Lamniform Shark Teeth from the Late Cretaceous of Southernmost South America (Santa Cruz Province,Argentina)

Here we report multiple lamniform shark teeth recovered from fluvial sediments in the (Campanian-Maastrichtian) Cerro Fortaleza Formation, Santa Cruz Province, Argentina. This small tooth assemblage is compared to various lamniform sharks possessing similar dental morphologies, including Archaeolamna, Cretalamna, Dwardius, Dallasiella, and Cretodus. Although the teeth share numerous morphological features with the genus Archaeolamna, including a developed neck that maintains a relatively consistent width along the base of the crown, the small sample size and incomplete nature of these specimens precludes definitive taxonomic assignment. Regardless, the discovery of selachian teeth unique from those previously described for the region broadens the known diversity of Late Cretaceous South American sharks. Additionally, the discovery of the teeth in fluvial sandstone may indicate a euryhaline paleobiology in the lamniform taxon or taxa represented by this tooth assemblage.     

New molecular evidence of wine yeast-bacteria interaction unraveled by non-targeted exometabolomic profiling

Introduction

Bacterial malolactic fermentation (MLF) has a considerable impact on wine quality. The yeast strain used for primary fermentation can systematically stimulate (MLF+ phenotype) or inhibit (MLF?) bacteria and the MLF process as a function of numerous winemaking practices, but the underlying molecular evidence still remains a mystery.

Objectives

The goal of the study was to elucidate such evidence by the direct comparison of extracellular metabolic profiles of MLF+ and MLF? phenotypes.

Methods

We have applied a non-targeted metabolomic approach combining ultrahigh-resolution FT-ICR-MS analysis, powerful statistical tools and a comprehensive wine metabolite database.

Results

We discovered around 2500 unknown masses and 800 putative biomarkers involved in phenotypic distinction. For the putative biomarkers, we also developed a biomarker identification workflow and elucidated the exact structure (by UPLC-Q-ToF–MS²) and/or exact physiological impact (by in vitro tests) of several novel biomarkers, such as D-gluconic acid, citric acid, trehalose and tripeptide Pro-Phe-Val. In addition to valid biomarkers, molecular evidence was reflected by unprecedented chemical diversity (around 3000 discriminant masses) that characterized both the yeast phenotypes. While distinct chemical families such as phenolic compounds, carbohydrates, amino acids and peptides characterize the extracellular metabolic profiles of the MLF+ phenotype, the MLF? phenotype is associated with sulphur-containing peptides.

Conclusion

The non-targeted approach used in this study played an important role in finding new and unexpected molecular evidence.

     

Long-Term Stability of a Vaccine Formulated with the Amphipol-Trapped Major Outer Membrane Protein from Chlamydia trachomatis

Chlamydia trachomatis is a major bacterial pathogen throughout the world. Although antibiotic therapy can be implemented in the case of early detection, a majority of the infections are asymptomatic, requiring the development of preventive measures. Efforts have focused on the production of a vaccine using the C. trachomatis major outer membrane protein (MOMP). MOMP is purified in its native (n) trimeric form using the zwitterionic detergent Z3–14, but its stability in detergent solutions is limited. Amphipols (APols) are synthetic polymers that can stabilize membrane proteins (MPs) in detergent-free aqueous solutions. Preservation of protein structure and optimization of exposure of the most effective antigenic regions can avoid vaccination with misfolded, poorly protective protein. Previously, we showed that APols maintain nMOMP secondary structure and that nMOMP/APol vaccine formulations elicit better protection than formulations using either recombinant or nMOMP solubilized in Z3–14. To achieve a greater understanding of the structural behavior and stability of nMOMP in APols, we have used several spectroscopic techniques to characterize its secondary structure (circular dichroism), tertiary and quaternary structures (immunochemistry and gel electrophoresis) and aggregation state (light scattering) as a function of temperature and time. We have also recorded NMR spectra of ¹⁵N-labeled nMOMP and find that the exposed loops are detectable in APols but not in detergent. Our analyses show that APols protect nMOMP much better than Z3–14 against denaturation due to continuous heating, repeated freeze/thaw cycles, or extended storage at room temperature. These results indicate that APols can help improve MP-based vaccine formulations.     

