bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary Reshaping of Fungal Mating Pathway Scaffold Proteins
Authors: Côte Pierre , Sulea Traian , Dignard Daniel , Wu Cunle , Whiteway Malcolm 
Published: January 2011

ABSTRACT

Scaffold proteins play central roles in the function of many signaling pathways. Among the best-studied examples are the Ste5 and Far1 proteins of the yeast
Saccharomyces cerevisiae
. These proteins contain three conserved modules, the RING and PH domains, characteristic of some ubiquitin-ligating enzymes, and a vWA domain implicated in protein-protein interactions. In yeast, Ste5p regulates the mating pathway kinases while Far1p coordinates the cellular polarity machinery. Within the fungal lineage, the
Basidiomycetes
and the
Pezizomycetes
contain a single Far1-like protein, while several
Saccharomycotina
species, belonging to the CTG (
Candida
) clade, contain both a classic Far1-like protein and a Ste5-like protein that lacks the vWA domain. We analyzed the function of
C. albicans
Ste5p (Cst5p), a member of this class of structurally distinct Ste5 proteins.
CST5
is essential for mating and still coordinates the mitogen-activated protein (MAP) kinase (MAPK) cascade elements in the absence of the vWA domain; Cst5p interacts with the MEK kinase (MEKK)
C. albicans
Ste11p (CaSte11p) and the MAPK Cek1 as well as with the MEK Hst7 in a vWA domain-independent manner. Cst5p can homodimerize, similar to Ste5p, but can also heterodimerize with Far1p, potentially forming heteromeric signaling scaffolds. We found direct binding between the MEKK CaSte11p and the MEK Hst7p that depends on a mobile acidic loop absent from
S. cerevisiae
Ste11p but related to the Ste7-binding region within the vWA domain of Ste5p. Thus, the fungal lineage has restructured specific scaffolding modules to coordinate the proteins required to direct the gene expression, polarity, and cell cycle regulation essential for mating.

IMPORTANCE
The mitogen-activated protein (MAP) kinase cascade is an extensively used signaling module in eukaryotic cells, and the ability to regulate these modules is critical for ensuring proper responses to a wide variety of stimuli. One way that cells regulate this signaling module is through scaffold proteins that insulate related pathways against cross talk, improve signaling efficiency, and ensure that signals are connected to the correct response. The Ste5 scaffold of the
S. cerevisiae
mating response is a well-studied representative of this class of proteins. Using bioinformatics, structural modeling, and molecular genetic approaches, we have investigated the equivalent scaffold in the pathogenic yeast
Candida albicans
. We show that the
C. albicans
protein is structurally distinct from that of
Saccharomyces cerevisiae
but still provides similar functions. Increases in pathway complexity have been associated with changes in scaffold connectivity, and overall, the tethering capacity of the scaffolds has been more conserved than their structural organization.
Utilization of the Mating Scaffold Protein in the Evolution of a New Signal Transduction Pathway for Biofilm Development
Authors: Yi Song , Sahni Nidhi , Daniels Karla J. , Lu Kevin L. , Huang Guanghua , Garnaas Adam M. , Pujol Claude , Srikantha Thyagarajan , Soll David R. 
Published: January 2011

ABSTRACT

Among the hemiascomycetes, only
Candida albicans
must switch from the white phenotype to the opaque phenotype to mate. In the recent evolution of this transition, mating-incompetent white cells acquired a unique response to mating pheromone, resulting in the formation of a white cell biofilm that facilitates mating. All of the upstream components of the white cell response pathway so far analyzed have been shown to be derived from the ancestral pathway involved in mating, except for the mitogen-activated protein (MAP) kinase scaffold protein, which had not been identified. Here, through binding and mutational studies, it is demonstrated that in both the opaque and the white cell pheromone responses, Cst5 is the scaffold protein, supporting the evolutionary scenario proposed. Although Cst5 plays the same role in tethering the MAP kinases as Ste5 does in
Saccharomyces cerevisiae
, Cst5 is approximately one-third the size and has only one rather than four phosphorylation sites involved in activation and cytoplasmic relocalization.

