Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior

A problemática dos Direitos Humanos Fundamentais na América Latina e na Europa: Desafios materiais e eficaciais

Trata-se de uma obra que reúne pesquisadores de universidades brasileiras e espanholas, que tem como escopo refletir sobre o tema dos direitos humanos fundamentais na América Latina e Europa.  As investigações levadas a cabo inserem-se num projeto conjunto da Universidade do Oeste de Santa Catarina (Unoesc) e da Càtedra de Cultura Jurídica da Universidade de Girona – Espanha. Entretanto, as contribuições têm origens institucionais diversas; do Brasil, há artigos de professores pesquisadores de várias instituições, a saber: Unoesc, Uninove, UFSC, Unisc e da Unifor;  da Espanha,  das seguintes Universidades:  Girona, Santo Antonio de Murcia, Rey Juan Carlos, Nacional de Educación a Distancia. Além das contribuições brasileiras e espanholas, há uma americana, da Universidade de Connecticut. Esta dividida em três capítulos e apresenta vinte e dois artigos sobre os diversos ramos do direito, sempre com as lentes voltadas, direta ou indiretamente, para os direitos humanos fundamentais. O primeiro capítulo trata da Teoria Geral dos direitos humanos fundamentais e sua trasnacionalidade, destacando aspectos históricos, filosóficos, sociológicos, doutrinários e jurisprudenciais dos direitos humanos fundamentais.  O segundo e o terceiro capítulos abordam as dimensões materiais e eficaciais dos direitos humanos fundamentais civis e sociais, respectivament

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder

Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans

A problemática dos Direitos Humanos Fundamentais na América Latina e na Europa: Desafios materiais e eficaciais

Trata-se de uma obra que reúne pesquisadores de universidades brasileiras e espanholas, que tem como escopo refletir sobre o tema dos direitos humanos fundamentais na América Latina e Europa.  As investigações levadas a cabo inserem-se num projeto conjunto da Universidade do Oeste de Santa Catarina (Unoesc) e da Càtedra de Cultura Jurídica da Universidade de Girona – Espanha. Entretanto, as contribuições têm origens institucionais diversas; do Brasil, há artigos de professores pesquisadores de várias instituições, a saber: Unoesc, Uninove, UFSC, Unisc e da Unifor;  da Espanha,  das seguintes Universidades:  Girona, Santo Antonio de Murcia, Rey Juan Carlos, Nacional de Educación a Distancia. Além das contribuições brasileiras e espanholas, há uma americana, da Universidade de Connecticut. Esta dividida em três capítulos e apresenta vinte e dois artigos sobre os diversos ramos do direito, sempre com as lentes voltadas, direta ou indiretamente, para os direitos humanos fundamentais. O primeiro capítulo trata da Teoria Geral dos direitos humanos fundamentais e sua trasnacionalidade, destacando aspectos históricos, filosóficos, sociológicos, doutrinários e jurisprudenciais dos direitos humanos fundamentais.  O segundo e o terceiro capítulos abordam as dimensões materiais e eficaciais dos direitos humanos fundamentais civis e sociais, respectivament