Prakash Adhikari

Significance: Light is a good probe for studying the nanoscale-level structural or molecular-specific structural properties of brain cells/tissue due to stress, alcohol, or any other abnormalities. Chronic alcoholism during pregnancy, i.e., fetal alcoholism, being teratogenic, results in fetal alcohol syndrome, and other neurological disorders. Understanding the nano-to-submicron scale spatial structural properties of pup brain cells/tissues using light/photonic probes could provide a plethora of information in understanding the effects of fetal alcoholism. Aim: Using both light scattering and light localization techniques to probe alterations in nano- to-submicron scale mass density or refractive index fluctuations in brain cells/tissues of mice pups, exposed to fetal alcoholism. Approach: We use the mesoscopic physics-based dual spectroscopic imaging techniques, partial wave spectroscopy (PWS) and molecular-specific inverse participation ratio (IPR) using confocal imaging, to quantify structural alterations in brain tissues and chromatin/histone in brain cells, respectively, in 60 days postnatal mice pup brain, exposed to fetal alcoholism. Results: The finer focusing PWS analysis on tissues shows an increase in the degree of structural disorder strength in the pup brain tissues. Furthermore, results of the molecular-specific light localization IPR technique show an increase in the degree of spatial molecular mass density structural disorder in DNA and a decrease in the degree in histone. Conclusions: In particular, we characterize the spatial pup brain structures from the molecular to tissue levels and address the plausible reasons for such as mass density fluctuations in fetal alcoholism.

Fractal dimension, a measure of self-similarity in a structure, is a powerful physical parameter for the characterization of structural property of many partially filled disordered materials. Biological tissues are fractal in nature and reports show a change in self-similarity associated with the progress of cancer, resulting in changes in their fractal dimensions. Here, we report that fractal dimension measurement is a potential technique for the detection of different stages of cancer using transmission optical microscopy. Transmission optical microscopy of a thin tissue sample produces intensity distribution patterns proportional to its refractive index pattern, representing its mass density distribution. We measure fractal dimension detection of different cancer stages and find its universal feature. Many deadly cancers are difficult to detect in their early to different stages due to the hard-to-reach location of the organ and/or lack of symptoms until very late stages. To study these deadly cancers, tissue microarray (TMA) samples containing different stages of cancers are analyzed for pancreatic, breast, colon, and prostate cancers. The fractal dimension method correctly differentiates cancer stages in progressive cancer, raising possibilities for a physics-based accurate diagnosis method for cancer detection.

Molecular specific photonics localization method, the inverse participation ratio (IPR) technique, is a powerful procedure to probe the nano‐ to submicron scales structural alterations in cells/tissues in their abnormalities due to chronic alcoholism using confocal imaging. Chronic alcoholism introduces abnormalities in brain cells/tissue at the nanoscale level that results in behavioural and psychological disorders which are not well understood. On the other hand, probiotics such asLactobacillus plantarumenhances brain functions in chronic alcoholism. Using the IPR technique, we probe the molecular specific spatial structural alterations in glial brain cells astrocytes and microglia, as well as in chromatins in the nuclei of cortex brain cells, with or without probiotic treatments in chronic alcoholism. The results show chronic alcoholism alone harms brain cells and the probiotic treatment in chronic alcoholism reverses alcoholic damage in the brain cells/tissues toward normalcy.

Abnormalities within cells result in intracellular structural alterations ranging from nano to submicron scales. Accidental or deliberate exposure to total body irradiation has adverse effects on the nuclear DNAs of cells. Here, we study the molecular specific DNA spatial mass density fluctuations of chromatin of mice gut cell nuclei caused by the exposure to standard doses of 4-Gy total body irradiation, using the light localization technique called inverse participation ratio via confocal imaging. Results show radiation suppresses DNA spatial mass density fluctuations. And hence, the reduction and saturation in DNA mass density fluctuations are observed on different durations of post-irradiation.

