Articulations of Islamophobia: from the extreme to the mainstream?

This article will examine the construction and functions of, as well as relationship between, the diverse and changing articulations of Islamophobia. The aim is to contribute to debates about the definition of Islamophobia, which have tended to be contextually specific, fixed and/or polarized between racism and religious prejudice, between extreme and mainstream, state and non-state versions or undifferentiated, and offer a more nuanced framework to: (a) delineate articulations of Islamophobia as opposed to precise types and categories; (b) highlight the porosity in the discourse between extreme articulations widely condemned in the mainstream, and normalized and insidious ones, which the former tend to render more acceptable in comparison; (c) map where these intersect in response to events, historical and political conditions and new ideological forces and imperatives and (d) compare these articulations of Islamophobia in two contexts, France and the US.     

The onchocerciasis chronicle: from the beginning to the end?

The year 2012 marks the 25th anniversary of the donation of ivermectin to fight onchocerciasis and the projected date for elimination of transmission of the disease in the Americas. This review looks at the history of onchocerciasis, from its discovery through to 2025, by which time it is projected that the disease will have been eliminated as a public health problem, except in a handful of sub-Saharan countries, where it should be well on the way towards elimination.     

Transition from C3 to proto-Kranz to C3–C4 intermediate type in the genus Chenopodium (Chenopodiaceae)

The Chenopodiaceae is one of the families including C₄ species among eudicots. In this family, the genus Chenopodium is considered to include only C₃ species. However, we report here a transition from C₃ photosynthesis to proto-Kranz to C₃–C₄ intermediate type in Chenopodium. We investigated leaf anatomical and photosynthetic traits of 15 species, of which 8 species showed non-Kranz anatomy and a CO₂ compensation point (Γ) typical of C₃ plants. However, 5 species showed proto-Kranz anatomy and a C₃-like Γ, whereas C. strictum showed leaf anatomy and a Γ typical of C₃–C₄ intermediates. Chenopodium album accessions examined included both proto-Kranz and C₃–C₄ intermediate types, depending on locality. Glycine decarboxylase, a key photorespiratory enzyme that is involved in the decarboxylation of glycine, was located predominantly in the mesophyll (M) cells of C₃ species, in both M and bundle-sheath (BS) cells in proto-Kranz species, and exclusively in BS cells in C₃–C₄ intermediate species. The M/BS tissue area ratio, number of chloroplasts and mitochondria per BS cell, distribution of these organelles to the centripetal region of BS cells, the degree of inner positioning (vacuolar side of chloroplasts) of mitochondria in M cells, and the size of BS mitochondria also changed with the change in glycine decarboxylase localization. All Chenopodium species examined were C₃-like regarding activities and amounts of C₃ and C₄ photosynthetic enzymes and δ¹³C values, suggesting that these species perform photosynthesis without contribution of the C₄ cycle. This study demonstrates that Chenopodium is not a C₃ genus and is valuable for studying evolution of C₃–C₄ intermediates.

     

Xenotransplantation: from animal facility to the clinic?

Since 1960, clinical organ transplantation has evolved from an experimental procedure to highly successful ‘routine’, but as technical advances have extended eligibility to more victims of end-stage organ disease, the supply of donor organs has lagged behind. Urgency of need, probability of success and ability to pay are often used to limit waiting lists; without these, as many as 124 000 transplants per year could be performed in the USA alone. Although the supply of organs from human donors may well be assisted in future by increased public education and changes in donor laws, it is unlikely that the need for organs will ever be met by generosity and calamity alone — hence the enthusiasm for other sources of organs.     

Pushing cancer cells to commit suicide: Is 072RB,the new BH3 mimetic,up to the job?

It has been known since the early 90s that apoptosis is the mode of death of cancer cells during chemotherapy.1 Propensity of cells to undergo apoptosis is modulated by the balance of pro-apoptotic versus anti-apoptotic members of Bcl-2 family proteins.2 Mitochondrial outer membrane permeabilization (MOMP) which leads to release of cytochrome c and other apoptogenic factors triggering apoptosis occurs as a result of shift of this balance towards pro-apoptotic Bcl-2 proteins. Furthermore, constitutive prevalence of the anti-apoptotic Bcl-2 family proteins is considered to promote cancer development; the classic example is B-cell lymphoma. Anticancer strategies therefore, were designed that rely on promoting apoptosis of cancer cells via altering the balance among the interacting Bcl-2 proteins. One strategy involves the use of antisense oligonucleotides targeting anti-apoptotic Bcl-2 proteins. Preclinical and clinical investigations on the drugs developed along this strategy [e.g. Oblimersen (Genasense®)] are already well advanced. Another, attractive approach is to use agents that mimic the Bcl-2 homology 3 (BH3) domains of the pro-apoptotic Bcl-2 family proteins (BH3 mimetics). Their mode of action involves competitive binding to surface hydrophobic grooves of anti-apoptotic Bcl-2 members thereby releasing the pro-apoptotic Bcl-2 molecules otherwise sequestered in complexes with the anti-apoptotic ones.2-4 The most investigated BH3 mimetic ABT-737 demonstrated distinct antitumor activity in vitro and in vivo against some leukemia types and solid tumors.3,5

In the article published in this issue of Cell Cycle6 Ponassi and her collaborators describe a novel BH3 mimetic, named 072RB, constructed by replacing specific moieties of Bim-BH3 with natural and non-natural aminoacids and adding an internalizing sequence. In elegant studies the authors convincingly demonstrate internalization and mitochondrial localization of 072RB followed by suppression of growth and apoptotic death of cells of leukemia cell lines. They also observed lethal ex vivo effects of 072RB on AML leukemic cells as well as remarkable inhibition of growth of xenografted human AML cells in NOD/SCID mice with no evidence of toxicity to normal tissue. Normal human lymphocytes, whether quiescent or mitogenically stimulated, were resistant to this BH3 mimetic. An important virtue of 072RB is resistance to proteolysis conferring its stability when used in vivo.

The interplay between the pro-apoptotic and anti-apoptotic Bcl-2 family members is rather complex because depending on cell type and the agent that induces apoptosis different members interact with each other. The mechanism of these interactions is still not fully understood. According to the “different affinity” model the BH3-only proteins Bad and Bmf target Bcl-2, Bcl-w and Bcl-xL, Noxa targets Mcl-1 and A1 whereas Bim and Puma target all the above pro-survival Bcl-2 proteins with comparable affinities.3 In the “direct activator” model Bim, tBid and Puma are the most downstream molecules, directly binding to Bax/Bak and thereby preventing their release, oligomerization and MOMP. In either of these models therefore, the Bim-activating BH-3 mimetic, such as 072RB, is expected to have wider spectrum of activity towards different cell types and different inducers of apoptosis than for instance ABT-737, as the latter, because of its Bad-like structure, does not target Mcl-1.

It is too early to predict whether BH3 mimetics bestow the breakthrough in cancer therapy. Their unique mechanism of action specifically targeting apoptotic machinery raises hopes that this may be the case.3 The new BH3 mimetic 072RB described by Ponassi et al.6 has all attributes to become the leading member of this new class of anticancer drugs. 072RB definitely deserves further evaluation in clinical trials to reveal its therapeutic capabilities whether used as a single agent or in combinatorial therapy.

ReferencesGorczyca W, at al. Leukemia 1993; 7:659-70.Fletcher JI, et al. Cell Cycle 2008; 7:39-44.Labi V, et al. Cell Death Differ 2008; 15:977-87.Wade et al., Cell Cycle 2008; 7:1973-82.Konoplewa M, et al. Cancer Cell 2006; 10:375-88.Ponassi R, et al. Cell Cycle 2008; In this issue.     

