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In large river floodplains, the availability of trophic resources to the fish fauna is highly variable as a consequence of seasonal environmental change and habitat diversity. Young‐of‐the‐year fishes (YOY) must find suitable habitats to settle, feed and survive. However, very few in‐depth studies are available about the food preferences of the young fishes during their first growing season. Here, we investigated the composition of planktonic assemblages and the YOY diet of three generalist fish species Alburnus alburnus (Linnaeus, 1758), Squalius cephalus (Linnaeus, 1758) and Pseudorasbora parva (Temminck & Schlegel, 1846) from four floodplain sites of the French Upper Rhône River. More specifically, we studied their temporal and spatial variations in relation to five environmental variables: hydrology, dissolved oxygen, primary production, water temperature and conductivity. Stable flow conditions and the associated temperature and conductivity strongly structured the phytoplankton community in the floodplain channels, whereas water movements within channels and dissolved oxygen concentrations were significantly correlated to the zooplankton composition. A zooplankton density above ≈100 ind L−1 allowed the initiation of a YOY diet mainly based upon zooplankton for the three fish species. When zooplankton densities were insufficient, all three species used phytoplankton as their main food resource. Finally, the diet overlaps between species, differed significantly between sites. The study highlights the need to examine the diet of juvenile fishes and environmental variables in the floodplains. [ABSTRACT FROM AUTHOR]

Aggregation of the RNA‐binding protein TAR DNA‐binding protein 43 (TDP‐43) is the key neuropathological feature of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP‐43 is predominantly nuclear, forms oligomers, and is contained in biomolecular condensates assembled by liquid–liquid phase separation (LLPS). In disease, TDP‐43 forms cytoplasmic or intranuclear inclusions. How TDP‐43 transitions from physiological to pathological states remains poorly understood. Using a variety of cellular systems to express structure‐based TDP‐43 variants, including human neurons and cell lines with near‐physiological expression levels, we show that oligomerization and RNA binding govern TDP‐43 stability, splicing functionality, LLPS, and subcellular localization. Importantly, our data reveal that TDP‐43 oligomerization is modulated by RNA binding. By mimicking the impaired proteasomal activity observed in ALS/FTLD patients, we found that monomeric TDP‐43 forms inclusions in the cytoplasm, whereas its RNA binding‐deficient counterpart aggregated in the nucleus. These differentially localized aggregates emerged via distinct pathways: LLPS‐driven aggregation in the nucleus and aggresome‐dependent inclusion formation in the cytoplasm. Therefore, our work unravels the origins of heterogeneous pathological species reminiscent of those occurring in TDP‐43 proteinopathy patients. Synopsis: Loss of TDP‐43 oligomerization and RNA binding promotes diverse TDP‐43 pathologies providing insight into the origins of heterogeneous pathological species occurring in human disease. TDP‐43 oligomerization and RNA binding govern its stability, splicing regulation, LLPS, and subcellular localization.TDP‐43 oligomerization is modulated by RNA binding.Monomeric TDP‐43 forms inclusions in the cytoplasm, whereas its RNA binding‐deficient counterpart aggregates in the nucleus.TDP‐43 aggregates emerge via distinct pathways: LLPS‐driven aggregation in the nucleus and aggresome‐dependent inclusion formation in the cytoplasm.Our work unravels the origins of heterogeneous TDP‐43 inclusions reminiscent of those occurring in TDP‐43 proteinopathy patients. [ABSTRACT FROM AUTHOR]

Large river floodplains are dynamic environments, where alternating low and high flows are key ecological processes shaping aquatic biota. As a result of fluctuations in flow in floodplain channels, the diversity of benthic assemblages is assumed to result from the balance between surface flow connections, which are dominant during high flows, and groundwater inputs, which are dominant during low flows. However, the relative importance of these inputs in explaining aquatic invertebrate diversity has never been tested.The response of aquatic invertebrates to hydrological changes of a river floodplain was investigated in seven braided and six braided–anastomosed floodplain channels of the French upper Rhône River that are fed by three different processes: groundwater supply (which controls the thermal inertia of the water bodies), surface slow flow connections (i.e. diffuse overbank flows; passive overflow), and surface shear stress‐related connections (i.e. condensed flows; active overflow) during high flows.Generalised dissimilarity models indicated that floodplain invertebrate composition had complex relationships with the three processes considered. The relative importance of the latter appeared dependent upon the morphology of the floodplain channels. In the braided channels, the effects of shear stress‐related connections were more prominent than in the anastomosed ones, for which the effects of the three processes were more similar.Overall, the diversity of flow connections, that is, lateral surface water connections (both shear stress‐related and slow, as defined above) and vertical connection with groundwater (inferred through thermal inertia) enhanced the species turnover at the reach scale. Thermal inertia influenced invertebrate composition when, during low flow periods, surface flow connections had limited effect.Our results highlighted that the role of hydrologic connectivity upon floodplain diversity cannot be reduced to a single process. They also indicate the importance of vertical connectivity for maintaining biodiversity in floodplain habitats where surface flow connectivity is neither frequent nor constant. [ABSTRACT FROM AUTHOR]

