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© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Northcutt, A. J., Kick, D. R., Otopalik, A. G., Goetz, B. M., Harris, R. M., Santin, J. M., Hofmann, H. A., Marder, E., & Schulz, D. J. Molecular profiling of single neurons of known identity in two ganglia from the crab Cancer borealis. Proceedings of the National Academy of Sciences of the United States of America, 116 (52) (2019): 26980-26990, doi: 10.1073/pnas.1911413116., Understanding circuit organization depends on identification of cell types. Recent advances in transcriptional profiling methods have enabled classification of cell types by their gene expression. While exceptionally powerful and high throughput, the ground-truth validation of these methods is difficult: If cell type is unknown, how does one assess whether a given analysis accurately captures neuronal identity? To shed light on the capabilities and limitations of solely using transcriptional profiling for cell-type classification, we performed 2 forms of transcriptional profiling—RNA-seq and quantitative RT-PCR, in single, unambiguously identified neurons from 2 small crustacean neuronal networks: The stomatogastric and cardiac ganglia. We then combined our knowledge of cell type with unbiased clustering analyses and supervised machine learning to determine how accurately functionally defined neuron types can be classified by expression profile alone. The results demonstrate that expression profile is able to capture neuronal identity most accurately when combined with multimodal information that allows for post hoc grouping, so analysis can proceed from a supervised perspective. Solely unsupervised clustering can lead to misidentification and an inability to distinguish between 2 or more cell types. Therefore, this study supports the general utility of cell identification by transcriptional profiling, but adds a caution: It is difficult or impossible to know under what conditions transcriptional profiling alone is capable of assigning cell identity. Only by combining multiple modalities of information such as physiology, morphology, or innervation target can neuronal identity be unambiguously determined., We thank members of the D.J.S., H.A.H., and E.M. laboratories for helpful discussions. We thank the Genomic Sequencing and Analysis Facility (The University of Texas [UT] at Austin) for library preparation and sequencing and the bioinformatics consulting team at the UT Austin Center for Computational Biology and Bioinformatics for helpful advice. This work was supported by National Institutes of Health grant R01MH046742-29 (to E.M. and D.J.S.) and the National Institute of General Medical Sciences T32GM008396 (support for A.J.N.) and National Institute of Mental Health grant 5R25MH059472-18 and the Grass Foundation (support for Neural Systems and Behavior Course at the Marine Biological Laboratory).

Social monogamy, typically characterized by the formation of a pair bond, increased territorial defense, and often biparental care, has independently evolved multiple times in animals. Despite the independent evolutionary origins of monogamous mating systems, several homologous brain regions and neuropeptides and their receptors have been shown to play a conserved role in regulating social affiliation and parental care, but little is known about the neuromolecular mechanisms underlying monogamy on a genomic scale. Here, we compare neural transcriptomes of reproductive males in monogamous and nonmonogamous species pairs of Peromyscus mice, Microtus voles, parid songbirds, dendrobatid frogs, and Xenotilapia species of cichlid fishes. We find that, while evolutionary divergence time between species or clades did not explain gene expression similarity, characteristics of the mating system correlated with neural gene expression patterns, and neural gene expression varied concordantly across vertebrates when species transition to monogamy. Our study provides evidence of a universal transcriptomic mechanism underlying the evolution of monogamy in vertebrates.

Understanding circuit organization depends on identification of cell types. Recent advances in transcriptional profiling methods have enabled classification of cell types by their gene expression. While exceptionally powerful and high throughput, the ground-truth validation of these methods is difficult: If cell type is unknown, how does one assess whether a given analysis accurately captures neuronal identity? To shed light on the capabilities and limitations of solely using transcriptional profiling for cell-type classification, we performed 2 forms of transcriptional profiling—RNA-seq and quantitative RT-PCR, in single, unambiguously identified neurons from 2 small crustacean neuronal networks: The stomatogastric and cardiac ganglia. We then combined our knowledge of cell type with unbiased clustering analyses and supervised machine learning to determine how accurately functionally defined neuron types can be classified by expression profile alone. The results demonstrate that expression profile is able to capture neuronal identity most accurately when combined with multimodal information that allows for post hoc grouping, so analysis can proceed from a supervised perspective. Solely unsupervised clustering can lead to misidentification and an inability to distinguish between 2 or more cell types. Therefore, this study supports the general utility of cell identification by transcriptional profiling, but adds a caution: It is difficult or impossible to know under what conditions transcriptional profiling alone is capable of assigning cell identity. Only by combining multiple modalities of information such as physiology, morphology, or innervation target can neuronal identity be unambiguously determined.

