Molecular mechanisms of neurogenic aging in the adult mouse subventricular zone

In the adult rodent brain, the continuous production of new neurons by neural stem/progenitor cells (NSPCs) residing in specialized neurogenic niches and their subsequent integration into pre-existing cerebral circuitries supports odour discrimination, spatial learning, and contextual memory capabilities. Aging is recognized as the most potent negative regulator of adult neurogenesis. The neurogenic process markedly declines in the aged brain, due to the reduction of the NSPC pool and the functional impairment of the remaining NSPCs. This decline has been linked to the progressive cognitive deficits of elderly individuals and it may also be involved in the onset/progression of neurological disorders. Since the human lifespan has been dramatically extended, the incidence of age-associated neuropsychiatric conditions in the human population has increased. This has prompted efforts to shed light on the mechanisms underpinning the age-related decline of adult neurogenesis, whose knowledge may foster therapeutic approaches to prevent or delay cognitive alterations in elderly patients. In this review, we summarize recent progress in elucidating the molecular causes of neurogenic aging in the most abundant NSPC niche of the adult mouse brain: the subventricular zone (SVZ). We discuss the age-associated changes occurring both in the intrinsic NSPC molecular networks and in the extrinsic signalling pathways acting in the complex environment of the SVZ niche, and how all these changes may steer young NSPCs towards an aged phenotype

The Importance of Stereochemically Active Lone Pairs For Influencing Pb II and As III Protein Binding

The toxicity of heavy metals, which is associated with the high affinity of the metals for thiolate rich proteins, constitutes a problem worldwide. However, despite this tremendous toxicity concern, the binding mode of As III and Pb II to proteins is poorly understood. To clarify the requirements for toxic metal binding to metalloregulatory sensor proteins such as As III in ArsR/ArsD and Pb II in PbrR or replacing Zn II in δ‐aminolevulinc acid dehydratase (ALAD), we have employed computational and experimental methods examining the binding of these heavy metals to designed peptide models. The computational results show that the mode of coordination of As III and Pb II is greatly influenced by the steric bulk within the second coordination environment of the metal. The proposed basis of this selectivity is the large size of the ion and, most important, the influence of the stereochemically active lone pair in hemidirected complexes of the metal ion as being crucial. The experimental data show that switching a bulky leucine layer above the metal binding site by a smaller alanine residue enhances the Pb II  binding affinity by a factor of five, thus supporting experimentally the hypothesis of lone pair steric hindrance. These complementary approaches demonstrate the potential importance of a stereochemically active lone pair as a metal recognition mode in proteins and, specifically, how the second coordination sphere environment affects the affinity and selectivity of protein targets by certain toxic ions. Experimental and computational methods have been employed to study the influence of the lone pair of As III and Pb II for the binding of these ions in proteins using designed peptide models. The results show that the mode of coordination of As III and Pb II is greatly influenced by the steric bulk within the second coordination environment of the metals (see figure).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90414/1/chem_201102786_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90414/2/2040_ftp.pd

Post-lacustrine evolution of a tectonically-controlled intermontane basin: Drainage network analysis of the Mercure basin, southern Italy

Topographic analysis, drainage network morphometry, river profile analysis, and spatial distribution of fluvio-lacustrine terraces have been used to reconstruct the drainage network evolution in the Mercure River basin, a large intermontane tectonic basin of the axial zone of southern Apennines. Morphotectonic evolution of the study area is mainly controlled by poly-kinematics high-angle WNW-ESE and NE-SW faults, which promoted the development of a complex landscape with relict landscapes and/or low-relief erosional surfaces that occurred in a staircase arrangement at the top of the landscapes or at higher altitudes than the basin infill. The creation of the accommodation space for the deposition of the thick basin infill was related to an important tectonic phase of block-faulting along N120°-trending normal faults, which occurred in the final part of the Lower Pleistocene. Such an evolution strongly controls the longitudinal profile forms of channels draining the northern sector of the study area, which are featured by a well-developed concave-up segment in river profiles of these channels between an upward trait with lower values of channel steepness and the trace of the master fault. River profiles in north-western and south-east sectors of the Mercure River basin exhibit clear knickpoints at altitudes comparable with those of the superimposed orders of relict landscapes related to the initial formation of the tectonic basin and the subsequent evolution of the endorheic basin, with a post-lacustrine geomorphological evolution of the drainage network that is controlled by fluvial incision occurring at rates comparable than those reconstructed by independent morphotectonic markers. The erosion of the threshold of the endorheic basin occurring during the base-level fall of the MIS 12 promoted a dramatic base-level fall of about 150 m, which corresponds to a mean incision rate of about 0.35 mm/yr. Post-lacustrine evolution of the Mercure basin strongly controls the morphometric features of the drainage network, which preserves a centripetal pattern with several planimetric anomalies such as counterflow and high-angle confluences, local-scale fluvial capture phenomena and drainage divide migrations

"I rischi della specializzazione mono-funzionale turistica dei sistemi montani rivelati dal Covid-19"

La ricerca verifica la tesi secondo cui le economie locali mono-funzionali, come quelle della montagna basate sul turismo invernale di massa, non siamo sostenibili, né vantaggiose dal punto di vista economico e sociale. L’analisi si basa sulle rilevazioni condotte dall’Istat, relative alla perdita di fatturato dei Comuni italiani nel periodo di lockdown della primavera 2020. La dimostrazione passa attraverso l’analisi delle perdite di fatturato nei Comuni italiani. Nelle regioni Piemonte e Valle d’Aosta, tali perdite sono state messe in relazione con la specializzazione turistica (calcolata in base alle presenze di turisti) dei Comuni e con la loro dotazione di servizi. La perdita media dei 46 Comuni montani a forte specializzazione turistica è risultata in media più di quattro volte maggiore di quella media di tutti i 536 Comuni montani delle due regioni

