Nichima gen. nov. (Alismataceae) based on reproductive structures from the Oligocene-Miocene of Mexico.

PREMISE: Alismataceae, a sub-cosmopolitan family with ca. 17 genera and 113 species, is a large group of aquatic plants. Compression/impressions and bioinclusions of reproductive parts in amber support the documentation of the lineage in low-latitude North America. In Mexico, fossil aquatic plants have been infrequently documented. The new reproductive structures exhibit characteristics of Alismataceae, whose fossil record is mainly documented in the northern hemisphere through of fruits and seeds. METHODS: We described and compared 150 samples of reproductive structures preserved as impressions/compressions from the Oligocene Los Ahuehuetes locality in the state of Puebla, and two bioinclusions from the Miocene amber of Simojovel de Allende in the state of Chiapas, Mexico with extinct and extant taxa. Using a parsimony analysis based on 29 floral characters of 17 extant genera of the Alismataceae, we evaluated the relationship between the fossil material and potential living relatives. RESULTS: We discovered a new genus Nichima based on a perfect, actinomorphic flower with an expanded receptacle, three persistent sepals with multiple vasculatures, delicate and caducous petals, six stamens, and a gynoecium composed of three to more superior carpels, maturing into achenes. These characteristics resemble flowers of Alismataceae. Nichima represents an extinct member of the family, with two new species described here, Nichima magalloniae L. Hern., Cevallos-Ferriz et Hernández-Damián sp. nov. and Nichima gonzalez-medranoi L. Hern., Cevallos-Ferriz et Hernández-Damián, sp. nov. Their phylogenetic position suggests affinity with a clade that includes Baldiella, Echinodorus, and Alisma. CONCLUSIONS: Reproductive structures from the Cenozoic of Mexico support the identification of a new extinct genus, Nichima, evidencing the extensive history of Alismataceae in North America's low latitudes and suggesting a southern extension of the boreotropical flora.

Unsupervised Bayesian Ising Approximation for decoding neural activity and other biological dictionaries.

The problem of deciphering how low-level patterns (action potentials in the brain, amino acids in a protein, etc.) drive high-level biological features (sensorimotor behavior, enzymatic function) represents the central challenge of quantitative biology. The lack of general methods for doing so from the size of datasets that can be collected experimentally severely limits our understanding of the biological world. For example, in neuroscience, some sensory and motor codes have been shown to consist of precisely timed multi-spike patterns. However, the combinatorial complexity of such pattern codes have precluded development of methods for their comprehensive analysis. Thus, just as it is hard to predict a protein's function based on its sequence, we still do not understand how to accurately predict an organism's behavior based on neural activity. Here, we introduce the unsupervised Bayesian Ising Approximation (uBIA) for solving this class of problems. We demonstrate its utility in an application to neural data, detecting precisely timed spike patterns that code for specific motor behaviors in a songbird vocal system. In data recorded during singing from neurons in a vocal control region, our method detects such codewords with an arbitrary number of spikes, does so from small data sets, and accounts for dependencies in occurrences of codewords. Detecting such comprehensive motor control dictionaries can improve our understanding of skilled motor control and the neural bases of sensorimotor learning in animals. To further illustrate the utility of uBIA, we used it to identify the distinct sets of activity patterns that encode vocal motor exploration versus typical song production. Crucially, our method can be used not only for analysis of neural systems, but also for understanding the structure of correlations in other biological and nonbiological datasets.

Inferring a Property of a Large System from a Small Number of Samples.

Inferring the value of a property of a large stochastic system is a difficult task when the number of samples is insufficient to reliably estimate the probability distribution. The Bayesian estimator of the property of interest requires the knowledge of the prior distribution, and in many situations, it is not clear which prior should be used. Several estimators have been developed so far in which the proposed prior us individually tailored for each property of interest; such is the case, for example, for the entropy, the amount of mutual information, or the correlation between pairs of variables. In this paper, we propose a general framework to select priors that is valid for arbitrary properties. We first demonstrate that only certain aspects of the prior distribution actually affect the inference process. We then expand the sought prior as a linear combination of a one-dimensional family of indexed priors, each of which is obtained through a maximum entropy approach with constrained mean values of the property under study. In many cases of interest, only one or very few components of the expansion turn out to contribute to the Bayesian estimator, so it is often valid to only keep a single component. The relevant component is selected by the data, so no handcrafted priors are required. We test the performance of this approximation with a few paradigmatic examples and show that it performs well in comparison to the ad-hoc methods previously proposed in the literature. Our method highlights the connection between Bayesian inference and equilibrium statistical mechanics, since the most relevant component of the expansion can be argued to be that with the right temperature.

