Toward hydrogenase mimicry : subjecting the problem to three different approaches

In this work, the challenging task of modelling Hydrogenase is subjected to three different approaches. The first strategy used here is bioorganometallic. A wide range of sulfur containing ferrocene-peptide derivatives were synthesized and fully characterized. A new class of structural mimic of Fe-only hydrogenase with ferrocene-peptide backbone was obtained. In the second approach, a theoretical computational study of the ferrocene peptide derivatives is led. In order to investigate a wider range of ferrocene-peptide as a molecular scaffold, a molecular force field was successfully implemented in CHARMM27. As a third approach, organic self-assembled oligoquinoline were studied as potential scaffold of hydrogenase mimics

Toward Hydrogenase mimicry : subjecting the problem to three different approaches

In this work, the challenging task of modelling Hydrogenase is subjected to three different approaches. The first strategy used here is bioorganometallic. A wide range of sulfur containing ferrocene-peptide derivatives were synthesized and fully characterized. As a second approach, organic self-assembled oligoquinoline were designed and synthesized. These two kind of structures were further used a scaffold for Hydrogenase mimics. In the third approach, a theoretical computational study of the ferrocene-peptide derivatives is led. In order to investigate a wider range of ferrocene-peptide as a molecular scaffold, a molecular force field was successfully implemented and validated for CHARMM. After the deprotection of the thiol group in the bioorganometallic approach, the free SH groups were coordinated with iron-carbonyl, so as to mimic the Fe-only Hydrogenase active site. The complexes thus obtained were comprehensively characterized and their electronic and electrochemical properties were extensively studied

Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal-epithelial-like transition

In the developing mammalian brain, differentiating neurons mature morphologically via neuronal polarity programs. Despite discovery of polarity pathways acting concurrently with differentiation, it's unclear how neurons traverse complex polarity transitions or how neuronal progenitors delay polarization during development. We report that zinc finger and homeobox transcription factor-1 (Zeb1), a master regulator of epithelial polarity, controls neuronal differentiation by transcriptionally repressing polarity genes in neuronal progenitors. Necessity-sufficiency testing and functional target screening in cerebellar granule neuron progenitors (GNPs) reveal that Zeb1 inhibits polarization and retains progenitors in their germinal zone (GZ). Zeb1 expression is elevated in the Sonic Hedgehog (SHH) medulloblastoma subgroup originating from GNPs with persistent SHH activation. Restored polarity signaling promotes differentiation and rescues GZ exit, suggesting a model for future differentiative therapies. These results reveal unexpected parallels between neuronal differentiation and mesenchymal-to-epithelial transition and suggest that active polarity inhibition contributes to altered GZ exit in pediatric brain cancers.National Institute of Neurological Disorders and Stroke grant: (1R01NS066936); March of Dimes Foundation grant: (#1-FY12-455).info:eu-repo/semantics/publishedVersio

A Conversation with Robert Hatten about A Theory of Virtual Agency for Western Art Music

From August to October 2020, the Brazilian Society for Music Theory and Analysis (TeMA) held a series of five online meetings, each featuring a well-stablished theorist who presented one of his/her recent publications. Following the guest speaker’s presentation, a discussion session ensued, featuring guests from TeMA. On August 20th, TeMA received Robert Hatten to open the series, who was invited to talk about his most recent book: A Theory of Virtual Agency for Western Art Music (2018). Six guests from TeMA joined Hatten for the discussion session: Maria Lúcia Machado Pascoal, Cristina Capparelli Gerling, Flavio Santos Pereira, Diósnio Machado Neto, Guilherme Sauerbronn de Barros, and Paulo de Tarso Salles. Aiming at bringing Hatten’s presentation and the lively ensuing discussion to a wider audience, this essay presents an edited transcription of this meeting

Gene Expression Profiling of Preplate Neurons Destined for the Subplate: Genes Involved in Transcription, Axon Extension, Neurotransmitter Regulation, Steroid Hormone Signaling, and Neuronal Survival

