Proteomics Shows New Faces for the Old Penicillin Producer Penicillium chrysogenum

Fungi comprise a vast group of microorganisms including the Ascomycota (majority of all described fungi), the Basidiomycota (mushrooms or higher fungi), and the Zygomycota and Chytridiomycota (basal or lower fungi) that produce industrially interesting secondary metabolites, such as β-lactam antibiotics. These compounds are one of the most commonly prescribed drugs world-wide. Since Fleming's initial discovery of Penicillium notatum 80 years ago, the role of Penicillium as an antimicrobial source became patent. After the isolation of Penicillium chrysogenum NRRL 1951 six decades ago, classical mutagenesis and screening programs led to the development of industrial strains with increased productivity (at least three orders of magnitude). The new “omics” era has provided the key to understand the underlying mechanisms of the industrial strain improvement process. The review of different proteomics methods applied to P. chrysogenum has revealed that industrial modification of this microorganism was a consequence of a careful rebalancing of several metabolic pathways. In addition, the secretome analysis of P. chrysogenum has opened the door to new industrial applications for this versatile filamentous fungus

Effect of a heterotrimeric G protein α subunit on conidia germination, stress response, and roquefortine C production in Penicillium roqueforti

Summary. Heterotrimeric G protein signaling regulates many processes in fungi, such as development, pathogenicity, and secondary metabolite biosynthesis. For example, the Gα subunit Pga1 from Penicillium chrysogenum regulates conidiation and secondary metabolite production in this fungus. The dominant activating allele, pga1G42R, encoding a constitutively active Pga1 Gα subunit, was introduced in Penicillium roqueforti by transformation, resulting in a phenotype characterized by low sporulation and slow growth. In this work, the effect of the constitutively active Pga1G42R Gα subunit on conidial germination, stress tolerance, and roquefortine C production of P. roqueforti was studied. Pga1G42R triggered germination in the absence of a carbon source, in addition to negatively regulating thermal and osmotic stress tolerance. The presence of the Pga1G42R Gα subunit also had an important effect on roquefortine C biosynthesis, increasing production and maintaining high levels of the mycotoxin throughout a culture period of 30 days. Together, the results suggest that G protein-mediated signaling participates in the regulation of these three processes in P. roqueforti. [Int Microbiol 2009; 12(2):123-129

La hipótesis de la diferenciación y el efecto Flynn

Many studies have shown that IQs have been increasing over the last half century. These increases have come to be known as «the Flynn effect». The «Flynn effect» represents a difference on ability-level between groups of the same age but different cohort. The ability-level differentiation hypothesis represents a difference on the relevance of cognitive factors between groups of high and low ability. Hence, it should be possible to imitate the ability-level differentiation effect by comparing groups of the same age but different cohort. The indifferentiation hypothesis represents no differences on the elevance of cognitive abilities in all age groups within the same cohort. The aim of the present study is to test the relationships between these phenomena. For this purpose we analyzed the American standardisation samples of the WISC, WISC-R and WISC-III. Results support the link between the Flynn effect and the differentiation hypothesis. Also, reported evidence replicate previous findings supporting the indifferentiation hypothesis. Implications for the assessment of the intelligence are discussedMuchos estudios han mostrado que las puntuaciones en CI se han venido incrementando durante la última mitad del siglo pasado. Este incremento es conocido como «Efecto Flynn». El efecto Flynn representa una diferencia en el nivel cognitivo entre grupos de la misma edad pero de diferentes cohortes. La hipótesis de la diferenciación por nivel representa una diferencia en la relevancia de los factores cognitivos entre grupos de alto y bajo nivel de habilidad. Por tanto, puede ser posible imitar el efecto de la diferenciación por nivel mediante la comparación de grupos de la misma edad pero de diferente cohorte. La hipótesis de la indiferenciación representa la ausencia de diferencias en la relevancia de los factores cognitivos en todos los grupos de edad dentro de la misma cohorte. El objetivo del presente estudio es comprobar la relación entre estos fenómenos. Para ello, se analizarán las muestras de estandarización americanas del WISC, WISC-R y WISC-III. Los resultados mantienen la relación entre el Efecto Flynn y la hipótesis de la diferenciación. También aportan evidencia replican resultados previos que permiten mantener la hipótesis de la indiferenciación. Implicaciones para la evaluación de la inteligencia son discutida

