Glutamine deficiency promotes stemness and chemoresistance in tumor cells through DRP1-induced mitochondrial fragmentation

Cellular and Molecular Life Sciences - Glutamine is essential for maintaining the TCA cycle in cancer cells yet they undergo glutamine starvation in the core of tumors. Cancer stem cells (CSCs),...     

超滤法分级和纯化蛋白质的现状和前景(英文)

超滤法具有高产率、低成本、容易放大等显著优点,但其低选择性一直限制其在生物蛋白制品的分级和纯化中的应用。本文总结和分析了超滤法用于蛋白质分级和纯化的近期研究成果,对其低选择性的原因进行了分析,提出并论证了提高超滤选择性的技术途径。     

PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization

Polarity is a fundamental feature of cells. Protein complexes, including the PAR3–PAR6–aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3–PAR6–aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector molecules to establish neuronal polarity. Herein, we discuss the many signaling mechanisms and effector functions that have been linked to PAR3, PAR6, and aPKC during the establishment of neuronal polarity.     

Sequential interactions with Sec23 control the direction of vesicle traffic

How the directionality of vesicle traffic is achieved remains an important unanswered question in cell biology. The Sec23p/Sec24p coat complex sorts the fusion machinery (SNAREs) into vesicles as they bud from the endoplasmic reticulum (ER). Vesicle tethering to the Golgi begins when the tethering factor TRAPPI binds to Sec23p. Where the coat is released and how this event relates to membrane fusion is unknown. Here we use a yeast transport assay to demonstrate that an ER-derived vesicle retains its coat until it reaches the Golgi. A Golgi-associated kinase, Hrr25p (CK1δ orthologue), then phosphorylates the Sec23p/Sec24p complex. Coat phosphorylation and dephosphorylation are needed for vesicle fusion and budding, respectively. Additionally, we show that Sec23p interacts in a sequential manner with different binding partners, including TRAPPI and Hrr25p, to ensure the directionality of ER-Golgi traffic and prevent the back-fusion of a COPII vesicle with the ER. These events are conserved in mammalian cells.     

Metabolic priming by a secreted fungal effector

Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation.     

Design of radiation hard phase-locked loop at 2.5 GHz using SOS-CMOS

Abstract: A radiation hard phase-locked loop (PLL) is designed at 2.5 GHz using silicon on sapphire complementary metal-oxide-semiconductor process. Radiation hardness is achieved through improving circuit design without sacrificing real estate. Stability is guaranteed by a fully self-bias architecture. The lock time of PLL is minimized by maximizing the loop bandwidth. Frequency tuning range of voltage controlled oscillator is significantly enhanced by a novel load configuration. In addition, multiple bias stages, asynchronous frequency divider, and silicon on sapphire process jointly make the proposed PLL more radiation hard. Layout of this PLL is simulated by Cadence Spectre RF under both single event effect and total induced dose effect. Simulation results demonstrate excellent stability, lock time < 600 ns, frequency tuning range [1.57 GHz, 3.46 GHz], and jitter < 12 ps. Through comparison with PLLs in literatures, the PLL is especially superior in terms of lock time and frequency tuning range performances.     

Requirement for subplate neurons in the formation of thalamocortical connections

The neurons of layer 4 in the adult cerebral cortex receive their major ascending inputs from the thalamus. In development, however, thalamic axons arrive at the appropriate cortical area long before their target layer 4 neurons have migrated into the cortical plate. The axons accumulate and wait in the zone below the cortical plate, the subplate, for several weeks before invading the cortical plate. The subplate is a transient zone that contains the first postmitotic neurons of the telencephalon. These neurons mature well before other cortical neurons, and disappear by cell death after the thalamic axons have grown into the overlying cortical plate. The close proximity of growing thalamocortical axons and subplate neurons suggests that they might be involved in interactions important for normal thalamocortical development. Here we show that early in development the deletion of subplate neurons located beneath visual cortex prevents axons from the lateral geniculate nucleus of the thalamus from recognizing and innervating visual cortex, their normal target. In the absence of subplate neurons, lateral geniculate nucleus axons continue to grow in the white matter past visual cortex despite the presence of their target layer 4 neurons. Thus the transient subplate neurons are necessary for appropriate cortical target selection by thalamocortical axons.     

Orientation of Giemsa C-bands in interphase cells of Allium cepa L.

Orientation of Giemsa C-bands in Allium cepa was studied in both mitotic and interphase cells. It has been shown that telophase orientation of the chromosome is maintained throughout the interphase and early phophase. It has been assumed that this non-random orientation is due to anchorage of the telomeres with the nuclear membrane. Contrary to earlier observations, 2 by 2 pairing of the telomers could not be traced to this species.     

Orientation of Giemsa C-bands in interphase cells of Allium cepa L.

Summary Orientation of Giemsa C-bands in Allium cepa was studied in both mitotic and interphase cells. It has been shown that telophase orientation of the chromosome is maintained throughout the interphase and early prophase. It has been assumed that this non-random orientation is due to anchorage of the telomeres with the nuclear membrane. Contrary to earlier observations, 2 by 2 pairing of the telomeres could not be traced in this species.     

Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite

Malaria is estimated to cause 0.7 to 2.7 million deaths per year, but the actual figures could be substantially higher owing to under-reporting and difficulties in diagnosis. If no new control measures are developed, the malaria death toll is projected to double in the next 20 years. Efforts to control the disease are hampered by drug resistance in the Plasmodium parasites, insecticide resistance in mosquitoes, and the lack of an effective vaccine. Because mosquitoes are obligatory vectors for malaria transmission, the spread of malaria could be curtailed by rendering them incapable of transmitting parasites. Many of the tools required for the genetic manipulation of mosquito competence for malaria transmission have been developed. Foreign genes can now be introduced into the germ line of both culicine and anopheline mosquitoes, and these transgenes can be expressed in a tissue-specific manner. Here we report on the use of such tools to generate transgenic mosquitoes that express antiparasitic genes in their midgut epithelium, thus rendering them inefficient vectors for the disease. These findings have significant implications for the development of new strategies for malaria control.