Growth defects in the dorsal pallium after genetically targeted ablation of principal preplate neurons and neuroblasts: a morphometric analysis

The present study delineates the large-scale, organic responses of growth in the dorsal pallium to targeted genetic ablations of the principal PP (preplate) neurons of the neocortex. Ganciclovir treatment during prenatal development [from E11 (embryonic age 11) to E13] of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene; GPT linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP and lacZ reporters] localized in PP neurons and their intermediate progenitor neuroblasts. The volume, area and thickness of the pallium were measured in an E12–P4 (postnatal age 4) longitudinal study with comparisons between ablated (HSV-TK+/0) and control (HSV-TK0/0) littermates. The extent of ablations was also systematically varied, and the effect on physical growth was assessed in an E18 cross-sectional study. The morphological evidence obtained in the present study supports the conclusion that genetically targeted ablations delay the settlement of the principal PP neurons of the dorsal pallium. This leads to progressive and substantial reductions of growth, despite compensatory responses that rapidly replace the ablated cells. These growth defects originate from inductive cellular interactions in the proliferative matrix of the ventricular zone of the pallium, but are amplified by subsequent morphogenic and trophic cellular interactions. The defects persist during the course of prenatal and postnatal development to demonstrate a constrained dose–response relationship with the extent of specific killing of GPT neurons. The defects propagate simultaneously in both the horizontal and vertical cytoarchitectural dimensions of the developing pallium, an outcome that produces a localized shortfall of volume in the telencephalic vesicles

Probe of Spin Dynamics in Superconducting NbN Thin Films via Spin Pumping

The emerging field of superconductor (SC) spintronics has attracted intensive attentions recently. Many fantastic spin dependent properties in SC have been discovered, including the observation of large magnetoresistance, long spin lifetimes and the giant spin Hall effect in SC, as well as spin supercurrent in Josephson junctions, etc. Regarding the spin dynamic in SC films, few studies has been reported yet. Here, we report the investigation of the spin dynamics in an s-wave superconducting NbN film via spin pumping from an adjacent insulating ferromagnet GdN layer. A profound coherence peak of the Gilbert damping is observed slightly below the superconducting critical temperature of the NbN layer, which is consistent with recent theoretical studies. Our results further indicate that spin pumping could be a powerful tool for investigating the spin dynamics in 2D crystalline superconductors.Comment: 11 pages, 4 figures, and S

The Viral TRAF Protein (ORF111L) from Infectious Spleen and Kidney Necrosis Virus Interacts with TRADD and Induces Caspase 8-mediated Apoptosis

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus of the Iridoviridae family. It causes a serious and potentially pandemic disease in wild and cultured fishes. ISKNV infection induces evident apoptosis in mandarin fish (Siniperca chuatsi) and zebrafish (Danio renio). However, the mechanism is still unknown. After a genome-wide bioinformatics analysis of ISKNV-encoded proteins, the ISKNV open reading frame 111L (ORF111L) shows a high similarity to the tumour necrosis factor receptor-associated factor (TRAF) encoded by fish, mice and mammals, which is essential for apoptotic signal transduction. Moreover, ORF111L was verified to directly interact with the zebrafish TNF receptor type 1 associated death domain protein (TRADD). A recombinant plasmid containing the DNA sequence of ORF111L was constructed and microinjected into zebrafish embryos at the 1–2 cell stage to investigate its biological function in vivo. ORF111L overexpression in the embryos resulted in increased apoptosis. ORF111L-induced apoptosis was clearly associated with significant caspase 8 upregulation and activation. The knockdown of zebrafish caspase 8 expression effectively blocked the apoptosis induced by ORF111L overexpression. Significantly, ORF111L overexpression resulted in much stronger effect on caspase 8 and caspase 3 upregulation compared to zebrafish TRAF2. This is the first report of a viral protein similar to TRAF that interacts with TRADD and induces caspase 8-mediated apoptosis, which may provide novel insights into the pathogenesis of ISKNV infection

Targeted ablation and reorganization of the principal preplate neurons and their neuroblasts identified by golli promoter transgene expression in the neocortex of mice

The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11–E13; where E is embryonic day) of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP (τ-enhanced green fluorescent protein) and lacZ (lacZ galactosidase) reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0) and control (HSV-TK0/0) littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and permanently impairs its connectivity

Stemness And Chemotherapeutic Drug Resistance Induced By Eif5a2 Overexpression In Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P > 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.published_or_final_versio