Nanoscale structural alteration in the nuclei of cells with the progression of carcinogenesis is due to the rearrangements of the basic building blocks in the cell such as DNA, RNA, lipids, etc. Although epigenetic modifications underlie the development of cancer, exposure to carcinogenic chemicals such as alcohol also enhances the development of cancer. We report the effects of chronic alcoholism on early-carcinogenesis based on changes in the degree of nanoscale structural alterations ( L _d ) in nuclei. For this, transmission electron microscopy (TEM) imaging of the nuclei of colonic cells is performed for the following four mouse models: control mice; chronic alcoholic mice treated with ethanol (i.e., EtOH mice); mice treated with colonic carcinogen azoxymethane (AOM) and dextran sulfate sodium (DSS) that induced colitis (i.e., AOM + DSS mice); and chronic alcoholic or EtOH treated mice, together with AOM and DSS treatment (i.e., AOM + DSS + EtOH mice). The disordered optical lattices are constructed from their respective TEM images of thin colonic cell nuclei and the L _d values are calculated using the inverse participation ratio (IPR) technique from the spatially localized eigenfunctions of these lattices. Results show no significant difference in the average L _d value of the colon cell nuclei of alcohol treated mice relative to its control [i.e., L _d (C) ∼ L _d (EtOH)]; however, an increase in the L _d value of alcohol treated precancerous cells [i.e., L _d (AOM + DSS + EtOH) > L _d (AOM + DSS)], indicating that alcohol accelerates the early carcinogenic process.

We report the effectiveness of silver nanocluster (Ag-NC) against the biofilm of Pseudomonas aeruginosa (PA). Two DNA aptamers specific for PA and part of their sequences were chosen as templates for growing the Ag-NC. While circular dichroism (CD) studies determined the presence of secondary structures, UV/Vis absorption, and fluorescence spectroscopic studies confirmed the formation of the fluorescent Ag-NC on the DNA templates. Furthermore, mesoscopic physics-based partial wave spectroscopy (PWS) was used to analyze the backscattered light signal that can detect the degree of nanoscale mass density/refractive index fluctuations to identify the biofilm formation, comparatively among the different aptamers with respect to the control sample. The importance of the secondary structure of the aptamer DNA in targeting, successfully binding with the cells and delivering the Ag-NC, is evidenced by the decrease in disorder strength (L_d) of the Ag-NC treated samples compared to the untreated PA cells, which showed the abundance of higher L_d in the PWS studies. The higher L_d value attributed to the higher mass density fluctuations and the formation of biofilm. We envision this study to open a new avenue in using a powerful optical microscopic technique like PWS in detection, and DNA aptamer enclosed silver nanoclusters to prevent biofilms for opportunist pathogens like Pseudomonas aeruginosa.

A mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and drug-resistant cells.

Hydrogen bonding is a vital molecular interaction for bio-molecular systems, yet deep understanding of its ways of creating various complexes requires extensive empirical testing. A hybrid femtosecond/picosecond coherent Raman spectroscopic technique is applied to study pyridine-water complexes. Both the coherent Stokes and anti-Stokes Raman spectra are recorded simultaneously as the concentration of water in pyridine varied. A 3 ps and 10 cm ⁻¹ narrowband probe pulse enables us to observe well-resolved Raman spectra. The hydrogen bonding between pyridine and water forms the complexes that have altered vibrational frequencies. These red and blue shifts were observed to be uneven. This asymmetry was result of the generated background nonlinear optical processes of pyridine-water complexes. This asymmetry tends to disappear as probe pulse further delayed attaining background-free coherent Raman spectra. For better visualization, spectral analyses both traditional two-dimensional correlation spectroscopy and recent second-order correlation functions defined in frequency domain are employed. Recognized as a label-free and background-free technique, the coherent Raman spectroscopy, complemented with a known high-resolution spectroscopic correlation analysis, has potential in studying the hydrogen-bonded pyridine-water complexes. These complexes are of great biological importance both due to the ubiquitous nature of hydrogen bonds and due to the close resemblance to chemical bases in macro-biomolecules.