Antioxidant Capacity and Cytotoxic Effects of Catechins and Resveratrol Oligomers Produced by Enzymatic Oxidation against T24 Human Urinary Bladder Cancer Cells.

In this work the polymerization of catechin, epicatechin, and resveratrol was carried out through a peroxidase oxidation process in order to improve the biological activity of these phenolic compounds. The antioxidant activity of the oligomers was evaluated by their ability to scavenge reactive oxygen species (ROS) and their capacity to chelate metal ions Fe2+ and Cu2+. The antitumor effect of the oligomers was determined by their ability to induce toxicity in the T24 human bladder cancer cell line. By enzymatic peroxidase oxidation, it was possible to produce oligomers of catechin, epicatechin, and resveratrol with antioxidant capacity significantly higher than their preceding monomers. The ROS scavenging capacity of the oligomers was 20 times higher than that of the monomers, while the ability of the oligomers to chelate metal ions increased up to about 1000 times. Our data show the antitumor effect of the oligomers of catechin, epicatechin, and resveratrol in the T24 cell line, which was similar to that observed with cisplatin. Oligomers of catechin, epicatechin, and resveratrol have great potential to be used as therapeutic agents for the treatment of oxidative stress-related diseases and bladder cancer.

Estimating the Mutual Information between Two Discrete, Asymmetric Variables with Limited Samples.

Determining the strength of nonlinear, statistical dependencies between two variables is a crucial matter in many research fields. The established measure for quantifying such relations is the mutual information. However, estimating mutual information from limited samples is a challenging task. Since the mutual information is the difference of two entropies, the existing Bayesian estimators of entropy may be used to estimate information. This procedure, however, is still biased in the severely under-sampled regime. Here, we propose an alternative estimator that is applicable to those cases in which the marginal distribution of one of the two variables-the one with minimal entropy-is well sampled. The other variable, as well as the joint and conditional distributions, can be severely undersampled. We obtain a consistent estimator that presents very low bias, outperforming previous methods even when the sampled data contain few coincidences. As with other Bayesian estimators, our proposal focuses on the strength of the interaction between the two variables, without seeking to model the specific way in which they are related. A distinctive property of our method is that the main data statistics determining the amount of mutual information is the inhomogeneity of the conditional distribution of the low-entropy variable in those states in which the large-entropy variable registers coincidences.

The MLN4924 inhibitor exerts a neuroprotective effect against oxidative stress injury via Nrf2 protein accumulation.

It was explored the cytoprotective and antioxidant effect of MLN4924, a specific inhibitor of Nedd8-activating enzyme (NAE), against hydrogen peroxide (H2O2)-induced damage in cerebellar granule neurons (CGNs). Primary cultures of CGNs were exposed to H2O2 after preincubation with MLN4924. The compounds were removed, and CGNs were incubated in culture medium for 24h in order to determine cell viability by 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyl-tetrazolium bromide (MTT) and fluorescein diacetate (FDA) assays. It was demonstrated that MLN4924 remarkably attenuated H2O2-induced cell damage. Meanwhile reactive oxygen species (ROS) production was evaluated with the fluorescent probe dihydroethidium (DHE). Interestingly H2O2-induced ROS production was inhibited by pretreatment with MLN4924. MLN4924 treatment in CGNs resulted in nuclear factor E2-related factor 2 (Nrf2) protein accumulation. Intriguingly this effect was observed in the cytosolic and nuclear compartments of the CGNs. The cytoprotective effect of MLN4924 was associated with its ability to diminish ROS production induced by H2O2 and the accumulation of Nrf2 protein levels in the cytoplasm and nucleus of the CGNs.

Information-theoretical analysis of the statistical dependencies among three variables: Applications to written language.

