Cortical GABAergic inhibitory interneurons have crucial roles in the development and function of the cerebral cortex. In rodents, nearly all neocortical interneurons are generated from the subcortical ganglionic eminences. In humans and nonhuman primates, however, the developmental origin of neocortical GABAergic interneurons remains unclear. Here we show that the expression patterns of several key transcription factors in the developing primate telencephalon are very similar to those in rodents, delineating the three main subcortical progenitor domains (the medial, lateral and caudal ganglionic eminences) and the interneurons tangentially migrating from them. On the basis of the continuity of Sox6, COUP-TFII and Sp8 transcription factor expression and evidence from cell migration and cell fate analyses, we propose that the majority of primate neocortical GABAergic interneurons originate from ganglionic eminences of the ventral telencephalon. Our findings reveal that the mammalian neocortex shares basic rules for interneuron development, substantially reshaping our understanding of the origin and classification of primate neocortical interneurons.
It is of great interest to identify new neurons in the adult human brain, but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial. In the present study, we have described the general configuration of the RMS in adult monkey, fetal human and adult human brains. We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain. The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin, polysialylated neural cell adhesion molecule and βIII-tubulin. Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS, indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ. Interestingly, no neuroblasts are found in the adult human olfactory bulb. Taken together, our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.
High-capacity anode materials are one of the bottlenecks to further improve the energy density of Na-ion batteries (NIBs). Except for introducing more defects to increase the sloping capacity, tuning the closed porous structure to boost the plateau capacity is another direction. Here by adopting phenol-formaldehyde resin (PF) as the carbon precursor and ethanol (EtOH) as the pore-forming agent, through precise chemical regulation of their relative content during a solvothermal process before further carbonization, carbon anodes with appropriate microstructure are achieved. It is found that the function of EtOH rests on generating steam vapor to create a pore cavity among cross-linked matrixes. The obtained optimal anodes exhibit a high Na storage capacity of ca. 410 mAh/g. When pairing with an O3-NaNi1/3Fe1/3Mn1/3O2 cathode, the full cell delivers a high initial Coulombic efficiency of 83% and energy density of ca. 300 Wh/kg. The proposed chemical regulation approach via a pore-forming strategy is simple and practical to enable high-energy-density NIBs.
Cortical GABAergic interneurons in rodents originate from subpallial progenitors and tangentially migrate to the cortex. While the majority of mouse neocortical interneurons are derived from the medial and caudal ganglionic eminence (MGE and CGE, respectively), it remains unknown whether the lateral ganglionic eminence (LGE) also contributes to a subpopulation of cortical interneurons. Here, we show that the transcription factor Sp8 is expressed in one-fifth of adult cortical interneurons, which appear to be derived from both the dorsal LGE and the dorsal CGE (dLGE and dCGE, respectively). Compared with the MGE-derived cortical interneurons, dLGE/dCGE-derived Sp8-expressing (Sp8+) ones are born at later embryonic stages with peak production occurring at embryonic day 15.5. They tangentially migrate mainly along the subventricular/intermediate zone (SVZ/IZ) route; some continue to express mitotic markers (Ki67 and PH3) in the neonatal cortical SVZ/IZ. Sp8+ interneurons continue to radially migrate from the SVZ/IZ into the cortical layers at early postnatal stages. In contrast to MGE-derived interneurons, dLGE/dCGE-derived Sp8+ interneurons follow an outside-in layering pattern, preferentially occupying superficial cortical layers.
