News & Views |
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News & Views |
Each synapse to its own
A neuron can receive thousands of inputs that, together, tell it when to fire. New techniques can image the activity of many inputs, and shed light on how single neurons perform computations in response.
- Nicholas J. Priebe
- & David Ferster
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Review Article |
Genetics, pathogenesis and clinical interventions in type 1 diabetes
- Jeffrey A. Bluestone
- , Kevan Herold
- & George Eisenbarth
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Letter |
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity
Here, a new type of innate effector leukocyte cell — the nuocyte — is described and characterized. It is shown that interleukin (IL)25 and IL33 drive the expansion of the nuocyte population, that these cells secrete IL13, and that they are required for protection against helminth infection.
- Daniel R. Neill
- , See Heng Wong
- & Andrew N. J. McKenzie
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Article |
Dendritic organization of sensory input to cortical neurons in vivo
Many sensory neurons in the mammalian cortex are tuned to specific stimulus features — for example, some fire only when horizontal bars move from top to bottom in the visual field. But it has been unclear whether such tuning is encoded in a neuron's inputs, or whether the neuron itself computes its response. Here, a new technique for visualizing and mapping sensory inputs to the dendrites of neurons in the mouse visual cortex has shown that each neuron makes its own 'decision' as to the orientation preference of its output.
- Hongbo Jia
- , Nathalie L. Rochefort
- & Arthur Konnerth
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Letter |
IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses
Several non-haematopoietic-cell-derived cytokines, including interleukin (IL)25, have been implicated in inducing T helper 2 (TH2) cell-dependent inflammation, but their precise role has been unclear. Here, IL25 is shown to promote the accumulation of multipotent progenitor cells in gut-associated lymphoid tissue. These cells can give rise to macrophage or granulocyte lineages that promote the differentiation of TH2 cells and contribute to protective immunity against helminth infections.
- Steven A. Saenz
- , Mark C. Siracusa
- & David Artis
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Letter |
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
During atherosclerosis, crystals of cholesterol accumulate in atherosclerotic plaques. But are they a consequence or a cause of the inflammation associated with the disease? Here it is shown that small cholesterol crystals appear early in the development of atherosclerosis, and that they act as an endogenous danger signal, causing inflammation by activating the NLRP3 inflammasome pathway. Cholesterol crystals thus seem to be an early cause, rather than a late consequence, of inflammation.
- Peter Duewell
- , Hajime Kono
- & Eicke Latz
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Article |
N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
African sleeping sickness, caused by Trypanosoma brucei species, is responsible for some 30,000 human deaths each year. Available treatments are limited by poor efficacy and safety profiles. However, a new molecular target for potential treatments has now been identified. The protein target is T. brucei N-myristoyltransferase. In further experiments, lead compounds have been discovered that inhibit this protein, kill trypanosomes in vitro and in vivo, and can cure trypanosomiasis in mice.
- Julie A. Frearson
- , Stephen Brand
- & Paul G. Wyatt
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Letter
| Open AccessGenome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
Studies of identical twins are widely used to dissect the contributions of genes and the environment to human diseases. In multiple sclerosis, an autoimmune demyelinating disease, identical twins often show differences. This might suggest that environmental effects are most significant in this case, but genetic and epigenetic differences between identical twins have been described. Here, however, studies of identical twins show no evidence for genetic, epigenetic or transcriptome differences that could explain disease discordance.
- Sergio E. Baranzini
- , Joann Mudge
- & Stephen F. Kingsmore
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Letter |
Impaired hippocampal–prefrontal synchrony in a genetic mouse model of schizophrenia
A deletion on human chromosome 22 (22q11.2) is one of the largest genetic risk factors for schizophrenia. Mice with a corresponding deletion have problems with working memory, one feature of schizophrenia. It is now found that these mice also show disruptions in synchronous firing between neurons of the prefrontal cortex and of the hippocampus, an electrophysiological phenomenon that has been linked to learning and memory and which is also thought to be disrupted in schizophrenia patients.
- Torfi Sigurdsson
- , Kimberly L. Stark
- & Joshua A. Gordon
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Letter |
Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling
Although several synaptic adhesion proteins have been identified as genetic risk factors in schizophrenia, it is unclear as to what role they play in disease progression. Here, it is shown that two such proteins — neuregulin 1 and its receptor ErbB4 — function to regulate the connectivity of specific cortical circuits. The study not only implicates these proteins in the wiring of inhibitory synapses, about which little is known, but also provides a new perspective on their involvement in schizophrenia.
- Pietro Fazzari
- , Ana V. Paternain
- & Beatriz Rico
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Research Highlights |
Neurodevelopment: Baby talk
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Opinion |
Multiple personal genomes await
Genomic data will soon become a commodity; the next challenge — linking human genetic variation with physiology and disease — will be as great as the one genomicists faced a decade ago, says J. Craig Venter.
- J. Craig Venter
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Opinion |
Point: Hypotheses first
There is little to show for all the time and money invested in genomic studies of cancer, says Robert Weinberg — and the approach is undermining tried-and-tested ways of doing, and of building, science. This Opinion piece is part of a linked pair; see also Counterpoint: Data First by Todd Golub.
- Robert Weinberg
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Opinion |
Counterpoint: Data first
Large, unbiased genomic surveys are taking cancer therapeutics in directions that could never have been predicted by traditional molecular biology, says Todd Golub. This Opinion piece is part of a linked pair; see also Point: Hypothesis First by Robert Weinberg.
- Todd Golub
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News & Views |
Fat-free proteins kill parasites
The addition of a fatty acid to certain proteins is vital for the survival of protozoa that cause sleeping sickness and of their mammalian hosts. Compounds that target this process in the protozoa are now reported.
- George A. M. Cross
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News |
Gene flaw found in induced stem cells
Key difference between reprogrammed adult mouse cells and embryonic stem cells discovered.
- Elie Dolgin
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News Feature |
Human genome at ten: Life is complicated
The more biologists look, the more complexity there seems to be. Erika Check Hayden asks if there's a way to make life simpler.
- Erika Check Hayden
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News |
Breast cancer gene patents judged invalid
Court ruling may spell bad news for biotech industry.
- Meredith Wadman
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News |
Animal studies paint misleading picture
Unpublished negative results may explain limited translation of promising treatments to the clinic.
- Janelle Weaver
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Letter |
Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis
Cancer 'chemoprevention' uses substances to reverse, suppress or prevent the initial phase of carcinogenesis or the progression of neoplastic cells to cancer cells. Here it is shown that treatment with TRAIL proteins and all-trans-retinyl acetate can cause the death, in vitro and in vivo, of premalignant cells deficient in the adenomatous polyposis coli gene. Normal cells are unaffected. Selectively eliminating premalignant tumour cells in this way is thus an effective method for chemoprevention.
- Ling Zhang
- , Xiaoyang Ren
- & Xiangwei Wu
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Article |
Neurogenic radial glia in the outer subventricular zone of human neocortex
In the mammalian brain, the subventricular zone (SVZ) produces neural progenitor cells that migrate into the cortex to populate the upper layers. In humans this region is massively expanded, producing an outer SVZ (OSVZ). Here, live-cell imaging of developing human tissue was used to show that the OSVZ has similar characteristics to the SVZ, with progenitor cells proliferating in a way that depends on the Notch protein. The findings have implications for our understanding of how the complex human brain evolved.
- David V. Hansen
- , Jan H. Lui
- & Arnold R. Kriegstein
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Letter |
Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation
Zebrafish are able to replace lost heart muscle efficiently, and are used as a model to understand why natural heart regeneration — after a heart attack, for instance — is blocked in mammals. Here, and in an accompanying paper, genetic fate-mapping approaches reveal which cell population contributes prominently to cardiac muscle regeneration after an injury approximating myocardial infarction. The results show that cardiac muscle regenerates through activation and expansion of existing cardiomyocytes, without involving a stem-cell population.
- Chris Jopling
- , Eduard Sleep
- & Juan Carlos Izpisúa Belmonte
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Research Highlights |
Regenerative biology: Pregnancy boosts repair
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Editorial |
Buyer beware
Lack of US regulation is allowing dubious dietary supplements to be sold as life-enhancing elixirs.
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Review Article |
Neural mechanisms of ageing and cognitive decline
- Nicholas A. Bishop
- , Tao Lu
- & Bruce A. Yankner
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Letter |
Human memory strength is predicted by theta-frequency phase-locking of single neurons
Although explored in the rodent, the relationship between single neuron activity, oscillations and behavioural learning is unknown in humans. Here, successful memory formation in humans was predicted by the coordination of spike timing relative to the local theta oscillation. These data provide a direct connection between the behavioural modulation of oscillations and plasticity within specific circuits.
