Formacion de neuronas nuevas en el hipocampo adulto: neurogenesis [the new neuron formation in the adult hippocampus: neurogenesis]

New neuron formation in the adult brain was an interesting finding that extended the knowledge about brain plasticity. In 1966 Joseph Altman reported the incorporation of tritiated thymidine to neural cell DNA. This finding indicated the proliferation event in the adult brain. After twenty years of this finding, new information was generated that confirmed the new neuron formation in the adulthood. In this review, we will mention different aspects of the new neuron formation process called neurogenesis, as well as some of the factors that modulate such process, citing the information already known about the neuronal development stages that take place for the new neuron formation in the hippocampus. Finally, we will review some evidence about the neurogenic process in depression and in neurodegenerative diseases, as well as the possible role of the new neurons when they are integrated into the neuronal network. In the adult brain there are two regions where new neuron formation process takes place: the olfactory bulb and the hippocampus. New neurons are derived from neural stem cells, which reside in the subventricular zone of the lateral ventricles and in the subgranular zone of the dentate gyrus. Neural stem cells may proliferate and generate the rapid amplifying progenitor and neuroblast populations. These populations will migrate and differentiate in neurons to finally be integrated into the neuronal network. In the adult brain, neural stem cells have radial glial features expressing specific markers as the glial fibrilar acidic protein (GFAP), as well as the un-differentiated cell marker nestin. This characteristic makes suitable neural stem cells identification. Thus, the new neurons can be identified by both the specific marker expression and by electrophysiological properties. The different cell development stages during the neurogenic process have been characterized in the subventricular zone as well as in the subgranular zone of the dentate gyrus. In addition to the radial-glia features, neural stem cells show a slowly dividing ratio and once the neural stem cells divide by asymmetric division a rapid amplifying progenitor population is generated. In the hippocampus, phenotype analysis had allowed cell classification in three different types according to the kind of protein marker expression. These progenitors are generated during the expansion phase by symmetric cell division. Type 2a and 2b present short neuritic processes parallel to the granular cell layer and the Type 3 present longer processes integrated into the granular cell layer. During this step, where the migration and cell fate decision take place, the cells express different markers as the microtubule associated protein doublecortin, the homeobox gene related to the drosophila gene prospero Prox-1 and the neuron-specific nuclear protein Neu-N. Once the cells exit the cell cycle, immature neurons are generated showing longer dendritic processes crossing the granular cell layer. These immature neurons will fully differentiate to be integrated into the neuronal network. At this final stage the cells are fully differentiated and the new neurons express specific markers as the calcium binding protein calbindin and their electrophysiological properties are similar to the old neurons. Neurogenesis is a complex process that is modulated and regulated by different factors. One of these is the niche which is formed by the neural stem cells, astrocytes and endothelial cells. Adult neural stem cells proliferate and differentiate depending on the cellular and molecular composition of the niche. The three components work in synchrony in both neurogenic areas with active proliferation. The role of the niche is the maintenance of the stem cells pool. The astrocytes modulate the proliferation of the neural stem cell and of the rapid amplifying cell population, as well as the migration of these cells by the action of the secreting factors. The niche also plays a key role in maintaining the astrocytic and the endothelial cell populations. Besides the niche, other factors are involved in the neurogenic process, such as the neurotransmitters (GABA, glutamate, serotonin, dopamine), hormones (prolactin, growth hormone), growth factors (FGF, EGF) and neurotrophins (BDNF, NT3). All of them modulate different steps of the process. Some other factors that influence the new neuron formation include the physical activity, enrichment environment and social interaction. It has been shown that physical