265 research outputs found

    Evolving drug therapies for chronic hepatitis C

    Get PDF

    Assessing the agronomic and ecological relevance of mineral-associated organic matter

    Get PDF
    As the largest terrestrial sink for carbon (C) and a critical source of nitrogen (N) for plants, soil organic matter (SOM) is a major driver of ecosystem function. It is critical to understand the mechanistic controls on SOM in order to improve models of global C cycling and to develop accurate measures of soil fertility. SOM consists of a wide spectrum of compounds, varying in chemical characteristics and function. The chemical and physical fractionation of SOM is a valuable tool for distilling this complexity into meaningful and distinct pools: detrital or particulate organic matter (POM), which contains mostly recent litter inputs at early stages of decomposition, and mineral-associated organic matter (MAOM), which is far more processed, consisting of small organic compounds bound to reactive mineral surfaces. For decades, MAOM has been studied primarily for its capacity to sequester soil C and N. In this dissertation, my research reveals the under-appreciated role of clay minerals in mediating the short-term accrual and turnover of SOM. I examine the mechanistic controls on MAOM and specifically, how agricultural management and plant-microbe interactions influence C and N within MAOM. Agricultural practices can directly impact the capacity for soils to store MAOM. Approaches that minimize soil disturbance, such as conservation tillage, and those that increase crop residue input and diversity, such as cover cropping, can facilitate the rapid accrual of N within MAOM (Chapter 1). Through this research, I found that MAOM N may also be an important, but overlooked, source of N for crops. This work led me to develop a conceptual framework in which I synthesized literature from the fields of geochemistry and soil biology to investigate the potential mechanisms that drive MAOM turnover. Although this conceptual work stands alone (Chapter 2), the hypotheses and ideas therein form the basis for my experimental work. My overarching hypothesis addresses the biochemical strategies that plants employ to disrupt mineral-organic interactions and release both C and N from MAOM. Specifically, I examine two mechanisms by which plant root inputs may stimulate the destabilization and turnover of both C and N within MAOM: belowground root C inputs, specifically in the form of sugars and organic acids, can stimulate MAOM decomposition through indirect and direct mechanisms, respectively. Through a series of laboratory incubations, I demonstrate that simulated root exudates can stimulate the mobilization of both C and N from MAOM through microbial and non-microbial pathways (Chapter 3). Additions of a sugar substrate, glucose, were associated with the microbial-mediated mineralization of C and N from MAOM. The organic acid substrate, oxalic acid, was associated with the direct and concomitant mobilization of DON and metals into exchangeable and soluble pools. Most notably, both substrates stimulated the respiration of MAOM-C (i.e., positive priming), with total increases ranging from 35–89%. Our results provide evidence for pathways of MAOM destabilization, and more generally reveal that a pool of soil nutrients generally considered passive or inert has the potential to function as a significant source of C and N

    Evolving drug therapies for chronic hepatitis C

    Get PDF

    Evolving drug therapies for chronic hepatitis C: Immunomodulation and beyond

    Get PDF
    Chronic hepatitis C infection is a major health problem and a leading cause of chronic liver disease. The hepatitis C virus was discovered in 1989 (1, 2). The virus is a small, enveloped, single-stranded, positive sense RNA virus and is a member of the hepacivirus genus in the family Flaviridae (3). Six major genotypes have been identified with several subtypes within each genotype (4). Viral replication occurs predominantly within hepatocytes in the liver but there is some evidence that it might also replicate outside the liver, in peripheral blood mononuclear cells, in lymphoid cells and in neurons (5, 6). Chronic hepatitis C infection can cause cirrhosis, digestive hemorrhage, liver failure and liver cancer

    Crop rotational complexity affects plant-soil nitrogen cycling during water deficit

    Get PDF
    One of the biggest environmental challenges facing agriculture is how to both supply and retain nitrogen (N), especially as precipitation becomes more variable with climate change. We used a greenhouse experiment to assess how contrasting histories of crop rotational complexity affect plant-soil-microbe interactions that govern N processes, including during water stress. With higher levels of carbon and N cycling hydrolytic enzymes, higher mineral-associated organic matter N concentrations, and an altered microbial community, soils from the most complex rotation enabled 80% more corn N uptake under two moisture regimes, compared to soil from monoculture corn. Higher levels of plant N likely drove the changes in corn leaf gas exchange, particularly increasing intrinsic water use efficiency by 9% in the most complex rotation. The water deficit increased the standing pool of nitrate 44-fold in soils with a history of complex crop rotations, compared to an 11-fold increase in soils from the corn monoculture. The implications of this difference must be considered in a whole cropping systems and field context. Cycling of 15N-labeled fresh clover residue into soil N pools did not depend on the water regime or rotation history, with 2-fold higher recovery in the mineral vs. particulate organic N pool. In contrast, the water deficit reduced recovery of clover 15N in corn shoots by 37%, showing greater impacts of water deficit on plant N uptake compared to organic N cycling in soil. This study provides direct experimental evidence that long-term crop rotational complexity influences microbial N cycling and availability with feedbacks to plant physiology. Collectively, these results could help explain general observations of higher yields in more complex crop rotations, including specifically during dry conditions

