Três rearranjos diferentes, três fenótipos diferentes :Estudo Familiar Cromossoma 14

Introdução – Cromossomas derivativos são o resultado de rearranjos estruturais que tanto podem ocorrer num só, como entre dois ou mais cromossomas. Estes rearranjos dão origem a cromossomas estruturalmente anormais, podendo resultar um fenótipo normal ou mais ou menos grave, dependendo do tipo de anomalia encontrada. Materiais e métodos – Caso índex: homem de 55 anos, referenciado para estudos de citogenética clássica (cariótipo com bandas GTG de alta resolução) e molecular (MLPA – kits P036 e P070 e FISH com sonda subtelomérica especifica para o cromossoma 14) por apresentar um quadro clínico de atraso mental. Posteriormente realizaram-se estudos citogenéticos a uma irmã com atraso cognitivo e baixa estatura, e a mais quatro familiares com fenótipos normais. Resultados – O cariótipo do caso índex revelou a existência de uma anomalia cromossómica estrutural desequilibrada num dos cromossomas 14, sugerindo uma deleção da banda 14q32, e uma duplicação do braço curto localizada na parte terminal do braço longo. Nos estudos de citogenética molecular, a técnica de MLPA identificou uma deleção da região subtelomérica no braço longo do cromossoma 14, em ambos os kits e, posteriormente, a técnica de FISH comprovou essa deleção. Após estudos familiares, concluiu-se que dois dos irmãos apresentavam anomalias cromossómicas distintas do caso índex, envolvendo igualmente o cromossoma 14. Apesar de não ser possível efetuar o cariótipo à mãe (falecida), presume-se que estas alterações tenham tido origem numa anomalia cromossómica materna, uma vez que o pai deste indivíduo apresentava um cariótipo normal. Conclusões – Os autores apresentam os resultados citogenéticos dos vários indivíduos estudados, e realçam a raridade da existência de três rearranjos diferentes (um deles aparentemente equilibrado e dois desequilibrados), envolvendo o cromossoma 14, encontrados numa mesma família

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Biological interactions between nematophagous fungi, Esteya spp., and the pinewood nematode, Bursaphelenchus xylophilus

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a quarantine organism in several countries and the causal agent of pine wilt disease (PWD), a serious threat to pine forests worldwide. PWD results from complex interactions between the nematode, its insect vector, Monochamus spp., and host plants (conifers), being the nematode the common element in this interaction. The PWN is considered the sixth most economically important plant-parasitic nematode. In Europe, this pest was first reported in Portugal in 1999, in maritime pine, Pinus pinaster. Due to its economic importance and worldwide distribution, an enormous amount of effort is devoted to research on B. xylophilus and PWD. Scenarios strongly suggest that climate change is likely going to cause a spread of PWD and outbreaks in areas free of the disease. The urgent need for sustainable management strategies has led to an increasing interest in antagonists capable of suppressing the PWN. Nematophagous fungi belonging to the Esteya genus are reported as natural enemies of the PWN and promising biocontrol agents. There are currently two described species: E. vermicola and E. floridanum, the first of which is capable of mimicking volatile organic compounds produced naturally by Pinus spp. in order to attract PWN. However, few studies have been carried out on the development of Esteya spp. inside pine trees, and none using maritime pine, the main and most affected species in Portuguese forests and its largest carbon reservoir. It is therefore crucial to understand the plant-nematode-fungus interactions between P. pinaster, B. xylophilus and Esteya spp. In this sense, biological interactions between these two antagonists, the PWN and P. pinaster were investigated, namely fungus-fungus, fungus-nematode and fungus-tree, as well as feeding trials and chemotaxis assays, to determine the attractive power of both fungal species. These results will enlighten us on the most promising species for biocontrol and help us devise new ways to manage PWD

An algorithm for satellite-based burned area mapping using change point detection and Markov random fields

Area burned in tropical savannas of Brazil and Australia was mapped using SPOT-VGT daily 1km resolution imagery and a new algorithm based on change point detection techniques. Each study area covers about 250,000 km2 and the mapping exercise spans a 11-yr period (1999-2009). Our algorithm addresses each pixel as a time series and detects changes in the statistical properties (mean and variance) of NIR and SWIR reflectance values, toidentify potential burning dates. We compare the performance of binary segmentation (BinSeg) and Pruned Exact Linear Time (PELT) change point detection techniques. Mean reflectance values observed at a pixel over the week after a change point has been detected are compared with a biome-specific statistical distribution of burned area reflectance values, to assess the probability that the change point detected does correspond to a burn event. Change points corresponding to an increase in reflectance are dismissed as potential burn events, as are those occurring outside of a pre-defined fire season. In the last step of the algorithm, monthly burned area probability maps are converted to dichotomous (burned-unburned maps), using Markov Random Fields. A preliminary assessment of our results is performed by comparing them with those from the MODIS active fires and burned area products, taking into account differences in spatial resolution between the two sensors

Investigating Executive Working Memory and Phonological Short-Term Memory in Relation to Fluency and Self-Repair Behavior in L2 Speech

