Generalities on Private Equity and Venture Capital Funds: a current review of the industry and its environment in Mexico

Private Equity and Venture Capital Funds have shown an exceptional resilience in Mexico and there are good reasons to think they will experience a strong growth in the coming years, although they still represent a very small portion of the gross domestic investment in comparison with other countries of similar economic development. Nevertheless, it is necessary to implement many important legal and other institutional reforms that have proved to contribute to the successful evolution of this industry before it may be considered a new economic development engine for the country.Capital Privado, Capital Emprendedor, Fondos

The Conditions Needed for a Buffer to Set the pH in a System

It is a known fact that buffer systems are widely used in industry and in diverse laboratories to maintain the pH of a system within desired limits, occasionally narrow. Hence, the aim of the present work is to study the buffer capacity and buffer efficacy in order to determine the useful conditions to impose the pH on a given system. This study is based on the electroneutrality and component balance equations for a mixture of protons polyreceptors. The added volume equations were established, V, for strong acids or bases, as well as the buffer capacity equations with dilution effect, β dil, and the buffer efficacy, ε, considering that the analyte contains a mixture of the species of the same polyacid system or of various polyacid systems. The ε index is introduced to define the performance of a buffer solution and to find out for certain, whether the buffer is adequate or not to set the pH of a system, given the proper conditions and characteristics

Generalidades sobre los Fondos de Capital Privado y de Capital Emprendedor: una visión actualizada de la industria y de su entorno en México

Private Equity and Venture Capital Funds have shown an exceptional resilience in Mexico and there are good reasons to think they will experience a strong growth in the coming years, although they still represent a very small portion of the gross domestic investment in comparison with other countries of similar economic development. Nevertheless, it is necessary to implement many important legal and other institutional reforms that have proved to contribute to the successful evolution of this industry before it may be considered a new economic development engine for the country

Computational Design of Inhibitors Targeting the Catalytic β Subunit of Escherichia coli FOF1-ATP Synthase

With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search for new therapeutic targets, to develop drugs with novel modes of bactericidal action. FoF1-ATP synthase plays a crucial role in bacterial bioenergetic processes, and it has emerged as an attractive antimicrobial target, validated by the pharmaceutical approval of an inhibitor to treat multidrug-resistant tuberculosis. In this work, we aimed to design, through two types of in silico strategies, new allosteric inhibitors of the ATP synthase, by targeting the catalytic β subunit, a centerpiece in communication between rotor subunits and catalytic sites, to drive the rotary mechanism. As a model system, we used the F1 sector of Escherichia coli, a bacterium included in the priority list of multidrug-resistant pathogens. Drug-like molecules and an IF1-derived peptide, designed through molecular dynamics simulations and sequence mining approaches, respectively, exhibited in vitro micromolar inhibitor potency against F1. An analysis of bacterial and Mammalia sequences of the key structural helix-turn-turn motif of the C-terminal domain of the β subunit revealed highly and moderately conserved positions that could be exploited for the development of new species-specific allosteric inhibitors. To our knowledge, these inhibitors are the first binders computationally designed against the catalytic subunit of FOF1-ATP synthase. Keywords: FOF1-ATP synthase; allosteric inhibition; evolutionary and PPI algorithms; peptide design; structure-based drug design

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

<div><p>Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway <i>i</i>.<i>e</i>., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3–38 times <i>vs</i>. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation.</p></div

Marea roja producida por el dinoflagelado Peridinium quinquecorne en Veracruz, México (oct-nov, 2002): morfología del agente causal.

