Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control

Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ−1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ−1 in the adult ACC circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC neurons rescues or phenocopies the behaviors of the α2δ−1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.This work was supported by grants from the National Institutes of Health (NS096352 and AG059409 to CE, MH112883 and DA040701 to H.H.Y., MH117429 to I.H.K.). F.P.U.S. was supported by postdoctoral fellowships from the Regeneration Next Initiative and the Ramon y Cajal Young Investigator Award (RYC2021-033202-I). Illustrations were created with BioRender.com. We thank Donna Porter for helping with mouse colony maintenance; Drs. William Wetsel, Staci D. Bilbo, Dolores Irala, Dhanesh Sivadasan Bindu, Alessandro De Simone, and Sehwon Koh for their critical feedback on the manuscript. C.E. is an HHMI Investigator

An analysis of the FIR/RADIO Continuum Correlation in the Small Magellanic Cloud

The local correlation between far-infrared (FIR) emission and radio-continuum (RC) emission for the Small Magellanic Cloud (SMC) is investigated over scales from 3 kpc to 0.01 kpc. Here, we report good FIR/RC correlation down to ~15 pc. The reciprocal slope of the FIR/RC emission correlation (RC/FIR) in the SMC is shown to be greatest in the most active star forming regions with a power law slope of ~1.14 indicating that the RC emission increases faster than the FIR emission. The slope of the other regions and the SMC are much flatter and in the range of 0.63-0.85. The slopes tend to follow the thermal fractions of the regions which range from 0.5 to 0.95. The thermal fraction of the RC emission alone can provide the expected FIR/RC correlation. The results are consistent with a common source for ultraviolet (UV) photons heating dust and Cosmic Ray electrons (CRe-s) diffusing away from the star forming regions. Since the CRe-s appear to escape the SMC so readily, the results here may not provide support for coupling between the local gas density and the magnetic field intensity.Comment: 19 pages, 7 Figure

Pit 9 project: A private sector initiative

This report discusses the Pit 9 Comprehensive Demonstration which is intended to demonstrate a cost-effective approach to remediate an Idaho National Engineering Laboratory (INEL) waste disposal pit through a Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Interim Action. The remediation will include additional requirements, if needed, to provide high confidence that only minor additional work would be necessary to accomplish the final closure as part of the overall final closure strategy for the INEL's Subsurface Disposal Area (SDA)

Amenability of groups and GG-sets

This text surveys classical and recent results in the field of amenability of groups, from a combinatorial standpoint. It has served as the support of courses at the University of G\"ottingen and the \'Ecole Normale Sup\'erieure. The goals of the text are (1) to be as self-contained as possible, so as to serve as a good introduction for newcomers to the field; (2) to stress the use of combinatorial tools, in collaboration with functional analysis, probability etc., with discrete groups in focus; (3) to consider from the beginning the more general notion of amenable actions; (4) to describe recent classes of examples, and in particular groups acting on Cantor sets and topological full groups

Superhard Phases of Simple Substances and Binary Compounds of the B-C-N-O System: from Diamond to the Latest Results (a Review)

The basic known and hypothetic one- and two-element phases of the B-C-N-O system (both superhard phases having diamond and boron structures and precursors to synthesize them) are described. The attention has been given to the structure, basic mechanical properties, and methods to identify and characterize the materials. For some phases that have been recently described in the literature the synthesis conditions at high pressures and temperatures are indicated.Comment: Review on superhard B-C-N-O phase

The dust properties and physical conditions of the interstellar medium in the LMC massive star-forming complex N11

Interstellar matter and star formatio

High-time Resolution Astrophysics and Pulsars

The discovery of pulsars in 1968 heralded an era where the temporal characteristics of detectors had to be reassessed. Up to this point detector integration times would normally be measured in minutes rather seconds and definitely not on sub-second time scales. At the start of the 21st century pulsar observations are still pushing the limits of detector telescope capabilities. Flux variations on times scales less than 1 nsec have been observed during giant radio pulses. Pulsar studies over the next 10 to 20 years will require instruments with time resolutions down to microseconds and below, high-quantum quantum efficiency, reasonable energy resolution and sensitive to circular and linear polarisation of stochastic signals. This chapter is review of temporally resolved optical observations of pulsars. It concludes with estimates of the observability of pulsars with both existing telescopes and into the ELT era.Comment: Review; 21 pages, 5 figures, 86 references. Book chapter to appear in: D.Phelan, O.Ryan & A.Shearer, eds.: High Time Resolution Astrophysics (Astrophysics and Space Science Library, Springer, 2007). The original publication will be available at http://www.springerlink.co

Erratum: Dust and Gas in the Magellanic Clouds from the HERITAGE Herschel Key Project. I. Dust Properties and Insights into the Origin of the Submm Excess Emission (2014, ApJ, 797, 85)

Interstellar matter and star formatio

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

The Natural Products Atlas : an open access knowledge base for microbial natural products discovery

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries