Anhedonia is associated with reward-processing deficits of the dopamine system, which may increase the risk of depression. Nevertheless, few previous studies have examined the influence of hedonic ...tone on event-related potential (ERP) measures of reward processing in major depressive disorder. A simple gambling task was used to elicit feedback negativity (FN), an ERP component elicited by feedback indicating gain versus loss, in 27 patients with major depression and 27 healthy participants. We found that participants with depression were characterized by reduced FN responses, especially towards monetary gains, but not losses, compared with healthy individuals. In addition, the amplitude of FN to gain feedback in participants with depression was related to anhedonia severity and depressive symptoms. These findings indicate an association between low hedonic capacity and reduction in FN. As a neural measure of reward sensitivity, FN may be generated in part by reward-related activity.
•Depressed patients demonstrated reduced feedback negativity (FN).•The FN amplitude to gain in depressed patients was related to anhedonia severity and depressive symptoms.•Trait anhedonia may exert a direct influence on the neutral activities to feedback processing.
The Dawn Mission to Vesta and Ceres Russell, C. T.; Raymond, C. A.
Space science reviews,
12/2011, Letnik:
163, Številka:
1-4
Journal Article
Recenzirano
The Dawn mission journeys to the center of the main asteroid belt to orbit and explore the two most massive main belt asteroids, Vesta and Ceres. Dawn aims to increase our understanding not just of ...the present state of these two bodies, but also of the conditions during the time of their formation. It attempts this through achieving a set of measurement objectives in which the physical properties of these asteroids such as mass, slopes, size, density, and spin state are accurately determined, and in which the mineralogical and elemental composition of the surface and near-surface material are probed. Dawn employs ion propulsion technology to enable a modestly-sized launcher to start a moderately-sized spacecraft on its journey, to not only reach the two massive asteroids but also to orbit them, descending to near the surface. Unlike most orbital missions, the initial (Vesta) phase must be completed with sufficient reserves and within a time window that later allows Dawn to explore Ceres. Dawn carries a redundant framing camera, a visible and near-IR spectrometer, a gamma ray and neutron spectrometer, and achieves high-accuracy radiometric and optical navigation to enable gravity field determination. The spacecraft was developed by Orbital Sciences Corporation under the management of the Jet Propulsion Laboratory for the National Aeronautics and Space Administration. Dawn is a Principal Investigator-led mission of the Discovery Program. The PI institution, the University of California, Los Angeles, manages directly the science team, the Dawn Science Center, and the Education and Public Outreach program.
G protein-coupled receptors (GPCRs), which are modulated by a variety of endogenous and synthetic ligands, represent the largest family of druggable targets in the human genome. Recent structural and ...molecular studies have both transformed and expanded classical concepts of receptor pharmacology and have begun to illuminate the distinct mechanisms by which structurally, chemically, and functionally diverse ligands modulate GPCR function. These molecular insights into ligand engagement and action have enabled new computational methods and accelerated the discovery of novel ligands and tool compounds, especially for understudied and orphan GPCRs. These advances promise to streamline the development of GPCR-targeted medications.
Structural and computational approaches studying GPCR-ligand interactions are shaping fundamental principles in receptor signaling and uncovering new physiological functions for this protein family.
This paper presents projections of global methane emissions from coal mining under different coal extraction scenarios and with increasing mining depth through 2100. The paper proposes an updated ...methodology for calculating fugitive emissions from coal mining, which accounts for coal extraction method, coal rank, and mining depth and uses evidence-based emissions factors. A detailed assessment shows that coal mining-related methane emissions in 2010 were higher than previous studies show. This study also uses a novel methodology for calculating methane emissions from abandoned coal mines and represents the first estimate of future global methane emissions from those mines. The results show that emissions from the growing population of abandoned mines increase faster than those from active ones. Using coal production data from six integrated assessment models, this study shows that by 2100 methane emissions from active underground mines increase by a factor of 4, while emissions from abandoned mines increase by a factor of 8. Abandoned mine methane emissions continue through the century even with aggressive mitigation actions.
Global CMM and AMM emissions from coal mining, 2010–2100, bcm. Display omitted
•This study presents estimates of global coal mine methane emissions through 2100.•Methane emissions related to coal extraction are higher than reported from previous estimates.•Coal mines continue emitting methane even if coal production is ceased.•Evidence-based emission factors are applied to account for increasing mining depth.•A new methodology for calculating emissions from abandoned mines is proposed.