Baculoviruses can induce climbing behaviour in their caterpillar hosts to ensure they die at elevated positions to enhance virus transmission, providing an excellent model to study parasitic manipulation of host behaviour. Here, we demonstrate that climbing behaviour occurred mostly during daylight hours, and that the height at death of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV)‐infected larvae increases with the height of the light source. Phototaxic and electroretinogram (ERG) responses were enhanced after HearNPV‐infection in host larvae, and ablation of stemmata in infected larvae prevented both phototaxis and climbing behaviour. Through transcriptome and quantitative PCR, we confirmed that two opsin genes (a blue light‐sensitive gene, HaBL; and a long wave‐sensitive gene, HaLW) as well as the TRPL (transient receptor potential‐like channel protein) gene, all integral to the host's visual perception pathway, were significantly upregulated after HearNPV infection. Knockout of HaBL, HaLW, or TRPL genes using the CRISPR/Cas9 system resulted in significantly reduced ERG responses, phototaxis, and climbing behaviour in HearNPV‐infected larvae. These results reveal that HearNPV alters the expression of specific genes to hijack host visual perception at fundamental levels—photoreception and phototransduction—in order to induce climbing behaviour in host larvae. [ABSTRACT FROM AUTHOR]

Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues, included the central nervous system (CNS). As a main component of the CNS, neuropeptides are small protein‐like molecules functioning as neurohormones, neurotransmitters, or neuromodulators. These peptides are involved in regulating animal physiology and behavior and could be altered after baculovirus infection. In this study, we have investigated the effect of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) infection on expression of Spodoptera exigua neuropeptides and neuropeptide‐like genes. Expression of the gene encoding a polypeptide that resembles the well‐known insect neuropeptide proctolin and named as proctolin‐like peptide (PLP), was downregulated in the larval brain following infection and was chosen for further analysis. A recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) overexpressing the C‐terminal part of the PLP was generated and used in bioassays using S. exigua larvae to study its influence on the viral infection and insect behavior. AcMNPV‐PLP‐infected larvae showed less locomotion activity and a reduction in growth compared to larvae infected with wild type AcMNPV or mock‐infected larvae. These results are indicative of this new peptide as a neuromodulator that regulates visceral and skeletal muscle contractions and offers a novel effector involved in the behavioral changes during baculovirus infection. [ABSTRACT FROM AUTHOR]

Morphologically distinct TDP‐43 aggregates occur in clinically different FTLD‐TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP‐43 follows a prion‐like cascade, but the molecular determinants of this process remain unknown. We use advanced microscopy techniques to compare the seeding properties of pathological FTLD‐TDP‐A and FTLD‐TDP‐C aggregates. Upon inoculation of patient‐derived aggregates in cells, FTLD‐TDP‐A seeds amplify in a template‐dependent fashion, triggering neoaggregation more efficiently than those extracted from FTLD‐TDP‐C patients, correlating with the respective disease progression rates. Neoaggregates are sequentially phosphorylated with N‐to‐C directionality and with subtype‐specific timelines. The resulting FTLD‐TDP‐A neoaggregates are large and contain densely packed fibrils, reminiscent of the pure compacted fibrils present within cytoplasmic inclusions in postmortem brains. In contrast, FTLD‐TDP‐C dystrophic neurites show less dense fibrils mixed with cellular components, and their respective neoaggregates are small, amorphous protein accumulations. These cellular seeding models replicate aspects of the patient pathological diversity and will be a useful tool in the quest for subtype‐specific therapeutics. Synopsis: Pathological TDP‐43 derived from FTLD patient brains triggers de novo aggregation of physiological TDP‐43 in host cells via a prion‐like cascade. Different subtypes of FTLD‐TDP show distinct organization of TDP‐43 aggregates in patient brains, different seeding potencies, neoaggregate structures and C‐terminal serine phosphorylation timelines. Pathological TDP‐43 triggers template‐dependent aggregation and amplification of neoaggregatesFTLD‐TDP‐A and FTLD‐TDP‐C aggregates have different seeding potency (high vs. low) and follow distinct timelines of C‐terminal serine phosphorylationNeoaggregates triggered by FTLD‐TDP‐A and FTLD‐TDP‐C display different aggregation profiles (fibrillar vs. amorphous) resembling the original aggregates in patient brains (densely vs. loosely packed fibrils) [ABSTRACT FROM AUTHOR]

From the management of microtubules to the production of pathological species: liquid–liquid phase separation may tune the behavior of the protein tau in health and neurodegenerative disease. In this issue of The EMBO Journal, Hochmair et al (2022) demystify important aspects of tau condensate compilation. [ABSTRACT FROM AUTHOR]

rctt‐Octatriazolyl‐ortho‐methyl‐tetra‐C‐naphthyl‐calix[4]resorcinarenes containing triazole moieties on the horizontally and vertically arranged benzene rings of the macrocyclic core; rctt tetra‐triazolyl‐tetra‐phosphato‐ortho‐methyl‐tetra‐C‐naphthyl‐calix[4]resorcinarene with triazole groups being bound only to the vertically arranged benzene rings of the macrocycle and the phosphate groups being immobilized on the horizontally arranged benzene rings; di‐ and tetra‐triazolyl‐dinaphthylmethanes differing in the number and spatial orientation of chelate pairs; and 2,2′‐diphosphonato‐dinaphthylmethanes in which exocyclic substituents include the phosphonate and the terminal triazole moieties connected by linkers differing in the steric crowding were synthesized, isolated in high yields, and characterized. In all cases, the catalytic azide‐alkyne cycloaddition click reaction was the key step of the synthesis. One octatriazole calix[4]resorcinarene derivative was subjected to subsequent transformations in which the terminal ester groups in the triazole rings were converted to carboxyl and amide groups. The alkylation of rctt resorcinarenes with propargyl bromide and modification of octatriazole resorcinarene derivative with terminal ester groups by biologically active phenethylamine proceeded efficiently only under microwave irradiation. [ABSTRACT FROM AUTHOR]

