Biosorption and desorption of lanthanum(III) and neodymium(III) in fixed-bed columns with Sargassum sp.: perspectives for separation of rare earth metals

Rare earth (RE) metals are essentials for the manufacturing of high-technology products. The separation of RE is complex and expensive; biosorption is an alternative to conventional processes. This work focuses on the biosorption of monocomponent and bicomponent solutions of lanthanum(III) and neodymium(III) in fixed-bed columns using Sargassum sp. biomass. The desorption of metals with HCl 0.10 mol L(-1) from loaded biomass is also carried out with the objective of increasing the efficiency of metal separation. Simple models have been successfully used to model breakthrough curves (i.e., Thomas, Bohart-Adams, and Yoon-Nelson equations) for the biosorption of monocomponent solutions. From biosorption and desorption experiments in both monocomponent and bicomponent solutions, a slight selectivity of the biomass for Nd(III) over La(III) is observed. The experiments did not find an effective separation of the RE studied, but their results indicate a possible partition between the metals, which is the fundamental condition for separation perspectives.     

Importance of Arsenic Speciation in Populations Exposed to Arsenic in Drinking Water

Total arsenic in urine is often the principal means for assessing chronic exposure to arsenic-contaminated drinking water. This approach ignores many components of the human diet, especially fish and seafood that contain arsenic at significant concentrations. The toxicity differences between the inorganic forms and the dietary forms suggest both should be evaluated when attempting to assess risk from arsenic exposure. Urine biomonitoring for 53 participants was used to confirm reduction in arsenic exposure resulting from well water remediation removing inorganic arsenic from drinking water. Initially, only total arsenic urine assays were performed, but spikes in total arsenic urine concentrations were determined to be diet related and demonstrated the need for analytical methods that differentiate the arsenic species. A secondary analysis was added that quantified inorganic-related arsenic in urine and the dietary forms related to fish and seafood by subtraction from total arsenic. Significant differences were found between the inorganic arsenic component and the total arsenic measured in their urine. On average, approximately 76% of total arsenic in urine was attributed to fish and other organo-arsenic dietary sources, implying a potential significant overestimate of exposure, and demonstrating the need for differentiation of the inorganic-related arsenic from dietary arsenic.     

A Novel HLA-B18 Restricted CD8+ T Cell Epitope Is Efficiently Cross-Presented by Dendritic Cells from Soluble Tumor Antigen

NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8⁺ T cell epitope, NY-ESO-1_88–96 (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1_157–165 epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1_88–96 is much more efficiently cross-presented from the soluble form, than NY-ESO-1_157–165. On the other hand, NY-ESO-1_157–165 is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A_26–35; whereas NY-ESO-1_88–96 was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1_88–96 is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18⁺ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1_88–96 from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8⁺ T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed.     

Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury

Gliomas are the most common and devastating type of primary brain tumor. Many non-neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity. Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro-inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression.     

Variation in functional leaf traits among beech provenances during a Spanish summer reflects the differences in their origin

We assessed the response of 11-year-old saplings from six beech provenances growing in a common-garden trial at the southwestern range limit. Provenances from distinct climatic regions across the European beech distribution were selected. The local Spanish provenance appeared well suited to the site conditions, maintaining high rates of assimilation even in midsummer, but so did the provenance of southern continental origin, from Gotze-Delchev, Bulgaria. Those provenances from cooler sites in central Europe, a continental mountain climate in the Czech Republic and a continental range-edge site in eastern Poland, along with a German provenance of mild maritime origin, had good physiological functionality in early summer but reduced carbon assimilation (A _area) and apparent soil?Cleaf hydraulic conductivity (K _L) in midsummer. The northern maritime provenance from Sweden demonstrated severely-reduced photosynthetic capacity. These groupings of provenances according to their photosynthetic performance, stable carbon isotope composition (??¹³C; a proxy for water-use efficiency) and leaf water potential under marginal conditions, during late summer in the trial, suggest that they have divergent strategies for water use. The research highlights large intraspecific differences among beech provenances of distinct origin and strategies which are expected to modify their response to drought, requiring future genetic studies to explicitly determine the basis of this ecophysiological differentiation.     

Polymorphic toxin systems: comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics

