Melanin-like nanoparticles were synthesized with size control through neutralization of dopamine hydrochloride with NaOH, followed by spontaneous air oxidation of dopamine. Although the particle characteristic of natural melanins was understood to be significantly affected by the biological and structural environment, melanin-lke nanoparticles can be realized through the chemical reactions only. Melanin-like nanoparticles that are <100 nm showed excellent dispersion stability in water as well as biological media and good biocompatibility to HeLa cells after the appropriate surface modification with thiol-terminated methoxy-poly(ethylene glycol) (mPEG-SH). Furthermore, the demonstrated ability of melanin-like nanoparticles to reduce 2,2-diphenyl-1-picrylhydrazyl (DPPH) suggests free radical scavenging activity of the material.

Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular Mycobacterium tuberculosis. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.

Rice contains several MADS box genes. It has been demonstrated previously that one of these genes, OsMADS1 (for Oryza sativa MADS box gene1 ), is expressed preferentially in flowers and causes early flowering when ectopically expressed in tobacco plants. In this study, we demonstrated that ectopic expression of OsMADS1 in rice also results in early flowering. To further investigate the role of OsMADS1 during rice flower development, we generated transgenic rice plants expressing altered OsMADS1 genes that contain missense mutations in the MADS domain. There was no visible alteration in the transgenic plants during the vegetative stage. However, transgenic panicles typically exhibited phenotypic alterations, including spikelets consisting of elongated leafy paleae and lemmas that exhibit a feature of open hull, two pairs of leafy palea-like and lemma-like lodicules, a decrease in stamen number, and an increase in the number of carpels. In addition, some spikelets generated an additional floret from the same rachilla. These characteristics are very similar to those of leafy hull sterile1 ( lhs1 ). The map position of OsMADS1 is closely linked to that of lhs1 on chromosome 3. Examination of lhs1 revealed that it contains two missense mutations in the OsMADS1 MADS domain. A genetic complementation experiment showed that the 11.9-kb genomic DNA fragment containing the wild-type OsMADS1 gene rescued the mutant phenotypes. In addition, ectopic expression of the OsMADS1 gene isolated from the lhs1 line resulted in lhs1 -conferred phenotypes. These lines of evidence demonstrate that OsMADS1 is the lhs1 gene. INTRODUCTIONIn response to floral induction, the inflorescence meristem becomes committed to flowering. LEAFY ( LFY ) and APE-TALA1 ( AP1 ) in Arabidopsis and FLORICAULA ( FLO ) and SQUAMOSA ( SQUA ) in Antirrhinum are responsible for promoting the specification of floral meristem identity (reviewed in Ma, 1994). The genes required for specifying the fate of floral organ primordia include AP1 , AP2 , AGAMOUS ( AG ), PISTILATA ( PI ), and AP3 in Arabidopsis and SQUA , PLENA ( PLE ), GLOBOSA ( GLO ), and DEFICIENS ( DEF ) in Antirrhinum (reviewed in Weigel and Meyerowitz, 1994). Excluding AP2 , these floral homeotic genes encode MADS box proteins that are highly conserved transcription factors in plants, animals, yeast, and fungi and that are regulated by the floral meristem identity gene LFY (Parcy et al., 1998;Wagner et al., 1999).Several other MADS box genes have more subtle functions associated with floral meristem and floral organ identity. Expression of AG-LIKE2 ( AGL2 ), AGL4 , and AGL9 of Arabidopsis begins after the onset of expression of floral meristem identity genes but before the activation of floral organ identity genes (Flanagan and Ma, 1994;Savidge et al., 1995;Mandel and Yanofsky, 1998). DEFH72 and DEFH200 of Antirrhinum appear to function in mediating interactions between the meristem and organ identity genes through direct interaction with PLE (Davies et al., 1996). FLORAL BINDING PROTEIN2 ( FBP2 ) o...

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The scaffolding adaptor protein p62/SQSTM1 (p62) has been shown to be an autophagy receptor that acts as a link between the ubiquitination and autophagy machineries. However, the roles of autophagy and p62 in human keratinocytes are not well understood. In this study, we show that keratinocyte autophagy negatively regulates p62 expression, which is essential for the prevention of excessive inflammation and the induction of cathelicidin in human keratinocytes. Stimulation of TLR2/6 or TLR4 in primary human keratinocytes robustly activated autophagy pathways and up-regulated p62 expression through induction of NADPH oxidases 2 and 4 and the generation of reactive oxygen species. MyD88 and TNFR-associated factor 6, key signaling molecules that mediate TLR activation, played an essential role in the induction of autophagy and p62 expression. Additionally, blockade of autophagy significantly increased the generation of inflammatory cytokines and expression of p62 in primary human keratinocytes. Notably, silencing hp62 through RNA interference resulted in a significant decrease in NF-κB activation, inflammatory cytokine production, cathelicidin expression, and cell proliferation (as well as cyclin D1 expression) in keratinocytes. Epidermal expression of p62 was further found to be significantly higher in psoriatic skin than in skin affected by atopic dermatitis or from healthy controls. Collectively, our data provide new insights into the roles of autophagy and p62 in controlling cutaneous inflammation.

The development of nontoxic and biocompatible imaging agents will create new opportunities for potential applications in clinical MRI diagnosis. Synthetic melanin-like nanoparticles (MelNPs), analogous to natural sepia melanin (a major component of the cuttlefish ink), can be used as contrast agent for MRI. MelNPs complexed with paramagnetic Fe(3+) ions show much higher relaxivity values than existing MRI T1 contrast agents based on gadolinium (Gd) or manganese (Mn); MelNP values at 3T were r1 = 17 and r2 = 18 mM(-1) s(-1) (r2/r1 value of 1.1). With significant enhancement to MRI contrast, this biomimetic approach using MelNPs functionalized with paramagnetic Fe(3+) ions and surface-modified with biocompatible poly(ethylene glycol) units, could provide new insight into how melanin-based bioresponsive and therapeutic imaging probes integrate with their various biological functions.

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Increased longevity, expressed as number of individuals surviving to older adulthood, represents one of the ways the human life history pattern differs from other primates. We believe it is a critical demographic factor in the development of human culture. Here, we examine when changes in longevity occurred by assessing the ratio of older to younger adults in four hominid dental samples from successive time periods, and by determining the significance of differences in these ratios. Younger and older adult status is assessed by wear seriation of each sample. Whereas there is significant increased longevity between all groups, indicating a trend of increased adult survivorship over the course of human evolution, there is a dramatic increase in longevity in the modern humans of the Early Upper Paleolithic. We believe that this great increase contributed to population expansions and cultural innovations associated with modernity.