Summary Background During the assembly and maintenance of cilia, precursor proteins need to be transported from the cell body into the organelle. Intraflagellar transport (IFT) is assumed to be the predominant protein transport pathway in cilia but it remains largely unknown how ciliary proteins use IFT to reach their destination sites in the cilium and whether the amount of cargo transported by IFT is regulated. Results Single particle imaging showed that DRC4, a structural protein of the axoneme, moves in association with IFT particles inside Chlamydomonas reinhardtii cilia. IFT is required for DRC4 transport both into and within the cilium. DRC4 cargoes dissociate from IFT trains at the tip as well as at various sites along the length of the cilium. Unloaded DRC4 diffuses before docking at its axonemal assembly site. In growing cilia, DRC4 transport by IFT was strongly increased over the steady-state level and the frequency decreased linearly with the increasing ciliary length. The frequency of DRC4 transport was similarly elevated in short growth-arrested cilia and remained high even when the amount of DRC4 available in the cell body was reduced. Conclusions DRC4 is a bona fide cargo of IFT. Incompletely assembled cilia trigger an increase in the amount of DRC4 cargo transported by IFT particles and DRC4 transport is down-regulated as cilia approach their steady-state length. We propose a model in which ciliary length is controlled by regulating the amount of cargo transported by IFT.
D1bLIC is a subunit of the retrograde IFT motor. Knockdown or knockout of D1bLIC has dose-dependent effects on flagellar assembly, length, motility, and signaling. iTRAQ-based proteomics identifies novel proteins altered in d1blic mutant flagella. TIRF microscopy reveals the kinetics and remodeling of the retrograde motor at the flagellar tip.
Non-inflammatory alopecia is a frequent skin problem in dogs, causing damaged coat integrity and compromised appearance of affected individuals. In this study, we examined the Cesky Fousek breed, which displays atypical recurrent flank alopecia (aRFA) at a high frequency. This type of alopecia can be quite severe and is characterized by seasonal episodes of well demarcated alopecic areas without hyperpigmentation. The genetic component responsible for aRFA remains unknown. Thus, here we aimed to identify variants involved in aRFA using a combination of histological, genomic, and transcriptomic data. We showed that aRFA is histologically similar to recurrent flank alopecia, characterized by a lack of anagen hair follicles and the presence of severely shortened telogen or kenogen hair follicles. We performed a genome-wide association study (GWAS) using 216 dogs phenotyped for aRFA and identified associations on chromosomes 19, 8, 30, 36, and 21, highlighting 144 candidate genes, which suggests a polygenic basis for aRFA. By comparing the skin cell transcription pattern of six aRFA and five control dogs, we identified 236 strongly differentially expressed genes (DEGs). We showed that the GWAS genes associated with aRFA are often predicted to interact with DEGs, suggesting their joint contribution to the development of the disease. Together, these genes affect four major metabolic pathways connected to aRFA: collagen formation, muscle structure/contraction, lipid metabolism, and the immune system.
Students regard evolutionary theoiy differently than science in general. Students' reported confidence in their ability to understand science in general (e.g., posing scientific questions, interpreting tables and graphs, and understanding the content of their biology course) significantly outweighed their confidence in understanding evolution. We also show that those students with little incoming confidence in their understanding of evolution demonstrated more confidence and the most improved performance by the end of the semester Collectively, our data indicate that regardless of prior experiences with evolution education, and in spite of myriad social challenges to teaching evolution, students can learn evolution.
Cystic hygroma is a malformation of the lymphatic and vascular system and is recognized as a benign congenital tumor that affects humans and animals in the perinatal period. This congeni-tal disorder is rarely described in animals, and until today, cystic hygroma in pigs has not been described in the literature. In a purebred Piètrain litter with twelve live-born piglets, cystic hy-groma was noticed on the rump of two male pigs within the first week of life. In addition, a third case of a crossbred weaner (Large White × Landrace) was detected during a herd examina-tion. To rule out common differential diagnoses, e.g., abscess or hematoma, further clinical and pathological investigations were conducted. During clinical examination, a painless and soft mass, which was compressible, was detected on the rump of all affected animals. The ultra-sonographic examination revealed a fluid-filled and cavernous subcutaneous structure. In addi-tion, a puncture of the cyst was conducted, revealing a serosanguinous fluid with negative bacte-riological culture. In all cases, a necropsy was performed, showing that the animals had fluid-filled cysts lined by well-differentiated lymphatic endothelium. Based on the clinicopathological examination, cystic hygroma was diagnosed. Furthermore, SNP array genotyping and whole-genome sequencing was performed and provided no evidence for a chromosomal disorder. In the Piètrain family, several genome regions were homozygous in both affected piglets. None-theless, a dominant acting de novo germline variant could not be ruled out, and therefore differ-ent filtering strategies were used to find pathogenic variants. The herein presented lists of pri-vate variants after filtering against hundreds of control genomes provide no plausible candidate and no shared variants among the two sequenced cases. Therefore, further studies are needed to evaluate possible genetic etiology. In general, systematic surveillance is needed to identify ge-netic defects as early as possible and to avoid the occurrence of losses in the pig population.
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