IMPORTANCE
Candida albicans
must switch from white to opaque to mate. Opaque cells then release pheromone, which not only induces cells to mate but also in a unique fashion induces mating-incompetent white cells to form biofilms that facilitate opaque cell mating. All of the tested upstream components of the newly evolved white cell pheromone response pathway, from the receptor to the mitogen-activated protein (MAP) kinase cascade, are the same as those of the conserved opaque cell response pathway. One key element, however, remained unidentified, the scaffold protein for the kinase cascade. Here, we demonstrate that Cst5, a homolog of the
Saccharomyces cerevisiae
scaffold protein Ste5, functions as the scaffold protein in both the opaque and the white cell pheromone responses. Pheromone induces Cst5 phosphorylation, which is involved in activation and cytoplasmic localization of Cst5. However, Cst5 contains only one phosphorylation site, not four as in the
S. cerevisiae
ortholog Ste5. These results support the hypothesis that the entire upper portion of the newly evolved white cell pheromone response pathway is derived from the conserved pheromone response pathway in the mating process.
Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of Legionella pneumophila
Authors: Levi Assaf , Folcher Marc , Jenal Urs , Shuman Howard A. 
Published: January 2011

ABSTRACTProteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell division, differentiation, and virulence. The role of cyclic diguanylate signaling in the lifestyle ofLegionella pneumophila, the causative agent of Legionnaires’ disease, has not previously been examined. TheL. pneumophilagenome encodes 22 predicted proteins containing domains related to cyclic diguanylate synthesis, hydrolysis, and recognition. We refer to these genes ascdgS(cyclicdiguanylatesignaling) genes. Strains ofL. pneumophilacontaining deletions of all individualcdgSgenes were created and did not exhibit any observable growth defect in growth medium or inside host cells. However, when overexpressed, severalcdgSgenes strongly decreased the ability ofL. pneumophilato grow inside host cells. Expression of thesecdgSgenes did not affect the Dot/Icm type IVB secretion system, the major determinant of intracellular growth inL. pneumophila.L. pneumophilastrains overexpressing thesecdgSgenes were less cytotoxic to THP-1 macrophages than wild-typeL. pneumophilabut retained the ability to resist grazing by amoebae. In many cases, the intracellular-growth inhibition caused bycdgSgene overexpression was independent of diguanylate cyclase or phosphodiesterase activities. Expression of thecdgSgenes in aSalmonella entericaserovar Enteritidis strain that lacks all diguanylate cyclase activity indicated that severalcdgSgenes encode potential cyclases. These results indicate that components of the cyclic diguanylate signaling pathway play an important role in regulating the ability ofL. pneumophilato grow in host cells.IMPORTANCEAll bacteria must sense and respond to environmental cues. Intracellular bacterial pathogens must detect and respond to host functions that limit their ability to carry out a successful infection. Small-molecule second messengers play key roles in transmitting signals from environmental receptors to the proteins and other components that respond to signals. Cyclic diguanylate is a ubiquitous bacterial second messenger known to play an important role in many sensing and signaling systems in bacteria. The causative agent of Legionnaires’ disease,Legionella pneumophila, is an intracellular pathogen that grows inside environmental protists and human macrophages by subverting the normal processes that these cells use to capture and destroy bacteria. We show that the several cyclic diguanylate signaling components inLegionellaplay a role in the ability to grow inside both kinds of host cells. This work highlights the role of cyclic diguanylate signaling during intracellular growth.
Variation in floral morphology and ploidy among populations ofCollinsia parvifloraandCollinsia grandiflora
Authors: Tunbridge Nicole D. , Sears Chris , Elle Elizabeth 
Published: January 2011

Variation in floral form complicates species identification, and when variation in ploidy also occurs, taxonomic designations are significantly compromised. We studied morphological and ploidy variation in sister species Collinsia parviflora Lindl. (small-flowered form) and Collinsia grandiflora Douglas ex Lindl. (large-flowered form), sampling from California, where the species were previously described as diploids, to British Columbia, where morphologically variable populations were more recently designated tetraploid. We found continuous among-population variation in flower size and shape throughout our sampled range. Ploidy variation, estimated using a combination of chromosome counts and flow cytometry, was not associated with flower size. Diploid populations were rare, and both large-flowered and small-flowered diploids were identified. Tetraploid populations were common, geographically dispersed, and exhibited the full range of flower sizes. A few populations of small-flowered plants were putative hexaploids. When large- and small-flowered forms co-occurred, they were diploid and tetraploid, respectively, suggesting morphological differentiation from selection for reproductive isolation between co-occurring plants of different ploidy. Although diploid C. parviflora (small-flowered) and C. grandiflora (large-flowered) occur, the majority of our sample consisted of morphologically variable tetraploids, suggesting that the use of flower size to delineate species is inappropriate. Further research is needed to ensure a true description of species boundaries in this group.
Genetic and morphological variability in populations of the wild diploid potato speciesSolanum magliaandSolanum kurtzianumfrom Argentina
Authors: Marfil Carlos F. , Pigni Natalia B. , Camadro Elsa L. , Masuelli Ricardo W. 
Published: January 2011

