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LY-CoV1404 is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526 and binds to these variants in the presence of their underlying RBD mutations (which include K417N, L452R, E484K, and N501Y). LY-CoV1404 also neutralizes authentic SARS-CoV-2 in two different assays against multiple isolates. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, with the exception of N439 and N501; notably the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of variant binding, potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 is one in a panel of well-characterized, clinically developable antibodies that could be deployed rapidly to address current and emerging variants. New variant-resistant treatments such as LY-CoV1404 are desperately needed, given that some of the existing therapeutic antibodies are less effective or ineffective against certain variants and the impact of variants on vaccine efficacy is still poorly understood.

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As one of the most promising next-generation safe and green energy storage technologies, aqueous Zn-ion batteries have attracted considerable attention in recent years.

Sphingolipid dysregulation is often associated with insulin resistance, while the enzymes controlling sphingolipid metabolism are emerging as therapeutic targets for improving insulin sensitivity. We report herein that sphingosine kinase 2 (SphK2), a key enzyme in sphingolipid catabolism, plays a critical role in the regulation of hepatic insulin signaling and glucose homeostasis both in vitro and in vivo. Hepatocyte-specific Sphk2 knockout mice exhibit pronounced insulin resistance and glucose intolerance. Likewise, SphK2-deficient hepatocytes are resistant to insulin-induced activation of the phosphoinositide 3-kinase (PI3K)-Akt-FoxO1 pathway and elevated hepatic glucose production. Mechanistically, SphK2 deficiency leads to the accumulation of sphingosine that, in turn, suppresses hepatic insulin signaling by inhibiting PI3K activation in hepatocytes. Either reexpressing functional SphK2 or pharmacologically inhibiting sphingosine production restores insulin sensitivity in SphK2-deficient hepatocytes. In conclusion, the current study provides both experimental findings and mechanistic data showing that SphK2 and sphingosine in the liver are critical regulators of insulin sensitivity and glucose homeostasis.

The Beiya skarn gold deposit is located in the eastern Tethyan orogenic belt in western Yunnan province, China. It is one of the largest gold deposits in China, with significant amounts of silver and base metals. To the end of 2014, the estimated resources are 125 million tonnes (Mt) of ore, grading 2.42 g/t Au, 0.48 wt % Cu, 25.5 wt % Fe, 38.85 g/t Ag, 1.24 wt % Pb, and 0.53 wt % Zn. Skarn alteration and mineralization are related to shoshonitic quartz monzonite porphyries that were emplaced in Triassic carbonates (Beiya Formation). Re-Os dating on molybdenite from a skarn orebody indicates an ore-forming age of 36.82 ± 0.48 Ma, which is consistent with previous dating results of the quartz monzonite porphyries. At least two paragenetic stages of skarn minerals and associated sulfides were recognized, with the early stage typified by garnet ± pyroxene, magnetite, and calcite, and the late stage characterized by epidote, amphibole, chlorite, quartz, and calcite, containing up to 70% sulfides (pyrite, chalcopyrite, and minor pyrrhotite). The early skarn is dominated by anhydrous minerals, which were replaced by hydrous minerals formed during the late stage. The garnet in the Beiya deposit is andradite rich (Ad36-97Gr3-61), and pyroxene is relatively diopside rich (Di8-91Hd7-89). This mineral assemblage indicates an oxidized skarn system, similar to other Au-Cu, Fe-bearing skarn deposits around the world. Fluid inclusions from pyroxene indicate precipitation from high-temperature and high-to moderate-salinity fluids (420°-530°C, 11.1-43.3 wt % NaCl equiv), which probably results from boiling of a moderately saline magmatic fluid. Cooler (180°-365°C) and moderate-to low-salinity fluids (1.6-16.5 wt % NaCl equiv) were trapped in garnet and quartz and are interpreted to be responsible for gold deposition. Chlorite chemistry indicates ore-forming temperatures between 300° and 340°C, in agreement with fluid inclusion data. It appears that gold was transported as chloride complexes under oxidized conditions and was deposited at temperatures of about 300°C, when transport of chloride complexes as gold carriers was less efficient.

The complete nucleotide sequence and genetic map of pVT745 are presented. The 25-kb plasmid was isolated from Actinobacillus actinomycetemcomitans, a periodontal pathogen. Two-thirds of the plasmid encode functions related to conjugation, replication, and replicon stability. Among potential gene products with a high degree of similarity to known proteins are those associated with plasmid conjugation. It was shown that pVT745 derivatives not only mobilized a coresident nontransmissible plasmid, pMMB67, but also mediated their own conjugative transfer to different A. actinomycetemcomitans strains. However, transfer of pVT745 derivatives from A. actinomycetemcomitans to Escherichia coli JM109 by conjugation was successful only when an E. coli origin of replication was present on the pVT745 construct. Surprisingly, 16 open reading frames encode products of unknown function. The plasmid contains a conserved replication region which belongs to the HAP (Haemophilus-Actinobacillus-Pasteurella) theta replicon family. However, its host range appears to be rather narrow compared to other members of this family. Sequences homologous to pVT745 have previously been detected in the chromosomes of numerous A. actinomycetemcomitans strains. The nature and origin of these homologs are discussed based on information derived from the nucleotide sequence.The gram-negative bacterium Actinobacillus actinomycetemcomitans is a capnophilic coccobacillus. The organism has been associated with several forms of periodontal disease such as localized juvenile periodontitis and rapidly progressive periodontitis, as well as with soft tissue abscesses and endocarditis (58). In a previous study 39 isolates of this periodontal pathogen had been screened for the presence of indigenous plasmids in an effort to evaluate the role(s) of such genetic elements in oral bacteria (32). Three plasmids, pVT736-1 (2 kb), pVT736-2 (Ͼ30 kb), and pVT745 (25 kb), were identified in two strains, suggesting that the occurrence of plasmids in A. actinomycetemcomitans was rare. The ultimate goal was to determine the biological properties of these plasmids, to assess their potential contribution to the pathogenicity of A. actinomycetemcomitans, and to evaluate their usefulness as tools in recombinant DNA technology. Previous work has focused mainly on the characterization of pVT736-1, one of the first rolling circle replicating (RCR) plasmids isolated from gram-negative bacteria (17, 18). It was shown that pVT736-1 was cryptic, that it was not related to RCR plasmids found in gram-positive bacteria, and that it encoded a new type of partitioning system (20).Preliminary characterization suggested that there was no obvious phenotype associated with pVT745 (41). Its size was a strong indication that the plasmid replicated by a theta mechanism rather than by a rolling circle mode. Although pVT745 had been isolated from one strain of A. actinomycetemcomitans (VT745) only, it was demonstrated by Southern hybridization that this plasmid shared sequence homologies with chromos...

The upper part of the stratotype section of the Changcheng System in the Yanshan Range 100 km east of Beijing (Peking) has yielded small megascopic carbonaceous compressions assignable to Tyrasotaenia Gnilovskaya and Chuaria Walcott. These fossils are between 1700 and 1900 Ma old and may represent the oldest megascopic organisms now known.