This paper reports the findings of a study investigating the relationship of executive working memory (WM) and phonological short-term memory (PSTM) to fluency and self-repair behavior during an unrehearsed oral task performed by second language (L2) speakers of English at two levels of proficiency, elementary and lower intermediate. Correlational analyses revealed a negative relationship between executive WM and number of pauses in the lower intermediate L2 speakers. However, no reliable association was found in our sample between executive WM or PSTM and self-repair behavior in terms of either frequency or type of self-repair. Taken together, our findings suggest that while executive WM may enhance performance at the conceptualization and formulation stages of the speech production process, self-repair behavior in L2 speakers may depend on factors other than working memory

Tau mislocation in glucocorticoid-triggered hippocampal pathology

The exposure to high glucocorticoids (GC) triggers neuronal atrophy and cognitive deficits, but the exact cellular mechanisms underlying the GC-associated dendritic remodeling and spine loss are still poorly understood. Previous studies have implicated sustained GC elevations in neurodegenerative mechanisms through GC-evoked hyperphosphorylation of the cytoskeletal protein Tau while Tau mislocation has recently been proposed as relevant in Alzheimer's disease (AD) pathology. In light of the dual cytoplasmic and synaptic role of Tau, this study monitored the impact of prolonged GC treatment on Tau intracellular localization and its phosphorylation status in different cellular compartments. We demonstrate, both by biochemical and ultrastructural analysis, that GC administration led to cytosolic and dendritic Tau accumulation in rat hippocampus, and triggered Tau hyperphosphorylation in epitopes related to its malfunction (Ser396/404) and cytoskeletal pathology (e.g., Thr231 and Ser262). In addition, we show, for the first time, that chronic GC administration also increased Tau levels in synaptic compartment; however, at the synapse, there was an increase in phosphorylation of Ser396/404, but a decrease of Thr231. These GC-triggered Tau changes were paralleled by reduced levels of synaptic scaffolding proteins such as PSD-95 and Shank proteins as well as reduced dendritic branching and spine loss. These in vivo findings add to our limited knowledge about the underlying mechanisms of GC-evoked synaptic atrophy and neuronal disconnection implicating Tau missorting in mechanism(s) of synaptic damage, beyond AD pathology.We would like to thank Rui Fernandes for TEM technical support. IS was supported by the Portuguese Foundation for Science and Technology (FCT).This work was funded by the Portuguese Foundation for Science and Technology (FCT) (grant NMC-113934 to IS and grant SFRH/BPD/80118/2011 to JC), Canon Foundation and project DoIT - Desenvolvimento e Operacionalização da Investigação de Translação (N° do projeto 13853), funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through the Programa Operacional Fatores de Competitividade (POFC).info:eu-repo/semantics/publishedVersio

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Profiling mycobiota communities associated with the Pine Wilt Disease

Pine wilt Disease (PWD) is one of the most damaging diseases for conifer forests worldwide. This complex disease involves the interaction between three primary biological elements - the pinewood nematode (PWN) Bursaphelenchus xylophilus, the insect-vector Monochamus sp., and the host tree Pinus spp. – and other secondary elements such as endophytic bacteria and fungi. The development of B. xylophilus is strongly associated with fungi that colonize the declining trees, with special impact in their reproduction and number of individuals carried by the vector. In light of previous knowledge, we are focused in obtaining a detailed characterization of the structure and dynamics of the nematode-fungi interactions. Using the ITS2 amplicon-based metagenomic approach, we compared the fungal communities from PWN infected and non-infected P. pinaster trees collected in two distint study sites, Tróia (location where PWN was first detected in 1999) and Seia (northwestern of Portugal)

Dumb and Lazy? A Comparison of Color Learning and Memory Retrieval in Drones and Workers of the Buff-Tailed Bumblebee, Bombus terrestris, by Means of PER Conditioning

More than 100 years ago, Karl von Frisch showed that honeybee workers learn and discriminate colors. Since then, many studies confirmed the color learning capabilities of females from various hymenopteran species. Yet, little is known about visual learning and memory in males despite the fact that in most bee species males must take care of their own needs and must find rewarding flowers to obtain food. Here we used the proboscis extension response (PER) paradigm to study the color learning capacities of workers and drones of the bumblebee, Bombus terrestris. Light stimuli were paired with sucrose reward delivered to the insects’ antennae and inducing a reflexive extension of the proboscis. We evaluated color learning (i.e. conditioned PER to color stimuli) in absolute and differential conditioning protocols and mid-term memory retention was measured two hours after conditioning. Different monochromatic light stimuli in combination with neutral density filters were used to ensure that the bumblebees could only use chromatic and not achromatic (e.g. brightness) information. Furthermore, we tested if bees were able to transfer the learned information from the PER conditioning to a novel discrimination task in a Y-maze. Both workers and drones were capable of learning and discriminating between monochromatic light stimuli and retrieved the learned stimulus after two hours. Drones performed as well as workers during conditioning and in the memory test, but failed in the transfer test in contrast to workers. Our data clearly show that bumblebees can learn to associate a color stimulus with a sugar reward in PER conditioning and that both workers and drones reach similar acquisition and mid-term retention performances. Additionally, we provide evidence that only workers transfer the learned information from a Pavlovian to an operant situation

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust