Convergence Circuit Mapping: Genetic Approaches From Structure to Function

Understanding the complex neural circuits that underpin brain function and behavior has been a long-standing goal of neuroscience. Yet this is no small feat considering the interconnectedness of neurons and other cell types, both within and across brain regions. In this review, we describe recent advances in mouse molecular genetic engineering that can be used to integrate information on brain activity and structure at regional, cellular, and subcellular levels. The convergence of structural inputs can be mapped throughout the brain in a cell type-specific manner by antero- and retrograde viral systems expressing various fluorescent proteins and genetic switches. Furthermore, neural activity can be manipulated using opto- and chemo-genetic tools to interrogate the functional significance of this input convergence. Monitoring neuronal activity is obtained with precise spatiotemporal resolution using genetically encoded sensors for calcium changes and specific neurotransmitters. Combining these genetically engineered mapping tools is a compelling approach for unraveling the structural and functional brain architecture of complex behaviors and malfunctioned states of neurological disorders

Evidence for charge delocalization crossover in the quantum critical superconductor CeRhIn5_5

The nature of charge degrees-of-freedom distinguishes scenarios for interpreting the character of a second order magnetic transition at zero temperature, that is, a magnetic quantum critical point (QCP). Heavy-fermion systems are prototypes of this paradigm, and in those, the relevant question is where, relative to a magnetic QCP, does the Kondo effect delocalize their $f$-electron degrees-of-freedom. Herein, we use pressure-dependent Hall measurements to identify a finite-temperature scale $E_\text{loc}$ that signals a crossover from $f$-localized to $f$-delocalized character. As a function of pressure, $E_\text{loc}(P)$ extrapolates smoothly to zero temperature at the antiferromagnetic QCP of CeRhIn$_5$ where its Fermi surface reconstructs, hallmarks of Kondo-breakdown criticality that generates critical magnetic and charge fluctuations. In 4.4% Sn-doped CeRhIn$_5$, however, $E_\text{loc}(P)$ extrapolates into its magnetically ordered phase and is decoupled from the pressure-induced magnetic QCP, which implies a spin-density-wave (SDW) type of criticality that produces only critical fluctuations of the SDW order parameter. Our results demonstrate the importance of experimentally determining $E_\text{loc}$ to characterize quantum criticality and the associated consequences for understanding the pairing mechanism of superconductivity that reaches a maximum $T_\text{c}$ in both materials at their respective magnetic QCP.Comment: 19 pages, 5 figures, published in Nature Communication

Endogenous metabolic markers for predicting the activity of dihydropyrimidine dehydrogenase

Five-fluorouracil (5-FU) is a chemotherapeutic agent that is mainly metabolized by the rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a DPYD single nucleotide polymorphism on 5-FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of DPYD in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into two groups based on DHU/U ratio. The calculated DHU/U ratios ranged from 0.52 to 7.12, and the two groups were classified into the 10th percentile and 90th percentile for untargeted metabolomics analysis using liquid chromatography-quantitative time-of-flight-mass spectrometry. A total of 4440 compounds were detected and filtered out based on a coefficient of variation below 30%. Our results revealed that six metabolites differed significantly between the high activity group and low activity group (false discovery rate q-value \u3c 0.05). Uridine was significantly higher in the low DPD activity group and is a precursor of U involved in pyrimidine metabolism; therefore, we speculated that DPD deficiency can influence uridine levels in plasma. Furthermore, the cutoff values for detecting DPD deficient patients from previous studies were unsuitable for Koreans. Our metabolomics approach is the first study that reported the DHU/U ratio distribution in healthy Korean subjects and identified a new biomarker of DPD deficiency

Spectroscopic Evidence for Multigap Superconductivity of Y at Megabar Pressures

The recent discovery of room-temperature superconductivity (RTSC) at pressures of several megabars has led to intensive efforts to probe the origin of superconducting (SC) electron pairs. Although the signatures of the SC phase transition have been well established, few reports of the SC properties of RTSCs have been published because of the diamond anvil cell (DAC) environments. Here, we report the first direct evidence of two SC gaps in Y metal via point-contact spectroscopy (PCS) in DAC environments, where a sharp peak at the zero-bias voltage in the differential conductance is overlaid with a broad peak owing to Andreev reflection. Analysis based on the Blonder-Tinkham-Klapwijk (BTK) model reveals the existence of two SC gaps: the larger gap is 3.63 meV and the smaller gap is 0.46 meV. The temperature dependence of the two SC gaps is well explained by the BCS theory, indicating that two-band superconductivity is realized in Y metal. The successful application of PCS to Y in DAC environments is expected to guide future research on the SC gap in megabar high-Tc superconductors.Comment: 17 pages, 4 figure