Membrane Delivery to the Yeast Autophagosome from the Golgi�CEndosomal System

While many of the proteins required for autophagy have been identified, the source of the membrane of the autophagosome is still unresolved with the endoplasmic reticulum (ER), endosomes, and mitochondria all having been evoked. The integral membrane protein Atg9 is delivered to the autophagosome during starvation and in the related cytoplasm-to-vacuole (Cvt) pathway that occurs constitutively in yeast. We have examined the requirements for delivery of Atg9-containing membrane to the yeast autophagosome. Atg9 does not appear to originate from mitochondria, and Atg9 cannot reach the forming autophagosome directly from the ER or early Golgi. Components of traffic between Golgi and endosomes are known to be required for the Cvt pathway but do not appear required for autophagy in starved cells. However, we find that pairwise combinations of mutations in Golgi-endosomal traffic components apparently only required for the Cvt pathway can cause profound defects in Atg9 delivery and autophagy in starved cells. Thus it appears that membrane that contains Atg9 is delivered to the autophagosome from the Golgi-endosomal system rather than from the ER or mitochondria. This is underestimated by examination of single mutants, providing a possible explanation for discrepancies between yeast and mammalian studies on Atg9 localization and autophagosome formation.     

Multi-element isotope fractionation concepts to characterize the biodegradation of hydrocarbons — from enzymes to the environment

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Applying new tools to cephalopod trophic dynamics and ecology: perspectives from the Southern Ocean Cephalopod Workshop, February 2–3, 2006

A two day workshop on Southern Ocean cephalopods was held in Hobart, Tasmania, Australia prior to the triennial 2006 Cephalopod International Advisory Council (CIAC) symposium. The workshop provided a second international forum to present the current state of research and new directions since the last Southern Ocean cephalopod meeting held in 1993. A major focus of the workshop was trophic ecology and the use of a variety of tools that can be applied in Southern Ocean trophic studies for both cephalopod and predator researchers. New tools that are being used as trophic indicators and tracers in food chain pathways include stable isotope, heavy metal and fatty acid signature analysis. Progress is also being made on understanding squid population dynamics in relation to other key components of the ecosystem by incorporating squid data in ecosystem models. Genetic barcoding is now of great value to fish taxonomy as well as other groups and it is expected that a cephalopod barcoding initiative will be an important tool for cephalopod taxonomy. There is a current initiative to produce a new cephalopod beak identification guide to assist predator biologists in identifying cephalopod prey items. There were also general discussions on specific taxonomic issues, Southern Ocean Cephalopod paralarvae and parasites, and suggestions for future CIAC workshop topics.     

A Novel β-N-Acetylglucosaminidase from Streptomyces thermoviolaceus OPC-520: Gene Cloning,Expression, and Assignment to Family 3 of the Glycosyl Hydrolases