    Új diagnosztikai és műtéti eljárások keresése a gyermekkorban végzett hólyagmegnagyobbító és -potló műtétek utáni postoperatív metabolikus zavarok megelőzésére és a malignizáció korai felismerésére = New diagnostic and surgical therapeutic possibilities for prevention of metabolic distrurbances and early detection of malignancy following bladder augmentation and substitution in children

    Get PDF
    Munkacsoportunk 1987 óta összesen 86 hólyagmegnagyobbítást vagy hólyagpótlást végzett gyermekekben és fiatal felnőttekben. A pályázat időtartama (2004-2008) alatt összesen 66, a fenti műtéteken átesett (ebből 35 több mint 10 éve operált) beteg visszarendelését és részletes után vizsgálatát végeztük el. 2008 végéig 57 beteg került a prospektíve nyomonkövetett betegek csoportjába, akiket a pályázatban leírt protokoll szerint követünk nyomon. A pályázat segítségével 4 nemzetközi közlemény született (1) a re-augmentatio szükségességérről, a hólyag-megnagyobbítás sikertelenségének okairól (2) a betegek cystometriás méréseinek eredményeiről (3) a betegek életminőségének alakulásáról valamint (4) összefoglaló tanulmány a húgyhólyag megnagyobbításáról. Az általunk, állatkísérletes modellben bevezetett, a húgyhólyag vastagbéllel és gyomorral egyszerre és egyidejűleg történő megnagyobbításáról (composite hólyag) metodikai közleményt jelent meg hazai folyóiratban. A betegek immunhisztokémiai és submikroszkópos vizsgálatainak alapján a hólyagmegnagyobbításra felhasznált tápcsatorna részben a MUC-2 fehérje expressziója idővel csökken. Az eredeti hólyagrész mucosajaban ugyanezen fehérje a húgyhólyag megnagyobbításakor nem mutatható ki, idővel azonban kis mértekben expresszalodik. A fenti marker változásai a hólyagmegnagyobbításra felhasznált szövetekben pre-malignus jelként értékelhetőek. A kutatás ezen eredményeit további vizsgálatokat követően, később kívánjuk publikálni. | Since 1987, our group has performed 86 bladder enlargement or bladder replacement surgeries in children and adolescents. During the tendering period (2004-2008), 66 patients out of the all operated cases have been under continuous follow up, 35 of them have more than 10 years of follow up. Until the end of 2008, 57 patients have been included in prospective follow up group. These patients are followed as described in the tendering protocol. By the help of the tender, 4 international manuscripts have been published: 1). Reasons of a repeated operation (re-augmentation) in 3 patients, failure of bladder enlargement and potential reasons for this failure. 2). Results of cystometry measurements. 3). Evaluation of patients? quality of life. 4). A review of the bladder augmentation in childhood. Another publication about experimental surgery of simultaneous bladder, large bowel and stomach enlargement (?composite? bladder) has been reported in Hungary. According to the immunohistochemistry and submicroscopic examinations, the level of MUC-2 protein of the bowel used for bladder enlargement has gradually declined by time. In the original bladder mucosa (normal urothelium), this protein cannot be detected during bladder enlargement, however, it is expressed gradually in small quantity. The changes of aforementioned protein can be used as a pre-malignant marker in the tissues. In future, we will report our results of submicroscopic results of these examinations

    Minerals in the rhizosphere: overlooked mediators of soil nitrogen availability to plants and microbes

    Get PDF
    Despite decades of research progress, ecologists are still debating which pools and fluxes provide nitrogen (N) to plants and soil microbes across different ecosystems. Depolymerization of soil organic N is recognized as the rate-limiting step in the production of bioavailable N, and it is generally assumed that detrital N is the main source. However, in many mineral soils, detrital polymers constitute a minor fraction of total soil organic N. The majority of organic N is associated with clay-sized particles where physicochemical interactions may limit the accessibility of N-containing compounds. Although mineral-associated organic matter (MAOM) has historically been considered a critical, but relatively passive, reservoir of soil N, a growing body of research now points to the dynamic nature of mineral-organic associations and their potential for destabilization. Here we synthesize evidence from biogeoscience and soil ecology to demonstrate how MAOM is an important, yet overlooked, mediator of bioavailable N, especially in the rhizosphere. We highlight several biochemical strategies that enable plants and microbes to disrupt mineral-organic interactions and access MAOM. In particular, root-deposited low-molecular-weight exudates may enhance the mobilization and solubilization of MAOM, increasing its bioavailability. However, the competitive balance between the possible fates of N monomers—bound to mineral surfaces versus dissolved and available for assimilation—will depend on the specific interaction between mineral properties, soil solution, mineral-bound organic matter, and microbes. Building off our emerging understanding of MAOM as a source of bioavailable N, we propose a revision of the Schimel and Bennett (Ecology 85:591–602, 2004) model (which emphasizes N depolymerization), by incorporating MAOM as a potential proximal mediator of bioavailable N
    corecore