Subtotal resection of vestibular schwannoma: evaluation with Ki-67 measurement, magnetic resonance imaging, and long-term observation

Purpose The aim of this study was to compare the postoperative clinical and radiological data of patients with vestibular schwannomas who were initially managed by near total resection (NTR) or subtotal resection (STR). The Ki-67 analysis results were compared with tumor regrowth to determine the presence of a correlation between this proliferative index and postoperative tumor regrowth. Study Design Seventeen adult patients (7 male, 10 female) were retrospectively reviewed. Nine (52.9%) and eight (47.1%) patients underwent NTR and STR, respectively. Postoperative clinical and radiological data associated with vestibular schwannoma growth were compared with the Ki-67 immunohistochemical analysis results. Results Evidence of clinically significant regrowth was observed in four (23.5%) patients. Patients who underwent NTR had a lower rate/incidence of tumor regrowth than did patients who underwent STR. Patients with a higher Ki-67 index had the highest tumor regrowth rates. Conclusions Our study indicates that assessment of the Ki-67 index may be useful for determining the probability of regrowth of vestibular schwannomas when only partial removal is accomplished

Sedimentological and morpho-evolution maps of the 'Bosco Pantano di Policoro' coastal system (Gulf of Taranto, southern Italy)

This paper presents the results of a sedimentological study performed to characterize the ‘Bosco Pantano di Policoro e Costa Ionica Foce Sinni’ coastal system, in Basilicata (southern Italy), as part of the PROVIDUNE LIFE Project. The study was focused on the morpho-sedimentological characterization of both the emerged and submerged sectors of the beach system developed along a 3.5 km-long segment of the Ionian coast. A multitemporal comparison of historical aerial photos of the studied coastline concerning the last 100 years was executed. A geomorphological survey was carried out along 36 topographic profiles (each up to 200-m long); these were coupled with bathymetric profiles, reaching a depth of 213 m. Both topographic and bathymetric profiles were measured on three occasions (July, October, December 2010). Textural and compositional analyses of sediments were also performed. The results of this study were synthesized in a series of maps illustrating a schematic geological outline of the study area, a reconstruction of the Sinni river course and shoreline changes from 1908 to 2010 (1:2,400 scale), significant topographic (1:1,300 scale) and bathymetric (1:5,000 scale) profiles, three bathymetric charts (1:31,000 scale) and morpho-sedimentological features of both the coastal and nearshore sectors (1:15,000 scale). This study provides a geological background that is crucial for any intervention planning, as well as for any coastal zone management projects. The results should be also used in order to protect coastal habitats, which is the ultimate goal of the LIFE project

Mechanistic Analysis of Nucleophilic Substrates Oxidation by Functional Models of Vanadium-Dependent Haloperoxidases: A Density Functional Theory Study

Density functional theory has been used to investigate the structural, electronic, and reactivity properties of an established functional model for vanadium-dependent haloperoxidases, K[VO(O 2 )Hheida] (Hheida 2– = 2,2′-[(2-hydroxyethyl)imino]diacetate). Possible solution species were determined on the basis of potential exogenous donors present under the conditions necessary for reactivity. The energetically favored solution-state species is a 1:1 complex of Hheida and vanadium with a coordinated hydroxyethyl donor trans to the vanadium–oxido bond which is in agreement with the reported solid-state structure for K[VO(O 2 )Hheida]. Transition states of the oxidation reaction were located for four substrates: chloride, bromide, iodide, and dimethyl sulfide. The role of protonation and its effects on reactivity were examined for each substrate. Protonation of the peroxido moiety leads to a significant drop in the activation barrier for oxidation. In contrast no transition states could be located for an oxido-transfer process involving the oxido ligand. Barriers of activation calculated for halide oxidation were similar, providing support to the hypothesis that the p K a of the halide in acetonitrile is responsible for the decrease in reactivity between I – , Br – , and Cl – . The results presented herein provide a mechanistic correlation between a functional model and the enzyme, making K[VO(O 2 )Hheida] a “complete” functional model for vanadium-dependent haloperoxidase.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55972/1/515_ftp.pd

Lactate production yield from engineered yeasts is dependent from the host background, the lactate dehydrogenase source and the lactate export

BACKGROUND: Metabolic pathway manipulation for improving the properties and the productivity of microorganisms is becoming a well established concept. For the production of important metabolites, but also for a better understanding of the fundamentals of cell biology, detailed studies are required. In this work we analysed the lactate production from metabolic engineered Saccharomyces cerevisiae cells expressing a heterologous lactate dehydrogenase (LDH) gene. The LDH gene expression in a budding yeast cell introduces a novel and alternative pathway for the NAD(+ )regeneration, allowing a direct reduction of the intracellular pyruvate to lactate, leading to a simultaneous accumulation of lactate and ethanol. RESULTS: Four different S. cerevisiae strains were transformed with six different wild type and one mutagenised LDH genes, in combination or not with the over-expression of a lactate transporter. The resulting yield values (grams of lactate produced per grams of glucose consumed) varied from as low as 0,0008 to as high as 0.52 g g(-1). In this respect, and to the best of our knowledge, higher redirections of the glycolysis flux have never been obtained before without any disruption and/or limitation of the competing biochemical pathways. CONCLUSION: In the present work it is shown that the redirection of the pathway towards the lactate production can be strongly modulated by the genetic background of the host cell, by the source of the heterologous Ldh enzyme, by improving its biochemical properties as well as by modulating the export of lactate in the culture media