroscience / Transgenic primate models inch forwardThe recent announcement of a primate transgenic model of Huntington's disease might appear to represent only a limited advance, but given the work's potential, it would be shortsighted to close the door on this line of research.
June 22, 0:00 AM / Nature Neuroscience / Rapid and modifiable neurotransmitter receptor dynamics at a neuronal synapse in vivoIn vivo, synaptic receptor densities were maintained over minutes by a rapid exchange with nonsynaptic receptor pools and over hours through turnover. These changes and receptor dynamics may represent the initial phases of synaptic efficacy modulation before eventual structural modification involving spine growth or retraction.
June 22, 0:00 AM / Nature Genetics / Estimating coverage and power for genetic association studies using near-complete variation dataTushar Bhangale, Mark Reider, and Deborah Nickerson report estimates of coverage and power by commercial genotyping arrays using a variation dataset for 76 genes resequenced as part of the SeattleSNPs program.
June 22, 0:00 AM / Nature Neuroscience / Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channelsSanshool, the compound responsible for the tingling sensations experienced when consuming Szechuan peppercorns, excites sensory neurons through a unique mechanism, the inhibition of two-pore potassium channels.
June 22, 0:00 AM / Nature Genetics / Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylationBen Tycko and colleagues report the identification of genotype-dependent allele-specific methylation at many loci through the use of genomic methylation-sensitive SNP array analysis. Using independent assays, they confirm allele-specific methylation at 16 SNP-tagged loci on various chromosomes.
June 22, 0:00 AM / Nature Neuroscience / The binding sites for cocaine and dopamine in the dopamine transporter overlapBeuming and colleagues determined that the binding site for cocaine overlaps with that of dopamine on the dopamine transporter. Detailed modeling and mutagenesis experiments revealed that this site is deeply buried amongst several transmembrane domains.
June 22, 0:00 AM / Nature Methods / Automated on-chip rapid microscopy, phenotyping and sorting of C. elegansA major bottleneck for genetic approaches in model organisms is the application of state-of-the-art technologies to phenotyping. Now, using a microfluidic chip, high-resolution imaging of fluorescent reporters and accurate sorting is demonstrated in an automated manner in Caenorhabditis elegans.
June 15, 0:00 AM / Nature Methods / Functional immobilization of signaling proteins enables control of stem cell fateCells in vivo are exposed not only to soluble factors but also to immobilized ligands. Controlled immobilization of functional growth factors yields dose-dependent responses in mouse embryonic stem cells in vitro and allows the effects of immobilized versus soluble ligands to be studied.
June 15, 0:00 AM / Nature Genetics / Integrating large-scale functional genomic data to dissect the complexity of yeast regulatory networksEric Schadt and colleagues report the construction of yeast regulatory networks from multiple sources of large-scale functional genomic data, and show that a network constructed from the integration of genotypic, transcription factor binding site, and protein–protein interaction data is the most predictive.
June 15, 0:00 AM / Nature Neuroscience / Population imaging of ongoing neuronal activity in the visual cortex of awake ratsGreenberg and colleagues directly compare the activity of cortical neurons in awake and subsequently anesthetized rats, finding that anesthesia modulates the relationship between firing rate and correlation, and suggesting that brain activity during wakefulness cannot be inferred from data gathered under anesthesia.
June 15, 0:00 AM / Nature Neuroscience / The orexigenic hormone ghrelin defends against depressive symptoms of chronic stressThe peptide hormone ghrelin has previously been linked to the regulation of metabolism. This study in mice finds that increasing levels of ghrelin, either through subcutaneous injections or calorie restriction, has an anxiolytic and antidepressive effect. This reveals a previously unknown function for ghrelin.
June 15, 0:00 AM / Nature Neuroscience / Direct measurement of somatic voltage clamp errors in central neuronsAlthough the technique of somatic voltage clamp is widely used, computational models have predicted that this controls voltage in the dendritic tree poorly. Williams and Mitchell directly quantify this error using simultaneous recordings from the soma and apical dendrites of rat neocortical pyramidal neurons. Spruston and Johnston also highlight this in an associated news and views.
June 15, 0:00 AM / Nature Neuroscience / A disproportionate role for the fornix and mammillary bodies in recall versus recognition memoryThe fornix is the major fiber tract connecting the medial temporal lobe and the medial diencephalon. This structural imaging study of individuals with fornix atropy finds that the fornix is important for recall, but not recognition, consistent with the idea that hippocampal inputs are selectively important for recall, rather than recognition.
June 15, 0:00 AM / Nature Genetics / Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cellsUsing Xenopus epidermis as a model, John Wallingford and colleagues show that the planar cell polarity protein Dishevelled, acting in concert with Inturned and Rho, controls the apical positioning of basal bodies. Subsequently, Dvl and Rho are also required for directional ciliary beating, suggesting that a common signaling apparatus governs both apical docking and planar polarization of basal bodies.
