Manipal University

About: Manipal University is a education organization based out in Manipal, Karnataka, India. It is known for research contribution in the topics: Population & Health care. The organization has 9525 authors who have published 11207 publications receiving 110687 citations.

CRYBA4, a novel human cataract gene, is also involved in microphthalmia.

Abstract: Genetic analysis of a large Indian family with an autosomal dominant cataract phenotype allowed us to identify a novel cataract gene, CRYBA4. After a genomewide screen, linkage analysis identified a maximum LOD score of 3.20 (recombination fraction [θ] 0.001) with marker D22S1167 of the β-crystallin gene cluster on chromosome 22. To date, CRYBA4 was the only gene in this cluster not associated with either human or murine cataracts. A pathogenic mutation was identified in exon 4 that segregated with the disease status. The c.317T→C sequence change is predicted to replace the highly conserved hydrophobic amino acid phenylalanine94 with the hydrophilic amino acid serine. Modeling suggests that this substitution would significantly reduce the intrinsic stability of the crystalline monomer, which would impair its ability to form the association modes critical for lens transparency. Considering that CRYBA4 associates with CRYBB2 and that the latter protein has been implicated in microphthalmia, mutational analysis of CRYBA4 was performed in 32 patients affected with microphthalmia (small eye). We identified a c.242T→C (Leu69Pro) sequence change in exon 4 in one patient, which is predicted here to disrupt the β-sheet structure in CRYBA4. Protein folding would consequently be impaired, most probably leading to a structure with reduced stability in the mutant. This is the first report linking mutations in CRYBA4 to cataractogenesis and microphthalmia.

FTIR and Raman microspectroscopy of normal, benign, and malignant formalin-fixed ovarian tissues.

Abstract: Ovarian cancer is the sixth most common cancer among women worldwide, and mortality rates from this cancer are higher than for other gynecological cancers This is attributed to a lack of reliable screening methods and the inadequacy of treatment modalities for the advanced stages of the disease FTIR and Raman spectroscopic studies of formalin-fixed normal, benign, and malignant ovarian tissues have been undertaken in order to investigate and attempt to understand the underlying biochemical changes associated with the disease, and to explore the feasibility of discriminating between these different tissue types Raman spectra of normal tissues indicate the dominance of proteins and lower contents of DNA and lipids compared to malignant tissues Among the pathological tissues studied, spectra from benign tissues seem to contain more proteins and less DNA and lipids compared to malignant tissue spectra FTIR studies corroborate these findings FTIR and Raman spectra of both normal and benign tissues showed more similarities than those of malignant tissues Cluster analysis of first-derivative Raman spectra in the 700–1700 cm−1 range gave two clear groups, one corresponding to malignant and the other to normal+benign tissues At a lower heterogeneity level, the normal+benign cluster gave three nonoverlapping subclusters, one corresponding to normal and two for benign tissues Cluster analysis of second-derivative FTIR spectra in the combined spectral regions of 1540–1680 and 1720–1780 cm−1 resulted into two clear clusters corresponding to malignant and normal+benign tissues The cluster corresponding to normal+benign tissues produced nonoverlapping subclusters for normal and benign tissues at a lower heterogeneity level The findings of this study demonstrate the feasibility of Raman and FTIR microspectroscopic discrimination of formalin-fixed normal, benign, and malignant ovarian tissues