Sources and accumulation of organic carbon in the Pearl River Estuary surface sediment as indicated by elemental, stable carbon isotopic, and carbohydrate compositions

Organic matter in surface sediments from the upper reach of the Pearl River Estuary and Lingdingyang Bay, as well as the adjacent northern South China Sea shelf was characterized using a variety of techniques, including elemental (C and N) ratio, bulk stable organic carbon isotopic composition (delta C-13), and carbohydrate composition analyses. Total organic carbon (TOC) content was 1.21 +/- 0.45% in the upper reach, down to 1.00 +/- 0.22% in Lingdingyang Bay and to 0.80 +/- 0.10% on the inner shelf and 0.58 +/- 0.06% on the outer shelf. delta C-13 values ranged from -25.1 parts per thousand to -21.3 parts per thousand in Lingdingyang Bay and the South China Sea shelf, with a trend of enrichment seawards. The spatial trend in C/N ratios mirrored that of delta C-13, with a substantial decrease in C/N ratio offshore. Total carbohydrate yields ranged from 22.1 to 26.7 mg (100 mg OC)(-1), and typically followed TOC concentrations in the estuarine and shelf sediments. Total neutral sugars, as detected by the nine major monosaccharides (lyxose, rhamnose, ribose, arabinose, fucose, xylose, galactose, mannose, and glucose), were between 4.0 and 18.6 mg (100 mg OC)(-1) in the same sediments, suggesting that significant amounts of carbohydrates were not neutral aldoses. Using a two end-member mixing model based on delta C-13 values and C/N ratios, we estimated that the terrestrial organic carbon contribution to the surface sediment TOC was ca. 78 +/- 11% for Lingdingyang Bay, 34 +/- 4% for the inner shelf, and 5.5 +/- 1% for the outer shelf. The molecular composition of the carbohydrate in the surface sediments also suggested that the inner estuary was rich in terrestrially derived carbohydrates but that their contribution decreased offshore. A relatively high abundance of deoxyhexoses in the estuary and shelf indicated a considerable bacterial source of these carbohydrates, implying that sediment organic matter had undergone extensive degradation and/or transformation during transport. Sediment budget based on calculated regional accumulation rates showed that only similar to 50% of the influxes of terrestrial organic carbon were accumulated in the estuary. This relatively low accumulation efficiency of terrestrial organic matter as compared to the total suspended solids (accumulation efficiency similar to 73%) suggested significant degradation of the terrestrial organic carbon within the estuarine system after its discharge from the river. This study demonstrated that the combination of the bulk organic matter properties together with the isotopic composition and molecular-level carbohydrate compositions can be an efficient way to track down the source and fate of organic matter in highly dynamic estuarine and coastal systems. The predominance of terrestrially originated organic matter in the sediment and its generally low accumulation efficiency within the estuary is not surprising, and yet it may have important implications in light of the heavy anthropogenic discharges into the Pearl River Estuary during the past thirty years.Natural Science Foundation of China [49825111, 40176025, 90211020

CRISPR interference to evaluate modifiers of C9ORF72-mediated toxicity in FTD

Treatments for neurodegenerative disease, including Frontotemporal dementia (FTD) and Amyotrophic lateral sclerosis (ALS), remain rather limited, underscoring the need for greater mechanistic insight and disease-relevant models. Our ability to develop novel disease models of genetic risk factors, disease modifiers, and other FTD/ALS-relevant targets is impeded by the significant amount of time and capital required to develop conventional knockout and transgenic mice. To overcome these limitations, we have generated a novel CRISPRi interference (CRISPRi) knockin mouse. CRISPRi uses a catalytically dead form of Cas9, fused to a transcriptional repressor to knockdown protein expression, following the introduction of single guide RNA against the gene of interest. To validate the utility of this model we have selected the TAR DNA binding protein (TDP-43) splicing target, stathmin-2 (STMN2). STMN2 RNA is downregulated in FTD/ALS due to loss of TDP-43 activity and STMN2 loss is suggested to play a role in ALS pathogenesis. The involvement of STMN2 loss of function in FTD has yet to be determined. We find that STMN2 protein levels in familial FTD cases are significantly reduced compared to controls, supporting that STMN2 depletion may be involved in the pathogenesis of FTD. Here, we provide proof-of-concept that we can simultaneously knock down Stmn2 and express the expanded repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene, successfully replicating features of C9-associated pathology. Of interest, depletion of Stmn2 had no effect on expression or deposition of dipeptide repeat proteins (DPRs), but significantly decreased the number of phosphorylated Tdp-43 (pTdp-43) inclusions. We submit that our novel CRISPRi mouse provides a versatile and rapid method to silence gene expression in vivo and propose this model will be useful to understand gene function in isolation or in the context of other neurodegenerative disease models

