A Search for the Intermediate Radical, ONOO', in the Reaction Between Oxygen and Nitric Oxide in Solution

The most probable initial reaction between NO and O₂ is direct addition to give the peroxyl radical ONOO. In view of the potential importance of this radical in biology, we have searched extensively for its formation, using EPR spectroscopy and rapid freezing techniques. At best, only extremely low concentrations were detected, and in most systems, no signals were detectable. We conclude that this radical is unlikely to be of major importance per se in biological systems, in contrast with its one electron adduct, the peroxynitrite anion.     

The N2A region of titin has a unique structural configuration

The N2A segment of titin is a main signaling hub in the sarcomeric I-band that recruits various signaling factors and processing enzymes. It has also been proposed to play a role in force production through its Ca²⁺-regulated association with actin. However, the molecular basis by which N2A performs these functions selectively within the repetitive and extensive titin chain remains poorly understood. Here, we analyze the structure of N2A components and their association with F-actin. Specifically, we characterized the structure of its Ig domains by elucidating the atomic structure of the I81-I83 tandem using x-ray crystallography and computing a homology model for I80. Structural data revealed these domains to present heterogeneous and divergent Ig folds, where I81 and I83 have unique loop structures. Notably, the I81-I83 tandem has a distinct rotational chain arrangement that confers it a unique multi-domain topography. However, we could not identify specific Ca²⁺-binding sites in these Ig domains, nor evidence of the association of titin N2A components with F-actin in transfected C2C12 myoblasts or C2C12-derived myotubes. In addition, F-actin cosedimentation assays failed to reveal binding to N2A. We conclude that N2A has a unique architecture that predictably supports its selective recruitment of binding partners in signaling, but that its mechanical role through interaction with F-actin awaits validation.     

The role of adipose tissue-associated macrophages and T lymphocytes in the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract that affect more than 3 million people worldwide, but the pathological etiology is still unknown. The overall purpose of our investigations was to elucidate the possibility of pathological causes of IBD, and therefore, we determined the difference of inflammatory cytokine profiles in adipose tissue macrophages (ATMs) and T lymphocytes (ATTs) obtained near active lesions of IBD; investigated whether the alteration in ATM activation induces genes involved in collagen formation; and evaluated the effects of fatty acid oxidation inhibitors on factors involved in inflammation and collagen production by ATMs in IBD. Adipose tissues (ATs) were collected near active lesions and also at the margin of resected segments of the bowel from IBD patients with ulcerative colitis (UC) and CD (n = 14/group). Normal appearing ATs from control subjects (n = 14) who had colon resection for adenocarcinoma were collected as far away from the cancer lesion as possible to rule out possible changes. Compared with inactive disease lesions, ATMs and ATTs from active lesions released more IL-6, IL-4 and IL-13. Treatments of cytokine IL-4 and/or IL-13 to ATMs reduced iNOS expression but increased Arg-I expression which were exacerbated when treated with T cell- and adipocyte-conditioned medium. However, fatty acid oxidation inhibitors prevented the effects of cytokines IL-4 and/or IL-13 on iNOS and Arg-I expressions. This study was the first to show the effect of IL-4 and IL-13 on collagen formation, through iNOS and Arg-I expressions, that was exacerbated in a condition that mimics in vivo condition of active lesions. Moreover, our study was the first to provide potential benefits of fatty acid oxidation inhibitors to ATMs on preventing collagen formation; thus, providing therapeutic implications for individuals with intestinal fibrosis and stricture lesions, although future study should be guaranteed to elucidate the underlying mechanisms.     

Impaired Eye Region Search Accuracy in Children with Autistic Spectrum Disorders

To explore mechanisms underlying reduced fixation of eyes in autism, children with Autistic Spectrum Disorders (ASD) and typically developing children were tested in five visual search experiments: simple color feature; color-shape conjunction; face in non-face objects; mouth region; and eye region. No group differences were found for reaction time profile shapes in any of the five experiments, suggesting intact basic search mechanics in children with ASD. Contrary to early reports in the literature, but consistent with other more recent findings, we observed no superiority for conjunction search in children with ASD. Importantly, children with ASD did show reduced accuracy for eye region search (p = .005), suggesting that eyes contribute less to high-level face representations in ASD or that there is an eye region-specific disruption to attentional processes engaged by search in ASD.     