Solanum maglia Schltdl., a wild potato species that has its widest geographical distribution in Chile, is restricted in Argentina to Quebrada La Cumbre (quebrada = gorge), Mendoza province, where no other potato species has been reported. During two collecting expeditions carried out in 2006 and 2007 in this gorge, tubers of two potato populations separated by 500 m (area 1 and 2) were sampled. The morphological and genetic diversity of these two newly sampled populations and of five accessions from the same gorge classified as S. maglia, a plant of Solanum kurtzianum collected outside this gorge, and a Chilean plant of S. maglia were examined by comparing 24 morphological characters and electrophoretic patterns for simple sequence repeat and amplified fragment length polymorphism markers, respectively. Based on the current taxonomic concept, the results support the classification of plants from area 1 as S. kurtzianum and those from area 2 as S. maglia, except for one plant from the former area, which shared electrophoretic bands from both species. This is the first report on the sympatry of populations of the two species in Quebrada La Cumbre. The importance of performing in situ population studies in the same sites over years is discussed.
Rapid juvenile development in old forest lichens
Authors: Larsson Per , Gauslaa Yngvar 
Published: January 2011

Generation time and juvenile growth rates are important but poorly known parameters in lichen population biology. By using a noninvasive method, we aimed to quantify these variables in juvenile thalli of Lobaria pulmonaria (L.) Hoffm., L. scrobiculata (Scop.) D.C., and Pseudocyphellaria crocata (L.) Vain., in situ, on twigs of Picea abies (L.) H. Karst in boreal rainforests. Growth was monitored during the summer months (May–August, 106 d), as well as in the remaining part of the year (259 d), for each of two sequential years, by means of repeated photography and imaging analysis. The mean relative thallus-area growth rates were 0.53 ± 0.02, 0.41 ± 0.02, and 0.57 ± 0.04 mm2·mm–2·year–1 (mean ±SE), respectively, in the three species, equivalent to a yearly growth of 101 ± 5%, 70 ± 6%, and 121 ± 12%. Growth was much slower during the winter (0.09–0.12 mm2·cm–2·d–1) than in summer (0.19–0.27 mm2·cm–2·d–1). Relative growth rates significantly declined with increasing thallus size. Estimated generation times in L. scrobiculata and P. crocata, based upon the first observed formation of reproductive structures, were 15–22 and 9–13 years, respectively. Studied L. pulmonaria thalli produced no diaspores during the experiment, consistent with a generation time >17 years. The relative growth rates we measured and our estimated generation times are faster than those earlier recorded. Thus, our noninvasive method can estimate parameters needed to model population growth within a reasonable period of time. The rapid juvenile development implies that the growth rates and generation times are unlikely to be the limiting factors that exclude these lichens from young forests.
PATH INTEGRAL ON THE EXTREME FIELD CONFIGURATIONS
Authors: KHATSYMOVSKY V. M. 
Published: January 2011

The canonical Hamiltonian path integral measure obeys certain rule which relates such measure on the paths defined on the whole time axis to the measures on the paths defined on the regions constituting the time axis. We show that this "gluing" rule can be reproduced without referring to Hamiltonian formalism, by substituting field configurations with arbitrarily fast change of the fields at the boundary points of these regions into action and viewing the path integral in the sense of generalized function. Now the coordinate along which gluing proceeds can be not only the time. The piecewise-flat (simplicial) minisuperspace gravity system is considered. Arbitrarily fast change of the (tangential component of) metric between the two 4-simplices with common 3-face is studied. That is, we generalize piecewise-flat anzats by allowing tangential metric to be function of the distance from the 3-face in the neighborhood of this 3-face. The action is nondegenerate (nonsingular) with respect to these additional generalized coordinates. The rule for gluing the path integral measures on separate 4-simplices is found. The resulting general expression covers a large variety of the measures including those usually used in numerical calculations and allows one to specify the measure in some applications.
MRM-FACTORS FOR THE PROBABILITY MEASURES IN THE MEIXNER CLASS
Authors: KUBO IZUMI , KUO HUI-HSIUNG 
Published: January 2011