activity increases the number of surviving newborn cells when rodents have free access to the running wheel. Another positive regulator of the neurogenic process is the enrichment environment. The influence of this factor on the new neuron formation was demonstrated when the animals were maintained in a cage with tunnels and toys. In addition, when the rodents were forced to learn a particular task, more new neurons were found in the dentate gyrus. Additionally, the social interaction has a positive influence on the new neuron formation. Even when neurogenesis is positively regulated by the afore mentioned factors, different conditions and factors have a negative influence on this process. It is known that psychological stress affects in a negative manner the neurogenic process. The stress decreases the proliferation of progenitor cells in the dentate gyrus. This negative effect involves glucocorticoids whose increased levels inhibit the new neuron formation. Also, an exogenous administered corticosterone suppresses the new neuron formation. Another negative factor on neurogenesis related to glucocorticoids, is the sleep deprivation, which impairs the neurogenic process by increasing corticosterone levels causing a reduction in cell proliferation. Also, the abuse drugs cause a negative effect in the new neuron formation. It is known that chronic alcoholism negatively impact eurogenesis as well as cocaine, drug that impairs the proliferation dynamics in the dentate gyrus. Psychiatric disorders, such as depression, have been associated with an impaired neurogenesis, which is reverted by antidepressant drugs. In contrast to the effects of stress, an antidepressant pharmacologic treatment increases the new neuron formation. The antidepressant effect is dependent on chronic treatment, consistent with the time course of the therapeutic action of these compounds. Recently, it has been shown that fluoxetine increases symmetric divisions of early progenitor cells and that these cells called or named neuronal progenitors targeted by fluoxetine in the adult brain. This report describes one mechanism for antidepressant; however, the mechanisms by which antidepressant drugs act is not known at all and can be complex. Nevertheless, it has been reported that antidepressants induce an increase in serotonin or norephinephrine levels which activate the corresponding receptors and their downstream signaling pathways. One of these signaling pathways is the cAMP-CREB cascade. This second messenger is upregulated in the hippocampus together with the activity of the cAMP-dependent protein kinase. On the same pathway, the cAMP response element binding protein (CREB) shows an increase in function and expression. In patients with neurodegeneration, a defect in the neurogenesis process has been described. In Alzheimer’s disease, cell proliferation and the potential regenerative factors levels are diminished. However, several studies have revealed an increase in the expression of the neurogenic marker doublecortin. Recently, it has been reported the presence of proliferative cells in presenile Alzheimer hippocampus without indications for altered dentate gyrus. In addition to this finding, the influence of the enrichment environment on the new neuron formation has been explored. In these studies, it was shown that rodents housed under enrichment conditions had an increased neurotrophin 3 (NT-3) and brain derived neurotrophic factor, as well as an increased hippocampal neurogenesis accomplished with the improvement in the water maze performance. In another study, described by Lazarov in 2005, the enrichment environment leads a reduction in the levels of cerebral beta-amyloid and an increase in the genes associated with learning-memory, neurogenesis and cell survival pathways. In amyotrophic lateral sclerosis that is characterized by motor neuron degeneration the new neuron formation is impaired. By using mutant mice for the superoxide dismutase-1 enzyme, an enzyme that is altered in amyotrophic lateral sclerosis and with the precursor cells isolated from the subventricular zone of the this mutants there is a reduction in the incorporation of the DNA synthesis marker bromodeoxyuridine(BrdU), and in the response to mitogen stimulation, in presymptomatic and symptomatic mice, respectively. Evidence obtained so far strongly suggest that neural stem cells manipulation can be a good possibility to induce the neuron replacement in the treatment of neurodegenerative and psychiatric illnesses. However it is necessary to go deeply in the mechanisms and signaling pathways involved in the neurogenesis processes