ALS and FTD are fatal and incurable neurodegenerative diseases, characterized by accumulation of pathologic forms of RNA‐binding proteins, predominantly TDP‐43. The functional consequences and potential neurotoxic effects of the highly heterogeneous TDP‐43 aggregates observed in postmortem brains are debated. Combining structural protein analysis with cellular systems we uncovered a novel and unexpected mechanism that counteracts pathologic aggregation of TDP‐43. More recently, we described two distinct mechanisms of aggregation resulting in either nuclear of cytoplasmic TDP‐43 aggregates, resembling the neuropathological heterogeneity described in FTD patients and potentially unravels the origins of heterogeneous pathological species occurring in TDP‐43 proteinopathies. We also showed that FTD heterogeneity is associated with alternate pathological TDP‐43 conformations, reminiscent of prion strains. We used advanced microscopy techniques to explore the differences in the physical and seeding properties between these pathological TDP‐43 aggregates. We found that the subcellular environment and organization of TDP‐43 aggregates differs in patient brains in a subtype‐specific manner. When isolated and introduced in cells, these distinct TDP‐43 assemblies triggered neoaggregate formation with seeding potencies and morphologies that mimicked human brain pathology. To study neurodegeneration phenotypes in human neurons, we developed a new methodology for generating human neuronal networks with remarkable maturity, longevity and reproducibility. Combining high density multielectron arrays and single cell RNA sequencing, we demonstrated the potential of these cultures for modeling neurodegeneration. In this new model, we identified novel RNA targets of TDP‐43, which we found abnormally accumulated in neurons with TDP‐43 pathology in human brains of ALS and FTD patients. The implications of these studies for understanding the mechanisms of neurodegeneration and inspiring therapeutic approaches will be discussed. [ABSTRACT FROM AUTHOR]

Zeolitic imidazolate framework (ZIF‐8, Zn(2‐meIm)2) and composites based on ZIF‐8 and alumina nanofibers (NafenTM), i.e. ZIF‐8/Nafen, were demonstrated to be efficient heterogeneous catalysts for the reaction of methanol with propylene oxide to produce propylene glycol methyl ether (PGME), which is a member of the family of glycol ether solvents used for a wide variety of consumer products and industrial applications. Both the reaction rate and the selectivity toward PGME were found to decrease with increasing crystal size of the ZIF‐8 material, which was related to the change in the number of basic sites and their accessibility. The investigation of ZIF‐8/Nafen composites revealed the dependence of their catalytic performance on the amount of the ZIF‐8 component. In particular, the activity was affected by the crystal size of the ZIF‐8 material and the nature of acid‐base sites in its framework. [ABSTRACT FROM AUTHOR]

Background: The prescription of parenteral nutrition (PN) in hospitalised patients requires an estimation of the energy requirements. Most studies employing prediction equations (PEs) to estimate energy requirements have focused on critically ill patients. The present study aimed to evaluate several PEs of the resting energy expenditure (REE) to identify the most accurate equation for estimating the REE required for PN. Methods: This cross‐sectional and descriptive study included patients hospitalised with medical or surgical diagnoses, making them candidates for PN. Epidemiological data, the reason for hospital admission, nutritional screening results, characteristics of the PN administered and REE by indirect calorimetry (IC) were recorded and, subsequently, PEs were calculated. Results: In total, 116 patients were recruited with a mean (SD) age of 56.7 (13.8) years and body mass index of 21.3 (4.25) kg m−2. The diagnosis was medical in 52% of patients and surgical in 48%. The mean (SD) REEs of patients, according to IC, were: 6.11 (1.18) MJ [1461 (281) kcal]; and according to PEs: Mifflin, 5.07 (1.05) MJ [1212 (252) kcal]; Owen, 5.43 (0.72) MJ [1298 (172) kcal]; Harris–Benedict, 5.38 (0.85) MJ [1285 (204) kcal]; Ireton‐Jones, 6.20 (1.69) MJ [1481 (403) kcal]; and short equation, 6.12 (0.92) MJ [1464 (220) kcal]. A comparison of the results obtained for the REE by IC and with PEs indicated that the short equation had less bias than the other equations, with an accuracy of 54% Conclusions: In hospitalised patients who receive PN, determination of the REE should ideally be made by IC. PEs are acceptable but not exact and so their estimation could overfeed or underfeed the patient. [ABSTRACT FROM AUTHOR]

