The acidification caused by the dissolution of anthropogenic carbon dioxide (CO₂) in the ocean changes the chemistry and hence the bioavailability of iron (Fe), a limiting nutrient in large oceanic ...regions. Here, we show that the bioavailability of dissolved Fe may decline because of ocean acidification. Acidification of media containing various Fe compounds decreases the Fe uptake rate of diatoms and coccolithophores to an extent predicted by the changes in Fe chemistry. A slower Fe uptake by a model diatom with decreasing pH is also seen in experiments with Atlantic surface water. The Fe requirement of model phytoplankton remains unchanged with increasing CO₂. The ongoing acidification of seawater is likely to increase the Fe stress of phytoplankton populations in some areas of the ocean.
Carbonic anhydrase, a zinc enzyme found in organisms from all kingdoms, catalyses the reversible hydration of carbon dioxide and is used for inorganic carbon acquisition by phytoplankton. In the ...oceans, where zinc is nearly depleted, diatoms use cadmium as a catalytic metal atom in cadmium carbonic anhydrase (CDCA). Here we report the crystal structures of CDCA in four distinct forms: cadmium-bound, zinc-bound, metal-free and acetate-bound. Despite lack of sequence homology, CDCA is a structural mimic of a functional beta-carbonic anhydrase dimer, with striking similarity in the spatial organization of the active site residues. CDCA readily exchanges cadmium and zinc at its active site--an apparently unique adaptation to oceanic life that is explained by a stable opening of the metal coordinating site in the absence of metal. Given the central role of diatoms in exporting carbon to the deep sea, their use of cadmium in an enzyme critical for carbon acquisition establishes a remarkable link between the global cycles of cadmium and carbon.
The production of methylmercury by some bacteria is a key first step in the accumulation and biomagnification of this toxic substance in aquatic food webs, a major human health concern. By direct ...measurement of cellular Hg(II) uptake in model iron and sulfate reducing bacteria, we have observed that specific trace metals, such as Zn(II) and Cd(II), inhibit uptake and methylation in these organisms, whereas other metals, such as Ni(II), Co(II), or Fe(II), do not. The inhibition of Hg(II) methylation by Zn(II) was competitive in nature and related to the concentration of inorganically complexed Zn(II) (Zn′). The inhibition of Hg(II) methylation was alleviated by decreasing the free Zn′ concentration through complexation with nitrilotriacetic acid without altering the speciation of Hg(II). The inhibitory effect by Zn(II) was observed when either Hg-cysteine complexes or neutral HgCl2 dominated the speciation of Hg(II), demonstrating that both charged and neutral species are transported into the cytosol by an active rather than passive process. We propose that Hg(II) uptake is the result of its accidental uptake by metal transporter(s), possibly one effecting the transport of Zn(II).
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Although many drugs/treatments are now available for most diseases, too often, resistance to these treatments impedes complete therapeutic success. Acquired resistance is a major ...problem in many pathologies but it is an acute one in cancers and infections. This is probably because these diseases often require long durations of treatment, which ascribe to the selection of resistant cells. However, the actual mechanisms implicated in the selection process are still under debate. It is becoming increasingly clear that resistance is associated with the heterogeneity of cancer cells or micro-organisms and that multiple mechanisms underlie the emergence of drug-resistant subpopulations. Recently, it has been suggested that a subpopulation of drug tolerant cells present in cancer populations and called “persisters” play a major role in this resistance. Recent studies have shown that microorganisms share similar properties. Still, how persister/tolerant cells intervene in the development of resistance is not completely elucidated but seems to be related to epigenetic changes in treated cells and the capacity of persisters to modulate and/or highjack their microenvironment. Due to the complexity of this process, the input from mathematicians, as well as new methods of bioinformatics and statistics, is necessary to fully comprehend the acquisition of resistance/tolerance deriving from and leading to the heterogeneous cell populations. The present review will give a brief overview of the most recent data available on drug tolerant cells in cancers and their similarities with microorganisms.
