2,469 research outputs found

    Vertical Stratification of Sediment Microbial Communities Along Geochemical Gradients of a Subterranean Estuary Located at the Gloucester Beach of Virginia, United States

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    Subterranean estuaries (STEs) have been recognized as important ecosystems for the exchange of materials between the land and sea, but the microbial players of biogeochemical processes have not been well examined. In this study, we investigated the bacterial and archaeal communities within 10 cm depth intervals of a permeable sediment core (100 cm in length) collected from a STE located at Gloucester Point (GP-STE), VA, United States. High throughput sequencing of 16S rRNA genes and subsequent bioinformatics analyses were conducted to examine the composition, diversity, and potential functions of the sediment communities. The community composition varied significantly from the surface to a depth of 100 cm with up to 13,000 operational taxonomic units (OTUs) based on 97% sequence identities. More than 95% of the sequences consisted of bacterial OTUs, while the relative abundances of archaea, dominated by Crenarchaea, gradually increased with sediment core depth. Along the redox gradients of GP-STE, differential distribution of ammonia-and methane-oxidizing, denitrifying, and sulfate reducing bacteria was observed as well as methanogenic archaea based on predicted microbial functions. The aerobic-anaerobic transition zone (AATZ) had the highest diversity and abundance of microorganisms, matching with the predicted functional diversity. This indicates the AATZ as a hotspot of biogeochemical processes of STEs. The physical and geochemical gradients in different depths have attributed to vertical stratification of microbial community composition and function in the GP-STE

    Disrupted-in-schizophrenia 1 (DISC1) and Syntaphilin collaborate to modulate axonal mitochondrial anchoring

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    In neuronal axons, the ratio of motile-to-stationary mitochondria is tightly regulated by neuronal activation, thereby meeting the need for local calcium buffering and maintaining the ATP supply. However, the molecular players and detailed regulatory mechanisms behind neuronal mitochondrial movement are not completely understood. Here, we found that neuronal activation-induced mitochondrial anchoring is regulated by Disrupted-in-schizophrenia 1 (DISC1), which is accomplished by functional association with Syntaphilin (SNPH). DISC1 deficiency resulted in reduced axonal mitochondrial movement, which was partially reversed by concomitant SNPH depletion. In addition, a SNPH deletion mutant lacking the sequence for interaction with DISC1 exhibited an enhanced mitochondrial anchoring effect than wild-type SNPH. Moreover, upon neuronal activation, mitochondrial movement was preserved by DISC1 overexpression, not showing immobilized response of mitochondria. Taken together, we propose that DISC1 in association with SNPH is a component of a modulatory complex that determines mitochondrial anchoring in response to neuronal activation.117Ysciescopu

    Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

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    Dysbindin and DISC1 are schizophrenia susceptibility factors playing roles in neuronal development. Here we show that the physical interaction between dysbindin and DISCI is critical for the stability of dysbindin and for the process of neurite outgrowth. We found that DISCI forms a complex with dysbindin and increases its stability in association with a reduction in ubiquitylation. Furthermore, knockdown of DISCI or expression of a deletion mutant, DISCI lacking amino acid residues 403-504 of DISC1 (DISC1(Delta 403-504)), effectively decreased levels of endogenous dysbindin. Finally, the neurite outgrowth defect induced by knockdown of DISCI was partially reversed by coexpression of dysbindin. Taken together, these results indicate that dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth.X111211Ysciescopu

    Regulation of the actin cytoskeleton by the Ndel1-Tara complex is critical for cell migration

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    Nuclear distribution element-like 1 (Ndel1) plays pivotal roles in diverse biological processes and is implicated in the pathogenesis of multiple neurodevelopmental disorders. Ndel1 function by regulating microtubules and intermediate filaments; however, its functional link with the actin cytoskeleton is largely unknown. Here, we show that Ndel1 interacts with TRIO-associated repeat on actin (Tara), an actin-bundling protein, to regulate cell movement. In vitro wound healing and Boyden chamber assays revealed that Ndel1- or Tara-deficient cells were defective in cell migration. Moreover, Tara overexpression induced the accumulation of Ndel1 at the cell periphery and resulted in prominent co-localization with F-actin. This redistribution of Ndel1 was abolished by deletion of the Ndel1-interacting domain of Tara, suggesting that the altered peripheral localization of Ndel1 requires a physical interaction with Tara. Furthermore, co-expression of Ndel1 and Tara in SH-SY5Y cells caused a synergistic increase in F-actin levels and filopodia formation, suggesting that Tara facilitates cell movement by sequestering Ndel1 at peripheral structures to regulate actin remodeling. Thus, we demonstrated that Ndel1 interacts with Tara to regulate cell movement. These findings reveal a novel role of the Ndel1-Tara complex in actin reorganization during cell movement.1142Ysciescopu

    Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA

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    Optimizing the in vivo stability of positron emission tomography (PET) tracers is of critical importance to cancer diagnosis. In the case of 64Cu-labeled monoclonal antibodies (mAb), in vivo behavior and biodistribution is critically dependent on the performance of the bifunctional chelator used to conjugate the mAb to the radiolabel. This study compared the in vivo characteristics of 64Cu-labeled TRC105 (a chimeric mAb that binds to both human and murine CD105), through two commonly used chelators: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Flow cytometry analysis confirmed that chelator conjugation of TRC105 did not affect its CD105 binding affinity or specificity. PET imaging and biodistribution studies in 4T1 murine breast tumor-bearing mice revealed that 64Cu-NOTA-TRC105 exhibited better stability than 64Cu-DOTA-TRC105 in vivo, which resulted in significantly lower liver uptake without compromising the tumor targeting efficiency. In conclusion, this study confirmed that NOTA is a superior chelator to DOTA for PET imaging with 64Cu-labeled TRC105
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