Two cDNAs encoding NADPH oxidases and constituting the thyroid H 2 O 2 generating system have been cloned. The strategy of cloning was based on the functional similarities between H 2 O 2 generation in leukocytes and the thyroid, according to the hypothesis that one of the components of the thyroid system would belong to the gp91 Phox /Mox1 gene family and display sequence similarities with gp91Phox . Screening at low stringency with a gp91Phox probe of cDNA libraries from thyroid cells in primary culture yielded two distinct human cDNA clones harboring open reading frames of 1551 (ThOX1) and 1548 amino acids (ThOX2), respectively. The encoded polypeptides display 83% sequence similarity and are clearly related to gp91Phox (53 and 47% similarity). The theoretical molecular mass of 177 kDa is close to the apparent molecular mass of 180 kDa of the native corresponding porcine flavoprotein and the protein(s) detected by Western blot in dog and human thyroid. ThOX1 and ThOX2 display sequence similarities of 53% and 61%, respectively, with a predicted protein of Caenorhabditis elegans over their entire length. They show along their first 500 amino acids a similarity of 43% with thyroperoxidase. The corresponding genes of ThOX1 and ThOX2 are closely linked on chromosome 15q15.3. The dog mRNA expression is thyroid-specific and up-regulated by agents activating the cAMP pathway as is the synthesis of the polypeptides they are coding for. In human thyroid the positive regulation by cAMP is less pronounced. The proteins ThOX1 and ThOX2 accumulate at the apical membrane of thyrocytes and are co-localized with thyroperoxidase.

We have recently cloned two thyroid-specific cDNAs encoding new members of the NADPH oxidase family. ThOX1 and ThOX2 proteins are colocalized with thyroperoxidase at the apical membrane of human thyroid cells. In the present study we have determined their subcellular localization and maturation in relation to their enzymatic activity. A majority of ThOX proteins accumulated inside the cell and only a small fraction was expressed at the surface. Western blots demonstrated that ThOX's are glycoproteins of 180,000 and 190,000. When totally deglycosylated the molecular weight of both ThOX1 and ThOX2 drops to 160,000. Ca(2+) stimulates the basal H(2)O(2) generation in PC Cl3 cells at a level corresponding to 20% of the leukocyte H(2)O(2) production stimulated by PMA. Nonthyroid cell lines transfected with ThOX1 and ThOX2 show only a single immunoreactive band in Western blot analysis, corresponding to the protein of 180,000. This "immature" protein remains exclusively intracellular and does not present any enzymatic activity. This is not modified by coexpression of thyroperoxidase and p22(Phox). Transfection of ThOX cDNAs into PLB-XCGD cells does not reconstitute their NADPH oxidase activity. We conclude that (1) the thyroid contains some elements of the leukocyte H(2)O(2)-generating system but not all of them; (2) ThOX's are predominantly or exclusively located inside the cell in thyrocytes or in transfected cells, respectively, and as such they are inactive; (3) ThOX's cannot replace gp91(Phox) in the leukocyte; and (4) the thyroid H(2)O(2)-generating system is analogous to the leukocyte system with regard to ThOX's and gp91(Phox) but very different in other aspects. Additional thyroid-specific components are probably required to get complete protein processing and full enzymatic activity in the thyroid.

Natural creatures have evolved elaborate photonic nanostructures on multiple scales and dimensions in a hierarchical, organized way to realize controllable absorption, reflection, or transmitting the desired wavelength of the solar spectrum. A bio-inspired strategy is a powerful and promising way for solar energy manipulation. This feature article presents the state-of-theart progress on bio-inspired photonic materials on this particular application. The article first briefly recalls the physical origins of natural photonic effects and catalogues the typical natural photonic prototypes including light harvesting, broadband reflection, selective reflection, and UV/IR response. Next, typical applications are categorized into two primary areas: solar energy utilization and reflection. Recent advances including solar-to-electricity, solar-to-fuels, solar-thermal (e.g., photothermal converters, infrared detectors, thermoelectric materials, smart windows, and solar steam generation) are highlighted in the first part. Meanwhile, solar energy reflection involving infrared stealth, radiative cooling, and micromirrors are also addressed. In particular, this article focuses on bioinspired design principles, structural effects on functions, and future trends. Finally, the main challenges and prospects for the next generation of bioinspired photonic materials are discussed, including new design concepts, emerging ideas, and possible strategies.

Mitochondrial reactive oxygen species (ROS) are believed to stabilize hypoxia-inducible factor (HIF)-1α, a transcriptional regulator of the immune response. Mclk1 encodes a mitochondrial protein that is necessary for ubiquinone biosynthesis. Heterozygote Mclk1+/− mutant mice are long-lived despite increased mitochondrial ROS and decreased energy metabolism. In this study, Mclk1+/− mutant mice in the C57BL/6J background displayed increased basal and induced expression of HIF-1α in liver and macrophages in association with elevated expression of inflammatory cytokines, in particular TNF-α. Mutant macrophages showed increased classical and decreased alternative activation, and mutant mice were hypersensitive to LPS. Consistent with these observations in vivo, knock-down of Mclk1 in murine RAW264.7 macrophage-like cells induced increased mitochondrial ROS as well as elevated expression of HIF-1α and secretion of TNF-α. We used an antioxidant peptide targeted to mitochondria to show that altered ROS metabolism is necessary for the enhanced expression of HIF-1α, which, in turn, is necessary for increased TNF-α secretion. These findings provide in vivo evidence for the action of mitochondrial ROS on HIF-1α activity and demonstrate that changes in mitochondrial function within physiologically tolerable limits modulate the immune response. Our results further suggest that altered immune function through a limited increase in HIF-1α expression can positively impact animal longevity.

The fields of medicine science and health informatics have made great progress recently and have led to in-depth analytics that is demanded by generation, collection and accumulation of massive data. Meanwhile, we are entering a new period where novel technologies are starting to analyze and explore knowledge from tremendous amount of data, bringing limitless potential for information growth. One fact that cannot be ignored is that the techniques of machine learning and deep learning applications play a more significant role in the success of bioinformatics exploration from biological data point of view, and a linkage is emphasized and established to bridge these two data analytics techniques and bioinformatics in both industry and academia. This survey concentrates on the review of recent researches using data mining and deep learning approaches for analyzing the specific domain knowledge of bioinformatics. The authors give a brief but pithy summarization of numerous data mining algorithms used for preprocessing, classification and clustering as well as various optimized neural network architectures in deep learning methods, and their advantages and disadvantages in the practical applications are also discussed and compared in terms of their industrial usage. It is believed that in this review paper, valuable insights are provided for those who are dedicated to start using data analytics methods in bioinformatics.