Una especie nueva de <Emphasis Type="Italic">Lepechinia</Emphasis> sección <Emphasis Type="Italic">Glomeratae</Emphasis> (Lamiaceae) de México

During the study of the Lamiaceae from Guerrero, Mexico, specimens of Lepechinia sect. Glomeratae were found, similar to L. glomerata, but different in having larger flowers that are orange at the base and red at the apex, with a tubular corolla that is invaginated at the base, and widely ovate bracts that are acuminate at the apex. The new species, Lepechinia flammea, is described and illustrated. A key to distinguish the species is included.

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Resumen  Durante el estudio de la familia Lamiaceae en el Guerrero, México, se encontraron algunos ejemplares de Lepechinia sección Glomeratae, cercanamente relacionados con L. glomerata, pero que difieren por presentar flores más grandes, anaranjadas en la base y rojas en el ápice, corola tubular, el tubo invaginado en la base y brácteas ampliamente ovadas, con el ápice acuminado. Se presenta una descripción de la nueva especie, Lepechinia flammea, así como ilustraciones y una clave para separar ambas especies.

     

Shotgun proteomics implicates extracellular matrix proteins and protease systems in neuronal development induced by astrocyte cholinergic stimulation

Astrocytes play an important role in neuronal development through the release of soluble factors that affect neuronal maturation. Shotgun proteomics followed by gene ontology analysis was used in this study to identify proteins present in the conditioned medium of primary rat astrocytes. One hundred and thirty three secreted proteins were identified, the majority of which were never before reported to be produced by astrocytes. Extracellular proteins were classified based on their biological and molecular functions; most of the identified proteins were involved in neuronal development. Semi-quantitative proteomic analysis was carried out to identify changes in the levels of proteins released by astrocytes after stimulation with the cholinergic agonist carbachol, as we have previously reported that carbachol-treated astrocytes elicit neuritogenesis in hippocampal neurons through the release of soluble factors. Carbachol up-regulated secretion of 15 proteins and down-regulated the release of 17 proteins. Changes in the levels of four proteins involved in neuronal differentiation (thrombospondin-1, fibronectin, plasminogen activator inhibitor-1, and plasminogen activator urokinase) were verified by western blot or ELISA. In conclusion, this study identified a large number of proteins involved in neuronal development in the astrocyte secretome and implicated extracellular matrix proteins and protease systems in neuronal development induced by astrocyte cholinergic stimulation.     

Notch signaling in cancer

The evolutionarily conserved developmental pathway driven by Notch receptors and ligands has acquired multiple post-natal homeostatic functions in vertebrates. Potential roles in human physiology and pathology are being studied by an increasingly large number of investigators. While the canonical Notch signaling pathway is deceptively simple, the consequences of Notch activation on cell fate are complex and context-dependent. The manner in which other signaling pathways cross-talk with Notch signaling appears to be extraordinarily complex. Recent observations have demonstrated the importance of endocytosis, multiple ubiquitin ligases, non-visual beta-arrestins and hypoxia in modulating Notch signaling. Structural biology is shedding light on the molecular mechanisms whereby Notch interacts with its nuclear partners. Genomics is slowly unraveling the puzzle of Notch target genes in several systems. At the same time, interest in modulating Notch signaling for medical purposes has dramatically increased. Over the last few years we have learned much about Notch signaling in cancer, immune disorders, neurological disorders and most recently, stroke. The role of Notch signaling in normal and transformed stem cells is under intense investigation. Some Notch-modulating drugs are already in clinical trials, and others at various stages of development. This review will focus on the most recent findings on Notch signaling in cancer and discuss their potential clinical implications.     

Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism

AKAP121 focuses distinct signaling events from membrane to mitochondria by binding and targeting cAMP-dependent protein kinase (PKA), protein tyrosine phosphatase (PTPD1), and mRNA. We find that AKAP121 also targets src tyrosine kinase to mitochondria via PTPD1. AKAP121 increased src-dependent phosphorylation of mitochondrial substrates and enhanced the activity of cytochrome c oxidase, a component of the mitochondrial respiratory chain. Mitochondrial membrane potential and ATP oxidative synthesis were enhanced by AKAP121 in an src- and PKA-dependent manner. Finally, siRNA-mediated silencing of endogenous AKAP121 drastically impaired synthesis and accumulation of mitochondrial ATP. These findings indicate that AKAP121, through its role in enhancing cAMP and tyrosine kinase signaling to distal organelles, is an important regulator in mitochondrial metabolism.     

Ultradeep Sequencing of a Human Ultraconserved Region Reveals Somatic and Constitutional Genomic Instability

Early detection of cancer-associated genomic instability is crucial, particularly in tumour types in which this instability represents the essential underlying mechanism of tumourigenesis. Currently used methods require the presence of already established neoplastic cells because they only detect clonal mutations. In principle, parallel sequencing of single DNA filaments could reveal the early phases of tumour initiation by detecting low-frequency mutations, provided an adequate depth of coverage and an effective control of the experimental error. We applied ultradeep sequencing to estimate the genomic instability of individuals with hereditary non-polyposis colorectal cancer (HNPCC). To overcome the experimental error, we used an ultraconserved region (UCR) of the human genome as an internal control. By comparing the mutability outside and inside the UCR, we observed a tendency of the ultraconserved element to accumulate significantly fewer mutations than the flanking segments in both neoplastic and nonneoplastic HNPCC samples. No difference between the two regions was detectable in cells from healthy donors, indicating that all three HNPCC samples have mutation rates higher than the healthy genome. This is the first, to our knowledge, direct evidence of an intrinsic genomic instability of individuals with heterozygous mutations in mismatch repair genes, and constitutes the proof of principle for the development of a more sensitive molecular assay of genomic instability.     

Accelerated idioventricular rhythm during ajmaline test: a case report

We present an unusual transient pro-arrhythmic effect of ajmaline in a patient with resuscitated cardiac arrest and a left ventricular apical aneurysm. We discuss the clinical presentation and the possible physio-pathological explanation for this new pro-arrhythmic effect linked to administration of intravenous ajmaline.     

Atrial fibrillation ablation: a single center comparison between remote magnetic navigation, cryoballoon and conventional manual pulmonary vein isolation

Background

The aim of the study was to compare in our center the effect of different ablation techniques on intermediate term freedom from atrial fibrillation (AF) or atrial tachycardia (AT) in patients affected by refractory AF.

Methods and Results

We retrospectively selected 94 patients who underwent AF ablation in our electrophysiological laboratory from June 2007 to December 2009. 29 patients underwent manual circumferential pulmonary vein isolation (mCPVI), 35 underwent remote magnetic navigation assisted CPVI (rmtCPVI) and 30 cryoballoon CPVI (cCPVI). Antiarrhythmic drugs were systematically stopped 2 months after the procedure (end of the "blanking period").At a mean follow-up of 12,64 ± 6,41 months (range 2-31), the success rate for mCPVI group was 65.5% (19 patients), 66.7 % (20 patients) for the rmtCPVI group and 65.7 % (23 patients) for the cCPVI group (p = 0.625). Procedural and fluoroscopy times were significantly reduced in the cCPVI group (both p < 0.001). Univariate Cox regression showed that no clinical variables were independently associated with recurrence.

Conclusions

In our center''s experience cCPVI and rmtCPVI have been demonstrated to be as effective as mCPVI. cCPVI seemed to be associated with lower procedural and fluoroscopy times.