During mammalian corticogenesis a series of transient cell layers establish laminar architectonics. The preplate, which forms from the earliest-generated neurons, separates into the marginal zone and subplate layer. To provide a systematic screen for genes involved in subplate development and function, we screened lines of transgenic mice, generated using bacterial artificial chromosome methodology (GENSAT Project), to identify transgenic lines of mice that express the enhanced green fluorescent protein (EGFP) reporter in preplate neurons destined for the subplate. Gene expression profiling of RNA purified from EGFP-positive neurons identified over 200 genes with enriched expression in future subplate neurons. Major classes of subplate-enriched genes included genes involved in transcriptional processes, cortical development, cell and axon motility, protein trafficking and steroid hormone signaling. Additionally, we identified 10 genes related to degenerative diseases of the cerebral and cerebellar cortex. Cre recombinase–based fate mapping of cells expressing Phosphodiesterase 1c (Pde1c) revealed beta-galactosidase positive cells in the ventricular zone, as well as the subplate, suggesting that subplate neurons and cortical projection neurons may be derived from common progenitors. These experiments therefore reveal genetic markers, which identify subplate neurons from the earliest stages of their development, and genes with enriched expression in subplate neurons during early stages of corticogenesis

Limited effects of preterm birth and the first enteral nutrition on cerebellum morphology and gene expression in piglets

Preterm pigs show many signs of immaturity that are characteristic of preterm infants. In preterm infants, the cerebellum grows particularly rapid and hypoplasia and cellular lesions are associated with motor dysfunction and cognitive deficits. We hypothesized that functional brain delays observed in preterm pigs would be paralleled by both structural and molecular differences in the cerebellum relative to term born piglets. Cerebella were collected from term (n=56) and preterm (90% gestation, n=112) pigs at 0, 5, and 26days after birth for stereological volume estimations, large-scale qPCR gene expression analyses (selected neurodevelopmental genes) and western blot protein expression analysis (Sonic Hedgehog pathway). Memory and learning was tested using a T-maze, documenting that preterm pigs showed delayed learning. Preterm pigs also showed reduced volume of both white and gray matter at all three ages but the proportion of white matter increased postnatally, relative to term pigs. Early initiation of enteral nutrition had limited structural or molecular effects. The Sonic Hedgehog pathway was unaffected by preterm birth. Few differences in expression of the selected genes were found, except consistently higher mRNA levels of Midkine, p75, and Neurotrophic factor 3 in the preterm cerebellum postnatally, probably reflecting an adaptive response to preterm birth. Pig cerebellar development appears more affected by postconceptional age than by environmental factors at birth or postnatally. Compensatory mechanisms following preterm birth may include faster white matter growth and increased expression of selected genes for neurotrophic factors and regulation of angiogenesis. While the pig cerebellum is immature in 90% gestation preterm pigs, it appears relatively mature and resilient toward environmental factor

The Role of Perceived University Support in the Formation of Students' Entrepreneurial Intention

Entrepreneurship education is central to student entrepreneurship. Previous research has attempted to understand the role of entrepreneurship education in the formation of students' entrepreneurial intention and behavior, albeit in an isolated manner. Universities can support entrepreneurship in many ways, but it is important to measure students' perception of the support that they receive in order to understand the extent of such support and its impact on students. The current study proposed and tested an integrative, multiperspective framework. We have hypothesized that the three dimensions of university support, that is, perceived educational support, concept development support, and business development support, together with institutional support, shape students' entrepreneurial self-efficacy. In turn, entrepreneurial self-efficacy and individual motivations constitute the fundamental elements of the intention to start a business. A sample of 805 university students took part in the study and data were analyzed using structural equation modeling. Our findings showed that perceived educational support exerted the highest influence on entrepreneurial self-efficacy, followed by concept development support, business development support, and institutional support. Self-efficacy in turn had a significant effect on entrepreneurial intention. Individual motivations such as self-realization, recognition, and role had an additional impact on intention. However, intention was not related to financial success, innovation, and independence. The findings suggest that a holistic perspective provides a more meaningful understanding of the role of perceived university support in the formation of students' entrepreneurial intention. Theoretical and practical implications are discussed