Systematic effects on dark energy from 3D weak shear

We present an investigation into the potential effect of systematics inherent in multi-band wide field surveys on the dark energy equation of state determination for two 3D weak lensing methods. The weak lensing methods are a geometric shear-ratio method and 3D cosmic shear. The analysis here uses an extension of the Fisher matrix framework to jointly include photometric redshift systematics, shear distortion systematics and intrinsic alignments. We present results for DUNE and Pan-STARRS surveys. We show that assuming systematic parameters are fixed, but possibly biased, results in potentially large biases in dark energy parameters. We quantify any potential bias by defining a Bias Figure of Merit. We also show the effect on the dark energy Figure of Merit of marginalising over each systematic parameter individually. We find that the largest effect on the Figure of Merit comes from uncertainty in the photometric redshift systematic parameters. These can reduce the Figure of Merit by up to a factor of 2 to 4 in both 3D weak lensing methods, if no informative prior on the systematic parameters is applied. Shear distortion systematics have a smaller overall effect. Intrinsic alignment effects can reduce the Figure of Merit by up to a further factor of 2. This, however, is a worst case scenario. By including prior information on systematic parameters the Figure of Merit can be recovered to a large extent. We conclude that, as a rule of thumb, given a realistic current understanding of intrinsic alignments and photometric redshifts, then including all three primary systematic effects reduces the Figure of Merit by at most a factor of 2, but that in reality this factor should be much less. [abridged]Comment: 20 pages, 11 figures, submitted to MNRA

Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration

Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We then used human induced pluripotent stem cell (iPSC)-derived neurons and 3D cerebral organoids from patients carrying the MAPT p.R406W mutation and CRISPR/Cas9, corrected controls to evaluate proteostasis. MAPT p.R406W was sufficient to induce morphological and functional deficits in the lysosomal pathway in iPSC-neurons. These phenotypes were reversed upon correction of the mutant allele with CRISPR/Cas9. Treatment with mTOR inhibitors led to tau degradation specifically in MAPT p.R406W neurons. Together, our findings suggest that MAPT p.R406W is sufficient to cause impaired lysosomal function, which may contribute to disease pathogenesis and serve as a cellular phenotype for drug screening

P‐NEXFS Analysis of Aerosol Phosphorus Delivered to the Mediterranean Sea

Biological productivity in many ocean regions is controlled by the availability of the nutrient phosphorus. In the Mediterranean Sea, aerosol deposition is a key source of phosphorus and understanding its composition is critical for determining its potential bioavailability. Aerosol phosphorus was investigated in European and North African air masses using phosphorus near‐edge X‐ray fluorescence spectroscopy (P‐NEXFS). These air masses are the main source of aerosol deposition to the Mediterranean Sea. We show that European aerosols are a significant source of soluble phosphorus to the Mediterranean Sea. European aerosols deliver on average 3.5 times more soluble phosphorus than North African aerosols and furthermore are dominated by organic phosphorus compounds. The ultimate source of organic phosphorus does not stem from common primary emission sources. Rather, phosphorus associated with bacteria best explains the presence of organic phosphorus in Mediterranean aerosols

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes

OBJECTIVE - To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS - Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (>8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. CONCLUSIONS - Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications. © 2010 by the American Diabetes Association.link_to_OA_fulltex

Evidence for the accelerated expansion of the Universe from weak lensing tomography with COSMOS

We present a tomographic cosmological weak lensing analysis of the HST COSMOS Survey. Applying our lensing-optimized data reduction, principal component interpolation for the ACS PSF, and improved modelling of charge-transfer inefficiency, we measure a lensing signal which is consistent with pure gravitational modes and no significant shape systematics. We carefully estimate the statistical uncertainty from simulated COSMOS-like fields obtained from ray-tracing through the Millennium Simulation. We test our pipeline on simulated space-based data, recalibrate non-linear power spectrum corrections using the ray-tracing, employ photometric redshifts to reduce potential contamination by intrinsic galaxy alignments, and marginalize over systematic uncertainties. We find that the lensing signal scales with redshift as expected from General Relativity for a concordance LCDM cosmology, including the full cross-correlations between different redshift bins. For a flat LCDM cosmology, we measure sigma_8(Omega_m/0.3)^0.51=0.75+-0.08 from lensing, in perfect agreement with WMAP-5, yielding joint constraints Omega_m=0.266+0.025-0.023, sigma_8=0.802+0.028-0.029 (all 68% conf.). Dropping the assumption of flatness and using HST Key Project and BBN priors only, we find a negative deceleration parameter q_0 at 94.3% conf. from the tomographic lensing analysis, providing independent evidence for the accelerated expansion of the Universe. For a flat wCDM cosmology and prior w in [-2,0], we obtain w<-0.41 (90% conf.). Our dark energy constraints are still relatively weak solely due to the limited area of COSMOS. However, they provide an important demonstration for the usefulness of tomographic weak lensing measurements from space. (abridged)Comment: 26 pages, 25 figures, matches version accepted for publication by Astronomy and Astrophysic