June 15, 0:00 AM / Nature Neuroscience / Expressing fear enhances sensory acquisitionThis behavioral study finds that when subjects pose expressions of fear, they have a subjectively larger visual field, faster eye movements, and an increase in nasal volume and air velocity during breathing in. Posing expressions of disgust, an expression objectively opposite to fear, produced opposite results. Emotional facial expressions may therefore modify preparedness for perception and action.
June 15, 0:00 AM / Nature Methods / Transgenesis via permanent integration of genes in repopulating spermatogonial cells in vivoConventional techniques for generating transgenic mice are quite costly, require substantial resources and necessitate killing the mouse. In contrast, in vivo electroporation of repopulating spermatogonial cells in the mouse testis can produce male mice for siring multiple distinctive transgenic founders for over a year.
June 15, 0:00 AM / Nature Methods / Isoform discovery by targeted cloning, 'deep-well' pooling and parallel sequencingThe complete set of coding sequences, including all splice isoforms, is not known for any metazoan organism. Combination of a normalized pooling scheme and a new assembly algorithm with 454 sequencing yields a methodological pipeline for isoform discovery. The validated pipeline may now be applied genome-wide.
June 15, 0:00 AM / Nature Genetics / Combinatorial patterns of histone acetylations and methylations in the human genomeKeji Zhao and colleagues report genome-wide maps of 18 histone lysine acetylations in human CD4+ T cells as detected by ChIP-sequencing. Analysis of the data along with genome-wide maps of histone lysine methylations revealed a common module of 17 modifications associated with 25% of genes.
June 8, 0:00 AM / Nature Neuroscience / Seizure termination by acidosis depends on ASIC1aAcidosis can stop seizures, but it is unclear how it does this. This study demonstrates that the acid-sensing channel ASIC1a is required for either spontaneous or CO2-induced termination of convulsant-induced seizures in mice. Moreover, ASIC1a strongly activates inhibitory interneurons under acidotic conditions, which may explain the effect.
June 8, 0:00 AM / Nature Neuroscience / Evolutionary expansion and anatomical specialization of synapse proteome complexityGrant and colleagues used comparative proteomics and genomics to examine the evolution of the postsynaptic density and MAGUK-associated signaling complexes implicated in learning and memory. They found conservation of synaptic components amidst diverse species, but also found species-specific adaptation and increased signaling complexity in vertebrates.
June 8, 0:00 AM / Nature Genetics / Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryosGeorge Daley and colleagues show that ectopic Ras activation diverts embryonic stem cells towards trophoblastic fates, and conversely, that inhibition of MAPK signaling reduces trophectoderm outgrowth from embryo explants. These results implicate Ras-MAPK signaling in this early and critical cell fate decision.
June 8, 0:00 AM / Nature Neuroscience / Absolute requirement of GDNF for adult catecholaminergic neuron survivalThe exact function of glial cell line–derived neurotrophic factor (GDNF) in catecholaminergic cell survival in adulthood is unclear. Using a conditional GDNF-null mouse that suppresses GDNF expression in adulthood, Pascual et al. show that GDNF is an essential factor whose downregulation results in massive catecholaminergic neuronal death. Carlos Ibáñez discusses this paper in an accompanying News and Views.
June 8, 0:00 AM / Nature Genetics / Bmi1 is expressed in vivo in intestinal stem cellsEugenio Sangiorgi and Mario Capecchi use lineage tracing in mice to identify Bmi1 as a specific marker of a stem cell population located at the +4 position of the small intestinal crypt. Their findings address a long-standing debate in the field and support the existence of two distinct intestinal stem cell populations near the crypt base.
June 8, 0:00 AM / Nature Genetics / A Gata6-Wnt pathway required for epithelial stem cell development and airway regenerationEdward Morrisey and colleagues show that mice lacking the transcription factor Gata6 in the lung epithelium have an increased number of bronchioalveolar stem cells during development and in the context of lung regeneration. Additional evidence suggests that a Gata6-Wnt pathway regulates the balance of stem cell expansion and epithelial differentiation in the lung.
June 8, 0:00 AM / Nature Neuroscience / Membrane potential shifts caused by diffusible guidance signals direct growth-cone turningDiffusible axon guidance molecules can modulate membrane potential shifts in the growth cone, producing either attraction or repulsion. This is accomplished through the manipulation of Na+ or Cl− currents by cGMP-based signaling mechanisms, producing a differential change in the Ca2+ influx into the growth cone.