A β-N-acetylglucosaminidase gene (nagA) of Streptomyces thermoviolaceus OPC-520 was cloned in Streptomyces lividans 66. The nucleotide sequence of the gene, which encodes NagA, revealed an open reading frame of 1,896 bp, encoding a protein with an M_r of 66,329. The deduced primary structure of NagA was confirmed by comparison with the N-terminal amino acid sequence of the cloned β-N-acetylglucosaminidase expressed by S. lividans. The enzyme shares no sequence similarity with the classical β-N-acetylglucosaminidases belonging to family 20. However, NagA, which showed no detectable β-glucosidase activity, revealed homology with microbial β-glucosidases belonging to family 3; in particular, striking homology with the active-site regions of β-glucosidases was observed. Thus, the above-mentioned results indicate that NagA from S. thermoviolaceus OPC-520 is classified as a family 3 glycosyl hydrolase. The enzyme activity was optimal at 60°C and pH 5.0, and the apparent K_m and V_max values for p-nitrophenyl-β-N-acetylglucosamine were 425.7 μM and 24.8 μmol min⁻¹ mg of protein⁻¹, respectively.Streptomycetes are gram-positive, mycelial soil bacteria with a high G+C content. In addition to having the ability to synthesize a wide variety of antibiotics and chemotherapeutic agents, they produce extracellular hydrolytic enzymes to obtain nutrients and energy by solubilizing polymeric compounds in soil. These enzymes include proteases, nucleases, lipases, and a variety of enzymes that hydrolyze different types of polysaccharides such as cellulose, chitin, and xylan (13). This last class of enzymes has received considerable attention not only from the standpoint of the utilization of renewable resources but also from that of basic research. Among actinomycetes, Streptomyces spp. make up one group regarded as particularly efficient in the breakdown of chitin (10). Following cellulose, chitin is the second most abundant polymer (β-1,4-linked polymer of N-acetylglucosamine) in nature. Efficient degradation of chitin by microorganisms is achieved by the concerted action of chitinase (EC 3.2.1.14) and β-N-acetylglucosaminidase (EC 3.2.1.30) (1, 19, 20).We have been studying the chitinolytic system of Streptomyces thermoviolaceus OPC-520 to clarify the roles of individual enzymes involved in chitin degradation, the relationship between structure and function, and the regulation of gene expression. When S. thermoviolaceus OPC-520 is cultivated in the presence of chitin, this strain secretes three different chitinases and only one β-N-acetylglucosaminidase and the production is repressed by glucose (unpublished data). Previously, we purified and characterized a major chitinase (Chi40) produced by the strain, which shows a high optimum temperature (70 to 80°C), high optimum pH (pH 8.0 to 10.0), and heat stability (22), and recently reported the cloning and expression of the Chi40 gene (23).While a number of chitinase genes have been isolated from a wide variety of organisms, including bacteria, fungi, insects, plants, and animals, examples of cloning of the β-N-acetylglucosaminidase gene involved in a chitinolytic system are few. To understand the role of β-N-acetylglucosaminidase in chitin degradation by strain OPC-520, its relationship to similar proteins isolated from other sources, and the regulatory system involved in the induction of the enzyme, we have isolated and expressed the gene encoding β-N-acetylglucosaminidase. Here we report the molecular cloning and biochemical characterization of a β-N-acetylglucosaminidase, designated NagA, from S. thermoviolaceus OPC-520. This novel enzyme, which is clearly different from the N-acetylglucosaminidases so far reported, is assigned to family 3 of the glycosyl hydrolases on the basis of sequence comparison. This is the first report of a β-N-acetylglucosaminidase gene isolated from the genus Streptomyces.     

Mechanotransduction from the ECM to the genome: Are the pieces now in place?

A multitude of biochemical signaling processes have been characterized that affect gene expression and cellular activity. However, living cells often need to integrate biochemical signals with mechanical information from their microenvironment as they respond. In fact, the signals received by shape alone can dictate cell fate. This mechanotrasduction of information is powerful, eliciting proliferation, differentiation, or apoptosis in a manner dependent upon the extent of physical deformation. The cells internal "prestressed" structure and its "hardwired" interaction with the extra-cellular matrix (ECM) appear to confer this ability to filter biochemical signals and decide between divergent cell functions influenced by the nature of signals from the mechanical environment. In some instances mechanical signaling through the tissue microenvironment has been shown to be dominant over genomic defects, imparting a normal phenotype on cells that otherwise have transforming genetic lesions. This mechanical control of phenotype is postulated to have a central role in embryogenesis, tissue physiology as well as the pathology of a wide variety of diseases, including cancer. We will briefly review studies showing physical continuity between the external cellular microenvironment and the interior of the cell nucleus. Newly characterized structures, termed nuclear envelope lamina spanning complexes (NELSC), and their interactions will be described as part of a model for mechanical transduction of extracellular cues from the ECM to the genome.     