A novel important class of nanoporous crystalline solids, metal–organic frameworks (MOFs), composed of organic ligands (linkers) and metal ions, is now considered as a platform for the development of various functional hybrid materials. In order to design new MOF‐based asymmetric catalysts, two terephthalic acid derivatives, namely 2‐{[1‐(1‐tert‐butoxycarbonyl)‐ l‐prolyl]amino}terephthalic acid, C18H22N2O7, (1), and 2‐( l‐prolylamino)terephthalic acid, C13H14N2O5, (2), which could find potential applications as chiral linkers for the construction of enantioselective MOFs, were synthesized and their powder samples were measured at synchrotron station ID22 (ESRF). Each sample contained two unknown crystalline phases, so four new crystal structures were determined, namely, the 2.24‐hydrate of (1), (1a) (space group C2221), and the 2.08‐hydrate of (1), (1b) (P2221), which are crystallohydrates, and two polymorphs of (2), i.e. (2a) (C2221) and (2b) (P212121), and were validated with DFT‐d (dispersion‐corrected density functional theory) optimizations. [ABSTRACT FROM AUTHOR]

Objectives: Treatment guidelines recommend single‐tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple‐pill formulations of the same regimen. Methods: We selected treatment‐naïve patients starting one‐, two‐ or three‐pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one‐pill regimen or a three‐pill regimen. Results: Among 11 739 treatment‐naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow‐up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01‐1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84‐1.68). We estimate that 77 patients would need to be exposed to a one‐pill regimen rather than a three‐pill regimen for 1 year to avoid one additional AIDS event or death. Conclusions: This particular single‐tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple‐pill formulations. [ABSTRACT FROM AUTHOR]

Abstract: Baculoviruses manipulate host climbing behaviour to ensure that the hosts die at elevated positions on host plants to facilitate virus proliferation and transmission, which is a process referred to as tree‐top disease. However, the detailed molecular mechanism underlying tree‐top disease has not been elucidated. Using transcriptome analysis, we showed that two hormone signals, juvenile hormone (JH) and 20‐hydroxyecdysone (20E), are key components involved in HaSNPV‐induced tree‐top disease in Helicoverpa armigera larvae. RNAi‐mediated knockdown and exogenous hormone treatment assays demonstrated that 20E inhibits virus‐induced tree‐top disease, while JH mediates tree‐top disease behaviour. Knockdown of BrZ2, a downstream signal of JH and 20E, promoted HaSNPV‐induced tree‐top disease. We also found that two miRNAs target BrZ2 and are involved in the cross‐talk regulation between 20E and JH manipulating HaSNPV replication, time to death and HaSNPV‐induced tree‐top disease. [ABSTRACT FROM AUTHOR]

Mercury (Hg) compounds represent an important risk to aquatic ecosystems because of their persistence, bioaccumulation, and biomagnification potential. In the present review, we critically examine state-of-the-art studies on the interactions of Hg compounds with freshwater biofilms, with an emphasis on Hg accumulation, transformations, and effects. Freshwater biofilms contain both primary producers (e.g., algae) and decomposers (e.g., bacteria and fungi), which contribute to both aquatic food webs and the microbial loop. Hence they play a central role in shallow water and streams, and also contribute to Hg trophic transfer through their consumption. Both inorganic and methylated mercury compounds accumulate in biofilms, which could transform them mainly by methylation, demethylation, and reduction. Accumulated Hg compounds could induce diverse metabolic and physiological perturbations in the microorganisms embedded in the biofilm matrix and affect their community composition. The bioavailability of Hg compounds, their transformations, and their effects depend on their concentrations and speciation, ambient water characteristics, biofilm matrix composition, and microorganism-specific characteristics. The basic processes governing the interactions of Hg compounds with biofilm constituents are understudied. The development of novel conceptual and methodological approaches allowing an understanding of the chemo- and biodynamic aspects is necessary to improve the knowledge on Hg cycling in shallow water as well as to enable improved use of freshwater biofilms as potential indicators of water quality and to support better informed risk assessment. Environ Toxicol Chem 2017;36:3194-3205. © 2017 SETAC [ABSTRACT FROM AUTHOR]

Background IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis. This study investigates associations between IL-33 polymorphisms during the development of childhood atopic diseases and underlying mechanisms including immune regulation of Tregs. Methods Genotyping of IL-33-polymorphisms (, ) was performed by MALDI- TOF- MS in 880 of 1133 PASTURE/ EFRAIM children. In 4.5-year-old German PASTURE/ EFRAIM children (n = 99), CD4+ CD25high FOXP3+ Tregs were assessed by flow cytometry following 24-h incubation of PBMCs with PMA/ionomycin, LPS or without stimuli (U). SOCS3, IL1 RL1, TLR4 mRNA expression and sST2 protein levels ex vivo were measured in PASTURE/ EFRAIM children by real-time PCR or ELISA, respectively. Health outcomes (hay fever, asthma) were assessed by questionnaires at the age of 6 years. Results and were positively associated with hay fever ( OR = 1.77, 95% CI = 1.02-3.08; OR = 1.79, 95% CI = 1.04-3.11) and CD4+ CD25high FOXP3+ Tregs (%) decreased in minor allele homozygotes/heterozygotes compared to major allele homozygotes (p(U) = 0.004; p( LPS) = 0.005; p(U) = 0.001; p( LPS) = 0.012). SOCS3 mRNA expression increased in minor allele homozygotes and heterozygotes compared with major allele homozygotes for both IL-33-polymorphisms (p() = 0.032, p() = 0.019) and negatively correlated to Tregs. Conclusions IL-33-polymorphisms and may account for an increased risk of hay fever with the age of 6 years. Lower Tregs and increased SOCS3 in combined heterozygotes and minor allele homozygotes may be relevant for hay fever development, pointing towards dysbalanced immune regulation and insufficient control of allergic inflammation. [ABSTRACT FROM AUTHOR]