June 8, 0:00 AM / Nature Methods / Lifeact: a versatile marker to visualize F-actinCurrent approaches for live imaging of cellular actin dynamics have several drawbacks. Now the use of Lifeact, a 17-aa actin-binding peptide from yeast that is not present in higher eukaryotes, allows imaging of actin dynamics in live mammalian cells without disruption of function and without competition with endogenous binding proteins.
June 6, 7:34 PM / Nature Biotechnology / What you don't know will hurt youThe heparin scare highlights the need not only for more effective systems of adverse event reporting and product tracking, but also for drug makers to tighten scrutiny of their suppliers.
June 6, 7:34 PM / Nature Biotechnology / HIV vaccine developers battle on, despite high-profile failures
June 6, 7:34 PM / Nature Biotechnology / FDA balks at Myozyme scale-up
June 6, 7:34 PM / Nature Biotechnology / Millennium ends Takeda's US shopping spree
June 6, 7:34 PM / Nature Biotechnology / GSK moves on Sirtris
June 6, 7:34 PM / Nature Biotechnology / Agency on hiring spree
June 6, 7:34 PM / Nature Biotechnology / University patents probed
June 6, 7:33 PM / Nature Biotechnology / Industry welcomes Genetic Information Nondiscrimination Act
June 6, 7:33 PM / Nature Biotechnology / Patent reform stalls
June 6, 7:33 PM / Nature Biotechnology / In silico vaccine
June 6, 7:33 PM / Nature Biotechnology / FDA scrutinizes human stem cell therapies
June 6, 7:33 PM / Nature Biotechnology / Canada charts biologics path
June 6, 7:33 PM / Nature Biotechnology / FDA gets personal
June 6, 7:33 PM / Nature Biotechnology / Profile: Fred KavliFred Kavli is a visionary philanthropist who began selling wood briquettes in wartime Norway and is now investing his fortune in keeping blue-sky research alive.
June 6, 7:33 PM / Nature Biotechnology / Partnerships remain buoyant
June 6, 7:33 PM / Nature Biotechnology / When animal rights turns uglyDespite tightened legislation against animal rights extremism, activists are increasing attacks on academics and researchers in big pharma. How much of a threat do they pose to researchers working in biotech? Brady Huggett investigates.
June 6, 7:33 PM / Nature Biotechnology / Predicting disease outcomes in the clinic
June 6, 7:33 PM / Nature Biotechnology / Response to Predicting disease outcomes in the clinic
June 6, 7:33 PM / Nature Biotechnology / Caring about microenvironments
June 6, 7:33 PM / Nature Biotechnology / Fallout from flip-flops
June 6, 7:33 PM / Nature Biotechnology / Forest biotech and climate change
June 6, 7:33 PM / Nature Biotechnology / A cautionary note on pathogen-derived sequences
June 6, 7:33 PM / Nature Biotechnology / The FDA and safety—beyond the heparin crisisThe discovery of a contaminant in batches of heparin throws into stark relief the difficulties, not only for the US Food and Drug Administration, but also for international regulatory agencies, to ensure the safety and quality of active pharmaceutical ingredients.
June 6, 7:33 PM / Nature Biotechnology / Canaries, coal mines and the drug supplyThe heparin safety crisis sends a strong signal that urgent changes in regulatory and manufacturing oversight are needed to ensure the safety of the global drug supply.
June 6, 7:33 PM / Nature Biotechnology / Brazilian health biotech—fostering crosstalk between public and private sectorsBrazil boasts world-class biomedical science, but tension between the public and private sectors hinders progress in health biotech innovation.
June 6, 7:33 PM / Nature Biotechnology / Patent protection and access to genetic resourcesDeveloping countries and patent offices have shown differing approaches to patent specification disclosure requirements and benefit sharing.
June 6, 7:33 PM / Nature Biotechnology / Recent patent applications in biological imaging
June 6, 7:33 PM / Nature Biotechnology / Next-generation sequencing-by-hybridizationA new hybridization-based technology offers advantages in sequencing genomes for which a reference genome exists.
June 6, 7:33 PM / Nature Biotechnology / Targeted mutagenesis in zebrafishDirected gene knockout in a vertebrate has been achieved using zinc-finger nucleases.
June 6, 7:33 PM / Nature Biotechnology / Proteases' prime targets revealedMass spectrometry analysis of proteome-derived peptide libraries enables high-throughput determination of protease substrate specificity.
June 6, 7:33 PM / Nature Biotechnology / Stable transgenes bear fruitAnalysis of the transgenic papaya genome sequence suggests that transgenes generally stay put following integration and can achieve stable expression level from generation to generation.
June 6, 7:33 PM / Nature Biotechnology / A new path to the cancer epigenomeA regulator of the spatial organization of chromatin may be a promising target to curb the invasiveness of breast cancer.
June 6, 7:33 PM / Nature Biotechnology / Research Highlights