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Low-cost gas sensors (LCS) often produce inaccurate measurements due to varying environmental conditions that are not consistent with laboratory settings, leading to inadequate productivity levels compared to high-quality sensors. To address this issue, we propose the use of Machine Learning (ML) to predict accurate concentrations of pollutant gases acquired by LCS integrated into an embedded Internet of Things platform. However, a key challenge is to optimize an accurate ML design under low memory and computation power constraints of microcontrollers (MCUs) while maintaining accurate ML scores. After data analysis and pre-processing, we assess and analyze the performance of five ML algorithms to predict the concentration of pollutants gases from multiple specifications (weather, presence of other gases etc.). To support the experiments, datasets from three sources are used: 1- VOCSens, 2- Belgian Interregional Environment Agency cell (IRCELINE), and 3- Visual-Crossing. Once the best model was optimized and validated, multiple hard constraints were added to the selected ML structure to satisfy material and expert requirements. Trained models were ported in order to be implemented locally in a microcontroller (MCU) after comparing several porting libraries. The assembled code obtained is evaluated based on two metrics: storage memory consumption and inference time, relative to the highest attainable capacities. The improved Random Forest (RF) is the best ML model for the used data set with an R2 score meeting of 0.72 and Root Means Square Error (RMSE) of 0.0028 ppm. The best generated Tiny ML model needs 3% of RAM and 98% of Flash storage. The empirical results prove that the developed ML algorithm applied to LCS provides high accuracy to predict pollutant gases. This algorithm can also be used to adjust the LCS systems to provide calibrated data in real-time, even if the platform being used is not particularly advanced or powerful.

The primary cilium is a central signaling component during embryonic development. Here we focus on CROCCP2, a hominid-specific gene duplicate from ciliary rootlet coiled coil (CROCC), also known as rootletin, that encodes the major component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex and human cortical cells and organoids results in decreased ciliogenesis and increased cortical progenitor amplification, particularly basal progenitors. CROCCP2 decreases ciliary dynamics by inhibition of the IFT20 ciliary trafficking protein, which then impacts neurogenesis through increased mTOR signaling. Loss of function of CROCCP2 in human cortical cells and organoids leads to increased ciliogenesis, decreased mTOR signaling, and impaired basal progenitor amplification. These data identify CROCCP2 as a human-specific modifier of cortical neurogenesis that acts through modulation of ciliary dynamics and mTOR signaling. ispartof: NEURON vol:111 issue:1 pages:65-+ ispartof: location:United States status: published

Summary During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition., Graphical Abstract, Highlights • Bcl6 ensures robust neurogenesis by repressing major extrinsic self-renewal pathways • Bcl6 inhibits the Notch, Wnt, SHH, and FGF signaling pathways at multiple levels • Bcl6 represses transcription through Sirt1 recruitment and histone deacetylation, Bonnefont et al. show that Bcl6 promotes neurogenesis by directly repressing genes belonging to the major signaling pathways promoting cortical progenitor self-renewal. These data indicate that a single cell-intrinsic factor represses multiple extrinsic signaling pathways to ensure irreversible neurogenic commitment.

SummaryDuring neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here we combine whole genome transcriptional and epigenetic analyses with in vivo functional studies and show that Bcl6, a transcriptional repressor known to promote neurogenesis, acts as a key driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 acts through both generic and pathway-specific mechanisms. Our data identify a molecular logic by which a single cell-intrinsic factor ensures robustness of neural cell fate transition by decreasing responsiveness to the extrinsic pathways that favor self-renewal.

The cerebral cortex underwent rapid expansion and increased complexity during recent hominid evolution. Gene duplications constitute a major evolutionary force, but their impact on human brain development remains unclear. Using tailored RNA sequencing (RNA-seq), we profiled the spatial and temporal expression of hominid-specific duplicated (HS) genes in the human fetal cortex and identified a repertoire of 35 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among them NOTCH2NL, human-specific paralogs of the NOTCH2 receptor, stood out for their ability to promote cortical progenitor maintenance. NOTCH2NL promote the clonal expansion of human cortical progenitors, ultimately leading to higher neuronal output. At the molecular level, NOTCH2NL function by activating the Notch pathway through inhibition of cis Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes active during human corticogenesis and reveals how human-specific NOTCH paralogs may have contributed to the expansion of the human cortex. Human-specific NOTCH2NL expands cortical progenitors and neuronal output and thus may have contributed to the expansion of the human cortex., SCOPUS: ar.j, info:eu-repo/semantics/published

Summary The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation., Graphical Abstract, Highlights • Human PSC-derived cortical neurons efficiently integrate into the adult mouse brain • PSC-derived human neurons reestablish axonal pathways in the lesioned adult cortex • Restoration of cortical pathways requires a donor and recipient area-identity match, Espuny-Camacho et al. show that transplanted ESC-derived human cortical neurons integrate functionally into the lesioned adult mouse brain. Transplanted neurons display visual cortical identity and show specific restoration of damaged cortical pathways following transplantation into the visual but not the motor cortex, suggesting the importance of areal-identity match for successful cortical repair.