The retina is a widely profiled tissue in multiple species by single-cell RNA sequencing studies. However, integrative research of the retina across species is lacking. Here, we construct the first ...single-cell atlas of the human and porcine ocular compartments and study inter-species differences in the retina. In addition to that, we identify putative adult stem cells present in the iris tissue. We also create a disease map of genes involved in eye disorders across compartments of the eye. Furthermore, we probe the regulons of different cell populations, which include transcription factors and receptor-ligand interactions and reveal unique directional signalling between ocular cell types. In addition, we study conservation of regulons across vertebrates and zebrafish to identify common core factors. Here, we show perturbation of KLF7 gene expression during retinal ganglion cells differentiation and conclude that it plays a significant role in the maturation of retinal ganglion cells.
Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response ...inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of
N
= 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers.
Bone is an active organ that continuously undergoes an orchestrated process of remodeling throughout life. Bone tissue is uniquely capable of adapting to loading, hormonal, and other changes ...happening in the body, as well as repairing bone that becomes damaged to maintain tissue integrity. On the other hand, diseases such as osteoporosis and metastatic cancers disrupt normal bone homeostasis leading to compromised function. Historically, the ability to investigate processes related to either physiologic or diseased bone tissue is limited by traditional models that fail to emulate the complexity of native bone. Organ‐on‐a‐chip models are based on technological advances in tissue engineering and microfluidics, enabling the reproduction of key features specific to tissue microenvironments within a microfabricated device. Compared to conventional in vitro and in vivo bone models, microfluidic models, and especially organ‐on‐a‐chip platforms, provide more biomimetic tissue culture conditions, with increased predictive power for clinical assays. In this review, microfluidic and organ‐on‐a‐chip technologies designed for understanding the biology of bone as well as bone‐related diseases and treatments are reported. Finally, the authors discuss the limitations of the current models and point toward future directions for microfluidics and organ‐on‐a‐chip technologies in bone research.
Compared to conventional in vitro and in vivo bone models, microfluidic models and especially organs‐on‐a‐chip platforms, provide more biomimetic tissue culture conditions, with increased predictive power for clinical assays. In this progress report, microfluidic and organ‐on‐a‐chip technologies designed for understanding the biology of bone as well as bone‐related diseases and treatments are covered.
New metal/polymer composite filaments for fused deposition modeling (FDM) processes were developed in order to observe the thermo-mechanical properties of the new filaments. The acrylonitrile ...butadiene styrene (ABS) thermoplastic was mixed with copper and iron particles. The percent loading of the metal powder was varied to confirm the effects of metal particles on the thermo-mechanical properties of the filament, such as tensile strength and thermal conductivity. The printing parameters such as temperature and fill density were also varied to see the effects of the parameters on the tensile strength of the final product which was made with the FDM process. As a result of this study, it was confirmed that the tensile strength of the composites is decreased by increasing the loading of metal particles. Additionally, the thermal conductivity of the metal/polymer composite filament was improved by increasing the metal content. It is believed that the metal/polymer filament could be used to print metal and large-scale 3-dimensional (3D) structures without any distortion by the thermal expansion of thermoplastics. The material could also be used in 3D printed circuits and electromagnetic structures for shielding and other applications.
JMJD2 lysine demethylases (KDMs) participate in diverse genomic processes. Most JMJD2 homologs display dual selectivity toward H3K9me3 and H3K36me3, with the exception of JMJD2D, which is specific ...for H3K9me3. Here, we report the crystal structures of the JMJD2D⋅2-oxoglutarate⋅H3K9me3 ternary complex and JMJD2D apoenzyme. Utilizing structural alignments with JMJD2A, molecular docking, and kinetic analysis with an array of histone peptide substrates, we elucidate the specific signatures that permit efficient recognition of H3K9me3 by JMJD2A and JMJD2D, and the residues in JMJD2D that occlude H3K36me3 demethylation. Surprisingly, these results reveal that JMJD2A and JMJD2D exhibit subtle yet important differences in H3K9me3 recognition, despite the overall similarity in the substrate-binding conformation. Further, we show that H3T11 phosphorylation abrogates demethylation by JMJD2 KDMs. Together, these studies reveal the molecular basis for JMJD2 site specificity and provide a framework for structure-based design of selective inhibitors of JMJD2 KDMs implicated in disease.
▸ JMJD2A and JMJD2D exhibit unexpected differences in H3K9me3 recognition ▸ Phosphorylation of T11 abolishes H3K9me3 demethylation by JMJD2 enzymes ▸ Steric clashes and loss of hydrogen bonds occlude H3K36me3 recognition by JMJD2D ▸ Differences in substrate recognition can be exploited in JMJD2 inhibitor design
Most members of the JMJD2 family demethylate H3K9me3 and H3K36me3. Structural and biochemical analysis by Krishnan and Trievel reveals the mechanism of H3K9me3 recognition and mode of H3K36me3 discrimination by JMJD2 homologs, providing insight into JMJD2 selectivity and a framework for designing JMJD2 inhibitors.
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