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<jats:p>On this week's show: NIH funding for people not projects and a roundup of stories from our daily news site.</jats:p>

<jats:sec> <jats:title>Background</jats:title> <jats:p> Neuronal networks in the brain include glutamatergic principal neurons and GABAergic interneurons (GABA, γ-aminobutyric acid). The latter may be a minority cell type, but they are vital for normal brain function because they regulate the activity of principal neurons. If interneuron function is impaired, higher brain function can be damaged and seizures may result. The fast-spiking, parvalbumin-positive interneurons (PV <jats:sup>+</jats:sup> interneurons) are readily characterized and, consequently, have been adopted as a research model for systematic and quantitative investigations. These cells contribute to feedback and feedforward inhibition and are critically involved in the generation of network oscillations. They can convert an excitatory input signal into an inhibitory output signal within a millisecond, but it is unclear how these signaling properties are implemented at the molecular and cellular levels, nor how PV <jats:sup>+</jats:sup> interneurons shape complex network functions. </jats:p> </jats:sec> <jats:sec> <jats:title>Advances</jats:title> <jats:p> Recent work sheds light on the subcellular signaling properties of PV <jats:sup>+</jats:sup> interneurons. PV <jats:sup>+</jats:sup> cells show a high degree of polarity. The weakly excitable dendrites allow PV <jats:sup>+</jats:sup> interneurons to sample activity in the surrounding network, whereas the highly excitable axons enable analog-to-digital conversion and fast propagation of the digital signal to a large number of target cells. Additionally, tight coupling of Ca <jats:sup>2+</jats:sup> channels and release sensors at GABAergic output synapses increases the efficacy and speed of the inhibitory output. </jats:p> <jats:p> Recent results also provide a better understanding of how PV <jats:sup>+</jats:sup> interneurons operate in neuronal networks. Not only are PV <jats:sup>+</jats:sup> interneurons involved in basic microcircuit functions, such as feedforward and feedback inhibition or gamma-frequency oscillations, but they also play a role in complex network operations, including expansion of dynamic activity range, pattern separation, modulation of place and grid field shapes, phase precession, and gain modulation of sensory responses. Thus, PV <jats:sup>+</jats:sup> interneurons are critically involved in advanced computations in microcircuits and neuronal networks. </jats:p> </jats:sec> <jats:sec> <jats:title>Outlook</jats:title> <jats:p> Parvalbumin-expressing interneurons may also play a key role in numerous brain diseases. These include epilepsy, but also complex psychiatric diseases such as schizophrenia. Thus, PV <jats:sup>+</jats:sup> interneurons may become important therapeutic targets in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will have a chance to successfully use PV <jats:sup>+</jats:sup> interneurons for therapeutic purposes. </jats:p> </jats:sec>

<jats:sec> <jats:title>Introduction</jats:title> <jats:p>The human genome is peppered with mobile repetitive elements called long interspersed nuclear element–1 (L1) retrotransposons. Propagating through RNA and cDNA intermediates, these molecular parasites copy and insert themselves throughout the genome, with potentially disruptive effects on neighboring genes or regulatory sequences. In the germ line, unique sequence downstream of L1 elements can also be retrotransposed if transcription continues beyond the repeat, a process known as 3′ transduction. There has been growing interest in retrotransposition and 3′ transduction as a possible source of somatic mutations during tumorigenesis.</jats:p> </jats:sec> <jats:sec> <jats:title>Rationale</jats:title> <jats:p>To explore whether 3′ transductions are frequent in cancer, we developed a bioinformatic algorithm for identifying somatically acquired retrotranspositions in cancer genomes. We applied our algorithm to 290 cancer samples from 244 patients across 12 tumor types. The unique downstream sequence mobilized with 3′ transductions effectively fingerprints the L1 source element, providing insights into the activity of individual L1 loci across the genome.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Across the 290 samples, we identified 2756 somatic L1 retrotranspositions. Tumors from 53% of patients had at least one such event, with colorectal and lung cancers being most frequently affected (93% and 75% of patients, respectively). Somatic 3′ transductions comprised 24% of events, half of which represented mobilizations of unique sequence alone, without any accompanying L1 sequence. Overall, 95% of 3′ transductions identified derived from only 72 germline L1 source elements, with as few as four loci accounting for 50% of events. In a given sample, the same source element could generate 50 or more somatic transductions, scattered extensively across the genome. About 5% of somatic transductions arose from L1 source elements that were themselves somatic retrotranspositions. In three of the cases in which we sequenced more than one sample from a patient’s tumor, we were able to place 3′ transductions on the phylogenetic tree. We found that the activity of individual source elements fluctuated during tumor evolution, with different subclones exhibiting much variability in which elements were “on” and which were “off.” The ability to identify the individual L1 source elements active in a given tumor enabled us to study the promoter methylation of those elements specifically. We found that 3′ transduction activity in a patient’s tumor was always associated with hypomethylation of that element. Overall, 2.3% of transductions distributed exons or entire genes to other sites in the genome, and many more mobilized deoxyribonuclease I (DNAse-I) hypersensitive sites or transcription factor binding sites identified by the ENCODE project. Occasionally, somatic L1 insertions inserted near coding sequence and redistributed these exons elsewhere in the genome. However, we found no general effects of retrotranspositions on transcription levels of genes at the insertion points and no evidence for aberrant RNA species resulting from somatically acquired transposable elements. Indeed, as with germline retrotranspositions, somatic insertions exhibited a strong enrichment in heterochromatic, gene-poor regions of the genome.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Somatic 3′ transduction occurs frequently in human tumors, and in some cases transduction events can scatter exons, genes, and regulatory elements widely across the genome. Dissemination of these sequences appears to be due to a small number of highly active L1 elements, whose activity can wax and wane during tumor evolution. The majority of the retrotransposition events are likely to be harmless “passenger” mutations.</jats:p> </jats:sec>

<jats:p>The United Nations (UN) designated 2014 as the International Year of Family Farming, recognizing that an estimated 500 million family farms, involving over 2 billion people, play a key role in food production and consumption worldwide. It is thus an opportune time to encourage a shift in tackling global hunger—from a “food security” focus to an agenda that promotes “nutrition security” instead. The drive to reduce hunger in the world has largely relied on crops such as wheat and rice that provide calories. But an increase in calories alone is not good enough. Improved diets and good health require bolstering nutrition.</jats:p>

<jats:p>A roundup of weekly science policy and related news.</jats:p>

<jats:p>Remission is seen as a more realistic goal.</jats:p>

<jats:p>Studies suggest that atoll islands will rise in step with a rising sea.</jats:p>

<jats:p>Stanford researchers unable to replicate findings linking immune response to sleep disorder.</jats:p>