Many parasites alter host behaviour to enhance their chance of transmission. Recently, the ecdysteroid UDP-glucosyl transferase ( egt) gene from the baculovirus Lymantria dispar multiple nucleopolyhedrovirus (Ld MNPV) was identified to induce tree-top disease in L. dispar larvae. Infected gypsy moth larvae died at elevated positions (hence the term tree-top disease), which is thought to promote dissemination of the virus to lower foliage. It is, however, unknown whether egt has a conserved role among baculoviruses in inducing tree-top disease. Here, we studied tree-top disease induced by the baculovirus Autographa californica multiple nucleopolyhedrovirus (Ac MNPV) in two different host insects, Trichoplusia ni and Spodoptera exigua, and we investigated the role of the viral egt gene therein. Ac MNPV induced tree-top disease in both T. ni and S. exigua larvae, although in S. exigua a moulting-dependent effect was seen. Those S. exigua larvae undergoing a larval moult during the infection process died at elevated positions, while larvae that did not moult after infection died at low positions. For both T. ni and S. exigua, infection with a mutant Ac MNPV lacking egt did not change the position where the larvae died. We conclude that egt has no highly conserved role in inducing tree-top disease in lepidopteran larvae. The conclusion that egt is a 'gene for an extended phenotype' is therefore not generally applicable for all baculovirus-host interactions. We hypothesize that in some baculovirus-host systems (including Ld MNPV in L. dispar), an effect of egt on tree-top disease can be observed through indirect effects of egt on moulting-related climbing behaviour. [ABSTRACT FROM AUTHOR]

Vegetated and shallow areas such as wetlands and salt marshes, as well as freshwater lakes and rivers, have been identified as hotspots for Hg methylation. The presence of aquatic macrophytes, the predominant primary producers in shallow waters, plays an important but still poorly understood role in the fate of Hg in these environments. The present review focuses on the influences of macrophytes on Hg speciation and distribution in sediments, the rhizosphere, and the water column; on Hg transformation; and on Hg release to the environment, including transfer to the trophic web. Future research will require an improved understanding of the mechanisms and the factors controlling these aspects as well as a broader general view. Thus, the main gaps in knowledge are also discussed. Environ Toxicol Chem 2014;33:1225-1237. © 2014 SETAC [ABSTRACT FROM AUTHOR]

The present review describes and discusses key interactions between mercury (Hg) and phytoplankton to highlight the role of phytoplankton in the biogeochemical cycle of Hg and to understand direct or indirect Hg effects on phytoplankton. Phytoplankton are exposed to various Hg species in surface waters. Through Hg uptake, phytoplankton affect the concentration, speciation, and fate of Hg in aquatic systems. The mechanisms by which phytoplankton take up Hg are still not well known, but several studies have suggested that both facilitated transport and passive diffusion could be involved. Once internalized, Hg will impact several physiological processes, including photosynthesis. To counteract these negative effects, phytoplankton have developed several detoxification strategies, such as the reduction of Hg to elemental Hg or its sequestration by intracellular ligands. Based on the toxicological studies performed so far in the laboratory, Hg is unlikely to be toxic to phytoplankton when they are exposed to environmentally relevant Hg concentrations. However, this statement should be taken with caution because questions remain as to which Hg species control Hg bioavailability and about Hg uptake mechanisms. Finally, phytoplankton are primary producers, and accumulated Hg will be transferred to higher consumers. Phytoplankton are a key component in aquatic systems, and their interactions with Hg need to be further studied to fully comprehend the biogeochemical cycle of Hg and the impact of this ubiquitous metal on ecosystems. Environ Toxicol Chem 2014;33:1211-1224. © 2013 SETAC [ABSTRACT FROM AUTHOR]