Observational Δν\Delta\nu-ρˉ\bar\rho relation for δ\delta Sct stars using eclipsing binaries and space photometry

Delta Scuti ($\delta$ Sct) stars are intermediate-mass pulsators, whose intrinsic oscillations have been studied for decades. However, modelling their pulsations remains a real theoretical challenge, thereby even hampering the precise determination of global stellar parameters. In this work, we used space photometry observations of eclipsing binaries with a $\delta$ Sct component to obtain reliable physical parameters and oscillation frequencies. Using that information, we derived an observational scaling relation between the stellar mean density and a frequency pattern in the oscillation spectrum. This pattern is analogous to the solar-like large separation but in the low order regime. We also show that this relation is independent of the rotation rate. These findings open the possibility of accurately characterizing this type of pulsator and validate the frequency pattern as a new observable for $\delta$ Sct stars.Comment: 11 pages, including 2 pages of appendix, 2 figures, 2 tables, accepted for publication in ApJ

Tunable magneto-photonic response of nickel nanostructures

In this letter, we present both experimental and numerical studies of the magneto-optical (MO) properties of nickel infiltrated opals. Ni can show interesting MO properties that can be controlled by nanostructuration through colloidal crystals templating. Nanostructuration allows the coupling of light to surface plasmon modes of Ni, and a clear dependence of the MO response as a function of the structural parameters of the template has been observed. This dependence can be used in future tunable devices such as switchers or MO modulators. © 2011 American Institute of Physics.This work has been partially supported by EU FP7 (NoE Nanophotonics 4 Energy Grant No. 248855 and NMP3-SL-2008-214107-Nanomagma); the CSIC PIF08-016, the Spanish MICINN (CSD2007-0046-Nanolight.es, CSD2008-00023-Funcoat, MAT2009-07841-GLUSFA, MAT2008-06765-C02-01/NAN-MAGPLAS) and Comunidad de Madrid (S2009/MAT-1756-PHAMA and S2009/TIC–1476- MICROSERES).Peer Reviewe

Intra-tumor heterogeneity in TP53 null high grade serous ovarian carcinoma progression

[Background]: High grade serous ovarian cancer is characterised by high initial response to chemotherapy but poor outcome in the long term due to acquired resistance. One of the main genetic features of this disease is TP53 mutation. The majority of TP53 mutated tumors harbor missense mutations in this gene, correlated with p53 accumulation. TP53 null tumors constitute a specific subgroup characterised by nonsense, frameshift or splice-site mutations associated to complete absence of p53 expression. Different studies show that this kind of tumors may have a worse prognosis than other TP53 mutated HGSC. [Methods]: In this study, we sought to characterise the intra-tumor heterogeneity of a TP53 null HGSC consisting of six primary tumor samples, two intra-pelvic and four extra-pelvic recurrences using exome sequencing and comparative genome hybridisation. [Results]: Significant heterogeneity was found among the different tumor samples, both at the mutational and copy number levels. Exome sequencing identified 102 variants, of which only 42 were common to all three samples; whereas 7 of the 18 copy number changes found by CGH analysis were presented in all samples. Sanger validation of 20 variants found by exome sequencing in additional regions of the primary tumor and the recurrence allowed us to establish a sequence of the tumor clonal evolution, identifying those populations that most likely gave rise to recurrences and genes potentially involved in this process, like GPNMB and TFDP1. Using functional annotation and network analysis, we identified those biological functions most significantly altered in this tumor. Remarkably, unexpected functions such as microtubule-based movement and lipid metabolism emerged as important for tumor development and progression, suggesting its potential interest as therapeutic targets. [Conclusions]: Altogether, our results shed light on the clonal evolution of the distinct tumor regions identifying the most aggressive subpopulations and at least some of the genes that may be implicated in its progression and recurrence, and highlights the importance of considering intra-tumor heterogeneity when carrying out genetic and genomic studies, especially when these are aimed to diagnostic procedures or to uncover possible therapeutic strategies.This work has been supported by grants from the AECC network-2012, Telemarató 2013, Instituto de Salud Carlos III (ISCIII) (PI13/00132 and RETIC-RD12/0036/0007), GEIS award 2013, and by the Community of Madrid (S2010/BMD-2303). AM is a predoctoral student supported by FPU fellowship (Spanish Education Ministry). PGS is founded by postdoc contracts from the AECC Scientific Foundation.Peer Reviewe

