Focus: A Multifaceted Battle Against Cancer: Extracting Knowledge from Chemical Imaging Data Using Computational Algorithms for Digital Cancer Diagnosis

Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer.     

Restriction enzyme digestion of heterochromatin inDrosophila nasuta

In situ digestion of metaphase and polytene chromosomes and of interphase nuclei in different cell types ofDrosophila nasuta with restriction enzymes revealed that enzymes like AluI, EcoRI, HaeIII, Sau3a and SinI did not affect Giemsa-stainability of heterochromatin while that of euchromatin was significantly reduced; TaqI and SalI digested both heterochromatin and euchromatin in mitotic chromosomes. Digestion of genomic DNA with AluI, EcoRI, HaeIII, Sau3a and KpnI left a 23 kb DNA band undigested in agarose gels while withTaqI, no such undigested band was seen. TheAluI resistant 23 kb DNA hybridized insitu specifically with the heterochromatic chromocentre. It appears that the digestibility of heterochromatin region in genome ofDrosophila nasuta with the tested restriction enzymes is dependent on the availability of their recognition sites.     

Colchicine inhibits plasmodium formation and disrupts pathways of sporopollenin secretion in the anther tapetum ofTradescantia virginiana L.

Summary During an earlier investigation, microtubules were observed at the periphery of invasion processes in the developing syncytial tapetum ofTradescantia virginiana L. They were also associated with membranous sacs that accumulate adjacent to tetrads, with putative fusion sites where the tapetal plasmodium is initiated, and, in postmeiotic stages, with the perispore membrane that encloses the developing spore cells. Colchicine was administered to developing flower buds to investigate the roles of these microtubules. The results indicate that microtubules neither initiate nor guide the tapetal invasion of the loculus. The treatments, however, resulted in absence of cell coat from invasion processes and prevention of cell fusion. They also inhibited polarized migration of membrane sacs and removed the associated microtubules. The development of an organized secretory apparatus at the perispore membrane was disrupted, with subsequent disordered deposition of sporopollenin in the extracellular spaces of the partially-fused plasmodium. The results suggest that microtubules participate in the formation and internal spatial organization of the tapetal plasmodium, and establishment of a secretory surface that normally produces sporopollenin at the tapetum-microspore interface.     

Constituents of roots of Boerhaavia diffusa

Hentriacontane, β-sitosterol and ursolic acid have been isolated from roots of Boerhaavia diffusa (Linn).     

Changes in phosphatases and lipids following scrotal gamma irradiation in adult rat testis.

Effects of localized low (2.5 Gy) and high (10 Gy) levels of gamma irradiation on the testis of albino rats were studied. A marked increase in the testicular total lipid, phospholipid and cholesterol content was observed at all post-treatment intervals except at 16 weeks where the contents decreased. A significant decrease in the activity of acid phosphatase/g of testis was seen at both the doses, the minimum value being at 4 weeks. The decrease in acid phosphatase activity is correlated with the state of germ cell population in seminiferous tubule which is found to be depleted at 4 week interval. The alkaline phosphatase activity/g testis however, showed a significant increase, the maximum being at 4 weeks post-treatment. Thereafter, the values of the enzyme activity showed a slight recovery at 16 weeks post-irradiation. ATPase activity increased initially followed by a significant decrease at all post-treatment intervals.     

The use of biofertilizer of Calothrix sp. M103, enhanced by addition of iron and siderophore production

Calothrix sp. M103, enhanced by addition of iron and siderophore production was used as a biofertilizer. The strain was isolated from a colony on the surface root of a rice plant from a rice field in Bangladesh. It showed a marked and immediate increase in nitrogenase activity in response to the addition of iron and also a normal activity (compared with the control) under siderophore production. The addition of iron to iron-limited cultures resulted in a rapid increase in algal iron (11-fold) followed by a marked increase (9-fold) in nitrogenase activity, reaching about 11.8 kg N/ha/crop. This was more than twice the amount of nitrogen usually fixed by the alga during normal growth (controlled conditions), suggesting that pulsing algal inocula with iron would increase the efficiency of algae as a biofertilizer. Indeed, the use of an iron-pulsed inoculum of this strain as a biofertilizer resulted in an increase in the yield of sweetcorn by ca 143% over that produced by the control (no algal inoculation) and to ca a 73% increase over that produced by the normal inoculum (unpulsed with iron). The ability of this strain to produce siderophores has also led to both normal (compared with the control) nitrogenase activity as well as normal growth, which shows a marked contrast to other circumstances where the non-siderophore producing strains showed no growth at all. The significance of these observations on the enhancement of biofertilizer technology is discussed.     

A study on biological activity measurements and heterotrophic bacteria in a small freshwater lake

A 6-m-deep lake has been sampled to measure the temporal and depth-wise distribution of heterotrophic bacteria and biological activity in the water. Surface, mid-depth and bottom waters were analysed at monthly intervals for a period of one year. The coefficient of heterotrophic activity, alkaline phosphatase activity and biological oxygen demand are used as an index of biological activity. The bacterial community was at maximum during spring, coinciding with high values of biological activity. Highest biological activity was observed in the bottom waters. Dissolved organic carbon showed a significant positive correlation with most of the biological activity parameters. This suggests that biological activity, as measured by the coefficient of heterotrophic activity, was more closely related to the concentration of substrates than to population density of heterotrophic bacteria.