SummaryThe human cerebral cortex has undergone rapid expansion and increased complexity during recent evolution. Hominid-specific gene duplications represent a major driving force of evolution, but their impact on human brain evolution remains unclear. Using tailored RNA sequencing (RNAseq), we profiled the spatial and temporal expression of Hominid-specific duplicated (HS) genes in the human fetal cortex, leading to the identification of a repertoire of 36 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among these we focused on NOTCH2NL, previously uncharacterized HS paralogs of NOTCH2. NOTCH2NL promote the clonal expansion of human cortical progenitors by increasing self-renewal, ultimately leading to higher neuronal output. NOTCH2NL function by activating the Notch pathway, through inhibition of Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes linking genomic evolution to human brain development, and reveals how hominin-specific NOTCH paralogs may have contributed to the expansion of the human cortex.

During neurogenesis, neural stem/progenitor cells (NPCs) undergo an irreversible fate transition to become neurons. The Notch pathway is important for this process, and repression of Notch-dependent Hes genes is essential for triggering differentiation. However, Notch signaling often remains active throughout neuronal differentiation, implying a change in the transcriptional responsiveness to Notch during the neurogenic transition. We identified Bcl6, an oncogene, as encoding a proneurogenic factor that is required for proper neurogenesis of the mouse cerebral cortex. BCL6 promoted the neurogenic conversion by switching the composition of Notch-dependent transcriptional complexes at the Hes5 promoter. BCL6 triggered exclusion of the co-activator Mastermind-like 1 and recruitment of the NAD(+)-dependent deacetylase Sirt1, which was required for BCL6-dependent neurogenesis. The resulting epigenetic silencing of Hes5 led to neuronal differentiation despite active Notch signaling. Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease.

Embryonic stem cells (ESCs) constitute a tool of great potential in neurobiology, enabling the directed differentiation of specific neural cell types. We have shown recently that neurons of the cerebral cortex can be generated from mouse ESCs cultured in a chemically defined medium that contains no morphogen, but in the presence of the sonic hedgehog inhibitor cyclopamine. Corticogenesis from ESCs recapitulates the most important steps of cortical development, leading to the generation of multipotent cortical progenitors that sequentially produce cortical pyramidal neurons displaying distinct layer-specific identities. The protocol provides a most reductionist cellular model to tackle the complex mechanisms of cortical development and function, thereby opening new perspectives for the modeling of cortical diseases and the design of novel neurological treatments, while offering an alternative to animal use. In this protocol, we describe a method by which millions of cortical neurons can be generated in 2-3 weeks, starting from a single frozen vial of ESCs.

Childhood abuse is an important risk factor for depression, anxiety disorders, and substance use later in life. One possible mechanism underlying this association could be deficits in cognitive processing of emotional information. This study tested the impact of distracting emotional information on working memory performance in 21 young women with a history of sexual and physical abuse during childhood/adolescence (mean age = 20.0), and compared their performance to 17 individuals reporting nonabuse-related childhood stress (mean age = 19.6) and a control group of 17 women without a history of childhood stress (mean age = 20.0). During the most difficult distractor condition, working memory accuracy for positive versus neutral incidental emotional stimuli was reduced in women reporting a history of abuse relative to both control groups (with and without nonabuse-related childhood stress). The current results reveal aberrant responses to positive stimuli and are consistent with the notion of persistent influence of childhood abuse on processes critical for emotional well-being and emotion control.

International audience; The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair.

Este trabajo comenta el modo en que, tanto en los conventos españoles como en los latinoamericanos, las religiosas del Siglo de Oro recurrieron a la palabra escrita para explayarse a su antojo sobre una variedad de temas. Saben que, aparte del primer lector, el padre espiritual que les manda escribir, otros contemporáneos tendrán acceso a su manuscrito. La escritura de la relación de su vida les abre un mundo distinto en el que descubren poco a poco la fuerza del poder que les es ofrecido. Aprovechan la ocasión para entablar una relación imaginaria con su(s) lector(es) que contiene alternativamente elementos de seducción y de transgresión. Además, suelen mostrar una voluntadde automanifestación que va más allá de lo comúnmente aceptado. Alzan la voz para reivindicar nuevos derechos, para expresar su creciente autonomía y el gusto con que empuñan la pluma.

FLWIN, info:eu-repo/semantics/published