Terpenoids and More Polar Compounds from the Male Cones of Wollemia nobilis

The analysis of metabolites contained in the male cones of Wollemia nobilis was investigated for the first time in this study. Several diterpenoids of chemosystematic relevance were recognized for the first time from the genus and/or from the Araucariaceae family, namely isocupressic acid ( 1 ), acetyl‐isocupressic acid ( 2 ), methyl (E )‐communate ( 3 ) and sandaracopimaric acid ( 4 ). All these terpenoids are also endowed with interesting biological activities and may play a primary role in the self defence toward herbivores. The presence of a new norlabdane (norlabda‐8(16)‐12‐dien‐14,17‐diol) trivially named as wollemol ( 5 ) was also recognized. Norditerpenes are scarcely distributed in Plant Kingdom and in particular in Gymnosperms and this aspect was discussed. The structure of 5 was determined by extensive NMR analysis employing mono‐ and bidimensional experiments. The 7‐4?‐dimethoxyagathisflavone ( 6 ), a biflavonoid already recognized in Araucariaceae and W. nobilis , was also isolated from male cones together with shikimic acid ( 7 ), a biogenetic precursor of polyphenolic compounds, besides carbohydrates such as glucose ( 8 ) and saccharose ( 9 ), and arginine ( 10 ) a quite common amino acid.     

A series of novel, potent, and selective histone deacetylase inhibitors

Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.     

Avian Influenza Virus (H11N9) in Migratory Shorebirds Wintering in the Amazon Region,Brazil

Aquatic birds are the natural reservoir for avian influenza viruses (AIV). Habitats in Brazil provide stopover and wintering sites for water birds that migrate between North and South America. The current study was conducted to elucidate the possibility of the transport of influenza A viruses by birds that migrate annually between the Northern and Southern Hemispheres. In total, 556 orotracheal/cloacal swab samples were collected for influenza A virus screening using real-time RT-PCR (rRT-PCR). The influenza A virus-positive samples were subjected to viral isolation. Four samples were positive for the influenza A matrix gene by rRT-PCR. From these samples, three viruses were isolated, sequenced and characterized. All positive samples originated from a single bird species, the ruddy turnstone (Arenaria interpres), that was caught in the Amazon region at Caeté Bay, Northeast Pará, at Ilha de Canelas. To our knowledge, this is the first isolation of H11N9 in the ruddy turnstone in South America.     

Trpm4 Gene Invalidation Leads to Cardiac Hypertrophy and Electrophysiological Alterations

Rationale

TRPM4 is a non-selective Ca²⁺-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear.

Objectives

We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4 ^-/-) model.

Methods and Results

Morpho-functional analysis revealed left ventricular (LV) eccentric hypertrophy in Trpm4 ^-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks) when compared to Trpm4^+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4^-/- mice were smaller than Trpm4^+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4^-/-neonatal stage, suggesting hyperplasia. Adult Trpm4 ^-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4^-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4 ^-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca²⁺ or K⁺ currents involved in the repolarizing phase.

Conclusions

TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular electrical activity which impact heart development.     

Shoot litter breakdown and zinc dynamics of an aquatic plant,Schoenoplectus californicus

Decomposition of plant debris is an important process in determining the structure and function of aquatic ecosystems. The aims were to find a mathematic model fitting the decomposition process of Schoenoplectus californicus shoots containing different Zn concentrations; compare the decomposition rates; and assess metal accumulation/mobilization during decomposition. A litterbag technique was applied with shoots containing three levels of Zn: collected from an unpolluted river (RIV) and from experimental populations at low (LoZn) and high (HiZn) Zn supply. The double exponential model explained S. californicus shoot decomposition, at first, higher initial proportion of refractory fraction in RIV detritus determined a lower decay rate and until 68 days, RIV and LoZn detritus behaved like a source of metal, releasing soluble/weakly bound zinc into the water; after 68 days, they became like a sink. However, HiZn detritus showed rapid release into the water during the first 8 days, changing to the sink condition up to 68 days, and then returning to the source condition up to 369 days. The knowledge of the role of detritus (sink/source) will allow defining a correct management of the vegetation used for zinc removal and providing a valuable tool for environmental remediation and rehabilitation planning.     

The occurrence of phenylpropanoid glycosides in Italian Orobanche spp.

The occurrence of phenylpropanoid glycosides in a number of Orobanche spp. collected in Italy is shown and chemosystematic implications are discussed.