Synthesizing cognition in neuromorphic electronic systems
Emre Neftci, Jonathan Binas, Ueli Rutishauser, Elisabetta Chicca, Giacomo Indiveri, and Rodney J. Douglas
Neuromorphic emulations express the dynamics of neural systems in analogous electronic circuits, offering a distributed, low-power technology for constructing intelligent systems. However, neuromorphic circuits are inherently imprecise and noisy, and there has been no systematic method for configuring reliable behavioral dynamics on these substrates. We describe (pp. E3468–E3476) such a method, which is able to install simple cognitive behavior on the neuromorphic substrate. Our approach casts light on the general question of how the neuronal circuits of the brain, and also future neuromorphic technologies, could implement cognitive behavior in a principled manner.
Tapping unsustainable groundwater stores for agricultural production in the High Plains Aquifer of Kansas, projections to 2110
David R. Steward, Paul J. Bruss, Xiaoying Yang, Scott A. Staggenborg, Stephen M. Welch, and Michael D. Apley
Society faces the multifaceted crossroads dilemma of sustainably balancing today’s livelihood with future resource needs. Currently, agriculture is tapping the High Plains Aquifer beyond natural replenishment rates to grow irrigated crops and livestock that augment global food stocks, and science-based information is needed to guide choices. We present new methods (pp. E3477–E3486) to project trends in groundwater pumping and irrigated corn and cattle production. Although production declines are inevitable, scenario analysis substantiates the impacts of increasing near-term water savings, which would extend the usable lifetime of the aquifer, increase net production, and generate a less dramatic production decline.
Comparative genomics boosts target prediction for bacterial small RNAs
Patrick R. Wright, Andreas S. Richter, Kai Papenfort, Martin Mann, Jörg Vogel, Wolfgang R. Hess, Rolf Backofen, and Jens Georg
This study (pp. E3487–E3496) presents a unique approach (CopraRNA, for Comparative Prediction Algorithm for sRNA Targets) towards reliably predicting the targets of bacterial small regulatory RNAs (sRNAs). These molecules are important regulators of gene expression. Their detailed analysis thus far has been hampered by the lack of reliable algorithms to predict their mRNA targets. CopraRNA integrates phylogenetic information to predict sRNA targets at the genomic scale, reconstructs regulatory networks upon functional enrichment and network analysis, and predicts the sRNA domains for target recognition and interaction. Our results demonstrate that CopraRNA substantially improves the bioinformatic prediction of target genes and opens the field for the application to nonmodel bacteria.
Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity
Sheena Pinto, Chloé Michel, Hannah Schmidt-Glenewinkel, Nathalie Harder, Karl Rohr, Stefan Wild, Benedikt Brors, and Bruno Kyewski
The ability of the immune system to distinguish self from foreign (“self-tolerance”) is largely established in the thymus, a primary lymphoid organ where T cells develop. Intriguingly, T cells encounter most tissue-specific constituents already in the thymus, thus imposing a broad scope of tolerance before T cells circulate through the body. This preemption of the “immunological self” is afforded by the “promiscuous” expression of numerous tissue-specific antigens in medullary thymic epithelial cells. Here (pp. E3497–E3505), we identified principles by which promiscuous gene expression at the single-cell level adds up to the full diversity of self-antigens displayed at the population level.
ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer
Alvaro Aytes, Antonina Mitrofanova, Carolyn Waugh Kinkade, Celine Lefebvre, Ming Lei, Vanessa Phelan, H. Carl LeKaye, Jason A. Koutcher, Robert D. Cardiff, Andrea Califano, Michael M. Shen, and Cory Abate-Shen
Although locally invasive prostate cancer is nearly always curable, metastatic prostate cancer usually results in lethality. Our study investigates the temporal progression and molecular mechanisms underlying prostate cancer metastasis using a new genetically engineered mouse model. Using lineage-tracing analyses, we show (pp. E3506–E3515) that dissemination of tumor cells occurs early in cancer progression, and well before the occurrence of metastases. We further show that metastasis is temporally coincident with expression of the oncogenic ETS gene Etv4, and that Etv4 promotes prostate cancer metastasis in vivo. Our findings suggest that Etv4 may be a target for therapeutic intervention in metastatic prostate cancer.
In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins
Andrea E. Granstedt, Jens B. Bosse, Stephan Y. Thiberge, and Lynn W. Enquist
Pseudorabies virus (PRV), an alphaherpesvirus related to human herpes simplex and varicella-zoster viruses, causes the characteristic “mad itch” in which infected animals scratch an afflicted area until self-mutilation. The mechanism by which PRV induces these symptoms is still poorly understood, and most work has been done in limited systems in vitro. Here we report studies (pp. E3516–E3525) performed in living mice. We observed that infection with a virulent PRV strain induces synchronous and cyclical neural activity, but this activity disappears during infection with a vaccine strain that does not cause mad itch. We demonstrate the aberrant activity depends on a viral fusion protein, and its trafficking specifically into axons. These findings correlate the disrupted physiology to the known neuropathy in vivo.
Natalisin, a tachykinin-like signaling system, regulates sexual activity and fecundity in insects
Hongbo Jiang, Ankhbayar Lkhagva, Ivana Daubnerová, Hyo-Seok Chae, Ladislav Šimo, Sung-Hwan Jung, Yeu-Kyung Yoon, Na-Rae Lee, Jae Young Seong, Dušan Žitňan, Yoonseong Park, and Young-Joon Kim
Successful courtship and reproduction, which are at the center of evolutionary processes, involve complex interactions between neural and endocrine systems. In this study (pp. E3526–E3534), we describe a group of neuropeptides that we have named “natalisin” (from the Latin natalis for “birth”) because of their function in promoting reproduction in arthropods. Three holometabolous insects, Drosophila melanogaster, Bombyx mori, and Tribolium castaneum were examined to understand the patterns of natalisin expression and to assess the phenotype of natalisin RNAi, and revealed the functions in courtship behavior and egg production. The natalisin receptor identified here warrants expanded study to elucidate the mechanisms of natalisin in arthropod reproduction.
An alternative polyadenylation mechanism coopted to the Arabidopsis RPP7 gene through intronic retrotransposon domestication
Tokuji Tsuchiya and Thomas Eulgem
We show (pp. E3535–E3543) the histone mark H3K9me2, which is known to mediate transposon silencing, to determine the choice between alternative polyadenylation sites within the Arabidopsis thaliana disease resistance gene RPP7. High H3K9me2 levels recruited to the first RPP7 intron by the COPIA-R7 retrotransposon suppress use of a promoter-proximal polyadenylation site. Modulating H3K9me2 levels at this site shifts the balance between full-length and incomplete RPP7 transcripts. By recruiting H3K9me2-dependent polyadenylation control to RPP7, the COPIA-R7 insertion provided a new switch to fine-tune RPP7 expression. Selective advantages resulting from this mechanism likely contributed to the domestication of COPIA-R7 at RPP7.