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Nature ; 624(7991): 333-342, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38092915


The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2-a recently developed spatial transcriptomics method with near-cellular resolution-across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource ( ), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.

Encéfalo , Perfilación de la Expresión Génica , Animales , Ratones , Encéfalo/anatomía & histología , Encéfalo/citología , Encéfalo/metabolismo , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Hipotálamo/citología , Hipotálamo/metabolismo , Mesencéfalo/citología , Mesencéfalo/metabolismo , Neuropéptidos/metabolismo , Neurotransmisores/metabolismo , Fenotipo , Rombencéfalo/citología , Rombencéfalo/metabolismo , Análisis de Expresión Génica de una Sola Célula , Transcriptoma/genética
Mater Sci Eng C Mater Biol Appl ; 117: 111304, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32919665


The present work highlights biosynthesis of nano-sized heterometalic spinel ZnCo2O4 particles using different green extracts as capping agent. In this work we have fabricated polygonal ZnCo2O4 with Punica granatum peel extract, Camellia sinensis extract, Moringa oleifera leaf extract and green coffee beans extract in an effortless green pathway. Phase pure material synthesis was confirmed using XRD. Microstructural, morphological, compositional and optical characterisations has been carried out using TEM, FESEM, EDX, FTIR, photoluminescence and UV-Vis spectroscopy. Punica granatum peel extract assisted ZnCo2O4 sample shows superior catalytic efficiency of ~84.96% for Rhodamine B pollutant. ZnCo2O4 sample synthesized using pomegranate peel extract shows highest conductivity of ~8.074 × 10-5 Ω-1 cm-1 with activation energy of 2.099 eV at 503 K. Synthesized nanoparticles also show antibacterial activity for B. megaterium, B. subtilis and B. cereus. To the best of our knowledge, synthesis of ZnCo2O4 using these four green extracts and their comparative degradation capability, electrical properties and antibacterial study is explained for the first time in this work.

Tecnología Química Verde , Nanopartículas del Metal , Óxido de Aluminio , Óxido de Magnesio , Extractos Vegetales
Eur J Neurosci ; 50(12): 4004-4017, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31344282


Traditionally, the dorsal lateral geniculate nucleus (LGN) and the inferior pulvinar (IPul) nucleus are considered as anatomically and functionally distinct thalamic nuclei. However, in several primate species it has also been established that the koniocellular (K) layers of LGN and parts of the IPul have a shared pattern of immunoreactivity for the calcium-binding protein calbindin. These calbindin-rich cells constitute a thalamic matrix system which is implicated in thalamocortical synchronisation. Further, the K layers and IPul are both involved in visual processing and have similar connections with retina and superior colliculus. Here, we confirmed the continuity between calbindin-rich cells in LGN K layers and the central lateral division of IPul (IPulCL) in marmoset monkeys. By employing a high-throughput neuronal tracing method, we found that both the K layers and IPulCL form comparable patterns of connections with striate and extrastriate cortices; these connections are largely different to those of the parvocellular and magnocellular laminae of LGN. Retrograde tracer-labelled cells and anterograde tracer-labelled axon terminals merged seamlessly from IPulCL into LGN K layers. These results support continuity between LGN K layers and IPulCL, providing an anatomical basis for functional congruity of this region of the dorsal thalamic matrix and calling into question the traditional segregation between LGN and the inferior pulvinar nucleus.

Cuerpos Geniculados/patología , Pulvinar/patología , Corteza Visual/patología , Vías Visuales/fisiología , Animales , Cuerpos Geniculados/fisiología , Neuronas/fisiología , Terminales Presinápticos/patología , Terminales Presinápticos/fisiología , Pulvinar/fisiología , Tálamo/patología , Tálamo/fisiología , Corteza Visual/fisiología
Ann Transl Med ; 6(11): 221, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30023384
Elife ; 4: e09215, 2015 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-26652162


Central thalamus plays a critical role in forebrain arousal and organized behavior. However, network-level mechanisms that link its activity to brain state remain enigmatic. Here, we combined optogenetics, fMRI, electrophysiology, and video-EEG monitoring to characterize the central thalamus-driven global brain networks responsible for switching brain state. 40 and 100 Hz stimulations of central thalamus caused widespread activation of forebrain, including frontal cortex, sensorimotor cortex, and striatum, and transitioned the brain to a state of arousal in asleep rats. In contrast, 10 Hz stimulation evoked significantly less activation of forebrain, inhibition of sensory cortex, and behavioral arrest. To investigate possible mechanisms underlying the frequency-dependent cortical inhibition, we performed recordings in zona incerta, where 10, but not 40, Hz stimulation evoked spindle-like oscillations. Importantly, suppressing incertal activity during 10 Hz central thalamus stimulation reduced the evoked cortical inhibition. These findings identify key brain-wide dynamics underlying central thalamus arousal regulation.

Corteza Cerebral/fisiología , Vías Nerviosas/fisiología , Neuronas/fisiología , Tálamo/fisiología , Animales , Estimulación Eléctrica , Electroencefalografía , Modelos Neurológicos , Ratas Sprague-Dawley
Mol Cell Biol ; 23(22): 8110-23, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14585971


At the G(1)/S phase cell cycle transition, multiple histone genes are expressed to ensure that newly synthesized DNA is immediately packaged as chromatin. Here we have purified and functionally characterized the critical transcription factor HiNF-P, which is required for E2F-independent activation of the histone H4 multigene family. Using chromatin immunoprecipitation analysis and ligation-mediated PCR-assisted genomic sequencing, we show that HiNF-P interacts with conserved H4 cell cycle regulatory sequences in vivo. Antisense inhibition of HiNF-P reduces endogenous histone H4 gene expression. Furthermore, we find that HiNF-P utilizes NPAT/p220, a substrate of the cyclin E/cyclin-dependent kinase 2 (CDK2) kinase complex, as a key coactivator to enhance histone H4 gene transcription. The biological role of HiNF-P is reflected by impeded cell cycle progression into S phase upon antisense-mediated reduction of HiNF-P levels. Our results establish that HiNF-P is the ultimate link in a linear signaling pathway that is initiated with the growth factor-dependent induction of cyclin E/CDK2 kinase activity at the restriction point and culminates in the activation of histone H4 genes through HiNF-P at the G(1)/S phase transition.

Histonas/genética , Fase S/genética , Fase S/fisiología , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN Complementario/genética , Regulación de la Expresión Génica , Células HeLa , Humanos , Datos de Secuencia Molecular , Peso Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Represoras , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/aislamiento & purificación , Dedos de Zinc/genética