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One of the defining characteristics of plant growth and morphology is the pivotal role of cell expansion. While the mechanical properties of the cell wall determine both the extent and direction of cell expansion, the cortical microtu-... more
One of the defining characteristics of plant growth and morphology is the pivotal role of cell expansion. While the mechanical properties of the cell wall determine both the extent and direction of cell expansion, the cortical microtu- bule array plays a critical role in cell wall organization and, consequently, determining directional (anisotropic) cell expansion [1–6]. The microtubule-severing enzyme katanin is essential for plants to form aligned microtubule arrays [7–10]; however, increasing severing activity alone is not sufficient to drive microtubule alignment [11]. Here, we demonstrate that katanin activity depends upon the behavior of the microtubule-associated protein (MAP) SPIRAL2 (SPR2). Petiole cells in the cotyledon epidermis exhibit well-aligned microtubule arrays, whereas adjacent pavement cells exhibit unaligned arrays, even though SPR2 is found at similar levels in both cell types. In pave- ment cells, however, SPR2 accumulates at microtubule crossover sites, where it stabilizes these crossovers and prevents severing. In contrast, in the adjacent petiole cells, SPR2 is constantly moving along the microtubules, exposing crossover sites that become substrates for severing. Consequently, our study reveals a novel mecha- nism whereby microtubule organization is determined by dynamics and localization of a MAP that regulates where and when microtubule severing occurs.
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Using the film "Expelled: No Intelligence Allowed' (2008) http://www.imdb.com/title/tt1091617/ to teach precepts of Judaism and Jewish Thought.
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The text for this essay is found in the second book of the Holy Bible, Exodus 7:20-21, "And all the waters that were in the river were turned ·into blood, and the fish that were in the river died; and the river stank. And all the... more
The text for this essay is found in the second book of the Holy Bible, Exodus 7:20-21, "And all the waters that were in the river were turned ·into blood, and the fish that were in the river died; and the river stank. And all the Egyptians digged round about the river for water to drink; for they could not drink of the water of the river."
It seems appropriate to begin a dissertation on the Red Tide with what I take to be the earliest recorded reference and, being in the Bible, unquestionably authentic.
Why should I be interested in the Red Tide? The reasons are three in number and I shall enumerate.
Unraveling the biochemical and genetic alterations that control the aggregation of protein tau is crucial to understand the etiology of tau-related neurodegenerative disorders. We expressed wild type and six clinical frontotemporal... more
Unraveling the biochemical and genetic alterations that control the aggregation of protein tau is crucial to understand the etiology of tau-related neurodegenerative disorders. We expressed wild type and six clinical frontotemporal dementia with parkinsonism (FTDP) mutants of human protein tau in wild-type yeast cells and cells lacking Mds1 or Pho85, the respective orthologues of the tau kinases GSK3β and cdk5. We compared tau phosphorylation with the levels of sarkosyl-insoluble tau (SinT), as a measure for tau aggregation. The deficiency of Pho85 enhanced significantly the phosphorylation of serine-409 (S409) in all tau mutants, which coincided with marked increases in SinT levels. FTDP mutants tau-P301L and tau-R406W were least phosphorylated at S409 and produced the lowest levels of SinT, indicating that S409 phosphorylation is a direct determinant for tau aggregation. This finding was substantiated by the synthetic tau-S409A mutant that failed to produce significant amounts of SinT, while its pseudophosphorylated counterpart tau-S409E yielded SinT levels higher than or comparable to wild-type tau. Furthermore, S409 phosphorylation reduced the binding of protein tau to preformed microtubules. The highest SinT levels were found in yeast cells subjected to oxidative stress and with mitochondrial dysfunction. Under these conditions, the aggregation of tau was enhanced although the protein is less phosphorylated, suggesting that additional mechanisms are involved. Our results validate yeast as a prime model to identify the genetic and biochemical factors that contribute to the pathophysiology of human tau.
