Biochemical and physiological characterization of a new Na+-channel specific peptide from the venom of the Argentinean scorpion Tityus trivittatus

A new peptide with 61 amino acids cross-linked by 4 disulfide bridges, with molecular weight of 6938.12 Da, and an amidated C-terminal amino acid residue was purified and characterized. The primary structure was obtained by direct Edman degradation and sequencing its gene. The peptide is lethal to mammals and was shown to be similar (95% identity) to toxin Ts1 (gamma toxin) from the Brazilian scorpion Tityus serrulatus; it was named Tt1g (from T. trivittatus toxin 1 gamma-like). Tt1g was assayed on several sub-types of Na⁺-channels showing displacement of the currents to more negative voltages, being the hNav1.3 the most affected channel. This toxin displays characteristics typical to the β-type sodium scorpion toxins. Lethality tests and physiological assays indicate that this peptide is probably the most important toxic component of this species of scorpion, known for causing human fatalities in the South American continent.     

Temporal fluctuations and experimental effects in desert plant communities

In the Chihuahuan Desert of the southwestern United States we monitored responses of both winter and summer annual plant communities to natural environmental variation and to experimental removal of seed-eating rodents and ants for 13 years. Analyses of data on population densities of the species by principal component analysis (PCA) followed by repeated measures analysis of variance (rmANOVA) on PCA scores showed that: (1) composition of both winter and summer annual communities varied substantially from year to year, presumably in response to interannual climatic variation, and (2) community composition of winter annuals was also significantly affected by the experimental manipulations of seed-eating animals, but the composition of the summer annual community showed no significant response to these experimental treatments. Canonical discriminant analysis (CDA) was then applied to the data for winter annuals to more clearly identify the responses to the different classes of experimental manipulations. This analysis showed that removing rodents or ants or both taxa caused distinctive changes in species composition. There was a tendency for large-seeded species to increase on rodent removal plots and to decrease on ant removal plots, and for small-seeded species to change in the opposite direction. In the winter annual community there was a significant time x treatment interaction: certain combinations of species that responded differently to removal of granivores also showed opposite fluctuations in response to long-term climatic variation. The large year-to-year variation in the summer annual community was closely and positively correlated across all experimental treatments. The use of multivariate analysis in conjunction with long-term monitoring and experimental manipulation shows how biotic interactions interact with variation in abiotic conditions to affect community dynamics.     

A short-range endemic species from south-eastern Atlantic Rain Forest shows deep signature of historical events: phylogeography of harvestmen Acutisoma longipes (Arachnida: Opiliones)

The Brazilian Atlantic Rain Forest is amongst the most diverse biomes in the world, but the processes that shaped its biodiversity are still poorly understood. We used one mitochondrial and two nuclear markers to evaluate the phylogeographic patterns of the endemic harvestman Acutisoma longipes and its closely related species to investigate the biogeographic history of this biome. The results showed low intrapopulation diversity and strong population structure, suggesting poor dispersion amongst locations. Phylogenetic analyses pointed to three main mitochondrial lineages congruent with the geomorphology of the south-eastern region of Brazil (Serra do Mar, Serra da Mantiqueira, and interior plateau). These older divergences occurred in the middle-Neogene, suggesting that events in this period drove the diversification of the species, but Quaternary events also affected the populations locally. We detected some congruence between A. longipes demographic patterns and the areas of endemism delimited for harvestmen, suggesting that some regions of the distribution could have been more stable in the past (especially in Serra da Mantiqueira). Our findings corroborate that harvestmen are a suitable group for the study of ancient biogeographic events in the Atlantic Rain Forest, even at small-scale ranges. Acutisoma hamatum is here considered as a new junior synonym of A. longipes.     

