Finding clues to the riddle of sex determination in zebrafish

How sex is determined has been one of the most intriguing puzzles in biology since antiquity. Although a fundamental process in most metazoans, there seems to be myriad of ways in which sex can be determined – from genetic to environmental sex determination. This variation is limited mainly to upstream triggers with the core of sex determination pathway being conserved. Zebrafish has gained prominence as a vertebrate model system to study development and disease. However, very little is known about its primary sex determination mechanism. Here we review our current understanding of the sex determination in zebrafish. Zebrafish lack identifiable heteromorphic sex chromosomes and sex is determined by multiple genes, with some influence from the environment. Recently, chromosome 4 has been identified as sex chromosome along with few sex-linked loci on chromosomes 5 and 16. The identities of candidate sex-linked genes, however, have remained elusive. Sex in zebrafish is also influenced by the number of meiotic oocytes in the juvenile ovary, which appear to instruct retention of the ovarian fate. The mechanism and identity of this instructive signal remain unknown. We hypothesize that sex in zebrafish is a culmination of combinatorial effects of the genome, germ cells and the environment with inputs from epigenetic factors translating the biological meaning of this interaction.     

Hybrid methods for automated diagnosis of breast tumors

OBJECTIVE: To design and analyze a new family of hybrid methods for the diagnosis of breast tumors using fine needle aspirates. STUDY DESIGN: We present a radically new approach to the design of diagnosis systems. In the new approach, a nonlinear classifier with high sensitivity but low specificity is hybridized with a linear classifier having low sensitivity but high specificity. Data from the Wisconsin Breast Cancer Database are used to evaluate, computationally, the performance of the hybrid classifiers. RESULTS: The diagnosis scheme obtained by hybridizing the nonlinear classifier ellipsoidal multisurface method (EMSM) with the linear classifier proximal support vector machine (PSVM) was found to have a mean sensitivity of 97.36% and a mean specificity of 95.14% and was found to yield a 2.44% improvement in the reliability of positive diagnosis over that of EMSM at the expense of 0.4% degradation in the reliability of negative diagnosis, again compared to EMSM. At the 95% confidence level we can trust the hybrid method to be 96.19-98.53% correct in its malignant diagnosis of new tumors and 93.57-96.71% correct in its benign diagnosis. CONCLUSION: Hybrid diagnosis schemes represent a significant paradigm shift and provide a promising new technique to improve the specificity of nonlinear classifiers without seriously affecting the high sensitivity of nonlinear classifiers.     

Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant

Background  

Optineurin is a multifunctional protein involved in several functions such as vesicular trafficking from the Golgi to the plasma membrane, NF-κB regulation, signal transduction and gene expression. Mutations in optineurin are associated with glaucoma, a neurodegenerative eye disease that causes blindness. Genetic evidence suggests that the E50K (Glu50Lys) is a dominant disease-causing mutation of optineurin. However, functional alterations caused by mutations in optineurin are not known. Here, we have analyzed the role of optineurin in endocytic recycling and the effect of E50K mutant on this process.     

Inhibition of soybean and potato lipoxygenases by bhilawanols from bhilawan (Semecarpus anacardium) nut shell liquid and some synthetic salicylic acid analogues

Bhilawanol diene (3) isolated from bhilawan nut shell liquid was found to be a potent inhibitor of both soybean and potato lipoxygenases with IC50 values of 0.85 microM and 1.1 microM, respectively. However, the monoene (2) and saturated (1) bhilawanols exhibited relatively lower inhibitory activity. In addition, inhibition studies with synthetic analogues of salicylic acid (4-8) suggested that the unsaturated lipophilic side chain may be an absolute requirement for inhibitory activity.     

Automated breast cancer diagnosis based on fine needle aspiration

OBJECTIVE: To design and analyze an automated diagnostic system for breast carcinoma based on fine needle aspiration (FNA). STUDY DESIGN: FNA is a noninvasive alternative to surgical biopsy for the diagnosis of breast carcinoma. Widespread clinical use of FNA is limited by the relatively poor interobserver reproducibility of the visual interpretation of FNA images. To overcome the reproducibility problem, past research has focused on the development of automated diagnosis systems that yield accurate, reproducible results. While automated diagnosis is, by definition, reproducible, it has yet to achieve diagnostic accuracy comparable to that of surgical biopsy. In this article we describe a sophisticated new diagnostic system in which the mean sensitivity (of FNA diagnosis) approaches that of surgical biopsy. The diagnostic system that we devised analyzes the digital FNA data extracted from FNA images. To achieve high sensitivity, the system needs to solve large, equality-constrained, integer nonlinear optimization problems repeatedly. Powerful techniques from the theory of Lie groups and a novel optimization technique are built into the system to solve the underlying optimization problems effectively. The system is trained using digital data from FNA samples with confirmed diagnosis. To analyze the diagnostic accuracy of the system > 8,000 computational experiments were performed using digital FNA data from the Wisconsin Breast Cancer Database. RESULTS: The system has a mean sensitivity of 99.62% and mean specificity of 93.31%. Statistical analysis shows that at the 95% confidence level, the system can be trusted to correctly diagnose new malignant FNA samples with an accuracy of 99.44-99.8% and new benign FNA samples with an accuracy of 92.43-93.93%. CONCLUSION: The diagnostic system is robust and has higher sensitivity than do all the other systems reported in the literature. The specificity of the system needs to be improved.     