Lipid oxidation is a recognized end point for the study of oxidative stress and is an important parameter to describe the mode of micropollutant action on aquatic microorganisms. Therefore, the development of quick and reliable methodologies probing the oxidative stress and damage in living cells is highly sought. In the present proof-of-concept work, we examined the potential of the fluorescent dye C11-BODIPY591/581 to probe lipid oxidation in the green microalga Chlamydomonas reinhardtii. C11-BODIPY591/581 staining was combined with flow cytometry measurements to obtain multiparameter information on cellular features and oxidative stress damage within single cells. First, staining conditions were optimized by exploring the capability of the dye to stain algal cells under increasing cell and dye concentrations and different staining procedures. Then lipid oxidation in algae induced by short- and long-term exposures to the three metallic micropollutants, copper, mercury, and nanoparticulate copper oxide, and the two organic contaminants, diethyldithiocarbamate (DDC) and diuron was determined. In this work we pointed out C11-BODIPY591/581 applicability in a wide range of exposure conditions, including studies of oxidation as a function of time and that it is suitable for in vivo measurements of lipid oxidation due to its high permeation and stability in cells and its low interference with algal autofluorescence. © 2013 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Parasitic infections are often followed by changes in host behaviour. Numerous and exquisite examples of such behavioural alterations are known, covering a broad spectrum of parasites and hosts. Most descriptions of such parasite-induced changes in host behaviour are observational reports, while experimentally confirmed examples of parasite genes inducing these changes are limited. In this study, we review changes in invertebrate host behaviour observed upon infection by parasites and discuss such changes in an evolutionary context. We then explore possible mechanisms involved in parasite-induced changes in host behaviour. Genes and pathways known to play a role in invertebrate behaviour are reviewed, and we hypothesize how parasites (may) affect these pathways. This review provides the state of the art in this exciting, interdisciplinary field by exploring possible pathways triggered in hosts, suggesting methodologies to unravel the molecular mechanisms that lead to changes in host behaviour. [ABSTRACT FROM AUTHOR]

Abstract: Smad anchor for receptor activation (SARA or ZFYVE9) has been proposed to mediate transforming growth factor β (TGF-β) signaling by direct interaction with the non-activated Smad proteins and the TGF-β receptors; however, these findings are controversial. We demonstrate no correlation between SARA expression and the levels of TGF-β-induced phosphorylation of Smads in various B-cell lymphomas. Moreover, knockdown of SARA in HeLa cells did not interfere with TGF-β-induced Smad activation, Smad nuclear translocation, or induction of TGF-β target genes. Various R-Smads and TGF-β receptors did not co-immunoprecipitate with SARA. Collectively, our results demonstrate that SARA is dispensable for functional TGF-β-mediated signaling. [Copyright &y& Elsevier]

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily. TGF-β can affect class switch recombination in human B cells, but whether BMPs also play a role have not been tested. We investigated the functional effects of exogenously added BMPs on CD27− naive and CD27+ memory B cells from healthy donors. BMP-2, -4, -6 and -7 inhibited CD40L/IL-21-induced production of IgM, IgG and IgA. BMP-6 reduced Ig production by 70% in memory B cells and more than 55% in naive B cells, whereas the other BMPs were slightly less potent. We observed a striking difference in functional effects between the structurally similar BMP-6 and BMP-7, as BMP-6 mainly inhibited plasmablast differentiation, and BMP-7 mainly induced apoptosis. In memory B cells, BMP-6 upregulated expression of DNA-binding protein inhibitor genes, but potently inhibited CD40L/IL-21-induced upregulation of the transcription factor XBP1, necessary for the late stages of plasmacytic differentiation. Expression of transcription factors regulating earlier stages (IRF4, PRDM1) was not affected by BMP-6. Taken together, these results show that BMPs are potent suppressors of naive and memory B cells. [ABSTRACT FROM AUTHOR]

Background The long-term efficacy of adalimumab in patients with ulcerative colitis is not well known. Aim To evaluate the short- and long-term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab. Methods Patients with active ulcerative colitis were treated with adalimumab after failure of other therapies including infliximab. Short-term clinical response and remission were assessed at weeks 4 and 12. The proportion of patients who continued on adalimumab and the proportion of patients who remained colectomy free were assessed over the long term. Results Clinical response at weeks 4 and 12 was achieved in 16 (53%) and 18 (60%) patients, respectively, and clinical remission was obtained in 3 (10%) and 8 (27%) patients, respectively. After a mean 48 weeks' follow-up, 15 patients (50%) continued on adalimumab. Six patients (20%) required colectomy. All patients who achieved clinical response at week 12 were colectomy free at long term. Conclusions Adalimumab was well tolerated and induced durable clinical response in many patients with otherwise medically refractory ulcerative colitis. Patients achieving clinical response at week 12 avoided colectomy over the long term. [ABSTRACT FROM AUTHOR]

In an effort to improve the understanding and prediction of Cd uptake by soil bacteria, adsorbed and intracellular Cd were determined in unpolluted and highly polluted model soil solutions within a concentration range spanning from 10-9 to 5 × 10-5 M Cd. In parallel, the free Cd ion concentrations ([Cd2+]) were measured by a hollow fiber permeation liquid membrane. Obtained results demonstrated that Cd uptake by bacterium Sinorhizobium meliloti was related to [Cd2+] in the solution. Addition of different complexing organic substances reduced [Cd2+] in the bacterial medium and decreased both adsorbed and intracellular Cd. The adsorbed Cd was considerably reduced in the presence of 10-4 to 5 × 10-2 M [Ca] or [Mg]. No effect on Cd adsorption was observed in the presence of Zn or Mn, even at 100-fold excess. Intracellular Cd decreased in the presence of a high excess of Ca and Zn, while no significant effect was observed in the presence of Mg. An increase of dissolved Mn from 10-9 to 10-8 M resulted in a twofold decrease of the intracellular Cd, but no clear trend was observed in the presence of 10-7 to 10-6 M Mn. Based on complexation and competition studies, the stability constants, necessary for quantitative description of Cd uptake by S. meliloti and the development of the bacterial biotic ligand model for Cd, were derived and validated in the solutions containing mixtures of Cd, Zn, Ca, and Mg. Further numerical simulations of Cd uptake by S. meliloti exposed to soil pore waters demonstrated the importance of Zn competition and the insignificant influence of Ca and H on Cd uptake. [ABSTRACT FROM AUTHOR]