In late October, 2002, a red tide was observed along the shore of the Port of Veracruz. Water samples were collected with bottle and fixed with lugols solution. Twelve days later a second set of samples was collected. In addition water temperature, dissolved oxygen and salinity measurements were taken from four stations. Species were identified with a Light microscope, and cells were counted using an inverted microscope, following the Utermöhl method. The species responsible, the armored dinoflagellate Peridinium quinquecorne Abé 1927, was studied in detail with scanning electron microscope, which showed a high morphological variation, mainly in both shape and size of the cell . The highest cell density reached to 2.5 x 106 cells l-1. The second samples set showed a notable decrease in the cell density of P. quinquecorne, which dropped to 4 975 cells l-1; other species occurring with lower densities were Dinophysis caudata and Pseudonitzschia spp., and surface temperature, salinity and dissolved oxygen were 26.3° C, 34 psu and 6.5 mg·l-1, respectively. Strong winds and cloudy sky were also recorded. No fish killings, odors or irritation were reported. This is the first report of a red tide caused by P. quinquecorne in Veracruz. As in other parts of the world no harmful effects were observed.A finales de octubre se observó una marea roja en la costa del Puerto de Veracruz. Se colectaron muestras superficiales de agua que se fijaron con acetato-lugol. Doce días después se efectuó un segundo muestreo en cuatro estaciones, además se midieron temperatura, oxígeno y salinidad. Las especies se identificaron con microscopio de luz, y se cuantificaron en microscopio invertido con el método Utermöhl, y en microscopio electrónico de barrido se confirmó la identidad del dinoflagelado tecado Peridinium quinquecorne Abé 1927, el cual mostró una alta variación morfológica, principalmente en forma y tamaño. La especie alcanzó una densidad de 2.5 x 106 cels l-1. En el segundo muestreo las concentraciones de P. quinquecorne descendieron hasta 4 975 cels l -1, otras especies ocurrieron en menores densidades, como fueron Dinophysis caudata y Pseudonitzschia spp; los valores de temperatura, salinidad y oxígeno disuelto fueron: 26.3°C, 34 ups y 6.5 mg l-1, respectivamente; se registraron vientos fuertes y cielo nublado. No hubo mortandad de peces, olores o irritación. Este es el primer registro de marea roja causada por P. quinquecorne en Veracruz donde, similar a otras partes del mundo, no fue nocivo

RB mutation and RAS overexpression induce resistance to NK cell-mediated cytotoxicity in glioma cells

Several theories aim to explain the malignant transformation of cells, including the mutation of tumor suppressors and proto-oncogenes. Deletion of Rb (a tumor suppressor), overexpression of mutated Ras (a proto-oncogene), or both, are sufficient for in vitro gliomagenesis, and these genetic traits are associated with their proliferative capacity. An emerging hallmark of cancer is the ability of tumor cells to evade the immune system. Whether specific mutations are related with this, remains to be analyzed. To address this issue, three transformed glioma cell lines were obtained (Rb(-/-), Ras(V12), and Rb(-/-)/Ras(V12)) by in vitro retroviral transformation of astrocytes, as previously reported. In addition, Ras(V12) and Rb(-/-)/Ras(V12) transformed cells were injected into SCID mice and after tumor growth two stable glioma cell lines were derived. All these cells were characterized in terms of Rb and Ras gene expression, morphology, proliferative capacity, expression of MHC I, Rae1delta, and Rae1alphabetagammadeltaepsilon, mult1, H60a, H60b, H60c, as ligands for NK cell receptors, and their susceptibility to NK cell-mediated cytotoxicity. Our results show that transformation of astrocytes (Rb loss, Ras overexpression, or both) induced phenotypical and functional changes associated with resistance to NK cell-mediated cytotoxicity. Moreover, the transfer of cell lines of transformed astrocytes into SCID mice increased resistance to NK cell-mediated cytotoxicity, thus suggesting that specific changes in a tumor suppressor (Rb) and a proto-oncogene (Ras) are enough to confer resistance to NK cell-mediated cytotoxicity in glioma cells and therefore provide some insight into the ability of tumor cells to evade immune responses.Xunta de GaliciaComisión EuropeaInstituto de Salud Carlos IIIConsejo Nacional de Ciencia y Tecnologia (CONACyT)Consejo Nacional de Ciencia y Tecnologia (CONACyT)FOSSISXunta de Galicia/PXIB208091PRISCIII/CB158340ISCIII/CB180851FOSSIS/18236

Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies

This is an open-access paper.-- et al.A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma cell, and from an indolent clonal plasma cell to a malignant plasma cell, we performed gene expression profiling in 20 patients with monoclonal gammopathy of undetermined significance, 33 with high-risk smoldering myeloma and 41 with multiple myeloma. The analysis showed that 126 genes were differentially expressed in monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma as compared to normal plasma cell. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules and zinc finger proteins. Several proapoptotic genes (AKT1 and AKT2) were down-regulated and antiapoptotic genes (APAF1 and BCL2L1) were up-regulated in multiple myeloma, both symptomatic and asymptomatic, compared to monoclonal gammopathy of undetermined significance. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation. In conclusion, our data show that although monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma are not clearly distinguishable groups according to their gene expression profiling, several signaling pathways and genes were significantly deregulated at different steps of the transformation process.This study was partially supported by Spanish FIS (PI080568, PS09/01450 and PS0901897), “Gerencia Regional de Salud, Junta de Castilla y León” (GRS 702/A/11) grant, and the Spanish Myeloma Network Program (RD06/0020/0006, RD12/0036/0058 and RD12/0036/0046).Peer Reviewe