The Drosophila male-specific lethal (MSL) dosage compensation complex increases transcript levels on the single male X chromosome to equal the transcript levels in XX females. However, it is not known how the MSL complex is linked to its DNA recognition elements, the critical first step in dosage compensation. Here, we demonstrate that a previously uncharacterized zinc finger protein, CLAMP (chromatin-linked adaptor for MSL proteins), functions as the first link between the MSL complex and the X chromosome. CLAMP directly binds to the MSL complex DNA recognition elements and is required for the recruitment of the MSL complex. The discovery of CLAMP identifies a key factor required for the chromosome-specific targeting of dosage compensation, providing new insights into how subnuclear domains of coordinate gene regulation are formed within metazoan genomes.

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An eco-friendly visible-light-induced decarboxylative acylation of quinoxalin-2(1H)-ones and α-oxo carboxylic acids with air as the oxidant under external-photocatalyst-free conditions was established.

With the development of electrification, automation, and interconnection of the automobile industry, the demand for vehicular computing has entered an explosive growth era. Massive low time-constrained and computation-intensive vehicular computing operations bring new challenges to vehicles, such as excessive computing power and energy consumption. Computation offloading technology provides a sustainable and low-cost solution to these problems. In this article, we study an adaptive wireless resource allocation strategy of computation offloading service under a three-layered vehicular edge cloud computing framework. We model the computation offloading process at the minimum assignable wireless resource block level, which can better adapt to vehicular computation offloading scenarios and can also rapidly evolve to the 5G network. Subsequently, we propose a method to measure the cost-effectiveness of allocated resources and energy savings, named value density function. Interestingly, with respect to the amount of allocation resource, it can obtain the maximum value density when offloading energy consumption equals to half of local energy consumption. Finally, we propose a low-complexity heuristic resource allocation algorithm based on this novel theoretical discovery. Numerical results corroborate that our designed algorithm can gain above 80% execution time conservation and 62% conservation on energy consumption, and it exhibits fast convergence and superior performance compared to benchmark solutions.

Blockade of immune checkpoint PD-1/PD-L1 has been a promising anticancer strategy; however, clinically available PD-1/PD-L1 small-molecule inhibitors are lacking. In view of the high potency of compound 2 (BMS-1002), structural fine tuning of the methoxy linkage together with diverse modification in the solvent interaction region was conducted. A series of novel derivatives featuring a difluoromethyleneoxy linkage were designed. Compound 43 was identified as the most promising PD-1/PD-L1 inhibitor with an IC50 value of 10.2 nM in the HTRF assay. This compound is capable of promoting CD8+ T cell activation through inhibiting PD-1/PD-L1 cellular signaling. Moreover, in the Hepa1-6 syngeneic mouse model, administration of compound 43 at 1 mg/kg dosage promoted CD8+ T cell activation and delayed the tumor growth with good tolerance. Notably, the tumor in one mouse of the compound 43-treated group was completely regressed. These results indicate that compound 43 is a promising candidate worthy of further investigation.

A general, effective and convenient protocol for the direct synthesis of various 2-aminoquinolines (39 examples) through AgBF4-catalyzed amination of quinoline N-oxides with isothiocyanates under base-, oxidant-free and mild conditions was developed.

No abstract

Background/Aims: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. Methods: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA. Results: The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects. Conclusion: These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.