Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.     

Mediators of vascular remodelling co-opted for sequential steps in lung metastasis

Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.     

Facile synthesis of FeFe2O4 magnetic nanomaterial for removing methylene blue from aqueous solution

A facile and simple chemical precipitation method was utilized to synthesize FeFe_2O_4 magnetic nanomaterial for removing methylene blue(MB) from aqueous solution. Characterizations of this material were examined by using XRD, SEM, FT-IR, TGA-DTG and BET methods. Factors affecting the uptake of methylene blue, including p H, adsorption time, and MB initial concentration were also studied. The measured data were fitted by using four isotherm models including Langmuir, Freundlich, Sips and Temkin. Results showed that the Sips model offers the best fit to the data. In addition, the monolayer MB adsorption capacity obtained from the Langmuir model was 42.35 mg g~(-1) under the optimal conditions of p H = 10 and adsorption time = 80 min. In particular, the uptake of MB onto FeFe_2O_4 magnetic nanomaterial obtained from the kinetic and mechanism studies of the adsorption was in good agreement with prediction of the pseudo-first-order model, whereas the electrostatic interaction was found to play a primary mechanism.     

New results on system of generalized quasi-Ky Fan inequalities with set-valued mappings in topological semilattice spaces

Under new assumptions, this paper obtains some extended versions of Ky Fan type inequality for a family of C-continuous set-valued mappings in the setting of topological semilattices. The obtained results are new and different from the corresponding known results in the literature. Some special cases of the main result are also discussed. Some examples are given to illustrate the results.     

Cycling or not cycling: cell cycle regulatory molecules and adult neurogenesis

The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs) residing both in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles continuously generate neurons that populate the dentate gyrus and the olfactory bulb, respectively. The regulation of NPC proliferation in the adult brain has been widely investigated in the past few years. Yet, the intrinsic cell cycle machinery underlying NPC proliferation remains largely unexplored. In this review, we discuss the cell cycle components that are involved in the regulation of NPC proliferation in both neurogenic areas of the adult brain.     

Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ～50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.     

Using human pluripotent stem cells to untangle neurodegenerative disease mechanisms

Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition, we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression of these neurological disorders.     

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease

Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.     

偶联剂对HDPE基竹塑复合材料性能的影响

以高密度聚乙烯(HDPE)、竹粉(BF)为原料,马来酸酐接枝聚丙烯(MAH-g-PP)作为偶联剂,通过混炼、平板热压成型制备竹粉/HDPE复合材料,研究了马来酸酐接枝聚丙烯添加量(0、2%、5%、8%)对竹粉/HDPE复合材料吸湿性、吸水性、弯曲强度、拉伸强度以及抗冲击强度等性能的影响。结果表明:MAH-g-PP能显著改善竹粉/HDPE复合材料的吸湿、吸水性能,明显提高复合材料的力学性能; 当MAH-g-PP添加量为5%时,复合材料的吸湿、吸水率最低,静曲强度与弹性模量分别提高68%和30.4%,拉伸强度与抗冲击强度分别增长53.7%和75%; 而当MAH-g-PP添加量为8%时,复合材料的力学性能在一定程度上有所降低。红外光谱(FTIR)分析显示,添加MAH-g-PP后竹粉的游离羟基与马来酸酐之间发生了酯化反应。