Philip Miller and the plants from the Chelsea Physic Garden presented to the Royal Society of London, 1723–1796

Summary

From 1723 to 1796 the Society of Apothecaries of London presented annually to the Royal Society of London 50 dried specimens of plants grown the previous year in the Chelsea Physic Garden, this being a condition of Sir Hans Sloane's deed of gift of the Garden to the Apothecaries in 1722. These herbarium specimens are now in the Department of Botany, British Museum (Natural History), London. Many represent plants recorded in successive editions of Philip Miller's Gardeners Dictionary and, together with Miller's own specimens also in the British Museum (Natural History) and Ehret's drawings, may serve to typify binomials published in the 8th edition (1768) of his Dictionary. They were listed from 1723 to 1774 in the Philosophical Transactions of the Royal Society; the lists here contain six long-overlooked binomials Galium verrucosum Huds. (syn. G. valantia Weber), Gypsophila pilosa Huds. (syn. G. porrigens (L.) Boiss), Briza pinnata Huds. (= Demazeria sicula (Jacq.) Dumort.) Euphorbia hispanica Huds. (= E. esula var. lanceolata Gren. & Godron), Pteris cheusanica Curtis (= P. ensiformis Burm. f.) and Saxifraga stolonifera Curtis (syn. S. sarmentosa L.). The deed of conveyance is printed as an appendix.     

Resistance of Aedes aegypti from the state of São Paulo,Brazil, to organophosphates insecticides

Since the reintroduction of Aedes aegypti in the state of S o Paulo, in the middle of the 1980-decade, organophosphate insecticides are being used to control the dengue vector. In 1996, an annual program for monitoring the susceptibility of Ae. aegypti to the insecticides was implemented. Some of the results of this monitoring program are presented. Ae. aegypti populations from ten localities have been submitted to bioassays with the diagnostic dose of temephos and fenitrothion. Only two (Mar lia and Presidente Prudente) remain susceptible to both insecticides and one (Santos) exhibits true resistance. Ae. aegypti from the remaining localities showed an incipient altered susceptibility. Resistance ratios varied from 1.2 to 2.9 for temephos and from 1.5 to 3.2 to fenitrothion, indicating moderate levels of resistance. Biochemical assays did not detect alterations in the enzyme acetilcholinesterase, but indicated that resistance is associated with esterases.     

3β-Acetoxyhopan-1β,22-diol,a triterpene from the lichen Pseudoparmelia texana

From the lichen Pseudoparmelia texana the triterpene 3β-acetoxyhopan-1β,22-diol has been isolated and its structure elucidated.     

Trap catches of the sweetpotato whitefly （Homoptera： Aleyrodidae） in the Imperial Valley, California, from 1996 to 2002

An outbreak of the sweetpotato whitefly, Bemisia tabaci （Gennadius）, biotype B occurred in the Imperial Valley, California in 1991. The insects destroyed melon crops and seriously damaged other vegetables, ornamentals and row crops. As a result of the need for sampling technology, we developed a whitefly trap （named the CC trap） that could be left in the field for extended time periods. We used the traps to monitor populations ofB. tabaci adults during year-round samplings from 1996 to 2002 to study variations in the weekly trap catches of the insect. The greatest number ofB. tabaci adults was recorded in 1996, followed by a continuing annual decrease in trap catches each year through 2002. The overall decline of B. tabaci is attributed in part to the adoption of an integrated pest management （IPM） program initiated in 1992 and reduced melon hectares from 1996 to 2002. Other factors may also have contributed to the population reductions. Seasonally, B. tabaci trap catches decreased during the late summer and fall concurrent with decreasing minimum tempera- tares that are suggested to be a significant factor affecting seasonal activity and reproduction.     