• Decreased soil water availability can stimulate production of the plant hormone ethylene and inhibit plant growth. Strategies aimed at decreasing stress ethylene evolution might attenuate its negative effects. • An environmentally benign (nonchemical) method of modifying crop ethylene relations – soil inoculation with a natural root-associated bacterium Variovorax paradoxus 5C-2 (containing the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase that degrades the ethylene precursor ACC), was assessed with pea ( Pisum sativum) plants grown in drying soil. • Inoculation with V. paradoxus 5C-2, but not with a transposome mutant with massively decreased ACC deaminase activity, improved growth, yield and water-use efficiency of droughted peas. Systemic effects of V. paradoxus 5C-2 included an amplified soil drying-induced increase of xylem abscisic acid (ABA) concentration, but an attenuated soil drying-induced increase of xylem ACC concentration. A local bacterial effect was increased nodulation by symbiotic nitrogen-fixing bacteria, which prevented a drought-induced decrease in nodulation and seed nitrogen content. • Successfully deploying a single bacterial gene in the rhizosphere increased yield and nutritive value of plants grown in drying soil, via both local and systemic hormone signalling. Such bacteria may provide an easily realized, economic means of sustaining crop yields and using irrigation water more efficiently in dryland agriculture. [ABSTRACT FROM AUTHOR]

Background Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis. Aim To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease. Methods Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid ( n = 5073). Results A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P = 0.012) and Crohn’s disease (CD) (OR 5.8 95% CI: 1.6–20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP ( n = 1477) (OR 5.2 95% CI: 1.8–14; P = 0.002). Conclusions The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD. [ABSTRACT FROM AUTHOR]

Eukaryotic translational termination is triggered by polypeptide release factors eRF1, eRF3, and one of the three stop codons at the ribosomal A-site. Isothermal titration calorimetry shows that (i) the separated MC, M, and C domains of human eRF1 bind to eRF3; (ii) GTP binding to eRF3 requires complex formation with either the MC or M + C domains; (iii) the M domain interacts with the N and C domains; (iv) the MC domain and Mg2+ induce GTPase activity of eRF3 in the ribosome. We suggest that GDP binding site of eRF3 acquires an ability to bind γ-phosphate of GTP if altered by cooperative action of the M and C domains of eRF1. Thus, the stop-codon decoding is associated with the N domain of eRF1 while the GTPase activity of eRF3 is controlled by the MC domain of eRF1 demonstrating a substantial structural uncoupling of these two activities though functionally they are interrelated. Proteins 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. Methods A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. Results No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. Conclusions In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss. [ABSTRACT FROM AUTHOR]

The peculiarities of the structure of the fluorescent dye N,N'-di-n-octadecylrhodamine advantage its using as an interfacial acid–base probe in aqueous micellar solution of colloidal surfactants. Two long hydrocarbon tails of the dye provide similar orientation of both cation and zwitterion on the micelle/water interface, with the ionizing group COOH exposed to the Stern region in all the systems studied. Further, the charge type of the acid–base couple, A+B±, ensures similar values of the ‘intrinsic’ contribution, pKia, to the ‘apparent’ pKaa value in micelles of different surfactants. This makes the indicator suitable for determination of electrical surface potentials, Ψ. The pKaas have been obtained in cationic, anionic, zwitterionic, and nonionic surfactant systems, at various salt background. In total 17 systems were studied. At bulk counterion concentration of ca. 0.05 M, the pKaa values vary from 2.14 ± 0.07 in n–C18H37N(CH3)3+Cl– micelles to 5.48 ± 0.06 in n–C16H33OSO3–Na+ micelles. The Ψ values, corresponding to the Stern region of micelles, have been evaluated as Ψ = 59.16 pKia–pKaa for T = 298.15 K. The pKia parameter was equated to the average value of 4.23 in nonionic surfactants (4.12–4.32, depending on the surfactant type). For cetyltrimethylammonium bromide and sodium n-dodecylsulfate micelles, the Ψ values (±(7–11) mV) appeared to be +118 mV and at bulk Br- concentration 0.019 M and -76 mV at bulk Na+ concentration 0.020 M, respectively. This satisfactorily agrees with the theoretical values +111 and -84 mV, estimated using the Oshima, Healy, and White equation for these well-defined colloidal systems. Finally, not only absorption, but also fluorescence spectra display the same response to changes in bulk pH. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Since 1999, the International Atomic Energy Agency (IAEA) has been leading a multinational, multi-agency effort to develop a set of energy indicators useful for measuring progress on sustainable development at the national level. This effort has included the identification of major relevant energy indicators, the development of a framework for implementation and the testing of the applicability of this tool in a number of countries. To achieve these goals, the IAEA has worked closely with other international organizations, leaders in energy and environmental statistics and analysis including the United Nations Department of Economic and Social Affairs (DESA), the International Energy Agency (IEA), Eurostat and the European Environment Agency (EEA). Also, the IAEA completed a three-year coordinated research project for the implementation and testing of the original set of indicators in seven countries — Brazil, Cuba, Lithuania, Mexico, the Russian Federation, the Slovak Republic and Thailand. This article provides an overview of the IAEA programme on Indicators for Sustainable Energy Development (ISED) and highlights its experiences and accomplishments. [ABSTRACT FROM AUTHOR]

