The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multiparental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.
Narrowband ultraviolet (NB‐UV)B is accepted as corner stone therapy for vitiligo. Its influence on the expression of IL‐17, IL‐ 22 and FoxP3 as markers for the Th17 and Tregs lineages has not been studied before in the context of non‐segmental vitiligo (NSV). The study included 20 active NSV patients who received 36 NB‐UVB sessions and 20 controls. Clinical evaluation Vitiligo Area Scoring Index (VASI) and determination of tissue expression of IL‐17, IL‐22 and FoxP3 by qRT‐PCR (lesional, perilesional) were carried out before and after therapy. Baseline levels of IL‐17 and IL‐22 were significantly higher in patients, whereas FoxP3 was significantly lower. After therapy, IL‐17 and IL‐22 significantly dropped, whereas FoxP3 significantly increased (lesional, perilesional). Baseline and post‐treatment VASI showed significant positive correlations with IL‐17 and IL‐22 and significant negative correlation with FoxP3 expression. Restoration of the balance between Th17 and Tregs might represent a novel pathway for the improvement that NB‐UVB exerts in vitiligo patients.
In the present work, patients with lichen planus were found to have higher makers of both metabolic and cardiovascular risk factors in relation to controls most probably due to long standing inflammation.
Using different techniques in M-K susp produces comparable results. However, the distal fingers showed better results using combination of donor NCECS and recipient cryoblebs.
Patients with PV have significantly lower serum vitamin D levels in comparison to controls and that these low levels were not related to age, BMI or pattern of sun exposure. The associated Vitamin D insufficiency in patients with PV may possibly exacerbate their disease through various immune related mechanisms.
Adipose tissue is now considered an endocrine organ secreting different cytokines known as adipocytokines. Lipocalin-2 has been recently identified as an adipokine present in the circulation, it is related to insulin resistance, obesity, atherosclerotic diseases and type 2 diabetes. Lipocalin-2 and psoriasis are assumed to be closely associated with the metabolic syndrome. The aim of the present study is to estimate the level of lipocalin-2 in the serum and tissue of psoriatic patients and to correlate these levels with markers of metabolic syndrome, CRP and disease severity. This study was done on 30 patients of psoriasis and 30 healthy controls. All patients and controls were subjected to clinical examination. Serum, tissue levels of lipocalin-2 and C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay technique. Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with psoriasis showed significant association with metabolic syndrome parameters than controls. Tissue lipocalin-2 was significantly higher than serum levels in psoriasis patients. A significant difference was detected in tissue levels of lipocalin-2 and not in the serum between patients and controls. Both tissue and serum lipocalin-2 correlated with CRP. Although there was a correlation between tissue and serum levels of lipocalin-2 in patients, there was no correlation between both of them with metabolic syndrome and related disorders. Our results revealed that patients with psoriasis are at increased risk of metabolic and cardiovascular complications, tissue lipocalin-2 is more specific to psoriasis than serum lipocalin-2. Lipocalin-2 has no role in determining severity of the disease. Neither tissue nor serum lipocalin-2 conveys cardiovascular risk in psoriasis patients.
This work aimed to assess the possible association between the presence of seminal mast cells and asthenozoospermia. One hundred and seventy-six male subjects were investigated: group (Gr)1 (n=46) normozoospermic fertile controls, Gr2 (n=62) idiopathic asthenozoospermia, Gr3 (n=32) asthenozoospermia with scrotal varicocele and Gr4 (n=36) asthenozoospermia with leucocytospermia. Four smear slides were prepared for each semen sample to be stained with toluidine blue-pyronin to detect mast cells. A significant increase was shown in mast cell-positive samples among varicocele-associated and idiopathic asthenozoospermic patients in comparison with fertile controls. Seminal mast cells were also detected at higher frequency among smokers and in age group over 40 years. It is concluded that mast cells and their products may play a pivotal role in the pathogenesis of asthenozoospermia, possibly proposing a new goal for medical treatment of infertile males to pursue. In addition, this concept may in a way detain smoking as a cause of male infertility considering the clear abundance of mast cells in semen samples of smokers.
Addition of different growth factors to the medium used in autologous melanocyte‐keratinocyte transplantation procedure (MKTP) was reported in the literature. The aim of the current study was comparison of response to MKTP in segmental vitiligo (SV) with and without adding growth factors to the suspension medium. Eighteen cases with SV were randomly divided into two groups. In group A: Ham F12 medium was used for suspension and in group B: 5 ng/mL recombinant basic fibroblast growth factor (bFGF) and 25 mg/500 mL 3′5′ cyclic adenosine monophosphate (cAMP) were added to the medium. All cases received NB‐UVB twice weekly for 24 weeks. The area of vitiligo lesions was measured before and after therapy by point‐counting technique and complications were recorded. Excellent response (90%‐100% repigmentation) occurred in 5/9 cases (56%) in group A and 7/9 cases (78%) in group B (with growth factors). A significant decrease in the area of treated lesions before and after therapy was found in both groups A and B (P = .0012 and .0004, respectively), however, a higher percentage of reduction in area of vitiligo was seen in group B cases (70% in group A vs 90% in group B; P value: .028). Marginal halo was seen in five cases in group A and six in group B. In conclusion addition of bFGF and cAMP to MKTP medium improved the results of the procedure. It could be considered if economically feasible.
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