Lkb1 Loss Promotes Tumor Progression of BRAFV600E-Induced Lung Adenomas

Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF^V600E) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAF^V600E-induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAF^V600E oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAF^V600E leads to lung adenoma development. Importantly, expression of BRAF^V600E concomitant with the loss of only a single-copy of Lkb1, overcomes senencence–like features of BRAF^V600E-mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAF^V600E mutated lung adenomas in human cancer patients.     

Angiopoietin-2 Serum Levels Improve Noninvasive Fibrosis Staging in Chronic Hepatitis C: A Fibrogenic-Angiogenic Link

Aims

Accurate liver fibrosis staging is crucial for the management of chronic hepatitis C (CHC). The invasiveness and cost burden of liver biopsy have driven the search for new noninvasive biomarkers of fibrosis. Based on the link between serum angiopoietin-1 and 2 levels and CHC progression, we aimed to determine the value of these angiogenic factors as noninvasive biomarkers of liver fibrosis.

Methods

Serum levels of angiopoietin-1 and -2 were measured by ELISA in 108 CHC patients who underwent pretreatment liver biopsy. The correlation between angiopoietins and clinical and demographic variables with liver fibrosis was analyzed by univariate regression. Significant factors were then subjected to multivariate analysis, from which we constructed a novel noninvasive liver fibrosis index (AngioScore), whose performance was validated in an independent series of 71 CHC patients. The accuracy of this model was compared with other documented fibrosis algorithms by De Long test.

Results

Angiopoietins correlated significantly with hepatic fibrosis; however, only angiopoietin-2 was retained in the final model, which also included age, platelets, AST, INR, and GGT. The model was validated and behaved considerably better than other fibrosis indices in discriminating all, significant, moderate and severe liver fibrosis (0.886, 0.920, 0.923). Using clinically relevant cutoffs, we classified CHC patients by discarding significant fibrosis and diagnosing moderate and severe fibrosis with greater accuracy, sensitivity, and specificity.

Conclusions

Our novel noninvasive liver fibrosis model, based on serum angiopoietin-2 levels, outperforms other indices and should help substantially in managing CHC and monitoring long-term follow-up prognosis.     

Biotic and abiotic factors driving the diversification dynamics of Crocodylia

Species diversity patterns are governed by complex interactions among biotic and abiotic factors over time and space, but are essentially the result of the diversification dynamics (differential speciation and extinction rates) over the long-term evolutionary history of a clade. Previous studies have suggested that temporal variation in global temperature drove long-term diversity changes in Crocodylia, a monophyletic group of large ectothermic organisms. We use a large database of crocodylian fossil occurrences (192 spp.) and body mass estimations, under a taxic approach, to characterize the global diversification dynamics of crocodylians since the Cretaceous, and their correlation with multiple biotic and abiotic factors in a Bayesian framework. The diversification dynamic of crocodylians, which appears to have originated in the Turonian (c. 92.5 Ma), is characterized by several phases with high extinction and speciation rates within a predominantly low long-term mean rate. Our results reveal long-term diversification dynamics of Crocodylia to be a highly complex process driven by a combination of biotic and abiotic factors which influenced the speciation and extinction rates in dissimilar ways. Higher crocodylian extinction rates are related to low body mass disparity, indicating selective extinctions of taxa at both ends of the body mass spectrum. Speciation rate slowdowns are noted when the diversity of the clade is high and the warm temperate climatic belt is reduced. Our finding supports the idea that temporal variations of body mass disparity, self-diversity, and the warm climate belt size provided more direct mechanistic explanations for crocodylian diversification than do proxies of global temperature.     

First estimates of metabolic rate in Atlantic bluefin tuna larvae

Atlantic bluefin tuna is an iconic scombrid species with a high commercial and ecological value. Despite their importance, many physiological aspects, especially during the larval stages, are still unknown. Metabolic rates are one of the understudied aspects in scombrid larvae, likely due to challenges associated to larval handling before and during respirometry trials. Gaining reliable estimates of metabolic rates is essential to understand how larvae balance their high growth needs and activity and other physiological functions, which can be very useful for fisheries ecology and aquaculture. This is the first study to (a) estimate the relationship between routine metabolic rate (RMR) and larval dry weight (DW) (mass scaling exponent) at a constant temperature of 26°C, (b) measure the RMR under light and darkness and (c) test whether the interindividual differences in the RMR are related to larval nutritional status (RNA/DNA and DNA/DW). The RMR scaled nearly isometrically with body size (b = 0.99, 0.60–31.56 mg DW) in contrast to the allometric relationship observed in most fish larvae (average b = 0.87). The results show no significant differences in larval RMR under light and darkness, suggesting similar larval activity levels in both conditions. The size explained most of the variability in RMR (97%), and nutritional condition was unrelated to the interindividual differences in routine metabolism. This is the first study to report the metabolic rates of Atlantic bluefin tuna larvae and discuss the challenges of performing bioenergetic studies with early life stages of scombrids.     