Spatial Heterogeneity in Grazing Pasture from Small Unmanned Aerial Vihicle (sUAV) with Structure from Motion (SfM) Photogrammetry

Oral Session

WATCHFUL OBSERVATION VERSUS EARLY AORTIC VALVE REPLACEMENT FOR SYMPTOMATIC PATIENTS WITH LOW-GRADIENT SEVERE AORTIC STENOSIS AND PRESERVED EJECTION FRACTION

Brief Communications Arising: arising from X. Dong, B. Milholland & J. Vijg Nature 538, 257–259 (2016); doi:10.1038/nature19793. Comments by: Beer, J.A.A. de, Bardoutsos, A. & Janssen, F. (2017)

GARNET – gene set analysis with exploration of annotation relations

<p>Abstract</p> <p>Background</p> <p>Gene set analysis is a powerful method of deducing biological meaning for an a priori defined set of genes. Numerous tools have been developed to test statistical enrichment or depletion in specific pathways or gene ontology (GO) terms. Major difficulties towards biological interpretation are integrating diverse types of annotation categories and exploring the relationships between annotation terms of similar information.</p> <p>Results</p> <p>GARNET (Gene Annotation Relationship NEtwork Tools) is an integrative platform for gene set analysis with many novel features. It includes tools for retrieval of genes from annotation database, statistical analysis & visualization of annotation relationships, and managing gene sets. In an effort to allow access to a full spectrum of amassed biological knowledge, we have integrated a variety of annotation data that include the GO, domain, disease, drug, chromosomal location, and custom-defined annotations. Diverse types of molecular networks (pathways, transcription and microRNA regulations, protein-protein interaction) are also included. The pair-wise relationship between annotation gene sets was calculated using kappa statistics. GARNET consists of three modules - <it>gene set manager</it>, <it>gene set analysis</it> and <it>gene set retrieval</it>, which are tightly integrated to provide virtually automatic analysis for gene sets. A dedicated viewer for annotation network has been developed to facilitate exploration of the related annotations.</p> <p>Conclusions</p> <p>GARNET (gene annotation relationship network tools) is an integrative platform for diverse types of gene set analysis, where complex relationships among gene annotations can be easily explored with an intuitive network visualization tool (<url>http://garnet.isysbio.org/</url> or <url>http://ercsb.ewha.ac.kr/garnet/</url>).</p

Vaccine effectiveness and the epidemiological characteristics of a COVID-19 outbreak in a tertiary hospital in Republic of Korea

Objectives Healthcare facilities are high-risk sites for infection. This study analyzed the epidemiological characteristics of a coronavirus disease 2019 (COVID-19) outbreak in a tertiary hospital after COVID-19 vaccination had been introduced in Republic of Korea. Vaccine effectiveness (VE) and shared anti-infection strategies are also assessed. Methods The risk levels for 4,074 contacts were evaluated. The epidemiological characteristics of confirmed cases were evaluated using the chi-square test. The “1 minus relative risk” method was used to determine VE in preventing infection, progression to severe disease, and death. In the largest affected area (the 8th floor), a separate relative risk analysis was conducted. A multivariate logistic regression analysis (with 95% confidence interval [CIs]) was used to identify transmission risk factors with a significance level <10% via the backward elimination method. Results In total, 181 cases of COVID-19 were confirmed, with an attack rate of 4.4%. Of those cases, 12.7% progressed to severe disease, and 8.3% died. In the cohort isolation area on the 8th floor, where 79.0% of the confirmed cases occurred, the adjusted odds ratio was 6.55 (95% CI, 2.99–14.33) and 2.19 (95% CI, 1.24–3.88) for caregivers and the unvaccinated group, respectively. VE analysis revealed that 85.8% of the cases that progressed to severe disease and 78.6% of the deaths could be prevented by administering a second vaccine. Conclusion Caregiver training for infection prevention and control is necessary to reduce infection risk. Vaccination is an important intervention to reduce the risk of progression to severe disease and death