Understanding circuit organization depends on identification of cell types. Recent advances in transcriptional profiling methods have enabled classification of cell types by their gene expression. While exceptionally powerful and high throughput, the ground-truth validation of these methods is difficult: If cell type is unknown, how does one assess whether a given analysis accurately captures neuronal identity? To shed light on the capabilities and limitations of solely using transcriptional profiling for cell-type classification, we performed 2 forms of transcriptional profiling—RNA-seq and quantitative RT-PCR, in single, unambiguously identified neurons from 2 small crustacean neuronal networks: The stomatogastric and cardiac ganglia. We then combined our knowledge of cell type with unbiased clustering analyses and supervised machine learning to determine how accurately functionally defined neuron types can be classified by expression profile alone. The results demonstrate that expression profile is able to capture neuronal identity most accurately when combined with multimodal information that allows for post hoc grouping, so analysis can proceed from a supervised perspective. Solely unsupervised clustering can lead to misidentification and an inability to distinguish between 2 or more cell types. Therefore, this study supports the general utility of cell identification by transcriptional profiling, but adds a caution: It is difficult or impossible to know under what conditions transcriptional profiling alone is capable of assigning cell identity. Only by combining multiple modalities of information such as physiology, morphology, or innervation target can neuronal identity be unambiguously determined.

Social monogamy, typically characterized by the formation of a pair bond, increased territorial defense, and often biparental care, has independently evolved multiple times in animals. Despite the independent evolutionary origins of monogamous mating systems, several homologous brain regions and neuropeptides and their receptors have been shown to play a conserved role in regulating social affiliation and parental care, but little is known about the neuromolecular mechanisms underlying monogamy on a genomic scale. Here, we compare neural transcriptomes of reproductive males in monogamous and nonmonogamous species pairs of Peromyscus mice, Microtus voles, parid songbirds, dendrobatid frogs, and Xenotilapia species of cichlid fishes. We find that, while evolutionary divergence time between species or clades did not explain gene expression similarity, characteristics of the mating system correlated with neural gene expression patterns, and neural gene expression varied concordantly across vertebrates when species transition to monogamy. Our study provides evidence of a universal transcriptomic mechanism underlying the evolution of monogamy in vertebrates.