A species-level total evidence phylogeny of the microteiid lizard family Alopoglossidae (Squamata: Gymnophthalmoidea)

Alopoglossidae is a family of Neotropical lizards composed of 23 species allocated in two genera (Alopoglossus and Ptychoglossus). There is a lack of knowledge about the phylogenetic relationships and systematics of this family. Published phylogenies that include alopoglossid species have very low taxon coverage within the family, and are usually based on limited character sampling. Considering these shortcomings, we infer the phylogenetic relationships of Alopoglossidae—including all but one species in the family—based on the combined analyses of DNA sequences and morphological characters. We use four loci (the mitochondrial 12S, 16S and ND4; the nuclear C-mos) and a matrix of 143 phenotypic characters from scutellation, tongue morphology, hemipenis morphology, and osteology. The dataset is analyzed with Maximum Parsimony, with four alternative weighting schemes: three under Extended Implied Weighting, and one with equal weighting. The respective resulting topologies are compared in a sensitivity analysis framework. Our analyses support the paraphyly of Ptychoglossus, with Alopoglossus nested within it. We provide an updated classification for the family, where Ptychoglossus Boulenger, 1890 is considered a junior synonym of Alopoglossus Boulenger, 1885.     

Lipid profile: causal relationship on cognitive performance in multiple sclerosis?

Molecular Biology Reports - Although cognitive impairment (CI) is classically associated with aging, it has been proposed that neurological pathologies may increase the risk to suffer CI. Despite...     

Rac1 is necessary for capacitation and acrosome reaction in guinea pig spermatozoa

Actin cytoskeleton remodeling is a critical process for the acquisition of fertilizing capacity by spermatozoa during capacitation. However, the molecular mechanism that regulates this process has not been fully elucidated. In somatic cells, Ras-related C3 botulinum toxin substrate 1 protein (Rac1) promotes the polymerization of actin by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane. Rac1 is expressed in mammalian spermatozoa; however, the role of Rac1 in sperm physiology is unknown. This study aimed to elucidate the participation of Rac1 in capacitation and acrosome reaction (AR). Rac1 was found to be dispersed throughout the acrosome and without changes in the middle piece. After 60 minutes of capacitation, Rac1 was found in the apical region of the acrosome only, which concurred with an increase in Rac1-GTP. Rac1 inhibition prevented such changes. In the middle piece, Rac1 localization remained unchanged. Besides, Rac1 inhibition blocked capacitation and AR. The present study demonstrates that Rac1 participates only in the actin cytoskeleton remodeling that occurs in the acrosomal apical region during capacitation, a region where a large amount of actin is polymerized and shaped in a diadem-like structure. Our data also show that this actin cytoskeleton organized by Rac1 interacts with filamin-1, and such interaction was blocked by the inhibition of Rac1, which led to a different organization of the actin cytoskeleton. All these outcomes imply that the formation of an F-actin cytoskeleton in the acrosomal apical region is a necessary event for capacitation and AR, and which is Rac1 driven.     

Expression of the Legume-Specific Nod Factor Receptor Proteins Alters Developmental and Immune Responses in Rice

Plant Molecular Biology Reporter - Legumes form symbiosis with rhizobia, which fix nitrogen for the benefit of host plant in return for carbon resources. Development of this unique symbiosis in...     

Characterization and removal of biofouling from reverse osmosis membranes (ROMs) from a desalination plant in Northern Chile,using Alteromonas sp. Ni1-LEM supernatant

Abstract

Biofouling control in reverse osmosis membranes (ROMs) is challenging due to the high cost of treatments, and reduction in the life of ROMs. This study characterizes the biofouling in the ROMs from a desalination plant and reports its effective removal using the supernatant obtained from Alteromonas sp. strain Ni1-LEM. The characterization of the bacterial community revealed that the most abundant taxa in ROMs were the genera Fulvivirga and Pseudoalteromonas, and unclassified species of the families Flavobacteriaceae and Sphingomonadaceae. This bacterial community significantly decreased upon treatment with the supernatant from Alteromonas sp. Ni1-LEM, resulting in the prevalence of the genus Pseudoalteromonas. Furthermore, this bacterial supernatant significantly inhibited cell adhesion of seven benthic microalgae isolated from ROMs as well as promoting cell detachment of the existing microbial biofilms. The study showed that the extracellular supernatant modified the conformation of extracellular polymeric substances (EPS) in the biofouling of ROMs without any biocidal effects.     

The Erwin equation of biodiversity: From little steps to quantum leaps in the discovery of tropical insect diversity

Almost 40 years ago, Terry L. Erwin published a seemingly audacious proposition: There may be as many as 30 million species of insects in the world. Here, we translate Erwin's verbal argument into a diversity-ratio model—the Erwin Equation of Biodiversity—and discuss how it has inspired other biodiversity estimates. We categorize, describe the assumptions for, and summarize the most commonly used methods for calculating estimates of global biodiversity. Subsequent diversity-ratio extrapolations have incorporated parameters representing empirical insect specialization ratios, and how insect specialization changes at different spatial scales. Other approaches include macroecological diversity models and diversity curves. For many insect groups with poorly known taxonomies, diversity estimates are based on the opinions of taxonomic experts. We illustrate our current understanding of insect diversity by focusing on the six most speciose insect orders worldwide. For each order, we compiled estimates of the (a) maximum estimated number of species, (b) minimum estimated number of species, and (c) number of currently described species. By integrating these approaches and considering new information, we believe an estimate of 5.5 million species of insects in the world is much too low. New molecular methodologies (e.g., metabarcoding and NGS studies) are revealing daunting numbers of cryptic and previously undescribed species, at the same time increasing our precision but also uncertainty about present estimates. Not until technologies advance and sampling become more comprehensive, especially of tropical biotas, will we be able to make robust estimates of the total number of insect species on Earth.