Solution structure of ψ(32)-modified anticodon stem–loop of Escherichia coli tRNA(Phe)

Nucleoside base modifications can alter the structures and dynamics of RNA molecules and are important in tRNAs for maintaining translational fidelity and efficiency. The unmodified anticodon stem–loop from Escherichia coli tRNA(Phe) forms a trinucleotide loop in solution, but Mg(2+) and dimethylallyl modification of A(37) N6 destabilize the loop-proximal base pairs and increase the mobility of the loop nucleotides. The anticodon arm has three additional modifications, ψ(32), ψ(39), and A(37) C2-thiomethyl. We have used NMR spectroscopy to investigate the structural and dynamical effects of ψ(32) on the anticodon stem-loop from E.coli tRNA(Phe). The ψ(32) modification does not significantly alter the structure of the anticodon stem–loop relative to the unmodified parent molecule. The stem of the RNA molecule includes base pairs ψ(32)-A(38) and U(33)–A(37) and the base of ψ(32) stacks between U(33) and A(31). The glycosidic bond of ψ(32) is in the anti configuration and is paired with A(38) in a Watson–Crick geometry, unlike residue 32 in most crystal structures of tRNA. The ψ(32) modification increases the melting temperature of the stem by ∼3.5°C, although the ψ(32) and U(33) imino resonances are exchange broadened. The results suggest that ψ(32) functions to preserve the stem integrity in the presence of additional loop modifications or after reorganization of the loop into a translationally functional conformation

Beneficios Juridicos del Tratado de Libre Comercio entre Chile y Canada para la Region del Maule

86 p.La presente memoria consta de cuatro capítulos: Cáp. I Integración Económica, Cáp. II Descripción de las relaciones de Chile con Canadá, Cáp. III Caracterización de la Economía de la Séptima Región, Cáp. IV normas a las que debe someterse el sector agrícola y Cáp. V Apreciaciones acerca del TLC Chile-Canadá. El objetivo principal es determinar cómo ha beneficiado el sector agrícola de la Séptima Región con el Acuerdo Libre Comercio Chile-Canadá y cómo la normativa vigente incentiva a las exportaciones de los agricultores Chilenos de esta Región. El método descriptivo se utilizara para realizar este trabajo. Los objetivos se pretenden lograr mediante recopilación de información mediante revisión bibliográfica y búsqueda de material por Internet. El objetivo principal es determinar cómo ha beneficiado el sector agrícola de la Séptima Región con el Acuerdo Libre Comercio Chile-Canadá y cómo la normativa vigente incentiva a las exportaciones de los agricultores Chilenos de esta Región. El método descriptivo se utilizara para realizar este trabajo. Los objetivos se pretenden lograr mediante recopilación de información mediante revisión bibliográfica y búsqueda de material por Internet. Los resultados se han logrado parcialmente puesto que existe poca información acerca de las exportaciones de la región del Maule a Canadá, no hay bastantes asociaciones o grupos de agricultores y los que existen no conocen los beneficios que reporta el acuerdo

Urohidrosis as an overlooked cooling mechanism in long-legged birds

Behavioural thermoregulation could buffer the impacts of climate warming on vertebrates. Specifically, the wetting of body surfaces and the resulting evaporation of body fluids serves as a cooling mechanism in a number of vertebrates coping with heat. Storks (Ciconiidae) frequently excrete onto their legs to prevent overheating, a phenomenon known as urohidrosis. Despite the increasingly recognised role of bare and highly vascularised body parts in heat exchange, the ecological and evolutionary determinants of urohidrosis have been largely ignored. We combine urohidrosis data from a scientifically curated media repository with microclimate and ecological data to investigate the determinants of urohidrosis in all extant stork species. Our phylogenetic generalised linear mixed models show that high temperature, humidity and solar radiation, and low wind speed, promote the use of urohidrosis across species. Moreover, species that typically forage in open landscapes exhibit a more pronounced use of urohidrosis than those mainly foraging in waterbodies. Substantial interspecific variation in temperature thresholds for urohidrosis prevalence points to different species vulnerabilities to high temperatures. This integrated approach that uses online data sources and methods to model microclimates should provide insight into animal thermoregulation and improve our capacity to make accurate predictions of climate change’s impact on biodiversityinfo:eu-repo/semantics/publishedVersio

Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation

Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. The most prevalent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN) associated with mutations in the gene of pantothenate kinase 2 (PANK2), which is essential for coenzyme A (CoA) synthesis. There is no cure for NBIA nor is there a standard course of treatment. In the current work, we describe that fibroblasts derived from patients harbouring PANK2 mutations can reproduce many of the cellular pathological alterations found in the disease, such as intracellular iron and lipofuscin accumulation, increased oxidative stress, and mitochondrial dysfunction. Furthermore, mutant fibroblasts showed a characteristic senescent morphology. Treatment with pantothenate, the PANK2 enzyme substrate, was able to correct all pathological alterations in responder mutant fibroblasts with residual PANK2 enzyme expression. However, pantothenate had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of pantothenate in particular mutations was also confirmed in induced neurons obtained by direct reprograming of mutant fibroblasts. Our results suggest that pantothenate treatment can stabilize the expression levels of PANK2 in selected mutations. These results encourage us to propose our screening model as a quick and easy way to detect pantothenate-responder patients with PANK2 mutations. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of pantothenate.Instituto de Salud Carlos III FIS PI16/00786Junta de Andalucía CTS-5725, BIO-122Dirección General de Investigación Científica y Técnica BFU2015-64536-

Associations between sitting time and a range of symptoms in mid-age women

Objective. The aim of this study was to explore longitudinal associations between sitting and physical and psychological symptoms in mid-age women

Structural and functional analysis of the Rous Sarcoma virus negative regulator of splicing and demonstration of its activation by the 9G8 SR protein

Retroviruses require both spliced and unspliced RNAs for replication. Accumulation of Rous Sarcoma virus (RSV) unspliced RNA depends upon the negative regulator of splicing (NRS). Its 5′-part is considered as an ESE binding SR proteins. Its 3′-part contains a decoy 5′-splice site (ss), which inhibits splicing at the bona fide 5′-ss. Only the 3D structure of a small NRS fragment had been experimentally studied. Here, by chemical and enzymatic probing, we determine the 2D structure of the entire RSV NRS. Structural analysis of other avian NRSs and comparison with all sequenced avian NRSs is in favour of a phylogenetic conservation of the NRS 2D structure. By combination of approaches: (i) in vitro and in cellulo splicing assays, (ii) footprinting assays and (iii) purification and analysis of reconstituted RNP complex, we define a small NRS element retaining splicing inhibitory property. We also demonstrate the capability of the SR protein 9G8 to increase NRS activity in vitro and in cellulo. Altogether these data bring new insights on how NRS fine tune splicing activity

How does neighbourhood socio-economic status affect the interrelationships between functioning dimensions in first episode of psychosis? A network analysis approach

The links between psychosis and socio-economic disadvantage have been widely studied. No previous study has analysed the interrelationships and mutual influences between functioning dimensions in first episode of psychosis (FEP) according to their neighbourhood household income, using a multidimensional and transdiagnostic perspective. 170 patients and 129 controls, participants in an observational study (AGES-CM), comprised the study sample. The WHO Disability Assessment Schedule (WHODAS 2.0) was used to assess functioning, whereas participants' postcodes were used to obtain the average household income for each neighbourhood, collected by the Spanish National Statistics Institute (INE). Network analyses were conducted with the aim of defining the interrelationships between the different dimensions of functioning according to the neighbourhood household income. Our results show that lower neighbourhood socioeconomic level is associated with lower functioning in patients with FEP. Moreover, our findings suggest that “household responsibilities” plays a central role in the disability of patients who live in low-income neighbourhoods, whereas “dealing with strangers” is the most important node in the network of patients who live in high-income neighbourhoods. These results could help to personalize treatments, by allowing the identification of potential functioning areas to be prioritized in the treatment of FEP according to the patient's neighbourhood characteristic

Crystal Structure Analysis Reveals Functional Flexibility in the Selenocysteine-Specific tRNA from Mouse

Selenocysteine tRNAs (tRNA(Sec)) exhibit a number of unique identity elements that are recognized specifically by proteins of the selenocysteine biosynthetic pathways and decoding machineries. Presently, these identity elements and the mechanisms by which they are interpreted by tRNA(Sec)-interacting factors are incompletely understood.We applied rational mutagenesis to obtain well diffracting crystals of murine tRNA(Sec). tRNA(Sec) lacking the single-stranded 3'-acceptor end ((ΔGCCA)RNA(Sec)) yielded a crystal structure at 2.0 Å resolution. The global structure of (ΔGCCA)RNA(Sec) resembles the structure of human tRNA(Sec) determined at 3.1 Å resolution. Structural comparisons revealed flexible regions in tRNA(Sec) used for induced fit binding to selenophosphate synthetase. Water molecules located in the present structure were involved in the stabilization of two alternative conformations of the anticodon stem-loop. Modeling of a 2'-O-methylated ribose at position U34 of the anticodon loop as found in a sub-population of tRNA(Sec)in vivo showed how this modification favors an anticodon loop conformation that is functional during decoding on the ribosome. Soaking of crystals in Mn(2+)-containing buffer revealed eight potential divalent metal ion binding sites but the located metal ions did not significantly stabilize specific structural features of tRNA(Sec).We provide the most highly resolved structure of a tRNA(Sec) molecule to date and assessed the influence of water molecules and metal ions on the molecule's conformation and dynamics. Our results suggest how conformational changes of tRNA(Sec) support its interaction with proteins