Vid24p,a Novel Protein Localized to the Fructose-1,6-bisphosphatase–containing Vesicles,Regulates Targeting of Fructose-1,6-bisphosphatase from the Vesicles to the Vacuole for Degradation

Glucose regulates the degradation of the key gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase), in Saccharomyces cerevisiae. FBPase is targeted from the cytosol to a novel type of vesicle, and then to the vacuole for degradation when yeast cells are transferred from medium containing poor carbon sources to fresh glucose. To identify proteins involved in the FBPase degradation pathway, we cloned our first VID (vacuolar import and degradation) gene. The VID24 gene was identified by complementation of the FBPase degradation defect of the vid24-1 mutant. Vid24p is a novel protein of 41 kD and is synthesized in response to glucose. Vid24p is localized to the FBPase-containing vesicles as a peripheral membrane protein. In the absence of functional Vid24p, FBPase accumulates in the vesicles and fails to move to the vacuole, suggesting that Vid24p regulates FBPase targeting from the vesicles to the vacuole. FBPase sequestration into the vesicles is not affected in the vid24-1 mutant, indicating that Vid24p acts after FBPase sequestration into the vesicles has occurred. Vid24p is the first protein identified that marks the FBPase-containing vesicles and plays a critical role in delivering FBPase from the vesicles to the vacuole for degradation.Protein degradation is an important process that is tightly regulated. In mammalian cells, serum starvation induces protein degradation by lysosomes (Dice, 1990; Hayes and Dice, 1996). Cytosolic proteins containing a pentapeptide sequence are targeted to the lysosome for degradation in a process mediated by a heat shock protein (Chiang and Dice, 1988; Chiang et al., 1989; Terlecky et al., 1992; Terlecky and Dice, 1993; Cuervo et al., 1994). The receptor protein for this selective proteolysis pathway has been identified recently to be LGP96 (Cuervo and Dice, 1996). Overexpression of the receptor protein increases the degradation of cytosolic proteins in lysosomes both in vivo and in vitro (Cuervo and Dice, 1996).In Saccharomyces cerevisiae, the vacuole is functionally homologous to the lysosome and takes up proteins by several mechanisms. Most vacuole resident proteinases such as carboxypeptidase Y (CPY)¹ enter the vacuole through the secretory pathway (Hasilik and Tanner, 1978; Hemmings et al., 1981; Rothman and Stevens, 1986; Banta et al., 1988; Jones, 1991). CPY is synthesized and processed sequentially in the ER and the Golgi. Sorting occurs in the late Golgi by the CPY receptor encoded by the PEP1/ VPS10 gene (Marcusson et al., 1994; Cooper and Stevens, 1996). CPY is delivered to the vacuole from the prevacuolar or endosomal compartment and the receptor protein recycles back to the Golgi (Marcusson et al., 1994; Cooper and Stevens, 1996). Other vacuolar proteins such as α-mannosidase or aminopeptidase I are imported from the cytosol to the vacuole, independent of the secretory pathway (Yoshihisa and Anraku, 1990; Klionsky et al., 1992; Harding et al., 1995, 1996; Scott et al., 1996). Plasma membrane proteins can be internalized by endocytosis and transported through early endosomes to late endosomes, from which they are directed to the vacuole for degradation (Davis et al., 1993; Raths et al., 1993; Kolling and Hollenberg, 1994; Schandel and Jennes, 1994; Lai et al., 1995; Riballo et al., 1995). Organelles such as peroxisomes or mitochondria can be engulfed by the vacuoles by autophagy (Takeshige et al., 1992; Tuttle and Dunn, 1995; Chiang et al., 1996). The key gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase), is induced when Saccharomyces cerevisiae cells are grown in medium containing poor carbon sources. When cells are transferred to medium containing fresh glucose, FBPase is rapidly inactivated (Gancedo, 1971). Using isogenic strains differing only at the PEP4 gene, we have demonstrated that FBPase is targeted from the cytosol to the vacuole for degradation when cells are transferred from poor carbon sources to fresh glucose (Chiang and Schekman, 1991). The PEP4 gene encodes proteinase