Ciudadanía activa y personas mayores: viejos conceptos,nuevos abordajes. Una revisión sistemática y metasíntesis cualitativa

The politics of active ageing present active citizenship of the elderly as a key challenge for the coming years. Active citizenship has been defined in different ways (as complimentary in most cases), outlining an eclecticism of participatory activities that includes political engagement in a participatory and deliberative manner, as well as community and voluntary action. This term is found in different contexts such as formal politics, work, civil society, and the home. This paper, based on a systematic review, identifies the context in which this concept emerges in relation to older people and people with dementia. It also analyses the different expressions of active citizenship used, and provides key elements to be taken into account in the formulation of policies in a context of accelerated demographic ageing and where dementia is a public health priority. The notion of active citizenship in old age is a step forward from active ageing to a broader concept that integrates the principle of equality between people irrespective of gender, age and the need for support.     

Temperature niche conservatism and strong genetic structure are involved in the trans-Panamanian colonization of Matudaea (Hamamelidaceae) to Andean forests

Matudaea is the only genus of the Hamamelidaceae found in South America. The genus is composed by two extant species, M. trinervia, from Mexico and Costa Rica, and Matudaea colombiana, from the Colombian Andes; additional fossil records are present in Central Europe. Population genetics, molecular phylogenetics and niche modelling approaches were applied to explain processes related with the trans-Panamanian M. trinervia/M. colombiana split and the putative colonization of the latter to the northern Andes. The split between the two Matudaea species was estimated during Middle Miocene. The colonization of Matudaea into South America could have been facilitated by the closure of the Isthmus of Panama and the global decreasing of temperature during Miocene. Five haplotypes of M. colombiana were identified, which show an eastwards decline of genetic diversity and suggest a founder effect in the colonization of Eastern cordillera of the Colombian Andes. We detected a niche conservatism signal between the two Matudaea species related with Temperature of Coldest Month and Mean Temperature of Driest Quarter bioclimatic variables; this signal might be related to the narrow altitudinal range occupied by the two species.     

Anatomy of the antennal dorsal organ in female of Neodryinus typhlocybae (Hymenoptera: Dryinidae): A peculiar sensory structure possibly involved in perception of host vibration

Neodryinus typhlocybae (Hymenoptera: Dryinidae) is a natural enemy of the planthopper Metcalfa pruinosa, which was introduced from North America into Europe and has become established in various regions as a pest species. Vibrational signals play a crucial role in the communication of M. pruinosa, which appears to be exploited by N. typhlocybae. Scanning and transmission electron microscopy have shown that the antennae of N. typhlocybae females have peculiar and complex sensory structures: deep longitudinal grooves that house long sensilla trichodea, termed here “Antennal Dorsal Organs.” Such structures were not present on male antennae. These sensilla extend for the length of the grooves, without contact with the groove cuticle. Their hair shaft is empty and aporous, and inserted into a specialized socket, underneath which there is a cuticular ampulla‐like chamber. Each sensillum is associated with two sensory neurons: one terminates at the proximal end of the dendritic sheath; the other continues into the sensillum sinus and is enclosed in the dendritic sheath. This second sensory neuron then enters the ampulla‐like chamber through the circular opening, and then terminates with a conspicuous tubular body at the shaft base. The possible involvement of this peculiar structure in the context of host recognition mechanism is discussed. J. Morphol. 277:128–137, 2016. © 2015 Wiley Periodicals, Inc.     

Discovery of isoquinolinone and naphthyridinone-based inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) as anticancer agents: Structure activity relationship and preclinical characterization

The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing’s sarcoma models.     

The structure and function of phytochrome A: the roles of the entire molecule and of its various parts

Phytochrome A is readily cleavable by proteolytic agents to yield an amino-terminal fragment of 66 kilodalton (kDa), which consists of residues 1 to approximately 600, and a dimer of the carboxy-terminal 55-kDa fragment, from residue 600 or so to the carboxyl terminus. The former domain, carrying the tetrapyrrole chromophore, has been studied extensively because of its photoactivity, while less attention has been paid to the non-chromophoric portion until quite recently. However, the evidence gathered to date suggests that this domain is also of great improtance. We present here a review of the structure and the biochemical and physiological functions of the two domains, of parts of these domains, and of the cooperation between them.