Information remains sparse about non-HIV patients with cryptococcal meningitis in the era of triazole therapy. Particularly of interest are the clinical manifestations and prognosis of the infection in these previously healthy patients. We retrospectively reviewed 154 non-HIV-infected patients with cryptococcal meningitis who presented in our hospital from 1997 to 2007. We compared the clinical features and outcomes between predisposed and otherwise healthy hosts. The number of cases per year showed a steady increase over time. The majority of patients were otherwise apparently healthy (103 patients, 66.9%) and predisposing factors were identified in only 51 (33.1%) patients. Corticosteroid medication accounted for the most common underlying factor in these cases (n = 21). Morbidity was appallingly high, with seizures in 28.6%, cranial nerves palsies in 51.5% and cerebral herniation in 19.5%. Despite these complications, overall mortality during 1 year was 28.7% (41/143), close to that reported from other centers with non-HIV patients. Death attributed to cryptococcosis occurred in 19.6% (28/143) patients with most receiving amphotericin B as a component of their initial therapy. Among surviving patients who had lumbar punctures at weeks 2 and 10, those given amphotericin B for initial therapy achieved higher rates of overall response than those receiving initial fluconazole therapy at either week 2 (84.4% of 96 patients vs. 33.3% of 24 patients, P <0.001) or week 10 (85.0% of 93 patients vs. 66.7% of 24 patients, P = 0.041). In multivariate analysis, coma, cerebral herniation, and initial antifungal therapy without amphotericin B were independently correlated with both increased overall and attributable mortality, while advanced age (>/= 60 years) was correlated with increased overall mortality only. Patients with apparently normal immune status were overall younger than those who were immunocompromised. In addition, previously healthy patients for whom diagnosis was delayed had more severe disease, experiencing more brain herniation, coma, seizures, hydrocephalus and more surgical shunt procedures. On the other hand, immunocompromised patients were more commonly found to have high fever and brain parenchymal involvement. However, both groups had a similar treatment response and 1-year survival.
SUMMARY Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs, and that Sp9 expression is maintained in postmitotic striatopallidal MSNs. Sp9 null mice lose most striatopallidal MSNs due to decreased proliferation of striatopallidal MSN progenitors and increased Bax-dependent apoptosis, whilethe development of striatonigral neurons is largely unaffected. ChIP-qPCR provides evidence that Ascl1 directly binds the Sp9 promoter. RNA-Seq and in situ hybridization reveal that Sp9 promotes expression of Adora2a, P2ry1, Gpr6 and Grik3 in the LGE and striatum. Thus, Sp9 is crucial for the generation, differentiation and survival of striatopallidal MSNs.
The comprehensive performance of carbon anodes for Na‐ion batteries (NIBs) is largely restricted by their inferior rate capability and safety issues. Herein, a slope‐dominated carbon anode is achieved at a low temperature of 800 °C, which delivers a high reversible capacity of 263 mA h g−1 at 0.15C with an impressive initial Coulombic efficiency (ICE) of 80 %. When paired with the NaNi1/3Fe1/3Mn1/3O2 cathode, the reversible capacity at 6C is still 75 % of that at 0.15C, and 73 % of the capacity is retained after 1000 cycles at 3C. The enhanced Na storage performance could be attributed to the unique microstructure with randomly oriented short carbon layers and the relatively higher defect concentration. Given its robustness, such a low‐temperature carbonization strategy could also be applicable to other precursors and provide a new opportunity to design slope‐dominated carbon anodes for high safety, low‐cost NIBs with excellent ICE and superior rate capability.
Na-ion batteries have been considered promising candidates for stationary energy storage. However, their wide application is hindered by issues such as high cost and insufficient electrochemical performance, particularly for cathode materials. Here, we report a solvent-free mechanochemical protocol for the in-situ fabrication of sodium vanadium fluorophosphates. Benefiting from the nano-crystallization features and extra Na-storage sites achieved in the synthesis process, the as-prepared carbon-coated Na3(VOPO4)2F nanocomposite exhibits capacity of 142 mAh g−1 at 0.1C, higher than its theoretical capacity (130 mAh g−1). Moreover, a scaled synthesis with 2 kg of product was conducted and 26650-prototype cells were demonstrated to proof the electrochemical performance. We expect our findings to mark an important step in the industrial application of sodium vanadium fluorophosphates for Na-ion batteries.
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