The Role of Thioredoxin Reductases in Brain Development

The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice lacking Txnrd1 in the NS were significantly smaller and displayed ataxia and tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation of the external granular layer (EGL) was strongly reduced and fissure formation and laminar organisation of the cerebellar cortex was impaired in the rostral portion of the cerebellum. Purkinje cells were ectopically located and their dendrites stunted. The Bergmann glial network was disorganized and showed a pronounced reduction in fiber strength. Cerebellar hypoplasia did not result from increased apoptosis, but from decreased proliferation of granule cell precursors within the EGL. Of note, neuron-specific inactivation of Txnrd1 did not result in cerebellar hypoplasia, suggesting a vital role for Txnrd1 in Bergmann glia or neuronal precursor cells

Lrp12/Mig13a Reveals Changing Patterns of Preplate Neuronal Polarity during Corticogenesis that Are Absent in Reeler Mutant Mice

During corticogenesis, the earliest generated neurons form the preplate, which evolves into the marginal zone and subplate. Lrp12/Mig13a, a mammalian gene related to the Caenorhabditis elegans neuroblast migration gene mig-13, is expressed in a subpopulation of preplate neurons that undergo ventrally directed tangential migrations in the preplate layer and pioneer axon projections to the anterior commissure. As the preplate separates, Lrp12/Mig13a-positive neurons polarize in the radial plane and form a pseudocolumnar pattern, prior to moving to a deeper position within the emerging subplate layer. These changes in neuronal polarity do not occur in reeler mutant mice, revealing the earliest known defect in reeler cortical patterning and suggesting that the alignment of preplate neurons into a pseudolayer facilitates the movement of later-born radially migrating neurons into the emerging cortical plate

Fire as a Removal Mechanism of Pyrogenic Carbon From the Environment: Effects of Fire and Pyrogenic Carbon Characteristics

Pyrogenic carbon (PyC, charcoal) is produced during vegetation fires at a rate of ~116–385 Tg C yr−1 globally. It represents one of the most degradation-resistant organic carbon pools, but its long-term fate and the processes leading to its degradation remain subject of debate. A frequently highlighted potential loss mechanism of PyC is its consumption in subsequent fires. However, only three studies to date have tested this hypothesis with reported losses of <8–37%, with the effects of PyC chemical characteristics and fire conditions on PyC loss in wildfires remaining unexplored. To address this, we placed materials with different degrees of thermal and chemical recalcitrance (A: wildfire charcoal, B: slash-pile charcoal, C: pine wood and D: cedar wood) on the ground surface just prior to a high-intensity and a low-intensity boreal forest wildfire. Mass losses were highly variable and dependent on fire- and sample characteristics. Mass losses across both fires (as % of dry weight) were for A: 66.5 ± 25.2, B: 41.7 ± 27.2, C: 78.2 ± 14.9, and D: 83.8 ± 18.9. Mass loss correlated significantly with maximum temperature (Tmax) recorded on sample surfaces (r = 0.65, p = 0.01), but only weakly (r = 0.33) with time >300°C. Mass losses also showed a significant negative correlation (r = −0.38, p = 0.05) with thermal recalcitrance (T50) determined using Differential Scanning Calorimetry (DSC) and Tmax with charcoal reflectance (Ro) determined after the fires (r = 0.46, p = 0.05). Losses in the high-intensity fire were significantly higher (p = 0.05) than in the low-intensity fire, but the latter had a higher rate of conversion of fuel to PyC. Our results demonstrate that exposure to fire can indeed be a significant removal mechanism for PyC that remains exposed on the ground after a previous fire. The losses found, however, are likely to represent an extreme upper range as most PyC produced in a fire would not remain exposed on the ground surface by the time the next fire occurs. Our data also demonstrate, for real wildfire conditions, the (i) contrasting resistance of different PyC types to combustion and (ii) contrasting net PyC losses between different fire intensities. The DSC and reflectance (Ro) results support the usefulness of these analyses in reflecting thermal degradation resistance and temperature exposure under actual wildfire conditions