We develop the information-theoretical concepts required to study the statistical dependencies among three variables. Some of such dependencies are pure triple interactions, in the sense that they cannot be explained in terms of a combination of pairwise correlations. We derive bounds for triple dependencies, and characterize the shape of the joint probability distribution of three binary variables with high triple interaction. The analysis also allows us to quantify the amount of redundancy in the mutual information between pairs of variables, and to assess whether the information between two variables is or is not mediated by a third variable. These concepts are applied to the analysis of written texts. We find that the probability that a given word is found in a particular location within the text is not only modulated by the presence or absence of other nearby words, but also, on the presence or absence of nearby pairs of words. We identify the words enclosing the key semantic concepts of the text, the triplets of words with high pairwise and triple interactions, and the words that mediate the pairwise interactions between other words.

Overview of Nrf2 as Therapeutic Target in Epilepsy.

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.

The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration.

Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. Upstream of mTOR the survival PI3K/AKT pathway modulates mTOR activity that is also altered in neurodegenerative diseases of Alzheimer and Parkinson. Nevertheless, the interplay between the PI3K/AKT/mTOR pathway and the autophagic process is complex and a more detailed examination of tissue from patients suffering neurodegenerative diseases and of animal and cellular models is needed. In the present work we review the recent findings on the role of the PI3K/AKT/mTOR pathway in the modulation of the autophagic process in neuronal protection.

Paradoxical cellular effects and biological role of the multifaceted compound nordihydroguaiaretic acid.

Nordihydroguaiaretic acid (NDGA) is a phenolic compound obtained from the leaves of the evergreen desert shrub Larrea tridentata (Creosote bush), which has been used anciently in folk medicine for the treatment of multiple diseases. At the molecular level, NDGA is a potent scavenger of reactive oxygen species. Lipoxygenase inhibition by NDGA has been broadly studied over several cell models; however, NDGA exerts other antioxidant properties and cytoprotective effects in non-tumor cells, which are related with its role as modulator of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) antioxidant pathway. In contrast, in tumor cells NDGA exerts pro-apoptotic activity and anti-tumor effects. Different effects of NDGA have been observed in mitochondria, where NDGA prevents mitochondrial damage in non-tumor cells and induces loss of mitochondrial function in tumor cells. Moreover, NDGA exerts beneficial effects in diverse diseases like cancer, renal damage, Huntington's disease, Alzheimer's disease, and other neurodegenerative pathologies. This work represents a critical review about relevant NDGA mechanisms, cellular effects, and signal pathways involved with possible useful effects.

Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl ß-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

A single residue in transmembrane domain 11 defines the different affinity for thiazides between the mammalian and flounder NaCl transporters.

Little is known about the residues that control the binding and affinity of thiazide-type diuretics for their protein target, the renal Na(+)-Cl(-) cotransporter (NCC). Previous studies from our group have shown that affinity for thiazides is higher in rat (rNCC) than in flounder (flNCC) and that the transmembrane region (TM) 8-12 contains the residues that produce this difference. Here, an alignment analysis of TM 8-12 revealed that there are only six nonconservative variations between flNCC and mammalian NCC. Two are located in TM9, three in TM11, and one in TM12. We used site-directed mutagenesis to generate rNCC containing flNCC residues, and thiazide affinity was assessed using Xenopus laevis oocytes. Wild-type or mutant NCC activity was measured using (22)Na(+) uptake in the presence of increasing concentrations of metolazone. Mutations in TM11 conferred rNCC an flNCC-like affinity, which was caused mostly by the substitution of a single residue, S575C. Supporting this observation, the substitution C576S conferred to flNCC an rNCC-like affinity. Interestingly, the S575C mutation also rendered rNCC more active. Substitution of S575 in rNCC for other residues, such as alanine, aspartate, and lysine, did not alter metolazone affinity, suggesting that reduced affinity in flNCC is due specifically to the presence of a cysteine. We conclude that the difference in metolazone affinity between rat and flounder NCC is caused mainly by a single residue and that this position in the protein is important for determining its functional properties.

Giardia duodenalis: effects of an ozonized sunflower oil product (Oleozon) on in vitro trophozoites.

The ozonized sunflower oil product (Oleozon) was investigated to explore its cytotoxic activity on Giardia duodenalis in vitro cultivated trophozites. Oleozon produced inactivation of Giardia trophozoites in a dose- and cell density-dependent manner. Thirty microliter of Oleozon with peroxide index value of 500 equivalent-mmol of activated oxygen per kilogram were used to achieve a 100% inhibition (<-4.00 log unit) of trophozoites from an initial inoculum of 15x10(4) cells. This potent effect was confirmed by transmission electron microscopy where morphological deterioration of superficial structures mainly in the ventral disc, and formation of a great number of micro vesicles in the cytoplasm were found. We concluded that a direct chemical-oxidation attack by the active substances from Oleozon is one of the causes of the parasitocidal effect of this product. We suggest that the dose and cell density-dependent effect must be taken into account when prescription of this product for giardiasis treatment in humans.