Persistent anthropogenic legacies structure depth dependence of regenerating rooting systems and their functions

Biotically-mediated weathering helps to shape Earth’s surface. For example, plants expend carbon (C) to mobilize nutrients in forms whose relative abundances vary with depth. It thus is likely that trees’ nutrient acquisition strategies—their investment in rooting systems and exudates—may function differently following disturbance-induced changes in depth of rooting zones and soil nutrient stocks. These changes may persist across centuries. We test the hypothesis that plant C allocation for nutrient acquisition is depth dependent as a function of rooting system development and relative abundances of organic vs. mineral nutrient stocks. We further posit that patterns of belowground C allocation to nutrient acquisition reveal anthropogenic signatures through many decades of forest regeneration. To test this idea, we examined fine root abundances and rooting system C in organic acid exudates and exo-enzymes in tandem with depth distributions of organically- and mineral-bound P stocks. Our design permitted us to estimate C tradeoffs between organic vs. mineral nutrient benefits in paired forests with many similar aboveground traits but different ages: post-agricultural mixed-pine forests and older reference hardwoods. Fine roots were more abundant throughout the upper 2 m in reference forest soils than in regenerating stands. Rooting systems in all forests exhibited depth-dependent C allocations to nutrient acquisition reflecting relative abundances of organic vs. mineral bound P stocks. Further, organic vs. mineral stocks underwent redistribution with historic land use, producing distinct ecosystem nutritional economies. In reference forests, rooting systems are allocating C to relatively deep fine roots and low-C exudation strategies that can increase mobility of mineral-bound P stocks. Regenerating forests exhibit relatively shallower fine root distributions and more diverse exudation strategies reflecting more variable nutrient stocks. We observed these disparities in rooting systems’ depth and nutritional mechanisms even though the regenerating forests have attained aboveground biomass stocks similar to those in reference hardwood forests. These distinctions offer plausible belowground mechanisms for observations of continued C sink strength in relatively old forests, and have implications for soil C fates and soil development on timescales relevant to human lifetimes. As such, depth-dependent nutrient returns on plant C investments represent a subtle but consequential signal of the Anthropocene.

     

Elaeocarpus reticulatus fruit extracts reduce viability and induce apoptosis in pancreatic cancer cells in vitro

Molecular Biology Reports - Treatment options for pancreatic cancer (PC) are severely limited due to late diagnosis, early metastasis and the inadequacy of chemotherapy and radiotherapy to combat...     

Mutualism and asexual reproduction influence recognition genes in a fungal symbiont

Mutualism between microbes and insects is common and alignment of the reproductive interests of microbial symbionts with this lifestyle typically involves clonal reproduction and vertical transmission by insect partners. Here the Amylostereum fungus–Sirex woodwasp mutualism was used to consider whether their prolonged association and predominance of asexuality have affected the mating system of the fungal partner. Nucleotide information for the pheromone receptor gene rab1, as well as the translation elongation factor 1α gene and ribosomal RNA internal transcribed spacer region were utilized. The identification of rab1 alleles in Amylostereum chailletii and Amylostereum areolatum populations revealed that this gene is more polymorphic than the other two regions, although the diversity of all three regions was lower than what has been observed in free-living Agaricomycetes. Our data suggest that suppressed recombination might be implicated in the diversification of rab1, while no evidence of balancing selection was detected. We also detected positive selection at only two codons, suggesting that purifying selection is important for the evolution of rab1. The symbiotic relationship with their insect partners has therefore influenced the diversity of this gene and influenced the manner in which selection drives and maintains this diversity in A. areolatum and A. chailletii.