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of anti-bursin monoclonal antibody on immunosuppression in the duck (Cherry Valley duck)

To study the immunologic function of bursin, we analyzed the effects of anti-bursin monoclonal antibody (mAb) on the immunosuppression in ducks (Cherry Valley duck) by injecting various doses of the anti-bursin mAb into 13-d duck embryos. After hatch, cell-mediated immune activity and humoral responses were studied using lymphocyte proliferation test, tube agglutination test, and indirect enzyme-linked immuno-sorbent assay to detect anti-Escherichia coli antibodies and antibodies to Riemerella anatipester, respectively. Simultaneously, relative weights (BW-adjusted) of bursa of Fabricius (BF), spleen, and thymus were determined. Additionally, the morphology of BF, spleen, and thymus was examined at various ages using conventional histology. Follicle morphology of BF was analyzed by image analysis. The results indicated that anti-bursin mAb markedly decreased duck lymphocyte proliferation, the antibody-producing ability to bacteria, as well as the relative BF weight. Moreover, the anti-bursin mAb hindered the development of BF follicles.To study the immunologic function of bursin, we analyzed the effects of anti-bursin monoclonal antibody (mAb) on the immunosuppression in ducks (Cherry Valley duck) by injecting various doses of the anti-bursin mAb into 13-d duck embryos. After hatch, cell-mediated immune activity and humoral responses were studied using lymphocyte proliferation test, tube agglutination test, and indirect enzyme-linked immuno-sorbent assay to detect anti-Escherichia coli antibodies and antibodies to Riemerella anatipester, respectively. Simultaneously, relative weights (BW-adjusted) of bursa of Fabricius (BF), spleen, and thymus were determined. Additionally, the morphology of BF, spleen, and thymus was examined at various ages using conventional histology. Follicle morphology of BF was analyzed by image analysis. The results indicated that anti-bursin mAb markedly decreased duck lymphocyte proliferation, the antibody-producing ability to bacteria, as well as the relative BF weight. Moreover, the anti-bursin mAb hindered the development of BF follicles

Enhanced phosphorylation of T153 in soluble tau is a defining biochemical feature of the A152T tau risk variant

Abstract Pathogenic mutations in the tau gene (microtubule associated protein tau, MAPT) are linked to the onset of tauopathy, but the A152T variant is unique in acting as a risk factor for a range of disorders including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). In order to provide insight into the mechanism by which A152T modulates disease risk, we developed a novel mouse model utilizing somatic brain transgenesis with adeno-associated virus (AAV) to drive tau expression in vivo, and validated the model by confirming the distinct biochemical features of A152T tau in postmortem brain tissue from human carriers. Specifically, TauA152T-AAV mice exhibited increased tau phosphorylation that unlike animals expressing the pathogenic P301L mutation remained localized to the soluble fraction. To investigate the possibility that the A152T variant might alter the phosphorylation state of tau on T152 or the neighboring T153 residue, we generated a novel antibody that revealed significant accumulation of soluble tau species that were hyperphosphorylated on T153 (pT153) in TauA152T-AAV mice, which were absent the soluble fraction of TauP301L-AAV mice. Providing new insight into the role of A152T in modifying risk of tauopathy, as well as validating the TauA152T-AAV model, we demonstrate that the presence of soluble pT153-positive tau species in human postmortem brain tissue differentiates A152T carriers from noncarriers, independent of disease classification. These results implicate both phosphorylation of T153 and an altered solubility profile in the mechanism by which A152T modulates disease risk