Magneto-optical effects in interacting localized and propagating surface plasmon modes

We report that the effect of an external magnetic field on the propagation of surface plasmons can be effectively modified through the coupling between localized (LSP) and propagating (SPP) surface plasmons. When these plasmon modes do not interact, the main effect of the magnetic field is a modification of the wavevector of the SPP mode, leaving the LSP virtually unaffected. Once both modes start to interact, there is a strong variation of the magnetic field induced modification of the SPP dispersion curve and, simultaneously, the LSP mode becomes sensitive to the magnetic field.This work was supported by the EU (NMP3-SL- 2008-214107-Nanomagma), the Spanish MICINN (“MAGPLAS” MAT2008-06765-C02-01/NAN and “FUNCOAT” CONSOLIDER INGENIO 2010 CSD2008-00023), the Comunidad de Madrid (“NANOBIOMAGNET” S2009/MAT-1726 and “MICROSERES-CM” S2009/TIC-1476), and CSIC (“CRIMAFOT” PIF08-016-4). We thank A. Cebollada and J. M. García-Martín for growing and characterizing the Au/Co/Au trilayers and reading this manuscript, and R. Quidant and G.Badenes for fruitful discussions.Peer reviewe

HLA Allele E∗01:01 Is associated with a reduced risk of EBV-related classical hodgkin lymphoma independently of HLAA∗01/∗02

Background An inefficient immune response against Epstein-Barr virus (EBV) infection is related to the pathogenesis of a subgroup of classical Hodgkin lymphomas (cHL). Some EBV immuneevasion mechanisms target HLA presentation, including the non-classical HLA-E molecule. HLA-E can be recognized by T cells via the TCR, and it also regulates natural killer (NK) cell signaling through the inhibitory CD94/NKG2A receptor. Some evidences indicate that EBVinfected B-cells promote the proliferation of NK subsets bearing CD94/NKG2A, suggesting a relevant function of these cells in EBV control. Variations in CD94/NKG2A-HLA-E interactions could affect NK cell-mediated immunity and, consequently, play a role in EBV-driven transformation and lymphomagenesis. The two most common HLA-E alleles, E*01:01 and E*01:03, differ by a single amino acid change that modifies the molecule function. We hypothesized that the functional differences in these variants might participate in the pathogenicity of EBV. Aim We studied two series of cHL patients, both with EBV-positive and-negative cases, and a cohort of unrelated controls, to assess the impact of HLA-E variants on EBV-related cHL susceptibility. Results We found that the genotypes with at least one copy of E*01:01 (i.e., E*01:01 homozygous and heterozygous) were underrepresented among cHL patients from both series compared to controls (72.6% and 71.6% vs 83%, p = 0.001). After stratification by EBV status, we found low rates of E*01:01-carriers mainly among EBV-positive cases (67.6%). These reduced frequencies are seen independently of other factors such as age, gender, HLAA* 01 and HLA-A*02, HLA alleles positively and negatively associated with the disease (adjusted OR = 0.4, p = 0.001). Furthermore, alleles from both HLA loci exert a cumulative effect on EBV-associated cHL susceptibility. Conclusions These results indicate that E*01:01 is a novel protective genetic factor in EBV-associated cHL and support a role for HLA-E recognition on the control of EBV infection and lymphomagenesisThis work was supported by Miguel Servet programs CP09/00182 (NGL) and CP08/00218 (PM) and the Spanish Cancer Network (RTICC RD 06/ 0020/0047) all from Instituto de Salud Carlos III (FEDER)

Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway

<p>Abstract</p> <p>Background</p> <p>The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway.</p> <p>Results</p> <p>Using the secretion of bovine chymosin in <it>Aspergillus awamori </it>as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells.</p> <p>Conclusions</p> <p>In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins.</p