- Ueli Rutishauser
- , Ian B. Ross
- & Erin M. Schuman
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News |
US health bill promises changes for biomedical researchers
Translational work set to receive a boost.
- Meredith Wadman
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News |
Cancer genes silenced in humans
Tiny particles carrying short strands of RNA can interfere with protein production in tumours.
- Janet Fang
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Article |
Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
A new mouse model is developed in which haematopoietic malignancies are caused by genetic changes in the microenvironment of blood cells. Deletion in bone progenitor cells of Dicer1, a gene involved in microRNA processing, leads to a myelodysplastic syndrome-like phenotype which can progress to leukaemia. Deregulation of Sbds, which is mutated in human Schwachman–Bodian–Diamond syndrome, may be involved in this process.
- Marc H. G. P. Raaijmakers
- , Siddhartha Mukherjee
- & David. T. Scadden
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Letter |
Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
It has previously been shown in mice and non-human primates that systemically delivered short RNA molecules can inhibit gene expression. Here it is shown that a short interfering RNA (siRNA) can be systemically delivered, using nanoparticles, to a solid tumour in humans. The siRNA mediates cleavage of its target mRNA, thereby also reducing levels of the encoded protein. This proof-of-principle study confirms the potential of this technology for treating human disease.
- Mark E. Davis
- , Jonathan E. Zuckerman
- & Antoni Ribas
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Letter |
Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells
In multicellular organisms, apoptotic cells are removed from tissues by phagocytes, which recognize and engulf the dying cells. The molecular mechanisms underlying the subsequent degradation of the cells have been unclear. Here, two evolutionarily conserved genes have been identified that are required for such processing in Caenorhabditis elegans and mammals. An understanding of these events could lead to new treatments for diseases associated with poor engulfment and destruction of dying cells.
- Jason M. Kinchen
- & Kodi S. Ravichandran
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Article |
Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
Cellular senescence — an irreversible cell-cycle arrest — has been implicated in suppressing tumour formation or growth. A new cellular signalling pathway that drives senescence has now been identified. This pathway does not involve most known mediators of senescence, and instead signals via the proteins Atf4, p27 and p21. Inactivating the proto-oncogene Skp2 in the context of oncogenic signalling can induce senescence through this new pathway, indicating that drugs that target Skp2 might be useful in cancer treatment.
- Hui-Kuan Lin
- , Zhenbang Chen
- & Pier Paolo Pandolfi
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Editorial |
Handle with care
Britain's Department of Health must respond to concerns about electronic medical records.
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Research Highlights |
Virology: Infectious inheritance
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News & Views |
Closing in on an oral treatment
At present, only injectable drugs are available for treating multiple sclerosis. So clinical trials indicating that the drug fingolimod might be a step towards an oral treatment for the disease are exciting indeed.
- Roland Martin
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News & Views |
A lower bar for senescence
Cellular senescence is a physiological mechanism for thwarting the proliferation of tumour cells. Encouraging cancer-prone cells to senesce might therefore be a way to nip this disease in the bud.
- Manuel Serrano
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News & Views |
Inhibitors that activate
Inhibitors of RAF enzymes can suppress or activate the same signalling pathway. The details of how this happens provide a cautionary note for those targeting the pathway for anticancer drug discovery.
- Karen Cichowski
- & Pasi A. Jänne
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News |
Reproducibility of brainscan studies questioned
Some magnetic resonance imaging studies could be less reliable than has been presumed.
- Richard A. Lovett
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News |
Cash crisis looms for vaccine drive
Rising demand for immunization programmes in developing countries could outstrip funding.
- Declan Butler
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News |
Snake infrared detection unravelled
Scientists have discovered the receptors that allow snakes to find prey in the dark.
- Janet Fang
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News |
A direct hit for thalidomide
The drug stunts limb development in zebrafish and chicks by binding to a protein called cereblon.
- Janet Fang
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Letter |
B-cell-derived lymphotoxin promotes castration-resistant prostate cancer
In a mouse model of prostate cancer it is shown that infiltrating B cells promote tumorigenesis by secreting lymphotoxin. Lymphotoxin accelerates the emergence of castration-resistant prostate tumours in this model. Interfering with this pathway may offer therapeutic strategies for androgen-independent prostate cancer.
- Massimo Ammirante
- , Jun-Li Luo
- & Michael Karin