Composition of dissolved organic matter within a lacustrine environment

Freshwater dissolved organic matter (DOM) is a complex mixture of chemical components that are central to many environmental processes, including carbon and nitrogen cycling. However, questions remain as to its chemical characteristics, sources and transformation mechanisms. Here, we employ 1- and 2-D nuclear magnetic resonance (NMR) spectroscopy to investigate the structural components of lacustrine DOM from Ireland, and how it varies within a lake system, as well as to assess potential sources. Major components found, such as carboxyl-rich alicyclic molecules (CRAM) are consistent with those recently identified in marine and freshwater DOM. Lignin-type markers and protein/peptides were identified and vary spatially. Phenylalanine was detected in lake areas influenced by agriculture, whereas it is not detectable where zebra mussels are prominent. The presence of peptidoglycan, lipoproteins, large polymeric carbo- hydrates and proteinaceous material supports the substantial contribution of material derived from microorganisms. Evidence is provided that peptidoglycan and silicate species may in part originate from soil microbes

The influence of organic alkalinity on the carbonate system in coastal waters

Total alkalinity (TA) is one of the four main carbonate system variables and is a conventionally measured parameter used to characterise marine water carbonate chemistry. It is an important indicator of a waterbody's buffering capacity and a measure of its ability to resist acidification, a matter of growing concern in the marine environment. Although TA is primarily associated with the inorganic components of seawater such as bicarbonate, there is a growing consensus that dissolved organic matter (DOM) can significantly contribute to TA in coastal waters. This organic fraction of TA (OrgAlk) is typically deemed negligible and is not accounted for in conventional TA expressions. However, omission of OrgAlk can lead to the propagation of errors in subsequent carbonate system calculations and to misinterpretation of key carbonate chemistry descriptors such as calcium carbonate saturation states. Here we provide an overview of OrgAlk contributions to TA and investigate the implications of its omission in carbonate system studies conducted in coastal waters. We examine the prevalence of OrgAlk across both coastal and pelagic waters using publicly available carbonate system data products, such as GLODAP and GOMECC. Current measures to account for, incorporate and characterise the contribution of OrgAlk to TA are also critically examined

Escuchando las Voces de Los Estudiantes y Profesores: Un Enfoque Fenomenológico de la Investigación Educativa

Many contemporary researchers claim to use a phenomenological approach but seldom connect their methods to tenets from phenomenological philosophy. We describe a distinctive approach, grounded in the writings of French philosopher Maurice Merleau-Ponty, for conducting educational research. Procedures are outlined for bracketing pre-understandings of a phenomenon, interviewing, and thematizing data with assistance of an interdisciplinary interpretive group. Using our approach, researchers capture the figural aspects of a phenomenon that dominate perception as well as the contextual background that is less visible but integral to understanding it. This phenomenological approach offers educational researchers a radical empiricism, a flexible structure, and a dialogical community of support.Muchos investigadores contemporáneos afirman utilizar un enfoque fenomenológico, pero rara vez conectan sus métodos con los principios de la filosofía fenomenológica. Se describe un enfoque distintivo para la realización de investigación educativa, basado en los escritos del filósofo francés Maurice Merleau-Ponty. Se esbozan procedimientos para acotar el pre-conocimiento de un fenómeno, para entrevistas y para tematizar datos con ayuda de un equipo interdisciplinario interpretativo. Usando nuestro enfoque, los investigadores captan los aspectos figurativos de un fenómeno que domina la percepción, así como el fondo contextual que es menos visible, aunque integral para su comprensión. Este enfoque fenomenológico ofrece a los investigadores educativos un empirismo radical, una estructura flexible, y una comunidad dialógica de apoyo

Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

Extensive studies of the structure–function relationship of antibodies have established that conventional immunoglobulins contain two copies of the antigen-binding fragment (Fab), each of which serves as an autonomous and complete unit for recognizing an antigen. In this paper, we report a previously unidentified mode of antibody–antigen recognition, dubbed “antigen clasping,” where two antigen-binding sites cooperatively clasp one antigen, and the design of a long-neck antibody format that facilitates antigen clasping. Antigen clasping led to recombinant antibodies for histone posttranslational modifications with extraordinarily high specificity, valuable tools for epigenetic research. This study substantially broadens the long-standing paradigm for antibody–antigen recognition

Chromatographic methods for the isolation, separation and characterisation of dissolved organic matter

This review presents an overview of the separation techniques applied to the complex challenge of dissolved organic matter characterisation. The review discusses methods for isolation of dissolved organic matter from natural waters, and the range of separation techniques used to further fractionate this complex material. The review covers both liquid and gas chromatographic techniques, in their various modes, and electrophoretic based approaches. For each, the challenges that the separation and fractionation of such an immensely complex sample poses is critically reviewed

Atomic Resonance and Scattering

Contains reports on nine research projects.National Science Foundation (Grant PHY79-09743)National Science Foundation (Grant PHY82-10486)Joint Services Electronics Program (Contract DAAG29-83-K-0003)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0183)National Bureau of Standards (Grant NB83-NAHA-4058)National Science Foundation (Grant CHE79-02967-A04)National Science Foundation (Grant PHY83-07172)Joint Services Electronics Program (Grant DAAG29-83-K-0003

Atomic Resonance and Scattering

Contains reports on eight research projects.National Science Foundation (Grant PHY83-06273)National Bureau of Standards (Grant NB83-NAHA-4058)National Science Foundation (Grant PHY84-11483)Joint Services Electronics Program (Contract DAAG29-83-K-0003)U.S. Navy - Office of Naval Research (Contract NO0014-79-C-0183)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0695)National Science Foundation (Grant PHY83-07172-A01

Treatment and Intervention for Opiate Dependence in the United Kingdom:Lessons from Triumph and Failure

The history of opiate treatment in the United Kingdom (UK) since the early 1980s is a rich source of learning about the benefits and pitfalls of drug treatment policy. We present five possible lessons to be learnt about how factors outside the clinic, including government, charities and researchers can influence treatment and outcomes. First, do not let a crisis go to waste. The philosophical shift from abstinence to harm reduction in the 1980s, in response to an HIV outbreak in injecting users, facilitated expansion in addiction services and made a harm reduction approach more acceptable. Second, studies of drug-related deaths can lead to advances in care. By elucidating the pattern of mortality, and designing interventions to address the causes, researchers have improved patient safety in certain contexts, though significant investment in Scotland has not arrested rising mortality. Third, collection of longitudinal data and its use to inform clinical guidelines, as pursued from the mid-1990s, can form an enduring evidence base and shape policy, sometimes in unintended ways. Fourth, beware of the presentation of harm reduction and recovery as in conflict. At the least, this reduces patient choice, and at worst, it has caused some services to be redesigned in a manner that jeopardises patient safety. Fifth, the relationship between the third and state sectors must be carefully nurtured. In the UK, early collaboration has been replaced by competition, driven by changes in funding, to the detriment of service provision

A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins

Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4−/− and Myd88−/−, but not TRIF−/− mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response