It is known that the gamma distribution γκ is MRM-applicable for h(x) = ex and for some hypergeometric functions also. We are interested in the problem to determine all possible MRM-factors of probability measures which are MRM-applicable for ex. We may say that the measures are in Meixner class. Such typical measures are Gaussian, Poisson, gamma, negative binomial and Meixner distributions and others are obtained from their modifications by affine transforms. We will give the complete list of MRM-factors different from ex up to trivial deformation: (1) [Formula: see text] for gamma distribution γκ. (2) [Formula: see text] for gamma distribution γκ. (3) [Formula: see text] for standard Gaussian distribution. (4) [Formula: see text] for shifted negative binomial distribution. σβ NegBin (κ,p) with κ = 2, β = 1, for Meixner distribution Mκ,η with κ = 2 and for gamma distribution γκ with κ = 2, which is a special case of (2) with c = 1.
ON THE QUADRATIC HEISENBERG GROUP
Authors: ACCARDI LUIGI , OUERDIANE HABIB , REBEÏ HABIB 
Published: January 2011

In this paper we introduce the quadratic Weyl operators canonically associated to the one mode renormalized square of white noise (RSWN) algebra as unitary operator acting on the one mode interacting Fock space {Γ, {ωn, n ∈ ℕ}, Φ} where {ωn, n ∈ ℕ} is the principal Jacobi sequence of the nonstandard (i.e. neither Gaussian nor Poisson) Meixner classes. We deduce the quadratic Weyl relations and construct the quadratic analogue of the Heisenberg Lie group with one degree of freedom. In particular, we determine the manifold structure of the group and introduce a local chart containing the identity on which the group law has a simple rational expression in the chart coordinates (see Theorem 6.3).
Hierarchical Convergence of a Double-Net Algorithm for Equilibrium Problems and Variational Inequality Problems
Authors: Yao Yonghong , Liou Yeong-Cheng , Chen Chia-Ping 
Published: January 2011

AbstractWe consider the following hierarchical equilibrium problem and variational inequality problem (abbreviated as HEVP): find a point "Equation missing" such that "Equation missing", for all "Equation missing", where "Equation missing", "Equation missing" are two monotone operators and "Equation missing" is the solution of the equilibrium problem of finding "Equation missing" such that "Equation missing", for all "Equation missing". We note that the problem (HEVP) includes some problems, for example, mathematical program and hierarchical minimization problems as special cases. For solving (HEVP), we propose a double-net algorithm which generates a net "Equation missing". We prove that the net "Equation missing" hierarchically converges to the solution of (HEVP); that is, for each fixed "Equation missing", the net "Equation missing" converges in norm, as "Equation missing", to a solution "Equation missing" of the equilibrium problem, and as "Equation missing", the net "Equation missing" converges in norm to the unique solution "Equation missing" of (HEVP).
Breast Cancer Stem Cells Are Regulated by Mesenchymal Stem Cells through Cytokine Networks
Authors: Liu Suling , Ginestier Christophe , Ou Sing J. , Clouthier Shawn G. , Patel Shivani H. , Monville Florence , Korkaya Hasan , Heath Amber , Dutcher Julie , Kleer Celina G. , Jung Younghun , Dontu Gabriela , Taichman Russell , Wicha Max S. 
Published: January 2011

Abstract
We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow–derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC–CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow–derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population. Cancer Res; 71(2); 614–24. ©2011 AACR.
A Novel Transgenic Mouse Model of the Human Multiple Myeloma Chromosomal Translocation t(14;16)(q32;q23)
Authors: Morito Naoki , Yoh Keigyou , Maeda Atsuko , Nakano Takako , Fujita Akiko , Kusakabe Manabu , Hamada Michito , Kudo Takashi , Yamagata Kunihiro , Takahashi Satoru 
Published: January 2011