A recent study of the effect of pH on Zn and Cd bioavailability shows that binding to weak organic ligands can increase the pool of metals available to phytoplankton in the presence of strong ...chelating agents. We explore the underlying mechanism in laboratory experiments with the model species Emiliania huxleyi and Thalassiosira weissflogii. Additions of L- and D- isomers of cysteine (Cys) result in similar increases in Zn uptake rates in the presence of the strong chelator ethylenediaminetetraacetic acid (EDTA) but decrease it in the absence of EDTA, ruling out uptake by a specific Zn-Cys transporter. The effect of Cys does not result from alleviating diffusion limitation of inorganic Zn. The enhancement of Zn uptake kinetics by weak ligands is consistent with a mechanism involving formation of a transient ternary complex with uptake molecules: (1) the enhancement is most dramatic in Zn limited cells whose high affinity transporters should be most effective at extracting Zn from weak ligands; (2) the enhancement occurs with a variety of weak ligands, demonstrating that the underlying mechanism has little chemical specificity; and (3) no enhancement of uptake is seen when Zn is bound in complexes that would make formation of multiligand complexes with uptake molecules difficult. Weak complexing agents which have received heretofore little attention may play a key role in the bioavailability of metals in natural waters.
Self-generated body movements require compensatory eye and head adjustments in order to avoid perturbation of visual information processing. Retinal image stabilization is traditionally ascribed to ...the transformation of visuovestibular signals into appropriate extraocular motor commands for compensatory ocular movements. During locomotion, however, intrinsic “efference copies” of the motor commands deriving from spinal central pattern generator (CPG) activity potentially offer a reliable and rapid mechanism for image stabilization, in addition to the slower contribution of movement-encoding sensory inputs.
Using a variety of in vitro and in vivo preparations of Xenopus tadpoles, we demonstrate that spinal locomotor CPG-derived efference copies do indeed produce effective conjugate eye movements that counteract oppositely directed horizontal head displacements during undulatory tail-based locomotion. The efference copy transmission, by which the extraocular motor system becomes functionally appropriated to the spinal cord, is mediated by direct ascending pathways. Although the impact of the CPG feedforward commands matches the spatiotemporal specificity of classical vestibulo-ocular responses, the two fundamentally different signals do not contribute collectively to image stabilization during swimming. Instead, when the CPG is active, horizontal vestibulo-ocular reflexes resulting from head movements are selectively suppressed.
These results therefore challenge our traditional understanding of how animals offset the disruptive effects of propulsive body movements on visual processing. Specifically, our finding that predictive efference copies of intrinsic, rhythmic neural signals produced by the locomotory CPG supersede, rather than supplement, reactive vestibulo-ocular reflexes in order to drive image-stabilizing eye adjustments during larval frog swimming, represents a hitherto unreported mechanism for vertebrate ocular motor control.
► A novel feedforward mechanism for gaze stabilization during vertebrate locomotion ► Locomotor efference copy drives compensatory eye movements in larval frogs ► The intrinsic CPG signals are conveyed directly to the extraocular motor nuclei ► The efference copy supersedes, rather than supplements, vestibulo-ocular reflexes
Mucosal surfaces are lined by epithelial cells, which provide a complex and adaptive module that ensures first-line defense against external toxics, irritants, antigens, and pathogens. The underlying ...mechanisms of host protection encompass multiple physical, chemical, and immune pathways. In the lung, inhaled agents continually challenge the airway epithelial barrier, which is altered in chronic diseases such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis. In this review, we describe the epithelial barrier abnormalities that are observed in such disorders and summarize current knowledge on the mechanisms driving impaired barrier function, which could represent targets of future therapeutic approaches.
Chelating agents can control the speciation and reactivity of trace metals in biological, environmental, and laboratory-derived media. A large number of trace metals (including Fe, Cu, Zn, Hg, and ...others) show characteristic isotopic fingerprints that can be exploited for the discovery of known and unknown organic metal complexes and related chelating ligands in very complex sample matrices using high-resolution liquid chromatography mass spectrometry (LC-MS). However, there is currently no free open-source software available for this purpose. We present a novel software tool, ChelomEx, which identifies isotope pattern-matched chromatographic features associated with metal complexes along with free ligands and other related adducts in high-resolution LC-MS data. High sensitivity and exclusion of false positives are achieved by evaluation of the chromatographic coherence of the isotope pattern within chromatographic features, which we demonstrate through the analysis of bacterial culture media. A built-in graphical user interface and compound library aid in identification and efficient evaluation of results. ChelomEx is implemented in MatLab. The source code, binaries for MS Windows and MAC OS X as well as test LC-MS data are available for download at SourceForge ( http://sourceforge.net/projects/chelomex ).
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