THE ROLE OF THE SVZ IN ISCHEMIC CONDITION

The occlusion of a cerebral artery or stroke often results in neuronal deficit and/or patient death. A partial recovery often follows non-fatal stroke and this may be due to the activation of the progenitor cells in the Sub- Ventricular Zone (SVZ) naturally occurring after ischemia. In order to clarify the role of the SVZ neurogenesis in animal recovery, the effect of neurogenesis inhibition and boosting were studied in the mouse Middle Cerebral Artery occlusion model (MCAo). 6 to 10-week-old male mice were pre-treated with intracranial injections of lentiviral vector (LV) or integration deficient lentiviral vectors (IDLV), in order to target the SVZ. The IDLV carried an expression cassette encoding for a precursor Glial cell-derived neurotrophic factor (GDNF) or the tetanus toxin fragment C (TTC), which recently has been demonstrated to have growth factor like behaviour. Another group of animals received the LV carrying a double promoter expression cassette encoding for an eGFP, and in order to inhibit the cell cycle in targeted cells the shRNA_Cyclin D1. All vectors were co-injected with the LV_ pHR'SIN-cPPT-SEW, which contains an eGFP cassette. Two weeks later the animals received the MCAo, and for three weeks the sensorimotor behaviour was tested. Neurological assessment showed the sensory-motor debilitation was significant increased after the treatment with the LV_shRNA_CyclinD1 (* p<0.05); the IDLV_GDNF and IDLV_TTC groups showed a trend to improve neurological deficit in the subjects alive until day 5. In the IDLV_GDNF, the SVZ's derived green cells were positively correlated with the ischemic volume, *p<0.05 R=0.68, and the neurodegeneration, ***p<0.001 R=0.92. Moreover, while the SVZ neurogenesis inhibition reduced life expectancy, the boosting significantly improved it. Immunofluorescence analysis showed a migration extended to the striatum and cortex with a max distance of 1.87 mm from the SVZ.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Dinámicas Eco protectora: Sanación y Apache en Nandayuri como sistema de buen vivir

El presente artículo reflexiona sobre los conceptos de protagonismo comunitario, dinámicas Eco protectora, Sanación y Apache, investigadas en la Comarca Nandayuri que es parte del territorio del Pueblo Indígena de Monimbó. Como ámbito de estudio, se ha elegido el comunitario indígena, porque el propósito es demostrar que el buen vivir es un modelo de vida y de practica todavía existente en muchas de las culturas indígenas de Nicaragua, así como de América Latina, aunque llamado en diferente manera o simplemente practicado y no conceptualizado. Escuchando la voz de sus habitantes, se intenta interpretar la concepción de vida deseable en Nandayuri, registrado los conocimientos y las prácticas sobre sus recursos biológicos y culturales (patrimonio biocultural), valores y saberes, que en su mayoría están transmitidos y basados en la tradición oral y por lo tanto están en riesgo de perderse y desaparecer

The Evolution of Sustainable Mobility and Urban Space Planning: Exploring the factors contributing to the Regeneration of Car Parking in Living Spaces

Strategies and actions to promote sustainable mobility must be based on the characterization of the mobility supply and the promotion of decarbonization policies (e.g. the management of public spaces). The presence of parkings, especially in urban areas, has a significant impact on the occupancy of physical spaces. In this framework, referring to the last decades and the recent pandemic, the paper focuses on the evaluation of influencing factors that have contributed to the changes of planned and designed parking spaces in urban areas. Parklets can support post COVID-19 (Phase 3) pandemics by improving the quality of public space and social distancing close to shops and activities, benefiting from this micro-urban regeneration. Moreover, they can be considered as an extension of the pavement and their implementation can encourage the reduction of private traffic by promoting soft mobility (i.e. walking and cycling). The article defines and highlights the features for the identification and planning of spaces where parklets can be implemented, to improve sustainability and support the post-pandemic recovery

Metabolic and cardiovascular response to exercise in patients with type 1 diabetes

Physical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population

Deep Chandra observations of the stripped galaxy group falling into Abell 2142

In the local Universe, the growth of massive galaxy clusters mainly operates through the continuous accretion of group-scale systems. The infalling group in Abell 2142 is the poster child of such an accreting group, and as such, it is an ideal target to study the astrophysical processes induced by structure formation. We present the results of a deep (200 ks) observation of this structure with Chandra that highlights the complexity of this system in exquisite detail. In the core of the group, the spatial resolution of Chandra reveals a leading edge and complex AGN-induced activity. The morphology of the stripped gas tail appears straight in the innermost 250 kpc, suggesting that magnetic draping efficiently shields the gas from its surroundings. However, beyond ~ 300 kpc from the core, the tail flares and the morphology becomes strongly irregular, which could be explained by a breaking of the drape, for example, caused by turbulent motions. The power spectrum of surface-brightness fluctuations is relatively flat (P2D ∝ k⁻²∙³ which indicates that thermal conduction is strongly inhibited even beyond the region where magnetic draping is effective. The amplitude of density fluctuations in the tail is consistent with a mild level of turbulence with a Mach number M3D ~ 0:1 -0:25. Overall, our results show that the processes leading to the thermalization and mixing of the infalling gas are slow and relatively inefficient

Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus

Introduction. Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. Materials and Methods. The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. Results. The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p&lt;0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p&lt;0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p&lt;0.001). Conclusions. The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk technique for diagnosing the SCD, at least in DM1. Clin Ter 2010; 161(1):e1-e1

A cascade of 24 histatins (histatin 3 fragments) in human saliva. Suggestions for a pre-secretory sequential cleavage pathway

The systematic search by tandem mass spectrometry of human saliva from four different subjects, of 136 possible fragments originated from histatin 3, allowed the detection of 24 different peptides. They include, with the exception of histatin 4, all the known histatin 3 fragments, namely histatins 5-12 and the peptides corresponding to 15-24, 26-32, 29-32 residues, and 13 new fragments corresponding to 1-11, 1-12, 1-13, 5-13, 6-11, 6-13, 7-11, 7-12, 7-13, 14-24, 14-25, 15-25, and 28-32 residues of histatin 3. On the contrary, none of 119 possible fragments of histatin 1, including histatin 2, was detected. The results suggest that the genesis of histatin 3-related peptides, being under the principal action of trypsin-like activities, is probably not a random process but rather follows a sequential fragmentation pathway. Lack of detection of C-terminal fragments, with the exception of 26-32, 28-32, and 29-32 fragments, suggested that arginine 25 should be the first cleavage site, generating histatin 6 and 26-32 fragments. The genesis of 28-32 and 29-32 fragments and histatin 5 should implicate a subsequent exo-protease action. Similarly, lack of detection of fragments having Lys-5 and Arg-6 at the N terminus and Arg-25 at the C terminus strongly suggested that sequences KRKF (11-14 residues) and AKR (4-6 residues) should be the second and the third cleavage sites, respectively. Lys-17 and Arg-22 are not cleaved at all

Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output

The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker, and variant histones, and a correspondingly reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and affects the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and can be modelled assuming that different nucleosomal sites compete for available histones. Sites with a high propensity to occupation are almost always packaged into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on sites with low propensity to occupation are disproportionately lost in nucleosome-depleted cells. We suggest that variation in nucleosome number, by affecting nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel layer of epigenetic regulation

The coding and long noncoding single-cell atlas of the developing human fetal striatum.

Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- and D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. This work delineates the cellular hierarchies governing MSN lineage commitment