Wesentliche Funktion der sich aus Art. 42 Abs. 1 und 3 GG ergebenen Öffentlichkeitsfunktion des Deutschen Bundestages ist die Gewährleistung einer umfassenden und effektiven Teilhabe, Kontrolle und Repräsentation des Volkes. Abzuleiten ist dies insbesondere aus dem Demokratieprinzip und dem Prinzip der Volkssouveränität. Ausgehend vom Wortlaut von Art 42 Abs. 1 GG sowie § 19 GOBT („Bundestag“) und unter Berücksichtigung des Wechselspiels zwischen öffentlichen Lesungen im Plenum und nichtöffentlichen Ausschussberatungen erstreckt sich die verfassungsrechtlich zu gewährleistende Parlamentsöffentlichkeit grundsätzlich nur auf das Plenum und nicht auch auf die (grundsätzlich nichtöffentlich tagenden) Ausschüsse des Deutschen Bundestages. Der Bundestag verhandelt im Sinne von Art. 42 Abs. 1 GG nur dann im Sinne einer allgemeinen Zugänglichkeit öffentlich, wenn der Bundestag dem deutschen Staatsvolk sowie der Presse als relevantes Publikum einen allgemeinen, freien und auch tatsächlichen Zugang zu seinen Verhandlungen ermöglicht. Die Parlamentsöffentlichkeit gemäß Art. 42 Abs. 1 und 3 GG umfasst neben einer formellen, auch eine materielle Komponente im Sinne einer hinreichenden Vorlaufzeit, Verständlichkeit und Nachvollziehbarkeit. Schließlich verlangt eine materielle Parlamentsöffentlichkeit eine hinreichende Beratung und Erörterung der Verhandlungsgegenstände sowie Einbeziehung der verschiedenen Interessen und Bedürfnisse des Volkes. Die Öffentlichkeitsarbeit des Bundestages ist ebenfalls Teil der Öffentlichkeitsfunktion des Bundestages gemäß Art. 42 Abs. 1 und 3 GG. Dem Bundestag ist es insofern grundsätzlich gestattet, alle Arten von Kommunikationsmitteln (Printmedien, Rundfunk, Telemedien bis zu modernen Kommunikationstechniken wie Chats, Twitter oder Facebook) für seine Öffentlichkeitsarbeit zu verwenden., The essential function of the public function of the German Bundestag arising from Art. 42 (1) and (3) GG is the guarantee of effective participation, checks and representation of the people. Based on the wording of Art. 42 (1) GG and § 19 GOBT ("Bundestag"), parliamentary committees are in principle not obliged to meet in public. Only the meetings and negotiations of the plenary have to be public. Within the meaning of Art. 42 (1) GG, the Bundestag is obliged to give the German people and the press free access to his negotiations and meetings. Art. 42 (1) and (3) GG Basic Law includes not only a formal but also a material component of public in the sense that meetings and negotiation of parliament have to be comprehensible, transparent and include timewise a reasonable lead time. Next to this, there is a material parliamentarian public which requires parliament to reasonably negotiate the topics placed on the agenda. In this sense parliament is obliged to consider the various interests and needs of the people. Also, public relations of the Bundestag is part of the public function of Art. 42 (1) and (3) GG. The Bundestag may use all kinds of communication for its public relations.

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification., De tre sista författarna delar sistaförfattarskapet.

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of 'reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at

Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet- induced obese mice.

The paper contains an overview on the design principles and main characteristics of a family of new, strictly object-oriented combat simulation models called COSIMAC (COmbat SImulation Model with Automated Control), developed at our Institute since 1995. They are designed as closed models, which means that a detailed modeling of the highly complicated C3I processes is indispensable. Additionally, the option of an interactive man/machine interface is implemented, which offers the possibility of manual control on different command and control levels for playing against computer generated (and controlled) forces, for experimenting with 'unconventional' decision, and for developing and improving the rule system in a trial-and-error fashion. Furthermore, the paper describes a general architecture for the design of command and control modules, which offers the possibility of describing tactical/operational intentions and concepts of operation in a kind of battle management language (multilayer tactical language concept), the terrain representation, attrition and movement modeling, the development of terrain and situation assessment modules, which are, together with a set of so called planning functions and spatial and procedural templates, a prerequisite for the rule systems that generate adequate tactical missions and orders for the assigned units or simulated objects, and, finally, the main results, conclusions and future developments of the project., Original document contains color images. Pres. at RTO Information Systems Technology Panel (IST), Istanbul, Turkey 9-11 Oct 2000. This article is from ADA391919 New Information Processing Techniques for Military Systems (les Nouvelles techniques de traitement de l'information pour les systemes militaires) p8-1/8-12.

Press kit for the exhibition held at the Metropolitan Museum of Art, New York, Includes biographical information on Hans Hofmann, Exhibition title: Hans Hofmann in the Metropolitan Museum of Art

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Circular courtyard, http://name.umdl.umich.edu/IC-UMMU-X-01-09654%5D01_09654, https://quod.lib.umich.edu/cgi/i/image/api/thumb/ummu/01-09654/01_09654/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. These materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Library Information Technology.; Publisher, https://www.lib.umich.edu/about-us/policies/copyright-policy

Main entrance, http://name.umdl.umich.edu/IC-UMMU-X-01-09652%5D01_09652, https://quod.lib.umich.edu/cgi/i/image/api/thumb/ummu/01-09652/01_09652/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. These materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Library Information Technology.; Publisher, https://www.lib.umich.edu/about-us/policies/copyright-policy

Exhibition catalog, Introduction by Cynthia Goodman, Exhibition title: Hans Hofmann as teacher, drawings by his students

Exhibition catalog, Introduction by Cynthia Goodman, Exhibition title: Hans Hofmann as teacher, drawings by his students