Large Cretaceous sphenodontian from Patagonia provides insight into lepidosaur evolution in Gondwana

Sphenodontian reptiles successfully radiated during Triassic and Jurassic times, but were driven almost to extinction during the Cretaceous period. The sparse Early Cretaceous record of sphenodontians has been interpreted as reflecting the decline of the group in favour of lizards, their suspected ecological successors. However, recent discoveries in Late Cretaceous beds in Patagonia partially modify this interpretation. Numerous skeletons of a new sphenodontian, Priosphenodon avelasi gen. et sp. nov., were collected from a single locality in the Cenomanian-Turonian Candeleros Formation, where it is more abundant than any other tetrapod group recorded in the quarry (for example, Crocodyliformes, Serpentes, Dinosauria and Mammalia). Adult specimens of Priosphenodon reached one metre in length, larger than any previously known terrestrial sphenodontian. Here we propose, using available evidence, that sphenodontians were not a minor component of the Cretaceous terrestrial ecosystems of South America, and that their ecological replacement by squamates was delayed until the early Tertiary. The new discovery helps to bridge the considerable gap in the fossil record (around 120 million years) that separates the Early Cretaceous sphenodontians from their living relatives (Sphenodon).     

Evolutionary conservation of motif constituents in the yeast protein interaction network

Understanding why some cellular components are conserved across species but others evolve rapidly is a key question of modern biology. Here we show that in Saccharomyces cerevisiae, proteins organized in cohesive patterns of interactions are conserved to a substantially higher degree than those that do not participate in such motifs. We find that the conservation of proteins in distinct topological motifs correlates with the interconnectedness and function of that motif and also depends on the structure of the overall interactome topology. These findings indicate that motifs may represent evolutionary conserved topological units of cellular networks molded in accordance with the specific biological function in which they participate.     

The Ras family of GTPases in cancer cell invasion

The ability of tumoral cells to invade surrounding tissues is a prerequisite for metastasis. This is the most life-threatening event of tumor progression, and so research is intensely focused on elucidating the mechanisms responsible for invasion and metastasis. The Ras superfamily of GTPases comprises several subfamilies of small GTP-binding proteins whose functions include the control of proliferation, differentiation, and apoptosis, as well as cytoskeleton organization. The development of metastasis is a multistep process that requires coordinated activation of proliferation, motility, changes in normal cell-to-cell and cell-to-substrate contacts, degradation of extracellular matrix, inhibition of apoptosis, and adaptation to an inappropriate tissue environment. Several members of the Ras superfamily of proteins have been implicated in these processes. The present review summarizes the current knowledge in this field.     

Bidirectional control of airway responsiveness by endogenous cannabinoids

Smoking marijuana or administration of its main active constituent, delta9-tetrahydrocannabinol (delta9-THC), may exert potent dilating effects on human airways. But the physiological significance of this observation and its potential therapeutic value are obscured by the fact that some asthmatic patients respond to these compounds with a paradoxical bronchospasm. The mechanisms underlying these contrasting responses remain unresolved. Here we show that the endogenous cannabinoid anandamide exerts dual effects on bronchial responsiveness in rodents: it strongly inhibits bronchospasm and cough evoked by the chemical irritant, capsaicin, but causes bronchospasm when the constricting tone exerted by the vagus nerve is removed. Both effects are mediated through peripheral CB1 cannabinoid receptors found on axon terminals of airway nerves. Biochemical analyses indicate that anandamide is synthesized in lung tissue on calcium-ion stimulation, suggesting that locally generated anandamide participates in the intrinsic control of airway responsiveness. In support of this conclusion, the CB1 antagonist SR141716A enhances capsaicin-evoked bronchospasm and cough. Our results may account for the contrasting bronchial actions of cannabis-like drugs in humans, and provide a framework for the development of more selective cannabinoid-based agents for the treatment of respiratory pathologies.     

Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process.     

Heart rate variability during high-intensity exercise

The aim of this paper is to describe and analyse the behaviour of heart rate variability (HRV) during constant-load, high-intensity exercise using a time frequency analysis (Wavelet Transform). Eleven elite cyclists took part in the study (age: 18.6±3.0 years; VO_2max: 4.88±0.61 litres·min^?1). Initially, all subjects performed an incremental cycloergometer test to determine load power in a constant load-test (379.55±36.02 W; 89.0%). HRV declined dramatically from the start of testing (p <0.05). The behaviour of power spectral density within the LF band mirrored that of total energy, recording a significant decrease from the outset LF peaks fell rapidly thereafter, remaining stable until the end of the test. HF-VHF fell sharply in the first 20 to 30 seconds. The relative weighting (%) of HF-VHF was inverted with the onset of fatigue, [1.6% at the start, 7.1 (p <0.05) at the end of the first phase, and 43.1% (p <0.05) at the end of the test]. HF-VHF_peak displayed three phases: a moderate initial increase, followed by a slight fall, thereafter increasing to the end of the test. The LF/HF-VHF ratio increased at the start, later falling progressively until the end of the first phase and remaining around minimal values until the end of the test.     

Corticosteroidogenesis by isolated human adrenal cells: effect of serotonin and serotonin antagonists.

The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid - particularly cortisol and aldosterone - biosynthesis.