Asynchronous reproduction in three species of crocodilians in south-eastern Amazonia

We studied reproduction of three species of crocodilians, Paleosuchus trigonatus, Caiman crocodilus and Melanosuchus niger, in the Xingu River, near the Belo Monte hydroelectric dam. The periods of laying and hatching of eggs were estimated for each nest before (2013–2014) and after (2016–2017) the river was dammed and the reservoir was formed. Nesting of the three species occurred between August and December, but was largely asynchronous; nest construction peaked in September for P. trigonatus, October for M. niger and November for C. crocodilus. Reservoir filling had little effect on the laying period of any of the species. Nests of P. trigonatus and M. niger were always within 0–12 m of the bank, whereas nests of C. crocodilus, which nests later in the season when flooding is more likely, were up to 100 m from the nearest water body. There was no relationship between distance from water and the number of eggs in nests, suggesting that larger and presumably more experienced females do not lay at different distances from the bank in any of the species.     

Diversity in enoyl-acyl carrier protein reductases

The enoyl-acyl carrier protein reductase (ENR) is the last enzyme in the fatty acid elongation cycle. Unlike most enzymes in this essential pathway, ENR displays an unusual diversity among organisms. The growing interest in ENRs is mainly due to the fact that a variety of both synthetic and natural antibacterial compounds are shown to specifically target their activity. The primary anti-tuberculosis drug, isoniazid, and the broadly used antibacterial compound, triclosan, both target this enzyme. In this review, we discuss the diversity of ENRs, and their inhibitors in the light of current research progress. Received 3 November 2008; received after revision 5 December 2008; accepted 8 December 2008     

Digoxin and ouabain increase the synthesis of cholesterol in human liver cells

Digoxin and ouabain are steroid drugs that inhibit the Na⁺/K⁺-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver HepG2 cells, enhancing the activity and the expression of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver cells. Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009     

Direct inhibition of phospholipid scrambling activity in erythrocytes by potassium ions

The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K⁺] and selective K⁺ channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes decreases by ~50% when the intracellular [K⁺] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling is inducible by raising the intracellular [Ca²⁺] and that K⁺ ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage and microvesicle formation, processes that are generally attributed to Ca²⁺-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca²⁺-sensitive K⁺ channels causes loss of intracellular K⁺ that results in reduced intrinsic inhibitory effect of these ions on scramblase activity. Received 11 September 2008; received after revision 17 October 2008; accepted 27 October 2008     

Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity

The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses. Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular signal transduction and immune defence. Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008     

Molecular function of the novel α7β2 nicotinic receptor

The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up to three β2 subunits are functional. As the number of β2 subunits increases in the pentameric arrangement, the durations of channel openings and activation episodes increase progressively probably due to decreased desensitization. The prolonged activation episodes conform the kinetic signature of α7β2 and may have an impact on neuronal excitability. For activation of α7β2 receptors, an α7/α7 binding-site interface is required, thus indicating that the three β2 subunits are located consecutively in the pentameric arrangement. α7-positive allosteric modulators (PAMs) are emerging as novel therapeutic drugs. The presence of β2 in the pentamer affects neither type II PAM potentiation nor activation by an allosteric agonist whereas it impairs type I PAM potentiation. This first single-channel study provides fundamental basis required to decipher the role and function of the novel α7β2 receptor and opens doors to develop selective therapeutic drugs.     

Predation on eggs of Schneider’s dwarf caiman,Paleosuchus trigonatus (Schneider, 1807), by armadillos and other predators

Nests of Schneider’s dwarf caiman, Paleosuchus trigonatus, were located in the forests around three streams that drain into the Xingu River, Brazilian Amazonia, in October 2014. Camera traps were installed at the edge of four nests to document predators and female parental care. At two nests, females unsuccessfully defended their nests against one or more giant armadillos, Priodontes maximus, and nine-banded armadillos, Dasypus novemcinctus. Both armadillo species responded to the attack by fleeing and returning on the opposite side of the nest by going around the tree under which the nest was located. Giant armadillos have never before been recorded consuming caiman eggs and their diet has been described as consisting mostly of ants and termites. Another species of armadillo, Cabassous unicinctus, was also registered digging into a nest and probably consuming eggs, though it is generally considered to be primarily insectivorous. A tayra (Eira barbara), lizard (Tupinambis teguixin) and coati (Nasua nasua) were also registered taking eggs from nests during the day, but we obtained no registers of nest defence by caimans during the day. The three nests were attacked after 60 days of incubation, when the eggs were well developed.     

Tribbles: novel regulators of cell function; evolutionary aspects

Identification of rate-limiting steps or components of intracellular second messenger systems holds promise to effectively interfere with these pathways under pathological conditions. The emerging literature on a recently identified family of signalling regulator proteins, called tribbles gives interesting clues for how these proteins seem to link several ‘independent’ signal processing systems together. Via their unique way of action, tribbles co-ordinate the activation and suppression of the various interacting signalling pathways and therefore appear to be key in determining cell fate while responding to environmental challenges. This review summarises our current understanding of tribbles function and also provides an evolutionary perspective on the various tribbles genes. Received 10 January 2006; received after revision 20 March 2006; accepted 5 April 2006     

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.