Radicicol, a heat shock protein 90 inhibitor, reduces glomerular filtration rate.

The heat shock protein subfamily of 90 kDa (HSP90) is composed of five isoforms. The more abundant proteins of this subfamily are cytosolic isoforms known as HSP90alpha and HSP90beta. More than 100 client proteins have been found to be regulated by HSP90. Several studies have shown that HSP90 regulates nitric oxide synthesis that is dependent on endothelial nitric oxide synthase (eNOS). Because eNOS regulates renal vascular tone and glomerular filtration rate (GFR), the present study was designed to evaluate the effect of acute HSP90 inhibition with radicicol on GFR and the eNOS pathway. Twenty male Wistar rats were divided into two groups: control vehicle animals and radicicol-infused animals (25 microg.ml(-1).min(-1)). Basal levels were taken before experimental measurements. Mean arterial pressure and renal blood flow (RBF) were recorded, as well as GFR, urinary nitrite and nitrate excretion (UNO2/NO3V). Additionally, we evaluated eNOS expression, Ser1177 and Thr495 eNOS phosphorylation levels, the eNOS dimer-to-monomer ratio, as well as oxidative stress by assessing renal lipoperoxidation and urinary isoprostane F(2alpha) and hydrogen peroxide. HSP90 inhibition with radicicol produced a fall in RBF and GFR that was associated with a significant reduction of UNO2/NO3V. The effects of radicicol were in part mediated by a significant decrease in eNOS phosphorylation and in the eNOS dimer-to-monomer ratio. Our findings suggest that GFR is in part maintained by HSP90-eNOS interaction.

Empleo de la diafiltración en el lavado de cultivos de Leptospira interrogans canicola canicola para la producción de la vacuna vax-SPIRAL / Use of diafiltration in the lavage of cultures of Leptospira interrogans canicola canicola for the production of vaccine vax-SPIRAL

Se propuso sustituir la tecnología actual de la operación de lavado por un sistema de microfiltración tangencial en las etapas de lavado del cultivo de Leptospira interrogans canicola canicola. Se demostró que es aplicable este sistema porque no hubo afectación celular y se obtuvieron altos niveles de eliminación de contaminantes

Escalado de la fermentación de Leptospira interrogans canicola canicola para la producción de la vacuna vax-SPIRAL / Scale-up of the fermentation of Leptospira interrogans canicola canicola for the production of vax-SPIRAL vaccine

Se establecieron las condiciones de operación para la producción de la vacuna vax-SPIRAL en la escala de 100 L. Se concluyó que debe efectuarse con un flujo de aire de 10 L/min (0,1 vvm) y sin agitación mecánica

[Use of diafiltration in the lavage of cultures of Leptospira interrogans canicola canicola for the production of vaccine vax-SPIRAL]. / Empleo de la diafiltración en el lavado de cultivos de Leptospira interrogans canicola canicola para la producción de la vacuna vax-SPIRAL.

It was proposed to substitute the present technology of the lavage operation for a tangential microfiltration system at the lavage stages of the culture of Leptospira interrogans canicola canicola. It was proved that this system may be applied, since no cellular affectation was observed and high pollutant elimination levels were obtained.

[Scale-up of the fermentation of Leptospira interrogans canicola canicola for the production of vax-SPIRAL vaccine]. / Escalado de la fermentación de Leptospira interrogans canicola canicola para la producción de la vacuna vax-SPIRAL.

The operational conditions for the production of vaccine vax-SPIRAL were established at the scale of 100 L. It was concluded that it should be carried out with an air flow of 10 L/min (0.1 vvm) and without mechanical agitation.

Movilización activa y control farmacológico en los injertos de los flexores de la mano / Active mobilization and pharmacological control in the grafts of the hand flexors

Se exponen los resultados obtenidos en el tratamiento de lesiones de los tendones flexores de la mano ocurridas en la zona II en 7 pacientes (10 dedos) empleando la movilización precoz activa y el control farmacológico de la respuesta inflamatoria y de las adherencias tendinosas con alopurinol. Se obtuvo resultados satisfactorios en 9 dedos