Search

Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimers disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Pluss utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Since the emergence of the highly pathogenic avian influenza (HPAI) A(H5N1) virus (A/chicken/ Scotland/59) in Scotland, UK, several outbreaks of H5Nx viruses have been reported in poultry worldwide (1). In [...]

Two new species of Clausidiidae, each belonging to the genera Clausidium Kossmann, 1875 and Hippomolgus G. O. Sars, 1917, are described from Korea. Clausidium maximus n. sp. is an associate of a burrowing decapod of the genus Callianassa living on the Korean coast of the Yellow Sea and has, as diagnostic characters, two inner setae on the second endopodal segment of legs 2-4, nine elements on the third exopodal segment of leg 4, an inner seta on the second exopodal segment of male leg 1, and a relatively large body size, exceeding 2.0 mm in the female. Hippomolgus limiticus n. sp. was found in the bottom sediments in the East China Sea. It is similar to H. furcifer G. O. Sars, but distinghuishable from the latter species by having shorter caudal rami, 4-segmented female maxilliped, and inner coxal spine (instead of seta) on legs 2 and 3. This is the first record on the genera Clausidium and Hippomolgus in the West Pacific.

The Chinese sea snake Laticauda semifasciata (Reinwardt in Schlegel, 1837) is newly reported from Korean waters based on three specimens collected from Jeju Island, Korea, in August, September, and November 2015. This is the first time that the genus Laticauda and subfamily Laticaudinae has been reported from Korean waters. The subfamily Laticaudinae has ventrals that are four to five times wider than the adjacent dorsals, which are unlike the ventrals that are similar or up to two times wider than adjacent dorsals in the subfamily Hydrophiinae. Laticauda semifasciata is distinct from other species because it has three prefrontals and its rostrals are horizontally divided into two. As the result of this report, four species (L. semifasciata, Hydrophis (Pelamis) platurus, Hydrophis cyanocinctus, and H. melanocephalus) of sea snakes have been reported in Korean waters.

Hamaticyclops ahni is described as a new genus and species from the Californian shore of the United States. It was discovered as a victim of the sea anemone Anthopleura elegantissima (Brandt). The new genus is closely related to the genus Hemicyclops but possesses, as significant autapomorphies, three strong claws on the second endopodal segment of antenna and a markedly elongate exopod of leg 5 with its protopod fused to somite.

Fifteen species of poecilostome copepods associated with marine invertebrates, including ten new species, are recorded from intertidal zone in Thailand. New species are Hemicyclops cornutus n. sp. and Hemicyclops parapiculus n. sp. in the family Clausidiidae, Presynaptiphilus trifurcatus n. sp. in the Synaptiphilidae, Anchimolgus kantariensis n. sp. and Anchimolgus palmatus n. sp. in the Anchimolgidae, Kelleria vasfera n. sp. in the Kelleridae, Pseudanthessius stenosus n. sp. and Pseudanthessius phuketensis n. sp. in the Pseudanthessiidae, Doricidola pattayensis n. sp., and Lambanetes mollis n. sp. in the Rhynchomolgidae. Five species are new records of Thailand: Critomolgus gemmatus (Humes, 1964), Doridicola cuspis (Humes, 1964), Doridicola inaequalis (Humes and Ho, 1966), Indomolgus brevisetosus (Humes and Ho, 1966), and Lambanetes stichodactylae Humes, 1982. The female of Lambanetes stichodectylae is described for the first time in the world.