A, whose activity is required for the maturation of proteinase B and proteinase C (Zubenko and Jones, 1981; Jones, 1991). As a result, the pep4 strain reduces the vacuolar proteolytic activity to 30% of the wild-type level (Zubenko and Jones, 1981; Jones, 1991; Chiang et al., 1996). The glucose-induced distribution of FBPase from the cytosol to the vacuole has been observed in the pep4 cell by cell fractionation techniques, immunofluorescence microscopy, and immunoelectron microscopy (Chiang and Schekman, 1991; Chiang et al., 1996). FBPase targeting into the vacuole always occurs, regardless of whether cells are transferred to glucose from acetate, ethanol, galactose, or oleate (Chiang and Schekman, 1994; Chiang et al., 1996).To dissect the FBPase degradation pathway, we have taken a genetic approach. Several vid (vacuolar import and degradation) mutants that fail to degrade FBPase in response to glucose have been isolated (Hoffman and Chiang, 1996). Most vid mutants block FBPase in the cytosol. However, in the vid14-1, vid15-1, and vid16-1 mutants, FBPase is found in punctate structures in the cytoplasm. When cell extracts from one of these mutants are fractionated, a substantial amount of FBPase is found in the high speed pellet, suggesting that FBPase is associated with intracellular structures in these mutants (Hoffman and Chiang, 1996). This association is also observed in wild-type cells (Huang and Chiang, 1997).The FBPase-containing vesicles have been purified from wild-type cells to near homogeneity using a combination of differential centrifugation, gel filtration, and equilibrium centrifugation in sucrose gradients (Huang and Chiang, 1997). The purified fractions contain 30–40-nm-diam vesicles and are essentially free of other organelles. Kinetic studies indicate that FBPase association with these vesicles is induced by glucose, occurs only transiently, and precedes the association with the vacuole. The FBPase-containing vesicles are distinct from mitochondria, peroxisomes, endosomes, vacuoles, ER, Golgi, or transport vesicles such as the coat protein (COPI or COPII)-containing vesicles as analyzed by protein markers and electron microscopy (Huang and Chiang, 1997).The vesicles were predicted to contain proteins involved in FBPase targeting and sequestration into the vesicles, as well as proteins participating in carrying FBPase from the vesicles to the vacuole for degradation. To identify such factors, we cloned our first VID gene. The VID24 gene was identified by complementation of the degradation defect of the vid24-1 mutant. Vid24p is a novel 41-kD protein and is synthesized in response to glucose. A significant portion of the Vid24p is localized to the FBPase-containing vesicles as a peripheral protein. The deletion of Vid24p abolishes the degradation of FBPase, but does not cause significant change in growth, sporulation, germination, osmolarity sensitivity, or processing of CPY. In the absence of functional Vid24p, FBPase accumulates in the vesicles and fails to move to the vacuole. FBPase is sequestered inside the vesicles in the vid24-1 mutant, suggesting that Vid24p acts after FBPase sequestration into the vesicles has occurred. Vid24p is the first protein identified that is localized to the FBPase-containing vesicles and plays a critical role in delivering FBPase from the vesicles to the vacuole for degradation.     

Where is the right path heading from the centromere to spindle microtubules?

The kinetochore is a large protein complex that ensures accurate chromosome segregation during mitosis by connecting the centromere and spindle microtubules. One of the kinetochore sub-complexes, the constitutive centromere-associated network (CCAN), associates with the centromere and recruits another sub-complex, the KMN (KNL1, Mis12, and Ndc80 complexes) network (KMN), which binds to spindle microtubules. The CCAN-KMN interaction is mediated by two parallel pathways (CENP-C- and CENP-T-pathways) in the kinetochore, which bridge the centromere and microtubules. Here, we discuss dynamic protein-interaction changes in the two pathways that couple the centromere with spindle microtubules during mitotic progression.