P-NEXFS analysis of aerosol phosphorus delivered to the Mediterranean Sea

Biological productivity in many ocean regions is controlled by the availability of the nutrient phosphorus. In the Mediterranean Sea, aerosol deposition is a key source of phosphorus and understanding its composition is critical for determining its potential bioavailability. Aerosol phosphorus was investigated in European and North African air masses using phosphorus near-edge X-ray fluorescence spectroscopy (P-NEXFS). These air masses are the main source of aerosol deposition to the Mediterranean Sea. We show that European aerosols are a significant source of soluble phosphorus to the Mediterranean Sea. European aerosols deliver on average 3.5 times more soluble phosphorus than North African aerosols and furthermore are dominated by organic phosphorus compounds. The ultimate source of organic phosphorus does not stem from common primary emission sources. Rather, phosphorus associated with bacteria best explains the presence of organic phosphorus in Mediterranean aerosols

2016+112: A Gravitationally Lensed Type-II Quasar

A single-screen model of the gravitational lens system 2016+112 is proposed, that explains recent Hubble Space Telescope} (HST) infrared (NICMOS-F160W) observations and new high-resolution European VLBI Network (EVN) 5-GHz radio observations, presented in this paper. In particular, we find that a massive `dark' structure at the lens position, previously suggested by X-ray, optical and spectroscopic observations of the field around 2016+112, is not necessarily required to accommodate the strong lensing constraints. A massive structure to the north-west of the lens system, suggested from a weak-lensing analysis of the field, is included in the model. The lensed source is an X-ray bright active galaxy at z=3.273 with a central bright optical continuum core and strong narrow emission lines, suggestive of a type-II quasar. The EVN 5-GHz radio maps show a radio-jet structure with at least two compact subcomponents. We propose that the diamond caustic crosses the counter-jet of the radio source, so that part of the counter-jet, host galaxy and narrow-line emission regions are quadruply imaged. The remainder of the radio source, including the core, is doubly imaged. Our lens model predicts a very high magnification (mu~300) at the bightness peaks of the inner two radio components of complex C. If the jet exhibits relativistic velocities on micro-arsecond scales, it might result in apparent hyperluminal motion. However, the lack of strong radio variability and the peaked radio spectrum imply that these motions need not be present in the source. Our model furthermore implies that the optical spectrum of C' can only show features of the AGN and its host galaxy.Comment: 10 pages, 3 figures, accepted by MNRAS; minor change

“Leaps of faith”: parents' and professionals' viewpoints on preparing adolescents on the autism spectrum for leaving school

Adolescents on the autism spectrum experience difficulty transitioning from secondary school to post-school activities, often due to transition planning processes that do not meet their unique needs. This study identified parents' and professionals' viewpoints on transition planning for adolescents on the autism spectrum. Interviews were completed with nine parents of adolescents on the autism spectrum and four professionals who worked with adolescents on the autism spectrum. A constant comparison approach was used to analyse the transcripts. Four themes were identified, reflecting parents' and professionals' viewpoints on how to meet the transition planning needs of adolescents on the autism spectrum. Supporting adolescents to grasp the big picture can enhance motivation to participate in transition planning. Autism can be an ‘invisible disability’; therefore, encouraging adolescents to be active participants and to be seen in transition planning ensures their individual needs are met. Encouraging adolescents to have high aspirations in transition planning develops their self-determination. Finally, to be prepared for the transition from school may reduce the adolescent's' anxiety. Adolescents on the autism spectrum face unique challenges in transition planning. The themes identified in this study provide insight into how parents and professionals might support adolescents with these challenges