Co-deletion of Bax rescued the Bcl-xLcKO phenotype, while co-deletion of Mcl-1 enhanced the phenotype. These findings show that CGNPs require BCL-xL to regulate BAX-dependent apoptosis, and that this role can be partially compensated by MCL-1. Our data further show that BCL-xL expression regulates MCL-1 abundance in CGNPs, and suggest that excessive MCL-1 in Bcl-xLcKO mice prolongs CGNP proliferation by binding SUFU, resulting in increased SHH pathway activation. Accordingly, we propose that BCL-xL and MCL-1 interact with each other and with developmental mechanisms that regulate proliferation, to adjust the apoptotic threshold as CGNPs progress through postnatal neurogenesis to CGNs.To evaluate extralesional microvascular and structural changes of the macula using optical coherence tomography angiography (OCTA) and structural OCT in cytomegalovirus retinitis (CMVR). An observational study of CMVR patients were performed. Complete ophthalmic examination, serial color fundus photography, structural OCT and OCTA were performed at baseline and follow-up visits for up to 12 months. The structural OCT was analyzed to evaluate macular areas within, bordering and beyond the CMVR lesions. Extralesional retinal capillary plexus of the macula were evaluated by OCT angiography and compared with the unaffected fellow eyes. Thirteen eyes from 13 patients were enrolled. SBI-0640756 solubility dmso At baseline, macular areas without CMVR lesions showed decreased vessel density (VD) of both the superficial (P = 0.0002) and deep (P  less then  0.0001) retinal capillary plexus in eyes with CMVR as compared with the corresponding macular areas of the unaffected fellow eyes. The decrease of VD persisted through the follow-up period for up to 12 months after adjusting for degree of vitreous haze. Structural macular OCT characteristics at the borders and beyond the lesions included intraretinal hyperreflective dots, cystoid macular edema, subretinal fluid and selective ellipsoid zone (EZ) loss. The selective EZ loss found in 6 of 12 eyes showed recovery in 4 eyes after receiving anti-viral treatment. In CMVR eyes, there were microvascular and microstructural abnormalities in the macular area without clinically visible CMVR lesions. Our results provided interesting insights into CMV infection of the retina.Genotype-phenotype correlations of humans and dogs with hereditary methemoglobinemia are not yet well characterized. We determined total hemoglobin and methemoglobin (MetHb) concentrations, cytochrome b5 reductase (CYB5R) enzyme activities, genotypes, and clinical signs in 30 dogs with persistent cyanosis without cardiopulmonary disease. Erythrocytic CYB5R enzyme activities were low in all dogs assayed. Owner-reported quality of life ranged from subclinical to occasional exertional syncope. Two previously reported and two novel CYB5R3 missense variants were identified among the methemoglobinemic cohort and were predicted to impair enzyme function. Two variants were recurrent a homozygous Ile194Leu substitution was found in Pomeranians and other small dogs, and a homozygous Arg219Pro change occurred predominately in pit bull terriers. The other two variants were Thr202Ala and Gly76Ser substitutions in single dogs. Of the two common CYB5R3 genotypes, Arg219Pro was associated with a more severe metabolic phenotype. We conclude that CYB5R3 deficiency is the predominate cause of canine hereditary methemoglobinemia. Although this finding is unlikely to alter the clinical approach to hereditary methemoglobinemia in dogs, it demonstrates the possibility of how genotype-phenotype cohort analysis might facilitate precision medicine in the future in veterinary medicine.Photoacoustics is a promising technique for in-depth imaging of biological tissues. However, the lateral resolution of photoacoustic imaging is limited by size of the optical excitation spot, and therefore by light diffraction and scattering. Several super-resolution approaches, among which methods based on localization of labels and particles, have been suggested, presenting promising but limited solutions. This work demonstrates a novel concept for extended-resolution imaging based on separation and localization of multiple sub-pixel absorbers, each characterized by a distinct acoustic response. Sparse autoencoder algorithm is used to blindly decompose the acoustic signal into its various sources and resolve sub-pixel features. This method can be used independently or as a combination with other super-resolution techniques to gain further resolution enhancement and may also be extended to other imaging schemes. In this paper, the general idea is presented in details and experimentally demonstrated.The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a subject of debate, even more since the ARUBA trial. Here, we report the obliteration rate, the risk of hemorrhage and the functional outcomes after Gamma Knife radiosurgery (GKRS) as first-line treatment for non-hemorrhagic AVMs treated before the ARUBA publication, in a reference university center with multimodal AVM treatments available. We retrospectively analyzed data from a continuous series of 172 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our Lille University Hospital, France, between April 2004 and December 2013. The primary outcome was obliteration rate. Secondary outcomes were the hemorrhage rate, the modified Rankin Scale (mRS), morbidity and epilepsy control at last follow-up. The minimal follow-up period was of 3 years. Median age at presentation was 40 years (IQR 28; 51). Median follow-up was 8.8 years (IQR 6.8; 11.3). Median target volume was 1.9 cm3 (IQR 0.8-3.3 cm3), median Spetzlas 84.6% seizure free at last follow-up. Permanent morbidity was reported in only 4.6%.Influenza A virus (IAV)-specific CD8+ T-cell response was shown to provide protection against pandemic and seasonal influenza infections. However, the response was often relatively weak and the mechanism was unclear. Here, we show that the composition of IAV released from infected cells is regulated by the neuraminidase (NA) activity and the cells infected by NA-defective virus cause intracellular viral protein accumulation and cell death. In addition, after uptake of NA-defective viruses by dendritic cells (DCs), an expression of the major histocompatibility complex class I is induced to activate IAV-specific CD8+ T-cell response. When mice were infected by NA-defective IAV, a CD8+ T-cell response to the highly conserved viral antigens including PB1, NP, HA, M1, M2 and NS1 was observed along with the increasing expression of IL10, IL12 and IL27. Vaccination of mice with NA-defective H1N1 A/WSN/33 induced a strong IAV-specific CD8+ T cell response against H1N1, H3N2 and H5N1. This study reveals the role of NA in the IAV-specific CD8+ T-cell response and virion assembly process, and provides an alternative direction toward the development of universal influenza vaccines.