The phosphate regulatory mechanism in yeast, known as the PHO pathway, is regulated by inorganic phosphate to control the expression of genes involved in the acquisition of phosphate from the medium. This pathway is also reported to... more
The phosphate regulatory mechanism in yeast, known as the PHO pathway, is regulated by inorganic phosphate to control the expression of genes involved in the acquisition of phosphate from the medium. This pathway is also reported to contribute to other nutritional responses and as such it affects several phenotypic characteristics known also to be regulated by protein kinase A, including the transcription of genes involved in the general stress response and trehalose metabolism. We now demonstrate that transcription of post-diauxic shift (PDS)-controlled stress-responsive genes is solely regulated by the Pho85–Pho80 complex, whereas regulation of trehalose metabolism apparently involves several Pho85 cyclins. Interestingly, both read-outs depend on Pho81 but, while the previously described minimum domain of Pho81 is sufficient to sustain phosphate-regulated transcription of PHO genes, full-length Pho81 is required to control trehalose metabolism and the PDS targets. Consistently, neither the expression control of stress-regulated genes nor the trehalose metabolism relies directly on Pho4. Finally, we present data supporting that the PHO pathway functions in parallel to the fermentable growth medium- or Sch9-controlled pathway and that both pathways may share the protein kinase Rim15, which was previously reported to play a central role in the integration of glucose, nitrogen and amino acid availability.
Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building... more
Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G0) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85–Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.
The ability to sense and to respond to changes in the nutrient availability is an essential feature for the survival of every organism. Saccharomyces cerevisiae has several signal transduction cascades to optimally adapt its metabolism to... more
The ability to sense and to respond to changes in the nutrient availability is an essential feature for the survival of every organism. Saccharomyces cerevisiae has several signal transduction cascades to optimally adapt its metabolism to the availability of nutrients in the environment. In this chapter, we focus on the convergence of signal transduction pathways for nutrient sensing in budding yeast. In the first part, we will give an overview of the glucose-induced signal transduction pathways, focusing in particular on the Ras/cAMP pathway and its pleiotropic characteristics. Secondly, the current knowledge of the protein kinases Sch9 and Pho85 in nutrient-induced signal transduction is reviewed. Finally, the interconnectivity between these multiple pathways in glycogen biosynthesis, control of Msn2 activity and pseudohyphal growth will be discussed. We conclude that complex networks are involved in the integration of nutrient signals, regulating the complete transcriptome and metabolome in an intriguingly dynamical manner.
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Hematopoietic stem and progenitor cells (HSPCs) are exposed to low levels of oxygen in the bone marrow niche, and hypoxia-inducible factors (HIFs) are the main regulators of cellular responses to oxygen variation. Recent studies using... more
Hematopoietic stem and progenitor cells (HSPCs) are exposed to low levels of oxygen in the bone marrow niche, and hypoxia-inducible factors (HIFs) are the main regulators of cellular responses to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role for HIF-1α in the maintenance of murine HSCs; however, the role of HIF-2α is still unclear. Here, we show that knockdown of HIF-2α, and to a much lesser extent HIF-1α, impedes the long-term repopulating ability of human CD34(+) umbilical cord blood cells. HIF-2α-deficient HSPCs display increased production of reactive oxygen species (ROS), which subsequently stimulates endoplasmic reticulum (ER) stress and triggers apoptosis by activation of the unfolded-protein-response (UPR) pathway. HIF-2α deregulation also significantly decreased engraftment ability of human acute myeloid leukemia (AML) cells. Overall, our data demonstrate a key role for HIF-2α in the maintenance of human HSPCs and in the survival of primary AML cells.
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Here we present a new bonding protocol for SU-8 negative tone photoresist that exploits the chemical modifications induced in the resin by exposure to 254 nm (UVC) light. Fourier Transform Infrared microspectroscopy (μ-FTIR) was used to... more
Here we present a new bonding protocol for SU-8 negative tone photoresist that exploits the chemical modifications induced in the resin by exposure to 254 nm (UVC) light. Fourier Transform Infrared microspectroscopy (μ-FTIR) was used to carry out a thorough study on the chemical processes and modifications occurring within the epoxy resin by exposure to 365 nm and 254 nm light. In particular, we established that UVC light promotes the opening of the epoxy rings bypassing the post-exposure bake. The possibility to promote a further activation of the resin, already patterned with standard UV lithography, was exploited to produce closed microfluidic devices. Specifically, we were able to fabricate fluidic chips, characterized by broadband transparency from mid-IR to UV and long term stability in continuous flow conditions. CaF2 was used as substrate, coated by sputtering with a nanometric silicon film, in order to make surface properties of this material more suitable for standard fabrication processes with respect to the original substrate. The fabricated microfluidic chips were used to study by μ-FTIR the biochemical response of live breast cancer MCF-7 cells to osmotic stress and their subsequent lysis induced by the injection of deionized water in the device. μ-FTIR analyses detected fast changes in protein, lipid and nucleic acid content as well as cytosol acidification.
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