Mouse Models for Blistering Skin Disorders

Genetically engineered mice have been essential tools for elucidating the pathological mechanisms underlying human diseases. In the case of diseases caused by impaired desmosome function, mouse models have helped to establish causal links between mutations and disease phenotypes. This review focuses on mice that lack the desmosomal cadherins desmoglein 3 or desmocollin 3 in stratified epithelia. A comparison of the phenotypes observed in these mouse lines is provided and the relationship between the mutant mouse phenotypes and human diseases, in particular pemphigus vulgaris, is discussed. Furthermore, we will discuss the advantages and potential limitations of genetically engineered mouse lines in our ongoing quest to understand blistering skin diseases

Computed tomography texture-based radiomics analysis in gallbladder cancer: initial experience

Aim of the study: To investigate computed tomography (CT) texture parameters in suspected gallbladder cancer (GBC) and assess its utility in predicting histopathological grade and overall survival. Material and methods: This retrospective pilot study included consecutive patients with clinically suspected GBC. CT images, clinical, and histological or cytological data were retrieved from the database. CT images were reviewed by two radiologists. A single axial CT section in the portal venous phase was selected for texture analysis. Radiomic feature extraction was done using commercially available research software. Results: Thirty-eight patients (31 females, mean age 53.1 years) were included. Malignancy was confirmed in 29 patients in histopathology or cytology analysis, and the rest had no features of malignancy. Exophytic gallbladder mass with associated gallbladder wall thickening was present in 22 (58%) patients. Lymph nodal, liver, and omental metastases were present in 10, 1, and 3 patients, respectively. The mean overall survival was 9.7 months. There were significant differences in mean and kurtosis at medium texture scales to differentiate moderately differentiated and poorly differentiated adenocarcinoma (p < 0.05). The only texture parameter that was significantly associated with survival was kurtosis (p = 0.020) at medium texture scales. In multivariate analysis, factors found to be significantly associated with length of overall survival were mean number of positive pixels (p = 0.02), skewness (p = -0.046), kurtosis (0.018), and standard deviation (p = 0.045). Conclusions: Our preliminary results highlight the potential utility of CT texture-based radiomics analysis in patients with GBC. Medium texture scale parameters including both mean and kurtosis, or kurtosis alone, may help predict the histological grade and survival, respectively

Characterization and evaluation of mountain sweet thorn (Flacourtia montana J. Grah) collections

Mountain sweet thorn (Flacourtia montana J. Grah) is an indigenous underutilized fruit of the Western Ghats and other regions of peninsular India. It is a close relative of Governor’s plum. It is a bushy shrub or small tree with spiny trunks and branches which may grow up to 2.5 m in height. The fruits are bright dark red 1-2 cm in diameter, sweet edible, and have the potential for processing into jams and jellies. The presence of thorn is one of the major hurdles for the commercialization of this crop. Thus, seeds of the thorny plants of the Mountain sweet thorn were collected from different locations, and seedlings were planted to identify the suitable line. The plant height ranged from 425 cm (accession 0208) to 710 cm (accession​ ​0202). The plant girth ranged from 34.5 cm to 82 cm. The growth data revealed that all​ ​the accessions are vigorous, fast-growing, and have various levels of thorniness. All the​ ​accessions were found to be spreading type. Significant variability was recorded for leaf​ ​characteristics among the accessions studied. Three major clusters were observed in​ ​cluster analysis for morphological and fruiting characters consisting&nbsp;of 1, 8, and 9 accessions,​ ​respectively. The number of fruits ranged from 0 to 4008. The highest yield (9.46 kg/plant)​ ​was obtained in accession - 0106 followed by accession- 0201 (7.83 kg). The average​ ​fruit weight ranged from 1.51 g to 3.94 g. The highest fruit weight (3.94g) was also recorded​ ​in 0106 followed by 2.84 (0102). The total soluble solids ranged from 10 0 Brix to 15.1 0​ ​Brix. Overall, accession 0201 was found better than others with respect to yield, regular​ ​bearing, and less thorniness

Plakoglobin as a regulator of desmocollin gene expression.

Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages, and the heart. The goal of this study was to investigate how desmocollins (DSCs), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with lymphoid enhancer-binding factor 1 (Lef-1) differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NF-κB pathway components, the downstream effectors of the ectodysplasin-A (EDA)/ ectodysplasin-A receptor (EDAR)/NF-κB signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and EDA/EDAR/NF-κB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. It is tempting to speculate that this shift is required for the invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation