CHF5074 restores visual memory ability and pre‐synaptic cortical acetylcholine release in pre‐plaque Tg2576 mice

CHF5074, a new microglial modulator, attenuates memory deficit in Alzheimer's disease transgenic mice. In this study, the effect of an acute or subacute CHF5074 treatment on in vivo novel object recognition test and on [³H]Acetylcholine (ACh) and GABA release in pre‐plaque (7‐month‐old) Tg2576 mice have been compared with those induced by the γ‐secretase inhibitor LY450139 (semagacestat). Vehicle‐treated Tg2576 mice displayed an impairment of recognition memory compared with wild‐type animals. This impairment was recovered in transgenic animals acutely treated with CHF5074 (30 mg/kg), while LY450139 (1, 3, 10 mg/kg) was ineffective. In frontal cortex synaptosomes from vehicle‐treated Tg2576 mice, K⁺‐evoked [³H]ACh release was lower than that measured in wild‐type mice. This reduction was absent in transgenic animals subacutely treated with CHF5074 (30 mg/kg daily for 8 days), while it was slightly, not significantly, amplified by LY450139 (3 mg/kg daily for 8 days). There were no differences between the groups on spontaneous [³H]ACh release as well as spontaneous and K⁺‐evoked GABA release. These results suggest that CHF5074 has beneficial effects on visual memory and cortical cholinergic dysfunctions in pre‐plaque Tg2576 mice. Together with previous findings, these data suggest that CHF5074 could be a possible candidate for early Alzheimer's disease therapeutic regimens.     

Species Diversity,Phylogeny and Large Scale Biogeographic Patterns of the Genus Padina (Phaeophyceae,Dictyotales)

The brown algal genus Padina (Dictyotales, Phaeophyceae) is distributed worldwide in tropical and temperate seas. Global species diversity and distribution ranges, however, remain largely unknown. Species‐level diversity was reassessed using DNA‐based, algorithmic species delineation techniques based on cox3 and rbcL sequence data from 221 specimens collected worldwide. This resulted in estimates ranging from 39 to 61 putative species (ESUs), depending on the technique as well as the locus. We discuss the merits, potential pitfalls, and evolutionary and biogeographic significance of algorithmic species delineation. We unveil patterns whereby ESUs are in all but one case restricted to either the Atlantic or Indo‐Pacific Ocean. Within ocean basins we find evidence for the vast majority of ESUs to be confined to a single marine realm. Exceptions, whereby ESUs span up to three realms, are located in the Indo‐Pacific Ocean. Patterns of range‐restricted species likely arise by repeated founder events and subsequent peripatric speciation, hypothesized to dominate speciation mechanisms for coastal marine organisms in the Indo‐Pacific. Using a three‐gene (cox3, psaA and rbcL), relaxed molecular clock phylogenetic analysis we estimated divergence times, providing a historical framework to interpret biogeographic patterns.     

The computationalist reformulation of the mind-body problem

Computationalism, or digital mechanism, or simply mechanism, is a hypothesis in the cognitive science according to which we can be emulated by a computer without changing our private subjective feeling. We provide a weaker form of that hypothesis, weaker than the one commonly referred to in the (vast) literature and show how to recast the mind-body problem in that setting.     

Integrating actin dynamics,mechanotransduction and integrin activation: The multiple functions of actin binding proteins in focal adhesions

Focal adhesions are clusters of integrin transmembrane receptors that mechanically couple the extracellular matrix to the actin cytoskeleton during cell migration. Focal adhesions sense and respond to variations in force transmission along a chain of protein-protein interactions linking successively actin filaments, actin binding proteins, integrins and the extracellular matrix to adapt cell-matrix adhesion to the composition and mechanical properties of the extracellular matrix. This review focuses on the molecular mechanisms by which actin binding proteins integrate actin dynamics, mechanotransduction and integrin activation to control force transmission in focal adhesions.     

The genus Gymnotus (Gymnotiformes: Gymnotidae) in Argentina. How bad taxonomy results in poor regulations and no conservation

Four species of the genus Gymnotus are present in Argentina: G. inaequilabiatus, G. omarorum, G. pantanal, and G. sylvius, the last three species being recorded for the first time in freshwater courses. Gymnotus omarorum, G. pantanal, and G. sylvius together with others of the genus Brachyhypopomus are the group of fishes that bear the greatest impact in the trade as live bait for sport fishing in the northeastern region of Argentina. Within this large area, only the provinces of Chaco, Corrientes, and Formosa have regulations for the catch, trade, and sale of species as live bait. Unfortunately, the species covered by legal regulations are Gymnotus carapo and Brachyhypopomus brevirostris, neither of which occurs in freshwater habitats of Argentina. Comments are included as to how this bad taxonomy affects the regulations and conservation status of these species.     

Seasonal Habitat Use of Agoutis (Dasyprocta azarae) is Driven by the Palm Attalea phalerata in Brazilian Pantanal

Resource availability can influence animal movement causing changes in home‐range size and arrangement between seasons. We investigated the influence of acuri palm (Attalea phalerata) on the occupancy of agouti Dasyprocta azare during both the dry and rainy seasons, as well as the abandonment probabilities in the transition between seasons in the Brazilian Pantanal. The agoutis occupied a high proportion of the forested areas in the rainy season (0.83), but the occupancy decreased in the dry season (0.39). In the rainy season, occupancy by agoutis was not correlated with acuri palm availability, while in the dry season, it was positively correlated with the palm's availability. The acuri palm availability also drove the agoutis' probability of site abandonment from the rainy to the dry season, with higher abandonment probability in sites with low acuri palm availability. These findings show that this large‐seeded palm can be an important resource for the agoutis' populations during the fruit‐scarcity period. The acuri palm seeds may be particularly important for agoutis using fragmented forests, given that the large‐seeded palms are able to persist even in small fragments, which is untrue for other important resource.     

Constitutive Activation of the Calcium Sensor STIM1 Causes Tubular-Aggregate Myopathy

Tubular aggregates are regular arrays of membrane tubules accumulating in muscle with age. They are found as secondary features in several muscle disorders, including alcohol- and drug-induced myopathies, exercise-induced cramps, and inherited myasthenia, but also exist as a pure genetic form characterized by slowly progressive muscle weakness. We identified dominant STIM1 mutations as a genetic cause of tubular-aggregate myopathy (TAM). Stromal interaction molecule 1 (STIM1) is the main Ca²⁺ sensor in the endoplasmic reticulum, and all mutations were found in the highly conserved intraluminal Ca²⁺-binding EF hands. Ca²⁺ stores are refilled through a process called store-operated Ca²⁺ entry (SOCE). Upon Ca²⁺-store depletion, wild-type STIM1 oligomerizes and thereby triggers extracellular Ca²⁺ entry. In contrast, the missense mutations found in our four TAM-affected families induced constitutive STIM1 clustering, indicating that Ca²⁺ sensing was impaired. By monitoring the calcium response of TAM myoblasts to SOCE, we found a significantly higher basal Ca²⁺ level in TAM cells and a dysregulation of intracellular Ca²⁺ homeostasis. Because recessive STIM1 loss-of-function mutations were associated with immunodeficiency, we conclude that the tissue-specific impact of STIM1 loss or constitutive activation is different and that a tight regulation of STIM1-dependent SOCE is fundamental for normal skeletal-muscle structure and function.