CX3CR1 expression is associated with the commitment of CSF-1R+ myeloid precursors to the macrophage/dendritic cell (DC) lineage. However, the relationship of the CSF-1R+ CX3CR1+ macrophage/DC precursor (MDP) with other DC precursors and the role of CX3CR1 in macrophage and DC development remain unclear. We show that MDPs give rise to conventional DCs (cDCs), plasmacytoid DCs (PDCs), and monocytes, including Gr1+ inflammatory monocytes that differentiate into TipDCs during infection. CX3CR1 deficiency selectively impairs the recruitment of blood Gr1+ monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs.

Mainzer-Saldino syndrome (MSS) is a rare disorder characterized by phalangeal cone-shaped epiphyses, chronic renal failure, and early-onset, severe retinal dystrophy. Through a combination of ciliome resequencing and Sanger sequencing, we identified IFT140 mutations in six MSS families and in a family with the clinically overlapping Jeune syndrome. IFT140 is one of the six currently known components of the intraflagellar transport complex A (IFT-A) that regulates retrograde protein transport in ciliated cells. Ciliary abundance and localization of anterograde IFTs were altered in fibroblasts of affected individuals, a result that supports the pivotal role of IFT140 in proper development and function of ciliated cells.

Leber congenital amaurosis (LCA) is a severe hereditary retinal dystrophy responsible for congenital or early-onset blindness. The most common disease-causing mutation (>10%) is located deep in intron 26 of the CEP290 gene (c.2991+1655A>G). It creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. In the present study, we show that the use of antisense oligonucleotides (AONs) allow an efficient skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients. These data support the feasibility of an AON-mediated exon skipping strategy to correct the aberrant splicing.

The short-term effects of delayed feeding (DF) for 2 d posthatching were measured in neonate chicks and compared to early feeding (EF). Chicks from 10 independent families were used in this study to determine whether genetic background control of growth may be influenced by EF and DF. Early feeding maintained significant interfamily body weight variations from hatch to 4 d of age, whereas there were no significant differences from 1 d of age when feeding was delayed to 48 h posthatching. These results suggest that posthatching feeding delay may distort genetic selection by masking the expression of genetic potential and disturbing the estimation of chick breeder value. In DF chicks, overall body growth was delayed until the beginning of feeding and body weight at 6 d of age was 25% lower than EF chicks. Availability of feed after the fasting period was not sufficient to compensate for the retardation of weight gain in either body weight or in intestine and breast muscle weight. However, initiation of intestine growth in DF chicks occurred from 1 d of age despite the lack of feeding, whereas feed intake was essential to enhance muscle growth. The potential for protein synthesis was lower in DF than in EF chicks during the first 2 d posthatching (P < 0.001) and then reached similar values after feed intake. These results confirm that initiation of growth in neonate chicks is improved by earlier feeding after hatching. Awareness of changes in overall body weight caused by posthatching food deprivation, especially in the intestine and muscle might help in the development of new diets which could minimize retardation of body weight gain in chicks.

AimsBlue light is an identified risk factor for age-related macular degeneration (AMD). We investigated oxidative stress markers and mitochondrial changes in A2E-loaded retinal pigment epithelium cells under the blue–green part of the solar spectrum that reaches the retina to better understand the mechanisms underlying light-elicited toxicity.ResultsPrimary retinal pigment epithelium cells were loaded with a retinal photosensitizer, AE2, to mimic aging. Using a custom-made illumination device that delivers 10 nm-wide light bands, we demonstrated that A2E-loaded RPE cells generated high levels of both hydrogen peroxide (H2O2) and superoxide anion (O2•−) when exposed to blue–violet light. In addition, they exhibited perinuclear clustering of mitochondria with a decrease of both their mitochondrial membrane potential and their respiratory activities. The increase of oxidative stress resulted in increased levels of the oxidized form of glutathione and decreased superoxide dismutase (SOD) and catalase activities. Furthermore, mRNA expression levels of the main antioxidant enzymes (SOD2, catalase, and GPX1) also decreased.ConclusionsUsing an innovative illumination device, we measured the precise action spectrum of the oxidative stress mechanisms on A2E-loaded retinal pigment epithelium cells. We defined 415–455 nm blue–violet light, within the solar spectrum reaching the retina, to be the spectral band that generates the highest amount of reactive oxygen species and produces the highest level of mitochondrial dysfunction, explaining its toxic effect. This study further highlights the need to filter these wavelengths from the eyes of AMD patients.