New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets

Colorectal cancer (CRC), despite numerous therapeutic and screening attempts, still remains a major life-threatening malignancy. CRC etiology entails both genetic and environmental factors. Macroautophagy/autophagy and the unfolded protein response (UPR) are fundamental mechanisms involved in the regulation of cellular responses to environmental and genetic stresses. Both pathways are interconnected and regulate cellular responses to apoptotic stimuli. In this review, we address the epidemiology and risk factors of CRC, including genetic mutations leading to the occurrence of the disease. Next, we discuss mutations of genes related to autophagy and the UPR in CRC. Then, we discuss how autophagy and the UPR are involved in the regulation of CRC and how they associate with obesity and inflammatory responses in CRC. Finally, we provide perspectives for the modulation of autophagy and the UPR as new therapeutic options for CRC treatment.     

施硼对番木瓜幼龄株硼形态含量及叶片光合作用的影响

探讨根外喷硼与土壤施硼对植株硼形态含量及叶片光合作用的影响。结果表明,两种供硼方式均可增加植株叶片、叶柄及根的硼形态含量及硼总量,其中以叶片水溶态硼、半束缚态硼及硼总量的增加最为显著。植株硼含量增加提高了叶片净光合速率,但硼过量却抑制了叶片光合能力的提升,而硼中毒导致光合能力显著下降。     

Mechanistic insights in recov-ER-phagy: micro-ER-phagy to recover from stress

ABSTRACT

Physiological and pathological stresses may cause swelling of the endoplasmic reticulum (ER), a biosynthetic organelle in eukaryotic cells. Upon conclusion of the stress, ER size and content return to physiological levels. The translocon component SEC62 decorates the portions of excess ER that must be cleared from cells. Our recent paper highlights the role of endosomal sorting complex required for transport (ESCRT)-III-driven micro-ER-phagy in ER remodeling during cell recovery from ER stress.     

FAM46C controls antibody production by the polyadenylation of immunoglobulin mRNAs and inhibits cell migration in multiple myeloma

FAM46C, frequently mutated in multiple myeloma (MM), has recently been shown to encode a non-canonical poly(A) polymerase (ncPAP). However, its target mRNAs and its role in MM pathogenesis remain mostly unknown. Using CRISPR-Cas9 technology and gene expression analysis, we found that the inactivation of FAM46C in MM down-regulates immunoglobulins (Igs) and several mRNAs encoding ER-resident proteins, including some involved in unfolded protein response and others that affect glycosylation. Interestingly, we show that FAM46C expression is induced during plasma cell (PC) differentiation and that Ig mRNAs encoding heavy and light chains are substrates of the ncPAP, as revealed by poly(A) tail-length determination assays. The absence of the ncPAP results in Ig mRNA poly(A) tail-shortening, leading to a reduction in mRNA and protein abundance. On the other hand, loss of FAM46C up-regulates metastasis-associated lncRNA MALAT1 and results in a sharp increase in the migration ability. This phenotype depends mainly on the activation of PI3K/Rac1 signalling, which might have significant therapeutic implications. In conclusion, our results identify Ig mRNAs as targets of FAM46C, reveal an important function of this protein during PC maturation to increase antibody production and suggest that its role as a tumour suppressor might be related to the inhibition of myeloma cell migration.     

两种氮素形态对药用植物三叶青中黄酮类活性成分积累的影响及相关分子机制的初步探讨

以珍稀濒危药用植物三叶青（Tetrastigma hemsleyanum Diels et Gilg）为材料,通过遮荫条件下（30%自然光）的盆栽试验,研究了硝态氮（NO₃^--N）和铵态氮（NH₄⁺-N）两种不同氮素形态对其根和叶中黄酮类活性成分含量的影响并探讨其机制。结果表明：NO₃^--N处理后的三叶青叶中原花青素B1、芦丁、山柰酚-3-O-芸香糖苷、槲皮素、异槲皮苷、山柰酚的含量比NH₄⁺-N处理的高;其根中的原花青素B1、芦丁、山柰酚-3-O-芸香糖苷、槲皮素、异槲皮苷、山柰酚的含量比NH₄⁺-N处理的高。进一步的研究发现NO₃^--N处理过的三叶青其根、叶中与黄酮类化合物合成相关的酶苯丙氨酸解氨酶（PAL）、查尔酮合成酶（CHS）转录与表达水平高于NH₄⁺-N处理的三叶青。此外,NO₃^--N处理的三叶青叶、根中的PAL和CHS酶活性也高于NH₄⁺-N处理。利用PAL特异性抑制剂AOA处理后,AOA能显著抑制PAL酶活性（P<0.05）并导致黄酮类成分含量极显著下降（P<0.01）。综上所述,施用NO₃^--N更有益于三叶青黄酮类化合物的生物合成,其主要是通过增加PAL代谢途径关键酶的基因表达量进而提高其酶活性来增强黄酮类化合物的合成。     

Technoscientific Infrastructures and Emergent Forms of Life: A Commentary

New forms of life, ethical plateaus, and civic political contests arise through the creation of new technoscientific infrastructures in which market, law, code, and norms compete for hegemonic control over the rules of play. A review of a panel of four articles interrogates agendas for ethnographies of the locally diverse peopling of such new infrastructures, including the continuing renegotiation of historical and emergent modalities of ethical and political reason.