Serious climate changes and energy-related environmental problems are currently critical issues in the world. In order to reduce carbon emissions and save our environment, renewable energy harvesting technologies will serve as a key solution in the near future. Among them, triboelectric nanogenerators (TENGs), which is one of the most promising mechanical energy harvesters by means of contact electrification phenomenon, are explosively developing due to abundant wasting mechanical energy sources and a number of superior advantages in a wide availability and selection of materials, relatively simple device configurations, and low-cost processing. Significant experimental and theoretical efforts have been achieved toward understanding fundamental behaviors and a wide range of demonstrations since its report in 2012. As a result, considerable technological advancement has been exhibited and it advances the timeline of achievement in the proposed roadmap. Now, the technology has reached the stage of prototype development with verification of performance beyond the lab scale environment toward its commercialization. In this review, distinguished authors in the world worked together to summarize the state of the art in theory, materials, devices, systems, circuits, and applications in TENG fields. The great research achievements of researchers in this field around the world over the past decade are expected to play a major role in coming to fruition of unexpectedly accelerated technological advances over the next decade.

Although various publicly reserved funds have recently come to the fore of academic and policy-making attention in Korea, researchers rarely take up the issue of the reserve fund retained from annual profits by the central bank (i.e., the Bank of Korea). Starting with the general public choice premise that bureaucrats seek to maximize their discretionary budget, this paper first provides a theoretical reasoning why central bank's bureaucrats would prefer retaining annual profits to turning them to the Treasury. The major tenet to be emphasized is that retained profits as a reserve fund can give the central bankers discretionary power in their disposition. In particular, we focus on the close relationship between the reserve fund and the discount windows. The latter, as a monetary instrument, has traditionally been demonstrated to cause secrecy, arbitrariness, and other bureaucratic amenities in the previous literature. Subsequently, this paper, based on 61 countries data, empirically verifies that the central bank's reserve fund is at least partially used to additionally increase the discount windows. Since an excessive use of discount windows results in inflationary bias, we conclude the paper with some policy suggestions to have such bureaucratic power of discretion in check. This paper, if in its experimental nature yet, is expected to shed a critical implication for establishing the meaningful independence of the central bank to a host of countries.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Mutations in the KRAS oncogene are found in more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), with Gly-to-Asp mutations (KRASG12D) being the most common. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in implantable and autochthonous PDAC models with an intact immune system. In vitro studies validated the specificity and potency of MRTX1133. In vivo, MRTX1133 prompted deep tumor regressions in all models tested, including complete or near-complete remissions after 14 days. Concomitant with tumor cell apoptosis and proliferative arrest, drug treatment led to marked shifts in the tumor microenvironment (TME), including changes in fibroblasts, matrix, and macrophages. T cells were necessary for MRTX1133's full antitumor effect, and T-cell depletion accelerated tumor regrowth after therapy. These results validate the specificity, potency, and efficacy of MRTX1133 in immunocompetent KRASG12D-mutant PDAC models, providing a rationale for clinical testing and a platform for further investigation of combination therapies.SignificancePharmacologic inhibition of KRASG12D in pancreatic cancer models with an intact immune system stimulates specific, potent, and durable tumor regressions. In the absence of overt toxicity, these results suggest that this and similar inhibitors should be tested as potential, high-impact novel therapies for patients with PDAC. See related commentary by Redding and Grabocka, p. 260. This article is highlighted in the In This Issue feature, p. 247.

Objective: Through the literature on the effect of Scolopendra subspinipes mutilans L. Koch, we are finding out the clinical possibility and revealing the more effective to untractable disease. Method: We investigated the literatures of Oriental Medicine and experimental reports about Scolopendra subspinipes mutilans L. Koch. Results: 1.The taste of Scolopendra subspinipes mutilans L. Koch is hot, wann and toxic, and the effect is dispelling wind, spasmolytic action and detoxication so it has been used for C.V.A, facial palsy, numbness of hands and feet, wounds and arthritis. 2. A toxic constituent of Scolopendra subspinipes mutilans L. Koch is mainly located in the 1st limbs, and we can prevent toxic symptoms, if taken a dosage moderately. 3. The pharmacological action of Scolopendra subspinipes mutilans L. Koch is anti-convulsive action, analgesic action, lowering blood pressure, anti-inflammatory action, anti-tumor action and microbe inhibition. On the study of Scolopendra subspinipes mutilans L. Koch, we thought it is effective to intractable disease, and it may be needed variable studies on toxicity and clinical effects.