Trace metal bioavailability is often evaluated on the basis of steady-state models such as the free ion activity model (FIAM) and the biotic ligand model (BLM). Some of the assumptions underlying these models were verified by examining Pb and Zn uptake by the green microalga Chlorella kesslerii. Transporter bound metal ({M-Rcell}) and free ion concentrations ([MZ+]) were related to experimentally determined uptake fluxes (Jint). Although the BLM and FIAM correctly predicted Pb uptake in the absence of competing ions, they failed to predict competitive interactions with Ca2+, likely because of modifications of the algal surface charge and the active nature of Ca2+ transport. Zinc transport is also active; in this case, both the internalization rate constant (kint) and the equilibrium constant for the binding of Zn to the transport sites (KZz-Rcell ) varied as a function of [Zn2+] in the bulk solution. For this reason, Zn uptake could not be modeled by the steady-state models either in the presence or absence of competitors (Cd and Ca). Furthermore, the role of Cu on Pb and Zn adsorption and uptake could not be predicted by either model because of secondary effects on the algal physiology and membrane permeability. Finally, a 17°C reduction in temperature resulted in a two- to five-fold decrease in membrane permeability of the metals, an observation that also is unaccounted for by either the FIAM or BLM. This paper emphasizes the limitations of the models in well-controlled laboratory systems with the goal of extrapolating the results to complex environmental systems. [ABSTRACT FROM AUTHOR]

A multicenter study was undertaken to determine the failure rate of a specific bipolar tined polyurethane ventricular pacing lead, the Medtronic 4004/4004M pacing lead. Seven centers in the United States and Canada implanted 586 Medtronic 4004/4004M pacing leads. The study was designed to determine the probability and clinical manifestations of lead failure. Only failures compatible with an insulation problem were included. The Kaplan-Meier estimate of the percentage of 4004/4004M lead failures within 4 years after implantation was 14.1% (95% confidence interval: 8.5%-19.3%). Failures were manifested as sensing abnormalities, failure to capture, early battery depletion, and significant decrease in measured impedance compared with previous impedance measurements. The observed rate of failure is unacceptable, and strong consideration should be given to replacing the 4004/4004M pacing lead in pacemaker dependent patients and closely monitoring nondependent patients. [ABSTRACT FROM AUTHOR]

The ATP/ADP-antiporter inhibitors and the substrate ADP suppress the uncoupling effect induced by low (10-20 µM) concentrations of palmitate in mitochondria from skeletal muscle and liver. The inhibitors and ADP are found to (a) inhibit the palmitate-stimulated respiration in the controlled state and (b) increase the membrane potential lowered by palmitate. The degree of efficiency decreases in the order: carboxyatractylate (CAtr) > ADP > bongkrekic acid, atractylate. GDP is ineffective, Mg. ADP is of much smaller effect, whereas ATP is effective at much higher concentration than is ADP. Inhibitor concentrations, which maximally suppress the palmitate-stimulated respiration, correspond to those needed for arresting the state 3 respiration. The extent of the CAtr-sensitive stimulation of respiration by palmitate has been found to decrease with an increase in palmitate concentration. Stimulation of the controlled respiration by p-trifluoromethoxycarbonylcyanide phenylhydrozone (FCCP) and gramicidin D at any concentrations of these uncouplers is CAtr-insensitive, whereas that caused by a low concentrations of 2,4-dinitrophenol and dodecyl sulfate is inhibited by CAtr. The above effect of palmitate develops immediately after addition of the fatty acid. It is resistant to EGTA as well as to inhibitors of phospholipase (nupercain) and of lipid peroxidation (ionol). Moreover, palmitate accelerates spontaneous release of the respiratory control, developing in rat liver rnitochondria under certain conditions. This effect takes several minutes, being sensitive to EGTA, nupercain and ionol. Like the fast uncoupling, this slow effect is inhibited by ADP but CAtr and atractylate are stimulatory rather than inhibitory. In artificial planar phospholipid membrane, palmitate does not increase the membrane conductance, FCCP increases it strongly and dinitrophenol only slightly. In cytochrome oxidase proteoliposomes, FCCP, gramicidin and dinitrophenol (less effectively) lower, whereas palmitate enhances the cytochrome-oxidase-generated membrane potential. In this system, monensin substitutes for palmitate. It is concluded that the ATP/ADP antiporter is somehow involved in the uncoupling effect caused by low concentrations of palmitate and, partially, of dinitrophenol, whereas uncoupling produced by FCCP and gramicidin is due to their action on the phospholipid part of the mitochondrial membrane. A possible mechanism of this effect is discussed. [ABSTRACT FROM AUTHOR]