Recent studies have shown that meningeal lymphatic vessels (MLVs), which are located both dorsally and basally beneath the skull, provide a route for draining macromolecules and trafficking immune cells from the central nervous system (CNS) into cervical lymph nodes (CLNs), and thus represent a potential therapeutic target for treating neurodegenerative and neuroinflammatory diseases. However, the roles of MLVs in brain tumor drainage and immunity remain unexplored. Here we show that dorsal MLVs undergo extensive remodeling in mice with intracranial gliomas or metastatic melanomas. RNA-seq analysis of MLV endothelial cells revealed changes in the gene sets involved in lymphatic remodeling, fluid drainage, as well as inflammatory and immunological responses. Disruption of dorsal MLVs alone impaired intratumor fluid drainage and the dissemination of brain tumor cells to deep CLNs (dCLNs). Notably, the dendritic cell (DC) trafficking from intracranial tumor tissues to dCLNs decreased in mice with defective dorsal MLVs, and increased in mice with enhanced dorsal meningeal lymphangiogenesis. Strikingly, disruption of dorsal MLVs alone, without affecting basal MLVs or nasal LVs, significantly reduced the efficacy of combined anti-PD-1/CTLA-4 checkpoint therapy in striatal tumor models. Furthermore, mice bearing tumors overexpressing VEGF-C displayed a better response to anti-PD-1/CTLA-4 combination therapy, and this was abolished by CCL21/CCR7 blockade, suggesting that VEGF-C potentiates checkpoint therapy via the CCL21/CCR7 pathway. Together, the results of our study not only demonstrate the functional aspects of MLVs as classic lymphatic vasculature, but also highlight that they are essential in generating an efficient immune response against brain tumors.

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ABSTRACT. The reproductive behavior of two captive harem breeding groups of golden monkeys was observed over one mating season and compared to non-seasonal reproductive behavior. Observation of over two thousand sexual interactions suggests that 1) females were responsible for 95% of all sexual solicitations (proceptive behavior), of which the typical pattern was prostration, while males were responsible for only 5070; 2) 17% of female solicitations were interrupted by another female; 3) 52% of female solicitations resulted in mounting by males; 4) the frequencies of solicitations and receipt of mounts and ejaculations varied greatly among females; 5) the frequency of ejaculations, the ratio of ejaculations to mountings, and ejaculation patterns were different between two males, and 6) the golden monkey is a seasonal breeding animal.

A topological dynamical system induces two natural systems, one is on the hyperspace and the other one is on the space of probability measures. The connection among some dynamical properties on the original space and on the induced spaces are investigated. Particularly, a minimal weakly mixing system which induces a P-system on the probability measures space is constructed and some disjointness result is obtained.