Development of transgenic rice plants expressing maize anthocyanin genes and increased blast resistance

The functional association of flavonoids with plant stress responses, though widely reported in the literature, remains to be documented in rice. Towards this end we chose a transgenic approach with well characterized regulatory and structural genes from maize involved in flavonoid biosynthesis. Activation of anthocyanin pathway in rice was investigated with the maize genes. Production of purple anthocyanin pigments were observed in transformed Tp309 (a japonica rice variety) calluses upon the introduction of the maize regulatory genes C1 (coloured-1), R (red) and the structural gene C2 (coloured-2, encoding chalcone synthase). In addition, stable transgenic plants carrying the maize C2 gene under the control of the maize Ubiquitin promoter were generated. A localized appearance of purple/red pigment in the leaf blade and leaf sheath of R₀ C2 transgenic seedlings was observed. Such a patchy pattern of the transgene expression appears to be conditioned by the genetic background of Tp309, which is homozygous for dominant color inhibitor gene(s) whose presence was unravelled by appropriate genetic crosses. Southern blot analysis of the transgenic plants demonstrated that c2 cDNA was integrated into the genome. Western blot analysis of these primary transgenics revealed the CHS protein while it was not detected in the control untransformed Tp3O9, suggesting that Tp309 might have a mutation at the corresponding C2 locus or that the expression of this gene is suppressed in Tp309. Further analysis of C2 transgenics revealed CHS protein only in three out of sixteen plants that were western-positive in the R₀ generation, suggesting gene silencing. Preliminary screening of these R₁ plants against the rice blast fungus Magnaporthe grisea revealed an increase in resistance.     

Unclonable fluorescence of MgO-ZrO2:Tb3+ nanocomposite for versatile applications in data security,dermatoglyphics

Latent fingerprints (LFPs) are one among the most important types of evidences at crime scenes because of the distinctiveness and tenacity of the friction ridges in fingerprints (FPs). Therefore, it is essential in forensic science to develop a reliable method to detect LFPs. Traditional detection methods still face a number of difficulties, such as limited sensitivity, low contrast, strong background, and complex processing stages. In this study, MgO-ZrO₂:Tb³⁺ (1–5 mol%) (MZ:Tb) nanocomposites (NCs) were prepared via a simple solution combustion (SC) method at low temperature. The photoluminescence (PL) investigation demonstrates that when excited at 379 nm, the produced NCs emits distinctive emission peaks of terbium ions (Tb³⁺). According to the photometric results, the NCs can be employed as warm light NCs and emit light in the green portion of the colour spectrum. The estimated optical band gap from diffuse reflectance spectra is found to be in the range 4.84–4.97 eV. Regardless of the type of surface being used, the optimized MgO-ZrO₂:Tb³⁺ (4 mol%) (MZ:4Tb) NCs has a strong ability to minimize background fluorescence interference. With high contrast LFP and I–V type of cheiloscopy, these NCs present a flexible fluorescent mark for the identification of levels 1–3 details in forensic investigation.     

The Soybean Rhg1 locus for resistance to the soybean cyst nematode Heterodera glycines regulates the expression of a large number of stress- and defense-related genes in degenerating feeding cells

To gain new insights into the mechanism of soybean (Glycine max) resistance to the soybean cyst nematode (Heterodera glycines), we compared gene expression profiles of developing syncytia in soybean near-isogenic lines differing at Rhg1 (for resistance to Heterodera glycines), a major quantitative trait locus for resistance, by coupling laser capture microdissection with microarray analysis. Gene expression profiling revealed that 1,447 genes were differentially expressed between the two lines. Of these, 241 (16.8%) were stress- and defense-related genes. Several stress-related genes were up-regulated in the resistant line, including those encoding homologs of enzymes that lead to increased levels of reactive oxygen species and proteins associated with the unfolded protein response. These results indicate that syncytia induced in the resistant line are undergoing severe oxidative stress and imbalanced endoplasmic reticulum homeostasis, both of which likely contribute to the resistance reaction. Defense-related genes up-regulated within syncytia of the resistant line included those predominantly involved in apoptotic cell death, the plant hypersensitive response, and salicylic acid-mediated defense signaling; many of these genes were either partially suppressed or not induced to the same level by a virulent soybean cyst nematode population for successful nematode reproduction and development on the resistant line. Our study demonstrates that a network of molecular events take place during Rhg1-mediated resistance, leading to a highly complex defense response against a root pathogen.