ABSTRACT: BACKGROUND: Proteinaceous toxins are observed across all levels of inter-organismal and intra-genomic conflicts. These include recently discovered prokaryotic polymorphic toxin systems implicated in intra-specific conflict. They are characterized by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. Prior analysis revealed a striking diversity of nuclease and deaminase domains among the toxin modules. We systematically investigated polymorphic toxin systems using comparative genomics, sequence and structure analysis. RESULTS: Polymorphic toxin systems are distributed across all major bacterial lineages and are delivered by at least eight distinct secretory systems. In addition to type-II, these include type-V, VI, VII (ESX), and the poorly characterized "Photorhabdus virulence cassettes (PVC)", PrsW-dependent and MuF phage-capsid-like systems. We present evidence that trafficking of these toxins is often accompanied by autoproteolytic processing catalyzed by HINT, ZU5, PrsW, caspase-like, papain-like, and a novel metallopeptidase associated with the PVC system. We identified over 150 distinct toxin domains in these systems. These span an extraordinary catalytic spectrum to include 23 distinct clades of peptidases, numerous previously unrecognized versions of nucleases and deaminases, ADP-ribosyltransferases, ADP ribosyl cyclases, RelA/SpoT-like nucleotidyltransferases, glycosyltranferases and other enzymes predicted to modify lipids and carbohydrates, and a pore-forming toxin domain. Several of these toxin domains are shared with host-directed effectors of pathogenic bacteria. Over 90 families of immunity proteins might neutralize anywhere between a single to at least 27 distinct types of toxin domains. In some organisms multiple tandem immunity genes or immunity protein domains are organized into polyimmunity loci or polyimmunity proteins. Gene-neighborhood-analysis of polymorphic toxin systems predicts the presence of novel trafficking-related components, and also the organizational logic that allows toxin diversification through recombination. Domain architecture and protein-length analysis revealed that these toxins might be deployed as secreted factors, through directed injection, or via inter-cellular contact facilitated by filamentous structures formed by RHS/YD, filamentous hemagglutinin and other repeats. Phyletic pattern and life-style analysis indicate that polymorphic toxins and polyimmunity loci participate in cooperative behavior and facultative 'cheating' in several ecosystems such as the human oral cavity and soil. Multiple domains from these systems have also been repeatedly transferred to eukaryotes and their viruses, such as the nucleo-cytoplasmic large DNA viruses. CONCLUSIONS: Along with a comprehensive inventory of toxins and immunity proteins, we present several testable predictions regarding active sites and catalytic mechanisms of toxins, their processing and trafficking and their role in intra-specific and inter-specific interactions between bacteria. These systems provide insights regarding the emergence of key systems at different points in eukaryotic evolution, such as ADP ribosylation, interaction of myosin VI with cargo proteins, mediation of apoptosis, hyphal heteroincompatibility, hedgehog signaling, arthropod toxins, cell-cell interaction molecules like teneurins and different signaling messengers.     

Plant response traits mediate the effects of subalpine grasslands on soil moisture

* In subalpine grasslands, changes in abiotic conditions with decreased management intensity alter the functional composition of plant communities, leading to modifications of ecosystem properties. Here, it is hypothesized that the nature of plant feedbacks on soil moisture is determined by the values of key traits at the community level. * As community functional parameters of grasslands change along a gradient of land uses, those traits that respond most to differences in abiotic conditions produced by land use changes were identified. A vegetation removal experiment was then conducted to determine how each plant community affected soil moisture. * Soil moisture was negatively correlated with community root length and positively correlated with canopy height, whereas average leaf area was associated with productivity. These traits were successfully used to predict the effects on soil moisture of each plant community in the removal experiment. This result was validated using data from an additional set of fields. * These findings demonstrate that the modification of soil moisture following land use change in subalpine grasslands can be mediated through those plant functional traits that respond to water availability.     

Adenovirus serotype 5 hexon mediates liver gene transfer

Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo.     

Human alpha-synemin interacts directly with vinculin and metavinculin

Synemin is a very large, unique member of the IF (intermediate filament) protein superfamily. Association of synemin with the major IF proteins, desmin and/or vimentin, within muscle cells forms heteropolymeric IFs. We have previously identified interactions of avian synemin with alpha-actinin and vinculin. Avian synemin, however, is expressed as only one form, whereas human synemin is expressed as two major splice variants, namely alpha- and beta-synemins. The larger alpha-synemin contains an additional 312-amino-acid insert (termed SNTIII) located near the end of the long C-terminal tail domain. Whether alpha- and beta-synemins have different cellular functions is unclear. In the present study we show, by in vitro protein-protein interaction assays, that SNTIII interacts directly with both vinculin and metavinculin. Furthermore, SNTIII interacts with vinculin in vivo, and this association is promoted by PtdIns(4,5)P(2). SNTIII also specifically co-localizes with vinculin within focal adhesions when transiently expressed in mammalian cells. In contrast, other regions of synemin show distinct localization patterns in comparison with those of SNTIII, without labelling focal adhesions. Our results indicate that alpha-synemin, but not beta-synemin, interacts with both vinculin and metavinculin, thereby linking the heteropolymeric IFs to adhesion-type junctions, such as the costameres located within human striated muscle cells.     

The annexin 2-S100A10 complex and its association with TRPV6 is regulated by cAMP/PKA/CnA in airway and gut epithelia

The formation of a heterotetrameric complex between annexin 2 (anx 2) and S100A10 plays an important role in regulating the cellular distribution and biochemical properties of anx 2. A major distinction between the anx 2-S100A10 complex and other annexin-S100 complexes is that S100A10 binding to anx 2 occurs independently of calcium. Here we describe a cyclic 3',5'-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA, EC 2.7.1.37)-dependent mechanism regulating anx 2-S100A10 complex formation and its interaction with the transient receptor potential vanilloid type 6 channel (TRPV6) in airway and gut epithelia. In both 16HBE14o- and Caco-2 cells, forskolin (FSK) stimulated increased anx 2-S100A10 complex formation, which was attenuated by either PKA inhibitors or calcineurin A (CnA) inhibitors. The anx 2-S100A10 complex association with TRPV6 was dependent on FSK-induced CnA-dependent dephosphorylation of anx 2. Analysis of the significance of the cAMP/PKA/CnA pathway on calcium influx showed that both PKA and CnA inhibitors attenuated Ca(45) uptake in Caco-2, but not 16HBE14o-, cells. Thus, the cAMP/PKA/CnA-induced anx 2-S100A10/TRPV6 complex may require additional factors for calcium influx or play a role independent of calcium influx in airway epithelia. In conclusion, our data demonstrates that cAMP/PKA/CnA signalling is important for anx 2-S100A10 complex formation and interaction with target molecules in both absorptive and secretory epithelia.