Abstract
Multiple myeloma (MM) is a currently incurable neoplasm of terminally differentiated B cells. The translocation and/or overexpression of c-MAF have been observed in human MM. Although c-MAF might function as an oncogene in human MM, there has been no report thus far describing the direct induction of MM by c-MAF overexpression in vivo. In this study, we have generated transgenic (TG) mice that express c-Maf specifically in the B-cell compartment. Aged c-Maf TG mice developed B-cell lymphomas with some clinical features that resembled those of MM, namely, plasma cell expansion and hyperglobulinemia. Quantitative RT-PCR analysis demonstrated that Ccnd2 and Itgb7, which are known target genes of c-Maf, were highly expressed in the lymphoma cells. This novel TG mouse model of the human MM t(14;16)(q32;q23) chromosomal translocation should serve to provide new insight into the role of c-MAF in tumorigenesis. Cancer Res; 71(2); 339–48. ©2011 AACR.
A Novel Sialyltransferase Inhibitor Suppresses FAK/Paxillin Signaling and Cancer Angiogenesis and Metastasis Pathways
Authors: Chen Jia-Yang , Tang Yen-An , Huang Sin-Ming , Juan Hsueh-Fen , Wu Li-Wha , Sun Ying-Chieh , Wang Szu-Chi , Wu Kuan-Wei , Balraj Gopula , Chang Tzu-Ting , Li Wen-Shan , Cheng Hung-Chi , Wang Yi-Ching 
Published: January 2011

AbstractIncreased sialyltransferase (ST) activity promotes cancer cell metastasis, and overexpression of cell surface sialic acid correlates with poor prognosis in cancer patients. To seek therapies targeting metastasis for cancer treatment, we developed a novel ST inhibitor, Lith-O-Asp, and investigated its antimetastatic and antiangiogenic effects and mechanisms. We found that cells treated with Lith-O-Asp showed a reduction of activity on various ST enzymes by in vitro and cell-based activity analyses. Lith-O-Asp inhibited migration and invasion abilities in various cancer cell lines and showed inhibitory effect on the angiogenic activity of human umbilical vein endothelial cells. Indeed, Lith-O-Asp treatment consequently delayed cancer cell metastasis in experimental and spontaneous metastasis assays in animal models. Importantly, Lith-O-Asp decreased the sialic acid modification of integrin-β1 and inhibited the expression of phospho-FAK, phospho-paxillin, and the matrix metalloprotease (MMP) 2 and MMP9. Lith-O-Asp attenuated the Rho GTPase activity leading to actin dynamic impairment. In addition, 2DE-MS/MS and immunoblotting analyses showed that Lith-O-Asp altered the protein expression level and phosphorylation status of various proteins involved in crucial metastasis and angiogenesis pathways such as vimentin and ribonuclease/angiogenin inhibitor RNH1. Furthermore, Lith-O-Asp treatment significantly inhibited the invasive ability exerted by ectopic overexpression of various ST enzymes catalyzing α-2,6- or α-2,3-sialylation. Our results provide compelling evidence that the potential pan-ST inhibitor, Lith-O-Asp, suppressed cancer cell metastasis likely by inhibiting FAK/paxillin signaling and expressing antiangiogenesis factors. Lith-O-Asp is worthy for further testing as a novel antimetastasis drug for cancer treatment. Cancer Res; 71(2); 473–83. ©2011 AACR.
Peptides and Aptamers Targeting HSP70: A Novel Approach for Anticancer Chemotherapy
Authors: Rérole Anne-Laure , Gobbo Jessica , De Thonel Aurelie , Schmitt Elise , Pais de Barros Jean Paul , Hammann Arlette , Lanneau David , Fourmaux Eric , Deminov Oleg , Micheau Olivier , Lagrost Laurent , Colas Pierre , Kroemer Guido , Garrido Carmen 
Published: January 2011

Abstract
The inhibition of heat shock protein 70 (HSP70) is an emerging strategy in cancer therapy. Unfortunately, no specific inhibitors are clinically available. By yeast two-hybrid screening, we have identified multiple peptide aptamers that bind HSP70. When expressed in human tumor cells, two among these peptide aptamers—A8 and A17—which bind to the peptide-binding and the ATP-binding domains of HSP70, respectively, specifically inhibited the chaperone activity, thereby increasing the cells' sensitivity to apoptosis induced by anticancer drugs. The 13-amino acid peptide from the variable region of A17 (called P17) retained the ability to specifically inhibit HSP70 and induced the regression of subcutaneous tumors in vivo after local or systemic injection. This antitumor effect was associated with an important recruitment of macrophages and T lymphocytes into the tumor bed. Altogether, these data indicate that peptide aptamers or peptides that target HSP70 may be considered as novel lead compounds for cancer therapy. Cancer Res; 71(2); 484–95. ©2011 AACR.